ANTISENSE OLIGONUCLEOTIDE OF ATN1

Abstract
The invention provides an antisense oligonucleotide capable of controlling ATN1 gene expression and treating dentatorubral-pallidoluysian atrophy. An inventive compound comprises a modified oligonucleotide consisting of 8 to 80 linked nucleosides and having a nucleobase sequence including at least 8 contiguous nucleobases that are complementary to a transcript of ATN1, or a pharmacologically acceptable salt thereof.
Description
TECHNICAL FIELD

The present invention relates to an antisense oligonucleotide of ATN1.


BACKGROUND ART

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration with lesions in a cerebellar dentate nucleus, a red nucleus, a pallidus, and a Luys body, caused by abnormal elongation of CAG repeats of an ATN1 gene. DRPLA is a progressive disease that causes ataxia, myoclonus, epilepsy, and progressive decline in intelligence in children, and ataxia, choreoathetosis, dementia, and personality change in adults. Onset ages widely range from less than one year to the seventies, with an average onset age of 31.5 years. It is known that the severity of clinical symptoms correlates with the number of CAG repeats (see, for example, Non Patent Literature 1).


As a substance that inhibits expression of an ATN1 gene, an RNaseH-independent antisense oligonucleotide against CAG repeats (see, for example, Non Patent Literature 2), ss-siRNA (see, for example, Patent Literature 1 and Non Patent Literature 3), and the like have been reported, and it is indicated that the substances selectively inhibit an allele in which repeats are abnormally elongated. In addition, it has been reported that a morpholino nucleic acid or an RNaseH-dependent LNA gapmer inhibits expression of an ATN1 gene, but the sequence thereof and the degree of inhibition are not described (see, for example, Non Patent Literature 4).


CITATION LIST
Patent Literature



  • Patent Literature 1: WO 2015/017675 A



Non Patent Literature



  • Non Patent Literature 1: Movement Disorders, 2010 Aug. 15, 25(11), pp 1694-700

  • Non Patent Literature 2: PLoS One, 2011, 6(9), e24308.

  • Non Patent Literature 3: Biochemistry, 2014 Jul. 22, 53(28), pp 4510-8

  • Non Patent Literature 4: The 38th Annual Meeting of the Japan Neuroscience Society 2015 2P107



SUMMARY OF INVENTION
Technical Problem

An object of the present invention is to provide a novel antisense oligonucleotide that inhibits expression of an ATN1 gene.


Solution to Problem

The present inventors intensively conducted studies in order to find a compound having an antisense effect on ATN1, and as a result, have found that a compound of the present invention has an excellent ATN1 gene expression inhibitory action, thereby completing the present invention.


That is, the present invention has the following features.


1.


A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770 (3 to 487, 488 to 716, and 718 to 770), or a pharmacologically acceptable salt thereof.


2.


The compound or pharmacologically acceptable salt thereof according to 1, comprising a modified oligonucleotide which has a nucleobase sequence including any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770 (3 to 487, 488 to 716, and 718 to 770).


3.


The compound or pharmacologically acceptable salt thereof according to 1 or 2, comprising a modified oligonucleotide which has any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770 (3 to 487, 488 to 716, and 718 to 770).


4.


A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 59 to 104, 109 to 133, 173 to 192, 207 to 272, 300 to 319, 353 to 372, 419 to 434, 458 to 509, 523 to 559, 561 to 618, 626 to 685, 766 to 785, 787 to 819, 838 to 855, 880 to 922, 924 to 943, 970 to 989, 994 to 1039, 1055 to 1074, 1079 to 1098, 1157 to 1176, 1196 to 1223, 1310 to 1329, 1339 to 1399, 1423 to 1442, 1614 to 1633, 1650 to 1670, 1806 to 1833, 1844 to 1865, 1896 to 1915, 1924 to 1992, 2023 to 2042, 2058 to 2081, 2103 to 2124, 2398 to 2417, 2480 to 2520, 2526 to 2562, 2568 to 2587, 2853 to 2872, 2876 to 2923, 2931 to 2950, 2972 to 3016, 3072 to 3099, 3109 to 3128, 3192 to 3211, 3267 to 3290, 3333 to 3379, 3419 to 3557, 3765 to 3784, 3789 to 3853, 3888 to 3926, 4022 to 4062, 4118 to 4139, 4141 to 4156, 4218 to 4236, and 4266 to 4281 of nucleobases of SEQ ID NO: 1, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 1, or a pharmacologically acceptable salt thereof.


5.


The compound or pharmacologically acceptable salt thereof according to 4, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence represented by position numbers 3419 to 3557 of nucleobases of SEQ ID NO: 1, wherein the modified oligonucleotide is at least 80% complementary to the part in the nucleobase sequence represented by position numbers 3419 to 3557 of the nucleobases of SEQ ID NO: 1.


6.


A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 383 to 398, 986 to 1001, 1004 to 1019, 1378 to 1393, 1398 to 1413, 1853 to 1868, 1971 to 1986, 2189 to 2204, 2522 to 2537, 2562 to 2577, 3662 to 3677, 3987 to 4002, 4217 to 4232, 4266 to 4281, 4335 to 4350, 4360 to 4375, 4477 to 4492, 4562 to 4577, 4636 to 4651, 4687 to 4702, 4734 to 4749, 4840 to 4855, 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 6963 to 6978, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9336 to 9351, 9534 to 9570, 9576 to 9595, 9923 to 9938, 10001 to 10016, 10056 to 10071, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12508 to 12680, 12723 to 12738, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2, or a pharmacologically acceptable salt thereof.


7.


The compound or pharmacologically acceptable salt thereof according to 6, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9534 to 9570, 9576 to 9595, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12572 to 12680, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2.


8.


A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 4320 to 4390 and 12508 to 12680 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2, or a pharmacologically acceptable salt thereof.


9.


The compound or pharmacologically acceptable salt thereof according to 6 or 7, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 10840 to 10865 and 12572 to 12680 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2.


10.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 9, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 696, 697, 699, 706, 713, 715, 716, 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.


11.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 10, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.


12.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 11, comprising a modified oligonucleotide which consists of 12 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 488, 489, 490, 491, 492, 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 696, 697, 699, 706, 713, 715, 716, 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.


13.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 12, comprising a modified oligonucleotide which consists of 12 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, and 241.


14.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 11, comprising a modified oligonucleotide which consists of 16 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.


15.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 14, wherein the modified oligonucleotide includes a phosphorothioate bond.


16.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 15, wherein the modified oligonucleotide includes at least one nucleoside selected from the group consisting of a 2′-modified nucleoside and a 2′-4′-bridged nucleoside.


17.


The compound or pharmacologically acceptable salt thereof according to 16, wherein the 2′-4′-bridged nucleoside is at least one selected from the group consisting of LNA, ENA, cEt, AmNA, scpBNA, and GuNA.


18.


The compound or pharmacologically acceptable salt thereof according to 17, wherein the 2′-4′-bridged nucleoside is LNA.


19.


The compound or pharmacologically acceptable salt thereof according to any one of 16 to 18, wherein the 2′-modified nucleoside is at least one selected from the group consisting of a 2′-O-MCE nucleoside, a 2′-O-MOE nucleoside, a 2′-O-NMA nucleoside, and a 2′-O-Me nucleoside.


20.


The compound or pharmacologically acceptable salt thereof according to 19, wherein the 2′-modified nucleoside is at least one selected from the group consisting of a 2′-O-MCE nucleoside and a 2′-O-MOE nucleoside.


21.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 20, wherein the modified oligonucleotide includes 5-methylcytosine.


22.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 21, wherein


the modified oligonucleotide includes a gap segment, a 5′ wing segment, and a 3′ wing segment,


the gap segment includes at least two deoxyribonucleosides, and a 5′-terminal and a 3′-terminal of the gap segment are deoxyribonucleosides,


the nucleoside at the 3′-terminal of the 5′ wing segment is a sugar-modified nucleoside and is linked to the 5′-terminal of the gap segment, and


the nucleoside at the 5′-terminal of the 3′ wing segment is a sugar-modified nucleoside and is linked to the 3′-terminal of the gap segment.


23.


The compound or pharmacologically acceptable salt thereof according to 22, wherein


the gap segment consists of 5 to 30 deoxyribonucleosides,


the 5′ wing segment and the 3′ wing segment each independently consist of 1 to 10 sugar-modified nucleosides independently selected from the group consisting of LNA, a 2′-O-MCE nucleoside, and a 2′-O-MOE nucleoside,


each of the wing segments includes at least one phosphorothioate bond, and


each of cytosines of the gap segment and each wing segment is replaced with 5-methylcytosine.


24.


The compound or pharmacologically acceptable salt thereof according to 23, wherein


the gap segment consists of 8 to 12 deoxyribonucleosides,


the 5′ wing segment and the 3′ wing segment each independently consist of 2 to 5 sugar-modified nucleosides independently selected from the group consisting of LNA and a 2′-O-MCE nucleoside, and include at least one 2′-O-MCE nucleoside, and


the gap segment includes at least one phosphorothioate bond.


25.


The compound or pharmacologically acceptable salt thereof according to 23, wherein


the gap segment consists of 8 to 12 deoxyribonucleosides,


the 5′ wing segment and the 3′ wing segment each independently consist of 3 to 6 sugar-modified nucleosides selected from the group consisting of a 2′-O-MOE nucleoside and a 2′-O-MCE nucleoside, and


the gap segment includes at least one phosphorothioate bond.


26.


The compound or pharmacologically acceptable salt thereof according to 25, wherein the 5′ wing segment and the 3′ wing segment each independently consist of five 2′-O-MOE nucleosides.


27.


The compound or pharmacologically acceptable salt thereof according to 25, wherein the 5′ wing segment and the 3′ wing segment each independently consist of five 2′-O-MCE nucleosides.


28.


The compound or pharmacologically acceptable salt thereof according to 24, wherein the 5′ wing segment and the 3′ wing segment are each independently selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, LLL, VVLL, VLVL, VLLV, LVLV, LLVV, LVVL, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL, in which L represents LNA, and V represents a 2′-O-MCE nucleoside.


29.


The compound or pharmacologically acceptable salt thereof according to 24, wherein the 5′ wing segment and the 3′ wing segment are each independently selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, VVLL, VLVL, LVLV, LLVV, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL, in which L represents LNA, and V represents a 2′-O-MCE nucleoside.


30.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 29, wherein the modified oligonucleotide consists of 15 to 25 nucleosides.


31.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 30, wherein the modified oligonucleotide is an antisense oligonucleotide.


32.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 31, wherein the compound including the modified oligonucleotide includes a prodrug moiety.


33.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 32, wherein the compound including the modified oligonucleotide includes a functional molecule.


34.


The compound or pharmacologically acceptable salt thereof according to any one of 1 to 33, consisting of the modified oligonucleotide.


35.


The salt according to any one of 1 to 34, wherein the pharmacologically acceptable salt is a sodium salt.


36.


A medicinal drug containing, as an active ingredient, the compound or pharmacologically acceptable salt according to any one of 1 to 35.


37.


A drug for treating, preventing, and/or ameliorating a disease or a condition to which an ATN1 gene expression inhibitory action is effective, the drug comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to any one oft 1 to 35.


38.


An ATN1 gene expression inhibitor comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to any one of 1 to 35.


39.


A drug for treating, preventing, and/or ameliorating dentatorubral-pallidoluysian atrophy, the drug containing, as an active ingredient, the compound or pharmacologically acceptable salt according to any one of 1 to 35.


Advantageous Effects of Invention

The present invention can provide a novel antisense oligonucleotide which has an excellent ATN1 gene expression inhibitory action and is useful particularly for treating, ameliorating, and/or preventing dentatorubral-pallidoluysian atrophy.







DESCRIPTION OF EMBODIMENTS

It is understood that both the above summary and the following detailed description are exemplary and explanatory only and do not limit the present invention as claimed. Herein, a singular form includes a plural form unless otherwise specified.


In the present description, an antisense oligonucleotide may be referred to as “ASO”.


A nucleic acid in nature is most basically composed of adenosine (A), thymidine (T) (or uridine (U)), cytidine (C), and guanosine (G). These basic nucleic acids are often referred to as AT(U)GC and the like. Therefore, herein, for example, regarding a sequence of an ATN1 gene and the like, when the sequence is indicated by “nucleobase sequence” or “SEQ ID NO”, the sequence is basically a sequence of A, T, G, C, and U.


On the other hand, a nucleic acid constituting an ASO of the present invention also includes those in which the basic nucleic acids (AT(U)CG) are structurally modified in addition to the basic nucleic acids (AT(U)CG). Although details of the modification will be described later, the modification includes modification of a sugar moiety, an internucleoside bond, a nucleobase, and/or the like.


Therefore, herein, for example, for the ASO or the like of the present invention, when a nucleobase sequence is described with A, T, G, C, and U in description of “compound” or “compound to which a compound number (M-number and L-number) is imparted”, A, T, G, C, and U also include those in which A, T, G, C, and U are structurally modified.


Hereinafter, the present invention will be described in more detail.


The following terms have the following meanings unless otherwise specified.


“May be substituted” means having no substituent or having a substituent.


“Nucleoside” is a term well known to a person skilled in the art, and is generally understood as a molecule to which a sugar and a nucleobase are bonded and which can be a unit constituting a nucleic acid. Herein, the nucleoside is a broader concept, and includes a deoxyribonucleoside, a ribonucleoside, and a sugar-modified nucleoside described later. The nucleobase may be modified.


“Deoxyribonucleoside” means a molecule having a nucleobase on a carbon atom at a 1′-position of 2′-deoxyribose. The deoxyribonucleoside in the present invention may be a naturally occurring deoxyribonucleoside or a deoxyribonucleoside in which a nucleobase moiety of a naturally occurring deoxyribonucleoside is modified. A plurality of modifications may be made to one deoxyribonucleoside in combination. The modified deoxyribonucleoside is described, for example, in Journal of Medicinal Chemistry, 2016, 59, pp 9645-9667, Medicinal Chemistry Communication, 2014, 5, pp 1454-1471, Future Medicinal Chemistry, 2011, 3, pp 339-365, WO 2018/155450 A and the like.


“Ribonucleoside” means a molecule having a nucleobase on a carbon atom at a 1′-position of ribose. The ribonucleoside in the present invention may be a naturally occurring ribonucleoside or a ribonucleoside in which a nucleobase moiety of a naturally occurring ribonucleoside is modified. A plurality of modifications may be made to one ribonucleoside in combination. The modified ribonucleoside is described, for example, in Journal of Medicinal Chemistry, 2016, 59, pp 9645-9667, Medicinal Chemistry Communication, 2014, 5, pp 1454-1471, Future Medicinal Chemistry, 2011, 3, pp 339-365, WO 2018/155450 A and the like.


“Modified sugar” means


(Z1) a molecule in which ribose or 2′-deoxyribose is partially substituted with one or more substituents,


(Z2) a pentasaccharide or a hexasaccharide different from ribose and 2′-deoxyribose (for example, hexitol, threose, or the like),


(Z3) a molecule in which the entire ribose or 2′-deoxyribose or a tetrahydrofuran ring thereof is replaced with a 5- to 7-membered saturated or unsaturated ring (for example, cyclohexane, cyclohexene, morpholine, or the like) or a partial structure in which a 5- to 7-membered ring can be formed by a hydrogen bond (for example, a peptide structure),


or


(Z4) a molecule in which ribose or 2′-deoxyribose is replaced with an alkylene glycol having 2 to 6 carbon atoms (for example, ethylene glycol, propylene glycol, or the like).


The modified sugar includes a “2′-modified sugar” and a “2′-4′-bridged sugar” described later.


Examples of the modified sugar and the sugar-modified nucleoside described later include sugars, sugar-modified nucleosides, and the like disclosed as being preferably used in an antisense method in JP H10-304889 A, WO 2005/021570 A, JP H10-195098 A, JP 2002-521310 A, WO 2007/143315 A, WO 2008/043753 A, WO 2008/029619 A, WO 2008/049085 A, WO 2017/142054 A and the like(hereinafter, these literatures are referred to as “literatures related to an antisense method”). The modified sugar and the sugar-modified nucleoside are also disclosed in Journal of Medicinal Chemistry, 2016, 59, pp 9645-9667, Medicinal Chemistry Communication, 2014, 5, pp 1454-1471, Future Medicinal Chemistry, 2011, 3, pp 339-365, WO 2018/155450 A, and the like.


Examples of a modified sugar that is partially substituted with one substituent include ribose or 2′-deoxyribose in which any position of a sugar moiety is substituted with the following (i) or (ii).


(i) C1-6 alkyl group.


(ii) A C1-6 alkyl group substituted with at least one selected from the group consisting of a halogen atom, a C1-6 alkoxy group, a halo C1-6 alkoxy group, a mono- or di-C1-6 alkylamino group, a 5- to 10-membered heterocyclic group, a carboxy group, a carbamoyl group, and an N-substituted carbamoyl group.


Here, examples of the N-substituted carbamoyl group include an N-methyl-carbamoyl group and an N-ethyl-carbamoyl group, and the methyl group and the ethyl group of the N-methyl-carbamoyl group and the N-ethyl-carbamoyl group may be substituted with a 5- to 10-membered heterocyclic group or a mono- or di-C1-6 alkylamino group. Specific examples of the N-substituted carbamoyl group include a N-methylcarbamoyl group, a N-ethylcarbamoyl group, a N-dimethylaminoethyl-carbamoyl group, a N-morpholinoethylcarbamoyl group, a N-(2-pyridylethyl) carbamoyl group, a N-((benzimidazol-1-yl) ethyl) carbamoyl group, and the like.


“Sugar-modified nucleoside” means a molecule having the “modified sugar” instead of a sugar moiety of a deoxyribonucleoside or a ribonucleoside. For example, the sugar-modified nucleoside includes “2′-modified nucleoside” and “2′-4′-bridged nucleoside” described later. When the modified sugar is (Z3) as defined above, the sugar-modified nucleoside also includes a molecule in which a modified sugar and a nucleobase are bonded to each other via a methylene chain or the like.


“2′-Modified sugar” means a non-bridged sugar in which an oxygen atom or a carbon atom at a 2′-position of ribose is modified, and includes “2′-O-Me”, “2′-O-MOE”, “2′-O-MCE”, “2′-O-NMA”, “2′-DMAECE”, “2′-MorECE”, “2′-PyECE”, and “BimECE”.


“2′-Modified nucleoside” means a molecule having a nucleobase at a 1′-position of the 2′-modified sugar, and examples thereof include “2′-O-Me nucleoside”, “2′-O-MOE nucleoside”, “2′-O-MCE nucleoside”, “2′-O-NMA nucleoside”, “2′-DMAECE nucleoside”, “2′-MorECE nucleoside”, “2′-PyECE nucleoside”, and “BimECE nucleoside”.


“2′-O-Me” (also referred to as 2′-O-methyl) means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a methoxy group.


“2′-O-Me nucleoside” (also referred to as 2′-O-methyl nucleoside) means a molecule having a nucleobase at a 1′-position of “2′-O-Me”.


“2′-O-MOE” (also referred to as 2′-O-methoxyethyl) means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a 2-methoxyethyloxy group.


“2′-O-MOE nucleoside” (also referred to as 2′-O-methoxyethyl nucleoside) means a molecule having a nucleobase at a 1′-position of “2′-O-MOE”.


“2′-O-MCE” (also referred to as 2′-O-methylcarbamoylethyl) means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a methylcarbamoylethyloxy group.


“2′-O-MCE nucleoside” (also referred to as 2′-O-methylcarbamoylethyl nucleoside) means a molecule having a nucleobase at a 1′-position of “2′-O-MCE”.


“2′-O-NMA” means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a [2-(methylamino)-2-oxoethyl]oxy group.


“2′-O-NMA nucleoside” means a molecule having a nucleobase at a 1′-position of “2′-O-NMA”.


“2′-AP” (“2′-O-AP”) means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a 3-aminopropyloxy group.


“2′-AP nucleoside” (“2′-O-AP nucleoside”) means a molecule having a nucleobase at a 1′-position of “2′-AP”.


“2′-F” means a sugar in which a hydroxy group at a 2′-position of ribose is replaced with a fluorine atom.


“2′-F nucleoside” means a molecule having a nucleobase at a 1′-position of “2′-F”.


“2′-DMAECE” is a modified sugar having the following structure.




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“2′-MorECE” is a modified sugar having the following structure.




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“2′-PyECE” is a modified sugar having the following structure.




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“BimECE” is a modified sugar having the following structure.




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“2′-DMAECE nucleoside”, “2′-MorECE nucleoside”, “2′-PyECE nucleoside”, and “BimECE nucleoside” mean molecules having a nucleobase at a 1′-position of “2′-DMAECE”, “2′-MorECE”, “2′-PyECE”, and “BimECE”, respectively.


“2′-4′-Bridged sugar” means a sugar substituted with a bridging unit at two positions of a 2′-position and a 4′-position in ribose. Examples of the bridging unit include a C2-6 alkylene group (the alkylene group has no substituent or has one or more substituents selected from the group consisting of a halogen atom, an oxo group, and a thioxo group, and one or two methylene groups of the alkylene group are not replaced or independently replaced with a group selected from the group consisting of —O—, —S—, and —NR′— (R′ represents a hydrogen atom, a C1-6 alkyl group, or a halo C1-6 alkyl group)).


“2′-4′-bridged nucleoside” (2′,4′-BNA) means a molecule having a nucleobase at a 1′-position of the 2′-4′-bridged sugar. Examples thereof include α-L-methyleneoxy (4′-CH2—O-2′) BNA or β-D-methyleneoxy (4′-CH2—O-2′) BNA also referred to as LNA (locked nucleic acid (registered trademark)) described later, ethyleneoxy (4′-(CH2)2—O-2′) BNA also referred to as ENA, β-D-thio (4′-CH2—S-2′) BNA, aminooxy (4′-CH2—O—N(R11)-2′) BNA (R11 is H or CH3), oxyamino (4′-CH2—N(R12)—O-2′) BNA (R12 is H or CH3) also referred to as 2′,4′-BNANC, 2′,4′-BNACOC, 3′-amino-2′,4′-BNA, 5′-methyl BNA, (4′-CH(CH3)—O-2′) BNA also referred to as cEt, (4′-CH(CH2OCH3)—O-2′) BNA also referred to as cMOE-BNA, amide-based BNA (4′-C(═O)—N(R13)-2′) BNA (R13 is H or CH3) also referred to as AmNA, (4′-C(spiro-cyclopropyl)-O-2′) BNA also referred to as scpBNA, (4′-CH2—N(R14)-2′) BNA (R14 is C(═NH2+)NHR15 and R15 is H or CH3) also referred to as GuNA, other BNAs known to a person skilled in the art, and the like.


In the “deoxyribonucleoside”, “ribonucleoside”, “2′-modified nucleoside”, “2′-4′-bridged nucleoside”, and the like, examples of a bond between a carbon atom at a 1′-position and a nucleobase include an α-glycosidic bond and a β-glycosidic bond, but the bond is usually a β-glycosidic bond.


“n-” means normal, “s-” means secondary, and “t-” means tertiary.


“Halogen atom” means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.


The “C1-6 alkyl group” means a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and examples thereof include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a s-butyl group, a t-butyl group, a n-pentyl group, an isopentyl group, a neopentyl group, a n-hexyl group, an isohexyl group, and the like.


“Halo C1-6 alkyl group” means a group in which a hydrogen atom at any position of the “C1-6 alkyl group” is substituted with one or more of the “halogen atoms”.


“C1-6 alkylene group” means a divalent group obtained by removing one hydrogen atom at any position from a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and examples thereof include a methylene group, an ethylene (ethanediyl) group, a propane-1,3-diyl (trimethylene) group, a propane-2,2-diyl group, a 2,2-dimethyl-propane-1,3-diyl group, a hexane-1,6-diyl (hexamethylene) group, a 3-methylbutane-1,2-diyl group, and the like.


“C2-6 alkylene group” means a linear or branched divalent group having 2 to 6 carbon atoms in the “C1-6 alkylene group”, and examples thereof are similar to those of the “C1-6 alkylene group” except for a methylene group.


“C2-20 alkylene group” means a divalent group obtained by removing one hydrogen atom at any position from a linear or branched saturated hydrocarbon group having 2 to 20 carbon atoms. Similarly, “C8-12 alkylene group” means a divalent group obtained by removing one hydrogen atom at any position from a linear or branched saturated hydrocarbon group having 8 to 12 carbon atoms.


“C2-20 alkenylene group” means a divalent group obtained by removing one hydrogen atom at any position from a linear or branched unsaturated hydrocarbon group having 2 to 20 carbon atoms and containing at least one double bond.


“C1-6 alkoxy group” means a group in which the “C1-6 alkyl group” is bonded to an oxy group.


“Halo C1-6 alkoxy group” means a group in which a hydrogen atom at any position of the “C1-6 alkoxy group” is substituted with one or more of the “halogen atoms”.


“Mono- or di-C1-6 alkylamino group” means a group in which one hydrogen atom of an amino group is replaced with one “C1-6 alkyl group” or a group in which two hydrogen atoms of an amino group are replaced with two identical or different “C1-6 alkyl groups”, and examples thereof include methylamino, ethylamino, propylamino, isopropylamino, butylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, a N-ethyl-N-methylamino group and the like.


“5- to 10-Membered heterocyclic group” means a 5- to 10-membered monocyclic or fused polycyclic aromatic or non-aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, a sulfur atom, and an oxygen atom as ring-constituting atoms in addition to a carbon atom.


Preferable examples of the “5- to 10-membered heterocyclic group” include thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazolyl, tetrazolyl, triazinyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, imidazolopyridinyl, thienopyridinyl, pyrrolopyridinyl, pyrazolopyridinyl, oxazolopyridinyl, thiazolopyridinyl, imidazopyradinyl, imidazolopyrimidinyl, aziridinyl, oxiranyl, azetidinyl, oxetanyl, thietanyl, tetrahydrothienyl, tetrahydrofuranyl, pyrrolinyl, pyrrolidinyl, oxopyrrolidinyl, imidazolinyl, oxoimidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, pyrazolinyl, pyrazolidinyl, thiazolinyl, thiazolidinyl, tetrahydroisothiazolyl, tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydropyridinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl and the like.


“Oxo group” refers to a group (═O) obtained by substitution with an oxygen atom via a double bond. When an oxo group is substituted with a carbon atom, the oxo group forms a carbonyl group together with the carbon atom.


“Thioxo group” refers to a group (═S) obtained by substitution with a sulfur atom via a double bond. When a thioxo group is substituted with a carbon atom, the thioxo group forms thiocarbonyl together with the carbon atom.


“Nucleobase” is a purine base or a pyrimidine base, and may be a naturally occurring nucleobase or one obtained by modifying a naturally occurring nucleobase. Examples of the naturally occurring nucleobase include adenine (A), guanine (G), thymine (T), cytosine (C), and uracil (U). The “nucleobase” includes the naturally occurring nucleobase and the “modified nucleobase” described later.


Examples of modification of a nucleobase in the “modified nucleobase” include halogenation, methylation, ethylation, n-propylation, isopropylation, cyclopropylation, n-butylation, isobutylation, s-butylation, t-butylation, cyclobutylation, hydroxylation, amination, thiation, demethylation, and the like. More specific examples thereof include: 5-methylation, 5-fluorination, 5-bromination, 5-iodination, and N4-methylation of cytosine; 2-thiation, 5-demethylation, 5-fluoration, 5-bromination, and 5-iodoation of thymine; 2-thiation, 5-fluorination, 5-bromination, and 5-iodination of uracil; N6-Methylation and 8-bromination of adenine; N2-methylation and 8-bromination of guanine; and the like. Examples of modification of a nucleobase moiety in a nucleoside are disclosed in Journal of Medicinal Chemistry, 2016, 59, pp 9645-9667, Medicinal Chemistry Communication, 2014, 5, pp 1454-1471, Future Medicinal Chemistry, 2011, 3, pp 339-365, WO 2018/155450 A, and the like.


The nucleobase in a nucleoside is preferably at least one selected from the group consisting of adenine, guanine, thymine, cytosine, uracil, and 5-methylcytosine.


“5-Methylcytosine” means a cytosine having a methyl group at a 5-position.


“Nucleobase sequence” means a sequence from a 5′ side to a 3′ side of nucleobases of each nucleoside contained in an oligonucleotide.


“Contiguous nucleobases” means a sequence from a 5′ side to a 3′ side of nucleobases in a contiguous part of the “nucleobase sequence”.


“Internucleoside bond” means a group or a bond that forms a covalent bond between adjacent nucleosides in an oligonucleotide. “Internucleoside bond” includes a phosphodiester bond and “modified internucleoside bond” described below.


“Modified internucleoside bond” means a modified phosphodiester bond, and examples thereof include a phosphorothioate bond, a methyl phosphonate bond (including a chiral-methyl phosphonate bond), a methyl thiophosphonate bond, a phosphorodithioate bond, a phosphoramidate bond, a phosphorodiamidate bond, a phosphoramidothioate bond, a boranophosphate bond, and the like. Examples of modification of a phosphodiester bond are disclosed in Journal of Medicinal Chemistry, 2016, 59, pp 9645-9667, Medicinal Chemistry Communication, 2014, 5, pp 1454-1471, Future Medicinal Chemistry, 2011, 3, pp 339-365, and the like, and can be used for a modified phosphodiester bond.


“Modified nucleoside” means a nucleoside having a modified sugar moiety and/or a modified nucleobase.


“Oligonucleotide” means a molecule having a structure in which two or more identical or different “nucleosides” are independently linked to each other by the “internucleoside bond” (for example, a phosphodiester bond or a modified phosphodiester bond).


“Modified oligonucleotide” means an oligonucleotide including at least one selected from the group consisting of a modified internucleoside bond, a modified sugar, and a modified nucleobase.


“Compound comprising a modified oligonucleotide” means a compound comprising a modified oligonucleotide in a chemical structure thereof, and may be the modified oligonucleotide itself. Examples of the compound comprising a modified oligonucleotide include a compound in which a functional molecule is directly or indirectly bonded to the modified oligonucleotide as described later, a compound including a prodrug moiety described later, and the modified oligonucleotide itself


“DNA” means a polynucleotide or an oligonucleotide in which the two or more identical or different “deoxyribonucleosides” are linked to each other by the “internucleoside bond”.


“RNA” means a polynucleotide or an oligonucleotide in which the two or more identical or different “ribonucleosides” are linked to each other by the “internucleoside bond”.


“Antisense effect” means that a target RNA selected corresponding to a target gene hybridizes with, for example, an oligonucleotide having a sequence complementary to a partial sequence of the target RNA to control a function of the target RNA. For example, when the target RNA is mRNA, the antisense effect means inhibition of translation of the target RNA by hybridization, a splicing function converting effect such as exon skipping, degradation of the target RNA by recognition of a portion that has hybridized, and the like.


In the present invention, the target RNA is “ATN1 mRNA” and/or “ATN1 pre-mRNA”.


“Antisense oligonucleotide” (ASO) is an oligonucleotide having the antisense effect. Examples thereof include DNA, a gapmer, a mixmer, and the like, but are not limited thereto, and may be RNA, an oligonucleotide designed to usually have the antisense effect, or the like.


“Hybridize” means an action of forming a double strand between oligonucleotides including sequences complementary to each other or portions thereof, and a phenomenon that oligonucleotides including sequences complementary to each other or portions thereof form a double strand therebetween.


“Complementary” means that two nucleobases can form a Watson-Crick base pair (natural base pair) or a non-Watson-Crick base pair (Hoogsteen base pair, and the like) via a hydrogen bond. Two oligonucleotides or portions thereof can “hybridize” with each other when their sequences are complementary to each other. In order for two oligonucleotides or portions thereof to hybridize with each other, they need not to be completely complementary to each other, but complementarity for two oligonucleotides or portions thereof to hybridize with each other is preferably 70% or more, more preferably 80% or more, and still more preferably 90% or more (for example, 95%, 96%, 97%, 98%, or 99% or more). Complementarity between sequences is determined by using a computer program that automatically identifies a partial sequence of an oligonucleotide. For example, OligoAnalyzer is one type of such software and is provided by Integrated DNA Technologies. This program can also be used in a website.


“Gapmer” means an oligonucleotide including a “gap segment”, a “5′ wing segment”, and a “3′ wing segment” described later.


“Gap segment” is a region including “at least four contiguous nucleosides recognized by RNaseH”, and is not particularly limited as long as it includes four or more contiguous nucleosides and is recognized by RNaseH. However, the contiguous nucleosides are preferably independently selected from a deoxyribonucleoside and a sugar-modified nucleoside. Nucleosides at a 5′-terminal and a 3′-terminal of the gap segment are preferably deoxyribonucleosides.


“5′ Wing segment” is a region linked to a 5′ side of the gap segment and including “at least one nucleoside” without including the “at least four contiguous nucleosides recognized by RNaseH”. Here, a sugar moiety of a nucleoside at a 3′-terminal of the 5′ wing segment is different from a sugar moiety of a nucleoside at a 5′-terminal of the gap segment. Due to the difference in sugar moiety, a boundary between the 5′ wing segment and the gap segment is confirmed. (For example, the nucleoside at the 5′-terminal of the gap segment is a deoxyribonucleoside, and the nucleoside at the 3′-terminal of the 5′ wing segment is a sugar-modified nucleoside.) The nucleoside at the 3′-terminal of the 5′ wing segment is generally a sugar-modified nucleoside. The 5′ wing segment is not particularly limited as long as it satisfies the above definition, but the at least one nucleoside is preferably independently selected from a deoxyribonucleoside and a sugar-modified nucleoside, and includes at least one sugar-modified nucleoside.


“3′ Wing segment” is a region linked to a 3′ side of the gap segment and including “at least one nucleoside” without including the “at least four contiguous nucleosides recognized by RNaseH”. Here, a sugar moiety of a nucleoside at a 5′-terminal of the 3′ wing segment is different from a sugar moiety of a nucleoside at a 3′-terminal of the gap segment. Due to the difference in sugar moiety, a boundary between the 3′ wing segment and the gap segment is confirmed. (For example, the nucleoside at the 3′-terminal of the gap segment is a deoxyribonucleoside, and the nucleoside at the 5′-terminal of the 3′ wing segment is a sugar-modified nucleoside.) The nucleoside at the 5′-terminal of the 3′ wing segment is generally a sugar-modified nucleoside. The 3′ wing segment is not particularly limited as long as it satisfies the above definition, but the at least one nucleoside is preferably independently selected from a deoxyribonucleoside and a sugar-modified nucleoside, and includes at least one sugar-modified nucleoside.


“RNaseH” is generally known as ribonuclease that recognizes a double strand in which DNA and RNA in a living body hybridize with each other, and cleaves the RNA to generate single-stranded DNA. RNaseH can recognize not only a double strand in which DNA and RNA hybridize with each other but also a double strand in which at least one of a nucleobase moiety, a phosphodiester bond moiety, and a sugar moiety of at least one of DNA and RNA is modified. For example, RNaseH can also recognize a double strand in which DNA modified with a phosphorothioate bond and RNA hybridize with each other.


Thus, DNA can be recognized by RNaseH when DNA hybridizes with RNA. In addition, RNA can be cleaved by RNaseH when RNA hybridizes with DNA. The same applies to a case where at least one of a nucleobase moiety, a phosphodiester bond moiety, and a sugar moiety is modified in at least one of DNA and RNA. For example, a typical example is an oligonucleotide in which a phosphodiester bond moiety of DNA is modified with phosphorothioate, and the like.


Examples of modification of DNA and/or RNA that can be recognized by RNaseH are described, for example, in Nucleic Acids Research, 2014, 42, pp 5378-5389, Bioorganic & Medicinal Chemistry Letters, 2008, 18, pp 2296-2300, Molecular BioSystems, 2009, 5, pp 838-843, Nucleic Acid Therapeutics, 2015, 25, pp 266-274, The Journal of Biological Chemistry, 2004, 279, pp 36317-36326, and the like.


RNaseH used in the present invention is preferably mammalian RNaseH, more preferably human RNaseH, and particularly preferably human RNaseH1.


“At least four contiguous nucleosides recognized by RNaseH” are not particularly limited as long as they include four or more contiguous nucleosides and are recognized by RNaseH, but examples thereof include “at least four contiguous deoxyribonucleosides”, and the like. The number of nucleosides constituting “at least four contiguous nucleosides recognized by RNaseH” is, for example, 5 to 30, preferably 5 to 15, more preferably 8 to 12, and particularly preferably 10.


A person skilled in the art can determine whether or not certain at least four contiguous nucleosides are “at least four contiguous nucleosides recognized by RNaseH” by the structure of a sugar moiety of the contiguous nucleosides.


“ATN1” (Atrophin1) means any protein of Atrophin1. “ATN1 mRNA” means mRNA encoding ATN1 protein, and “ATN1 pre-mRNA” means pre-mRNA encoding ATN1 protein. “ATN1 nucleic acid” means any nucleic acid encoding ATN1, and includes, for example, “ATN1 mRNA” and “ATN1 pre-mRNA”.


“ATN1 mRNA” is represented by, for example, SEQ ID NO: 1, and “ATN1 pre-mRNA” is represented by, for example, SEQ ID NO: 2 or 717. “ATN1 mRNA” and “ATN1 pre-mRNA” each have nucleosides linked to each other by a phosphodiester bond, and usually thymine is replaced with uracil. “ATN1 mRNA” and “ATN1 pre-mRNA” do not have a modified sugar, a modified nucleobase, or a modified internucleoside bond in addition to the nucleosides.


“Expression of a gene” means that coding information of a gene is converted into a structure in a cell or a function thereof. Such a structure is not limited, but examples thereof include products of transcription and translation (mRNA, pre-mRNA, protein, and the like).


Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar degeneration with lesions in a cerebellar dentate nucleus, a red nucleus, a pallidus, and/or a Luys body. It has been clarified that a cause of DRPLA is abnormal elongation of CAG repeats of an ATN1 gene. A healthy person has a sequence including 7 to 23 CAG repeats, whereas a DRPLA patient has, for example, a sequence including 49 or more CAG repeats.


Since the length of the CAG repeats in an ATN1 gene of a DRPLA patient varies from patient to patient, an antisense oligonucleotide and ss-siRNA targeting a CAG repeat sequence may have a large variation in efficacy thereof. In addition, CAG repeats are present in many genes other than ATN1, and therefore may have an off-target effect. The antisense oligonucleotide of the present invention has complementarity with ATN1 mRNA and/or ATN1 pre-mRNA, and does not target CAG repeats of an ATN1 gene, that is, has complementarity with a sequence other than a CAG repeat sequence. Therefore, it is expected that the antisense oligonucleotide of the present invention has a small variation in efficacy and has a small off-target effect.


“CAG repeat sequence” is a sequence in which three base units of cytosine (C), adenine (A), and guanine (G) are repeated in this order. A person skilled in the art can determine from a base sequence of an ASO that the CAG repeat sequence is not a target.


Next, preferable forms of the modified oligonucleotide of the present invention or a compound comprising the modified oligonucleotide will be described. Note that the following description will be made by using an antisense oligonucleotide (ASO) or a compound comprising the ASO, which is a preferable example of a modified oligonucleotide or a compound comprising the modified oligonucleotide, but the description is appropriately applied to a modified oligonucleotide or a compound comprising the modified oligonucleotide.


The ASO of the present invention targets mRNA or pre-mRNA of ATN1. The ASO of the present invention does not need to hybridize with the entire mRNA or pre-mRNA of ATN1, and usually hybridizes with at least a part thereof. For example, a part of mRNA or pre-mRNA of ATN1 hybridizes with an oligonucleotide having a sequence complementary to a partial sequence of mRNA or pre-mRNA of ATN1 (such as a gapmer, an oligonucleotide designed to usually have an antisense effect, or the like) to control expression of the ATN1 gene. In addition, the entire ASO does not need to hybridize, and a part of the ASO does not need to hybridize.


Complementarity between a nucleobase sequence of the ASO of the present invention and a partial sequence of mRNA or pre-mRNA of ATN1 is preferably 70% or more, more preferably 80% or more, and still more preferably 90% or more (for example, 95%, 96%, 97%, 98%, or 99% or more). In order for the ASO of the present invention to hybridize with at least a part of a partial sequence of mRNA or pre-mRNA of ATN1, the sequences do not need to be completely complementary to each other, but are more preferably completely complementary to each other.


The ASO of the present invention includes a gap segment, a 5′ wing segment, and a 3′ wing segment.


The gap segment consists of at least five nucleosides independently selected from the group consisting of a deoxyribonucleoside, a ribonucleoside, and a sugar-modified nucleoside, and 3′-terminals and 5′-terminals of the nucleosides are each independently a deoxyribonucleoside. The gap segment preferably includes “at least four contiguous deoxyribonucleosides”.


The number of nucleosides included in the gap segment is preferably 5 to 30, more preferably 5 to 15, still more preferably 8 to 12, further still more preferably 9 to 11, and particularly preferably 10.


In a certain embodiment, the gap segment consists of deoxyribonucleosides.


An internucleoside bond included in the gap segment is preferably at least one independently selected from a phosphodiester bond and a modified phosphodiester bond, and more preferably at least one independently selected from a phosphodiester bond and a phosphorothioate bond. The internucleoside bond included in the gap segment preferably includes at least one phosphorothioate bond, more preferably 50% or more of the internucleoside bonds are phosphorothioate bonds, still more preferably 75% or more of the internucleoside bonds are phosphorothioate bonds, further still more preferably 80% or more of the internucleoside bonds are phosphorothioate bonds, further still more preferably 90% or more of the internucleoside bonds are phosphorothioate bonds, and particularly preferably all of the internucleoside bonds are phosphorothioate bonds.


The 5′ wing segment consists of at least one nucleoside independently selected from the group consisting of a deoxyribonucleoside, a ribonucleoside, and a sugar-modified nucleoside. However, a 3′-terminal of the 5′ wing segment bonded to the gap segment is a sugar-modified nucleoside and does not include “at least four contiguous nucleosides recognized by RNaseH.”


The 3′ wing segment consists of at least one nucleoside independently selected from the group consisting of a deoxyribonucleoside, a ribonucleoside, and a sugar-modified nucleoside. However, a 5′-terminal of the 3′ wing segment bonded to the gap segment is a sugar-modified nucleoside and does not include “at least four contiguous nucleosides recognized by RNaseH.”


The 5′ wing segment and the 3′ wing segment each preferably do not include “at least four contiguous deoxyribonucleosides”.


Hereinafter, a property common to the 5′ wing segment and the 3′ wing segment will be described as a wing segment.


The number of nucleosides included in each of the wing segments is 1 to 15, preferably 1 to 10, more preferably 1 to 7, still more preferably 2 to 6, further still more preferably 3 to 5, and particularly preferably 3 or 5.


A sugar-modified nucleoside included in the wing segment is preferably a nucleoside having increased affinity for a partial sequence of ATN1 mRNA and/or ATN1 pre-mRNA or a nucleoside having increased resistance to a nucleolytic enzyme due to substitution or the like. More preferably, the sugar-modified nucleoside included in the wing segment is independently selected from a 2′-modified nucleoside and 2′,4′-BNA.


The 2′-modified nucleoside included in the wing segment is preferably at least one independently selected from the group consisting of a 2′-O-Me nucleoside, a 2′-O-MOE nucleoside, a 2′-AP nucleoside, a 2′-F nucleoside, a 2′-O-NMA nucleoside, a 2′-O-MCE nucleoside, a 2′-DMAECE nucleoside, a 2′-MorECE nucleoside, a 2′-PyECE nucleoside, and a BimECE nucleoside, more preferably at least one independently selected from the group consisting of a 2′-O-Me nucleoside, a 2′-O-MOE nucleoside, a 2′-O-NMA nucleoside, and a 2′-O-MCE nucleoside, and still more preferably at least one independently selected from a 2′-O-MOE nucleoside and a 2′-O-MCE nucleoside.


The 2′,4′-BNA included in the wing segment is preferably at least one independently selected from the group consisting of LNA, cEt, ENA, BNANC, AmNA, GuNA, and scpBNA, and more preferably LNA.


The sugar-modified nucleoside included in the wing segment is more preferably at least one independently selected from a 2′-O-MOE nucleoside, LNA, and a 2′-O-MCE nucleoside. Still more preferably the sugar-modified nucleoside included in the wing segment is a 2′-O-MOE nucleoside, or is a 2′-O-MCE nucleoside, or is LNA and a 2′-O-MCE nucleoside. Particularly preferably the sugar-modified nucleoside included in the wing segment is a 2′-O-MOE nucleoside, or is LNA and a 2′-O-MCE nucleoside.


Preferably, each of the wing segments consists of 1 to 10 nucleosides independently selected from the group consisting of a sugar-modified nucleoside and a deoxyribonucleoside, and includes at least one sugar-modified nucleoside. More preferably, each of the wing segments consists of 2 to 6 nucleosides independently selected from the group consisting of a sugar-modified nucleoside and a deoxyribonucleoside, and includes at least two sugar-modified nucleoside. Still more preferably, each of the wing segments consists of 2 to 6 nucleosides independently selected from the group consisting of a 2′-modified nucleoside and 2′,4′-BNA. Further still more preferably, each of the wing segments consists of 3 to 5 nucleosides independently selected from the group consisting of a 2′-modified nucleoside and 2′,4′-BNA.


More specifically, each of the wing segments consists of 1 to 10, preferably 2 to 6, more preferably 3 to 5 nucleosides independently selected from LNA, a 2′-O-MCE nucleoside, and a 2′-O-MOE nucleoside. More preferably, each of the wing segments consists of 2 to 5, more preferably 3 to 5 nucleosides independently selected from LNA and a 2′-O-MCE nucleoside. Among these, still more preferably, each of the wing segments includes at least one 2′-O-MCE nucleoside, and further still more preferably, each of the wing segments includes at least one LNA and at least one 2′-O-MCE nucleoside. Further still more preferably, each of the wing segments consists of two LNAs and one or two 2′-O-MCE nucleosides. Particularly preferably, each of the wing segments consists of two LNAs and one 2′-O-MCE nucleoside. As another aspect, each of the wing segments consists of preferably three to six, particularly preferably five 2′-O-MOE nucleosides. As still another aspect, each of the wing segments consists of preferably three to six, particularly preferably five 2′-O-MCE nucleosides.


As another preferable aspect, each of the wing segments is an oligonucleotide consisting of 2 to 5 nucleosides independently selected from the group consisting of 2′,4′-BNA and a deoxyribonucleoside and including at least two 2′,4′-BNAs. For such an oligonucleotide, WO 2016/127002 A and the like can be referred to.


In some embodiments of the present invention, the 5′ wing segment and the 3′ wing segment each independently include 3, 4, 5, or 6 sugar-modified nucleosides, and the gap segment consists of 8, 9, 10, 11, 12, 13, or 14 deoxyribonucleosides. The number of nucleosides in such a gapmer can be represented by ((5′ wing segment)-(gap segment)-(3′ wing segment)), and the gapmer includes 5-10-5, 5-11-4, 4-11-5, 4-12-4, 3-14-3, 6-8-6, 3-12-3, 3-10-3, 4-10-4, 3-10-4, 4-10-3, 3-9-3, 4-9-4, 3-9-4, 4-9-3, 3-8- 3, 3-8-4, 4-8-3, and 4-8-4 nucleosides.


In some embodiments, the ASO includes at least 11, 12, 13, 14, or 15 contiguous nucleosides, the gap segment includes at least 5, 6, 7, 8, or 9 contiguous nucleosides, and the 5′ wing segment and the 3′ wing segment are any of the following (i) to (iv):


(i) The 5′ wing segment and the 3′ wing segment each independently include three, four, five, or six 2′-O-MOE nucleosides.


(ii) The 5′ wing segment and the 3′ wing segment each independently include three, four, five, or six 2′-O-MCE nucleosides.


(iii) The 5′ wing segment and the 3′ wing segment each independently include two, three, four, five, or six LNAs.


(iv) The 5′ wing segment and the 3′ wing segment each independently include three or four selected from a 2′-O-MCE nucleoside and LNA, and include at least one 2′-O-MCE nucleoside and at least one LNA.


The 5′ wing segment and the 3′ wing segment in the ASO of the present invention are preferably selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, LLL, VVLL, VLVL, VLLV, LVLV, LLVV, LVVL, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL.


More preferably, the 5′ wing segment and the 3′ wing segment are selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, VVLL, VLVL, VLLV, LVLV, LLVV, LVVL, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL.


Still more preferably, the 5′ wing segment and the 3′ wing segment are selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, VVLL, VLVL, LVLV, LLVV, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL.


Further still more preferably, the 5′ wing segment is selected from the group consisting of VLL, VLV, VVL, VVLL, VLVL, VLLL, VLVV, VVLV, and VVVL, and the 3′ wing segment is selected from the group consisting of LLV, VLV, LVV, LLVV, LVLV, VLLV, VVLV, VLVV, and LVVV.


Further still more preferably, the 5′ wing segment is selected from the group consisting of VLL, VLV, VVL, and VLVL, and the 3′ wing segment is selected from the group consisting of LLV, VLV, LVV, and LVLV.


Particularly preferably, the 5′ wing segment is VLL, and the 3′ wing segment is LLV.


As another aspect, preferably, the 5′ wing segment is selected from the group consisting of LLL, VLL, LVL, VVL, LLV, VLVL, LVLV, LLVV, and VLLV, and the 3′ wing segment is selected from the group consisting of LLL, LLV, LVL, LVV, VLL, LVLV, and VLLV.


More preferably, the 5′ wing segment is selected from the group consisting of VLL, LVL, VVL, LLV, VLVL, and VLLV, and the 3′ wing segment is selected from the group consisting of LLV, LVL, LVV, VLL, LVLV, and VLLV.


Here, L and V in the 5′ wing segment and the 3′ wing segment are sugar-modified nucleosides having different modified sugars, and a left side represents a 5′ side and a right side represents a 3′ side. Preferably, L represents a 2′-4′-bridged nucleoside and V represents a 2′-modified nucleoside. Particularly preferably, L represents LNA and V represents a 2′-O-MCE nucleoside.


An internucleoside bond included in the 5′ wing segment is preferably at least one independently selected from a phosphodiester bond and a modified phosphodiester bond, and more preferably at least one independently selected from a phosphodiester bond and a phosphorothioate bond. The internucleoside bond included in the 5′ wing segment preferably includes at least one phosphorothioate bond, more preferably 50% or more of the internucleoside bonds are phosphorothioate bonds, still more preferably 60% or more of the internucleoside bonds are phosphorothioate bonds, further still more preferably 75% or more of the internucleoside bonds are phosphorothioate bonds, further still more preferably 80% or more of the internucleoside bonds are phosphorothioate bonds, further still more preferably 90% or more of the internucleoside bonds are phosphorothioate bonds, and particularly preferably all of the internucleoside bonds are phosphorothioate bonds.


The 3′ wing segment is similar to the 5′ wing segment.


As another aspect, all of the internucleoside bonds included in the wing segment may be phosphodiester bonds from a viewpoint that toxicity can be reduced. However, preferably, some of the internucleoside bonds are phosphodiester bonds.


An internucleoside bond at a 5′-terminal included in the 5′ wing segment is preferably a phosphorothioate bond. An internucleoside bond at a 3′-terminal included in the 3′ wing segment is preferably a phosphorothioate bond. Other internucleoside bonds of the 5′ wing segment other than the internucleoside bond at the 5′-terminal of the 5′ wing segment may be each a phosphodiester bond or a phosphorothioate bond. However, preferably, 50% or more of the internucleoside bonds are phosphodiester bonds, more preferably, 60% or more of the internucleoside bonds are phosphodiester bonds, still more preferably, 75% or more of the internucleoside bonds are phosphodiester bonds, further still more preferably, 80% or more of the internucleoside bonds are phosphodiester bonds, further still more preferably, 90% or more of the internucleoside bonds are phosphodiester bonds, and particularly preferably, all of the internucleoside bonds are phosphodiester bonds. Other internucleoside bonds of the 3′ wing segment other than the internucleoside bond at the 3′-terminal of the 3′ wing segment may be each a phosphodiester bond or a phosphorothioate bond. However, preferably, 50% or more of the internucleoside bonds are phosphodiester bonds, more preferably, 60% or more of the internucleoside bonds are phosphodiester bonds, still more preferably, 75% or more of the internucleoside bonds are phosphodiester bonds, further still more preferably, 80% or more of the internucleoside bonds are phosphodiester bonds, further still more preferably, 90% or more of the internucleoside bonds are phosphodiester bonds, and particularly preferably, all of the internucleoside bonds are phosphodiester bonds. Among the internucleoside bonds included in each of the wing segments, an internucleoside bond located closest to the gap segment is preferably a phosphodiester bond.


For example, when the 5′ wing segment includes two internucleoside bonds, the internucleoside bond at the 5′-terminal is preferably a phosphorothioate bond, and the internucleoside bond at a side of the gap segment is preferably a phosphodiester bond.


When the 5′ wing segment includes three internucleoside bonds, the internucleoside bond at the 5′-terminal is preferably a phosphorothioate bond, and the other two internucleoside bonds included in the 5′ wing segment are each independently preferably a phosphodiester bond or a phosphorothioate bond, and particularly preferably a phosphodiester bond.


When the 5′ wing segment includes four internucleoside bonds, the internucleoside bond at the 5′-terminal is preferably a phosphorothioate bond, and the other three internucleoside bonds included in the 5′ wing segment are each independently preferably a phosphodiester bond or a phosphorothioate bond, and particularly preferably a phosphodiester bond.


When the 3′ wing segment includes two internucleoside bonds, the internucleoside bond at the 3′-terminal is preferably a phosphorothioate bond, and the internucleoside bond at a side of the gap segment is preferably a phosphodiester bond.


When the 3′ wing segment includes three internucleoside bonds, the internucleoside bond at the 3′-terminal is preferably a phosphorothioate bond, and the other two internucleoside bonds included in the 3′ wing segment are each independently preferably a phosphodiester bond or a phosphorothioate bond, and particularly preferably a phosphodiester bond.


When the 3′ wing segment includes four internucleoside bonds, the internucleoside bond at the 3′-terminal is preferably a phosphorothioate bond, and the other three internucleoside bonds included in the 3′ wing segment are each independently preferably a phosphodiester bond or a phosphorothioate bond, and particularly preferably a phosphodiester bond.


In the ASO of the present invention, preferably, the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a phosphodiester bond or a modified phosphodiester bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a phosphodiester bond or a modified phosphodiester bond. More preferably, the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a modified phosphodiester bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a modified phosphodiester bond. Still more preferably, the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a phosphorothioate bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a phosphorothioate bond.


In another preferable embodiment of the ASO of the present invention, the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a phosphodiester bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a phosphorothioate bond.


The present invention includes an ASO in which the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a phosphorothioate bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a phosphodiester bond. The present invention includes an ASO in which the 3′-terminal of the 5′ wing segment and the 5′-terminal of the gap segment are linked to each other by forming a phosphodiester bond, and the 5′-terminal of the 3′ wing segment and the 3′-terminal of the gap segment are linked to each other by forming a phosphodiester bond.


The ASO of the present invention is preferably complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 59 to 104, 109 to 133, 173 to 192, 207 to 272, 300 to 319, 353 to 372, 419 to 434, 458 to 509, 523 to 559, 561 to 618, 626 to 685, 766 to 785, 787 to 819, 838 to 855, 880 to 922, 924 to 943, 970 to 989, 994 to 1039, 1055 to 1074, 1079 to 1098, 1157 to 1176, 1196 to 1223, 1310 to 1329, 1339 to 1399, 1423 to 1442, 1614 to 1633, 1650 to 1670, 1806 to 1833, 1844 to 1865, 1896 to 1915, 1924 to 1992, 2023 to 2042, 2058 to 2081, 2103 to 2124, 2398 to 2417, 2480 to 2520, 2526 to 2562, 2568 to 2587, 2853 to 2872, 2876 to 2923, 2931 to 2950, 2972 to 3016, 3072 to 3099, 3109 to 3128, 3192 to 3211, 3267 to 3290, 3333 to 3379, 3419 to 3557, 3765 to 3784, 3789 to 3853, 3888 to 3926, 4022 to 4062, 4118 to 4139, 4141 to 4156, 4218 to 4236, and 4266 to 4281 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


More preferably, the ASO of the present invention is complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 238 to 272, 537 to 559, 585 to 618, 664 to 683, 787 to 819, 838 to 855, 924 to 943, 972 to 987, 994 to 1029, 1055 to 1074, 1080 to 1095, 1204 to 1219, 1310 to 1329, 1362 to 1397, 1650 to 1670, 1806 to 1833, 1844 to 1865, 1896 to 1915, 1955 to 1992, 2058 to 2081, 2103 to 2124, 2480 to 2503, 2876 to 2923, 2931 to 2946, 2979 to 3016, 3109 to 3128, 3192 to 3211, 3267 to 3290, 3333 to 3379, 3419 to 3557, 3812 to 3833, 3888 to 3926, 4022 to 4062, 4118 to 4137, 4218 to 4236, and 4266 to 4281 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


Still more preferably, the ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3419 to 3557 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


Particularly preferable positions of ATN1 mRNA complementary to the ASO of the present invention are listed below.


The ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3452 to 3467 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


The ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3459 to 3474 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


The ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3460 to 3475 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


The ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3461 to 3476 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


The ASO of the present invention is complementary to a part of a nucleobase sequence represented by position numbers 3488 to 3503 of nucleobases of ATN1 mRNA represented by SEQ ID NO: 1.


Complementarity between the ASO of the present invention and a corresponding part of ATN1 mRNA represented by SEQ ID NO: 1 (for example, each of the above-described target regions) is at least 80%, preferably 85% or more, more preferably 90% or more, and still more preferably 95%, 96%, 97%, 98%, or 99% or more.


The ASO of the present invention preferably consists of 8 to 80 nucleosides complementary to a part of each of the above-described target regions of ATN1 mRNA represented by SEQ ID NO: 1. The ASO of the present invention consists of more preferably 10 to 50 nucleosides, still more preferably 16 to 20 nucleosides, particularly preferably 16 or 20 nucleosides.


The ASO of the present invention is preferably complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 383 to 398, 986 to 1001, 1004 to 1019, 1378 to 1393, 1398 to 1413, 1853 to 1868, 1971 to 1986, 2189 to 2204, 2522 to 2537, 2562 to 2577, 3662 to 3677, 3987 to 4002, 4217 to 4232, 4266 to 4281, 4335 to 4350, 4360 to 4375, 4477 to 4492, 4562 to 4577, 4636 to 4651, 4687 to 4702, 4734 to 4749, 4840 to 4855, 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 6963 to 6978, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9336 to 9351, 9534 to 9570, 9576 to 9595, 9923 to 9938, 10001 to 10016, 10056 to 10071, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12508 to 12680, 12723 to 12738, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is preferably complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 383 to 398, 986 to 1001, 1004 to 1019, 1378 to 1393, 1398 to 1413, 1853 to 1868, 1971 to 1986, 2189 to 2204, 2522 to 2537, 2562 to 2577, 3662 to 3677, 3987 to 4002, 4217 to 4232, 4266 to 4281, 4335 to 4350, 4360 to 4375, 4477 to 4492, 4562 to 4577, 4636 to 4651, 4687 to 4702, 4734 to 4749, 4840 to 4855, 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 6963 to 6978, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9336 to 9351, 9534 to 9570, 9576 to 9595, 9923 to 9938, 10001 to 10016, 10056 to 10071, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12508 to 12523, 12572 to 12680, 12723 to 12738, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is preferably complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9534 to 9570, 9576 to 9595, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12572 to 12680, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


More preferably, the ASO of the present invention is complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 986 to 1001, 1004 to 1019, 1378 to 1393, 1398 to 1413, 4217 to 4232, 4335 to 4350, 4360 to 4375, 4477 to 4492, 4562 to 4577, 4636 to 4651, 4687 to 4702, 4734 to 4749, 4840 to 4855, 5697 to 5715, 6963 to 6978, 7262 to 7284, 7310 to 7343, 7389 to 7408, 7512 to 7544, 7563 to 7580, 7649 to 7668, 7697 to 7712, 7719 to 7754, 7780 to 7799, 7805 to 7820, 7929 to 7944, 8035 to 8054, 8087 to 8122, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8680 to 8717, 8783 to 8806, 8828 to 8849, 9205 to 9228, 10297 to 10344, 10352 to 10367, 10400 to 10437, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12508 to 12523, 12572 to 12680, 12723 to 12738, 13477 to 13498, 13553 to 13591, 13687 to 13727, 13783 to 13802, 13883 to 13901, and 13931 to 13946 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


Still more preferably, the ASO of the present invention is complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 5697 to 5715, 7262 to 7284, 7310 to 7343, 7389 to 7408, 7512 to 7544, 7563 to 7580, 7649 to 7668, 7697 to 7712, 7719 to 7754, 7780 to 7799, 7805 to 7820, 7929 to 7944, 8035 to 8054, 8087 to 8122, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8680 to 8717, 8783 to 8806, 8828 to 8849, 9205 to 9228, 10297 to 10344, 10352 to 10367, 10400 to 10437, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12572 to 12680, 13477 to 13498, 13553 to 13591, 13687 to 13727, 13783 to 13802, 13883 to 13901, and 13931 to 13946 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


Further still more preferably, the ASO of the present invention is complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 10840 to 10865 and 12572 to 12680 of nucleobases.


Particularly preferably, the ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12572 to 12680 of nucleobases.


As another aspect, the ASO of the present invention is preferably complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 4320 to 4390 and 12508 to 12680 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


As another aspect, the ASO of the present invention is preferably complementary to a part in a nucleobase sequence represented by position numbers 4320 to 4390 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


As another aspect, the ASO of the present invention is more preferably complementary to a part in a nucleobase sequence represented by position numbers 12508 to 12680 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


Particularly preferable positions of ATN1 pre-mRNA complementary to the ASO of the present invention are listed below.


The ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12575 to 12590 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12582 to 12597 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12583 to 12598 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12584 to 12599 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


The ASO of the present invention is complementary to a part in a nucleobase sequence represented by position numbers 12611 to 12626 of nucleobases of ATN1 pre-mRNA represented by SEQ ID NO: 2.


Complementarity between the ASO of the present invention and a corresponding part of ATN1 pre-mRNA represented by SEQ ID NO: 2 (for example, each of the above-described target regions) is at least 80%, preferably 85% or more, more preferably 90% or more, and still more preferably 95%, 96%, 97%, 98%, or 99% or more.


The ASO of the present invention preferably consists of 8 to 80 nucleosides complementary to a part of each of the above-described target regions of ATN1 pre-mRNA represented by SEQ ID NO: 2. The ASO of the present invention consists of more preferably 10 to 50 nucleosides, still more preferably 16 to 20 nucleosides, particularly preferably 16 or 20 nucleosides.


The nucleobase sequence in the ASO of the present invention includes preferably at least 8, more preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any of nucleobase sequences of SEQ ID NOs: 3 to 716 and 717 to 770 (3 to 487, 488 to 716, and 717 to 770 in one aspect).


The nucleobase sequence in the ASO of the present invention more preferably includes any of nucleobase sequences of SEQ ID NOs: 3 to 716 and 717 to 770 (3 to 487, 488 to 716, and 717 to 770 in one aspect).


The nucleobase sequence in the ASO of the present invention preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group A (A1, A2, and A3), and more preferably has any one of nucleobase sequences of nucleobase sequence group A (A1, A2, and A3).


As another aspect, the nucleobase sequence in the ASO of the present invention more preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group B (B1, B2, and B3), and still more preferably has any one of nucleobase sequences of nucleobase sequence group B (B1, B2, and B3).


As another aspect, the nucleobase sequence in the ASO of the present invention further still more preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group C (C1 and C2), and further still more preferably has any one of nucleobase sequences of nucleobase sequence group C (C1 and C2).


Nucleobase sequence group A1:


A group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.


Nucleobase sequence group A2:


A group consisting of SEQ ID NOs: 488, 489, 490, 491, 492, 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 696, 697, 699, 706, 713, 715, and 716.


Nucleobase sequence group A3:


A group consisting of SEQ ID NOs: 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746,748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.


Nucleobase sequence group B1:


A group consisting of SEQ ID NOs: 19, 37, 38, 47, 55, 59, 61, 62, 67, 68, 70, 72, 75, 78, 82, 83, 84, 85, 86, 88, 89, 91, 101, 102, 103, 104, 105, 106, 107, 109, 111, 112, 113, 114, 117, 120, 121, 122, 124, 128, 138, 151, 152, 153, 154, 156, 157, 159, 160, 161, 163, 168, 169, 171, 174, 180, 181, 184, 185, 186, 187, 188, 189, 190, 192, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 298, 299, 302, 310, 316, 320, 326, 327, 328, 332, 333, 337, 345, 346, 350, 355, 357, 358, 361, 362, 363, 364, 365, 366, 367, 372, 375, 376, 377, 378, 379, 382, 394, 395, 397, 398, 400, 401, 403, 404, 407, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 477, 478, 479, 480, 482, 483, 484, 485, and 486.


Nucleobase sequence group B2:


A group consisting of SEQ ID NOs: 488, 489, 490, 491, 492, 513, 515, 533, 534, 585, 586, 589, 592, 593, 595, 596, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 697, 699, 706, 713, 715, and 716.


Nucleobase sequence group B3:


A group consisting of SEQ ID NOs: 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746,748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.


Nucleobase sequence group C1:


A group consisting of SEQ ID NOs: 128, 203, 204, 205, 206, 207, 208, 209, 215, 216, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 363, 364, 365, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442 444, 445, 446, 447, 448, 449, 450, 451, 452, 443, 454, 455, 456, 457, 458, 459, 460, 461, 462, 453 463, 464, 465, 466, and 467.


Nucleobase sequence group C2:


A group consisting of SEQ ID NOs: 488, 489, 490, 491, 492, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 715, and 716.


In another aspect, the nucleobase sequence in the ASO of the present invention preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence groups D1, D2, and D4, and more preferably has any one of nucleobase sequences of nucleobase sequence groups D1, D2, and D4. In such an aspect, the ASO of the present invention consists of preferably 8 to 80, more preferably 12 to 80, still more preferably 12 to 50, further still more preferably 16 to 20, further still more preferably 16 to 18, and particularly preferably 16 nucleosides.


In another aspect, the nucleobase sequence in the ASO of the present invention preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group D3, and more preferably has any one of nucleobase sequences of nucleobase sequence groups D3. In such an aspect, the ASO of the present invention consists of preferably 8 to 80, more preferably 12 to 80, still more preferably 12 to 50, further still more preferably 16 to 20, and particularly preferably 18 nucleosides.


As still another aspect, the nucleobase sequence in the ASO of the present invention more preferably has a nucleobase sequence including at least 8, preferably 8, 9, 10, 11, 12, 13, 14, or 15 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group E, and still more preferably has any one of nucleobase sequences of nucleobase sequence group E. In such an aspect, the ASO of the present invention consists of preferably 8 to 80, more preferably 16 to 80, still more preferably 16 to 50, further still more preferably 16 to 20, and particularly preferably 20 nucleosides.


Nucleobase sequence group D1:


A group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, and 241.


Among the SEQ ID NOs listed in nucleobase sequence group D1, particularly preferable SEQ ID NOs are listed below.


SEQ ID NOs: 208, 215, 220, 221, and 222.


Nucleobase sequence group D2:


A group consisting of SEQ ID NOs: 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 696, 697, 699, 706, and 713.


Nucleobase sequence group D3:


A group consisting of SEQ ID NOs: 488, 489, 490, 491, 492, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 715, and 716.


Nucleobase sequence group D4:


A group consisting of SEQ ID NOs: 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746,748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.


Nucleobase sequence group E:


A group consisting of SEQ ID NOs: 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.


An ASO having a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence groups D1 and D2 preferably includes at least one LNA and at least one 2′-O-MCE nucleoside in each of the wing segments. Above all, the ASO preferably includes one or two LNAs and one or two 2′-O-MCE nucleosides, and more preferably includes two LNAs and one 2′-O-MCE nucleoside, or one LNA and two 2′-O-MCE nucleosides. The ASO may include two LNAs and two 2′-O-MCE nucleosides. Particularly preferably, the ASO includes two LNAs and one 2′-O-MCE nucleoside.


An ASO having a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group E includes particularly preferably at least one 2′-O-MOE nucleoside or at least one 2′-O-MCE nucleoside in each of the wing segments. Above all, the ASO preferably includes five 2′-O-MOE nucleosides or five 2′-O-MCE nucleosides, and particularly preferably includes five 2′-O-MOE nucleosides.


An ASO having a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group D3 preferably includes at least one LNA and at least one 2′-O-MCE nucleoside in each of the wing segments. Above all, the ASO preferably includes one or two LNAs and one or two 2′-O-MCE nucleosides, and particularly preferably includes two LNAs and two 2′-O-MCE nucleosides.


An ASO having a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of nucleobase sequence group D4 preferably includes at least one LNA in each of the wing segments. Above all, the ASO preferably has one to three LNAs, and particularly preferably has three LNAs.


A functional molecule may be directly or indirectly bonded to the ASO of the present invention. The bond between the functional molecule and the ASO may be direct or indirect via another substance. However, the oligonucleotide and the functional molecule are preferably bonded to each other by a covalent bond, an ionic bond, or a hydrogen bond. More preferably, the oligonucleotide and the functional molecule are directly bonded to each other by a covalent bond or bonded to each other via a linker (linking group) by a covalent bond from a viewpoint of high bonding stability.


When the functional molecule is bonded to the ASO by a covalent bond, the functional molecule is preferably directly or indirectly bonded to a 3′-terminal or a 5′-terminal of the ASO molecule. The bonding between the linker or the functional molecule and a terminal nucleoside of the ASO molecule is selected depending on the functional molecule.


The linker or the functional molecule and the terminal nucleoside of the ASO molecule are preferably linked to each other by a phosphodiester bond or a modified phosphodiester bond, and more preferably linked to each other by a phosphodiester bond.


The linker or the functional molecule may be directly linked to an oxygen atom at a 3′ position of a nucleoside at a 3′-terminal or an oxygen atom at a 5′-position of a nucleoside at a 5′-terminal of the ASO molecule.


The structure of “functional molecule” (conjugate) is not particularly limited, and bonding of the functional molecule to the ASO imparts a desired function to the ASO. Examples of the desired function include a labeling function, a purification function, and a function of delivery to a target site. Examples of a molecule that imparts a labeling function include compounds such as a fluorescent protein, luciferase, and the like. Examples of a molecule that impart a purification function include compounds such as biotin, avidin, His tag peptide, GST tag peptide, FLAG tag peptide, and the like.


In addition, a molecule having a function of delivering the ASO to a target site is preferably bonded as the functional molecule from a viewpoint of highly specifically and efficiently delivering the ASO to a target site (for example, brain or spinal cord) with very effectively controlling expression of an ATN1 gene by the ASO. For the molecule having the function of delivery, for example, European Journal of Pharmaceutics and Biopharmaceutics, 2016, 107, pp 321-340, Advanced Drug Delivery Reviews, 2016, 104, pp 78-92, Expert Opinion on Drug Delivery, 2014, 11, pp 791-822, and the like can be referred to.


Examples of the functional molecule capable of efficiently delivering the ASO of the present invention to the brain, the spinal cord, and the like with high specificity include a lipid and a sugar (for example, glucose, sucrose, or the like). Examples of the lipid include: cholesterol; a fat-soluble vitamin such as vitamin E (a tocopherol or a tocotrienol), vitamin A, vitamin D, vitamin K, or the like; a fatty acid; an intermediate metabolite such as acylcarnitine, acyl-CoA or the like; a glycolipid; a glyceride; derivatives thereof; and the like.


As a functional molecule capable of delivering the ASO of the present invention to the liver with high specificity, a sugar derivative having an interaction with an asialoglycoprotein receptor may be used.


“Asialoglycoprotein receptor” is present on a surface of a liver cell, and has an action of recognizing a galactose residue of asialoglycoprotein and taking in and decomposing a molecule of the asialoglycoprotein into the cell. “Sugar derivative having an interaction with an asialoglycoprotein receptor” is preferably a compound that has a structure similar to that of a galactose residue and is taken into a cell by an interaction with an asialoglycoprotein receptor, and examples thereof include a GalNAc (N-acetylgalactosamine) derivative, a galactose derivative, and a lactose derivative.


Examples of a functional molecule capable of efficiently delivering the ASO to an organ with high specificity by interacting with various proteins on a surface of a cell of the organ include a ligand of a receptor, an antibody, and a peptide or a protein of fragments thereof.


The linker via which the functional molecule and the ASO are bonded to each other only needs to exhibit the function of the functional molecule as the ASO molecule, and therefore is not particularly limited as long as the linker stably bonds the functional molecule and the oligonucleotide to each other. Examples of the linker include a group derived from an oligonucleotide consisting of 1 to 20 nucleosides, a group derived from a polypeptide consisting of 1 to 20 amino acids, an alkylene consisting of 1 to 20 carbon atoms, and an alkenylene consisting of 2 to 20 carbon atoms. The group derived from an oligonucleotide consisting of 1 to 20 nucleosides is a divalent group obtained by removing a hydrogen atom or the like from each of a 3′-terminal and a 5′-terminal of an oligonucleotide consisting of 1 to 20 nucleosides (a nucleoside when the number of nucleosides is 1). For the group derived from an oligonucleotide consisting of 1 to 20 nucleosides, for example, WO 2017/053995 A can be referred to. WO 2017/053995 A describes, for example, a 3-base linker having a TCA motif, a 1- to 5-base linker having no TCA motif, and the like. The group derived from a polypeptide consisting of 1 to 20 amino acids is a divalent group obtained by removing two groups selected from hydroxy, a hydrogen atom, amino, and the like from a polypeptide consisting of 1 to 20 amino acids (an amino acid when the number of amino acids is 1).


A compound comprising the ASO of the present invention may include a prodrug moiety.


The prodrug is a derivative of a pharmaceutical compound having a group capable of being chemically or metabolically decomposed, and is a compound guided to a pharmacologically active pharmaceutical compound by solvolysis or decomposition in vivo under physiological conditions. A method for selecting and manufacturing an appropriate prodrug derivative is described, for example, in Design of Prodrugs (Elsevier, Amsterdam, 1985). Examples of a prodrug moiety such as an acyloxy derivative manufactured by reacting a hydroxy group of an ASO (or a compound containing an ASO) with a suitable acyl halide, a suitable acid anhydride, or a suitable halogenated alkyloxycarbonyl compound include —O—C(═O)C2H5, —O—C(═O)(t-Bu), —O—C(═O)C15H31, —O—C(═O)-(m-CO2Na-Ph), —O—C(═O)CH2CH2CO2Na, —OC(═O)CH(NH2)CH3, —O—C(═O)CH2N(CH3)2, —O—CH2OC(═O)CH3, and the like.


The prodrug of the compound comprising the ASO of the present invention also includes, for example, a complex obtained by hybridization of two or more oligonucleotides. Examples of such a preferable structure (prodrug) include a double-stranded oligonucleotide (for example, WO 2013/089283 A, WO 2017/068791 A, WO 2017/068790 A, or WO 2018/003739 A), which includes an oligonucleotide complementary to an ASO (or a compound comprising an ASO), in which the complementary oligonucleotide includes an oligonucleotide including a ribonucleoside (for example, RNA), an oligonucleotide including a peptide nucleic acid (PNA), or an oligonucleotide including a deoxyribonucleoside (for example, DNA). Examples of the preferable structure (prodrug) include a single-stranded oligonucleotide in which an RNA complementary to an ASO is bonded by a linker (for example, WO 2017/131124 A or WO 2018/143475 A), and the like. The linker may be an oligonucleotide linker or a linker including a non-nucleoside structure. Examples of the preferable structure (prodrug) also include a single-stranded oligonucleotide in which an RNA complementary to ASO is directly linked (WO 2019/022196 A).


The compound of the present invention includes a compound in which two identical or different ASOs are linked to each other. For a structure in which two ASOs are linked to each other, for example, WO 2017/131124 A and WO 2018/143475 A can be referred to.


The compound comprising an ASO includes those present via tautomerism thereof or geometric isomerism thereof, and also includes those present as a mixture thereof or a mixture of isomers thereof. When an asymmetric center is present, or when an asymmetric center is generated as a result of isomerization, the compound comprising an ASO also includes those present as each optical isomer and those present as a mixture thereof at any ratio. In a case of a compound having two or more asymmetric centers, diastereomers due to optical isomerism of each of the asymmetric centers are also present. The present invention also includes those including all these types at any ratio. An optically active form can be obtained by a well-known method for this purpose.


For example, when the compound comprising the ASO of the present invention includes a modified phosphodiester bond (for example, a phosphorothioate bond) and the phosphorus atom is an asymmetric atom, both forms of an oligonucleotide in which a stereoscopic effect of the phosphorus atom is controlled and an oligonucleotide in which the stereoscopic effect of the phosphorus atom is not controlled are included in the scope of the present invention.


The compound comprising the ASO of the present invention, a prodrug thereof, or a pharmacologically acceptable salt thereof can be present in any crystalline form depending on manufacturing conditions, and can be present in any hydrate, but these crystalline forms, hydrates, and mixtures thereof are also included in the scope of the present invention. In addition, the compound comprising the ASO of the present invention, a prodrug thereof, or a pharmacologically acceptable salt thereof may be present as a solvate containing an organic solvent such as acetone, ethanol, 1-propanol, or 2-propanol, but all of these forms are included in the scope of the present invention.


The compound comprising the ASO of the present invention can be converted into a pharmacologically acceptable salt or can be liberated from a generated salt, as necessary. Examples of the pharmacologically acceptable salt of the compound comprising the ASO include salts with an alkali metal (lithium, sodium, potassium, or the like), an alkaline earth metal (calcium or the like), magnesium, ammonium, an organic base (triethylamine, trimethylamine, or the like), an amino acid (glycine, lysine, glutamic acid, or the like), an inorganic acid (hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, or the like), or an organic acid (acetic acid, citric acid, maleic acid, fumaric acid, tartaric acid, benzenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid, or the like).


In particular, a partial structure represented by —P(═O)(OH)— may be converted into an anionic partial structure represented by —P(═O)(O)— to form a salt with an alkali metal (lithium, sodium, potassium, or the like), an alkaline earth metal (calcium or the like), magnesium, ammonium, or the like. A partial structure represented by —P(═O)(SH)— that forms a phosphorothioate bond may be converted into an anionic partial structure represented by —P(═O)(S)— to form a salt with an alkali metal, an alkaline earth metal, ammonium, or the like similarly. The same applies to other modified phosphodiester bonds.


The pharmacologically acceptable salt is particularly preferably a sodium salt.


The compound comprising the ASO of the present invention can be prepared by appropriately selecting a method known to a person skilled in the art. For example, a person skilled in the art can synthesize the compound comprising the ASO of the present invention by designing a nucleoside sequence of the ASO based on information of a nucleoside sequence of a target RNA, and using a commercially available automatic nucleic acid synthesizer (manufactured by Applied Biosystems, manufactured by Beckman, manufactured by GeneDesign Inc., or the like). The compound comprising the ASO of the present invention can also be synthesized by a reaction using an enzyme. Examples of the enzyme include polymerase, ligase, restriction enzyme, and the like, but are not limited thereto. That is, the method for manufacturing the compound comprising the ASO according to the present embodiment can include a step of extending a nucleoside chain at a 3′-terminal or a 5′-terminal.


Many methods for bonding a functional molecule and an oligonucleotide to each other are well known in the present field. For example, European Journal of Pharmaceutics and Biopharmaceutics, 2016, 107, pp 321-340, Advanced Drug Delivery Reviews, 2016, 104, pp 78-92, Expert Opinion on Drug Delivery, 2014, 11, pp 791-822, and the like can be referred to. For example, a functional molecule and a linker are bonded to each other by a known method, then the bonded product is guided to an amidite form with an amiditization reagent or an H-phosphonate form with an H-phosphonate reagent, and can be bonded to an oligonucleotide.


By purifying the resulting oligonucleotide by reverse phase column chromatography or the like, a compound comprising an ASO can be prepared.


The compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof can effectively inhibit expression of an ATN1 gene. A disease that can be treated, prevented, and ameliorated by a nucleic acid pharmaceutical using the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof is not particularly limited as long as it is a disease to which an ATN1 gene expression inhibitory action is effective, but examples thereof include dentatorubral-pallidoluysian atrophy.


The present invention can provide a composition containing the compound comprising the ASO as an active ingredient, for example, for inhibiting expression of an ATN1 gene by an antisense effect. In particular, the compound comprising the ASO of the present invention can also provide a pharmaceutical composition for treating, preventing, and/or ameliorating a disease to which inhibition of expression of an ATN1 gene is effective, such as dentatorubral-pallidoluysian atrophy.


A pharmaceutical composition containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof can be formulated by a known pharmaceutical method. For example, the pharmaceutical composition can be used transintestinally (orally or the like) or non-transintestinally as an injection, a capsule, a tablet, a pill, a liquid, a powder, a granule, a fine granule, a film coating agent, a pellet, a troche, a sublingual agent, a chewing agent, a buccal agent, a paste, a syrup, a suspension agent, an elixir agent, an emulsion, a coating agent, an ointment, a plaster, a cataplasm, a transdermal absorption formulation, a lotion, an inhalation agent, an aerosol agent, a suppository, or the like.


In the formulation, the pharmaceutical composition can be appropriately combined with a pharmacologically acceptable carrier or a carrier acceptable as food/drink, specifically, sterile water, physiological saline, vegetable oil, a solvent, a base, an emulsifier, a suspension agent, a surfactant, a pH adjuster, a stabilizer, a flavoring agent, a fragrance, an excipient, a vehicle, a preservative, a binder, a diluent, an isotonizing agent, a soothing agent, an extender, a disintegrant, a buffer, a coating agent, a lubricant, a coloring agent, a sweetening agent, a thickening agent, a corrective, a solubilizing agent, other additives, or the like.


An administration form of the composition containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof is not particularly limited, and examples thereof include transintestinal (oral or the like) and non-transintestinal administration. More preferable examples thereof include intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intradermal administration, airway administration, rectal administration, intramuscular administration, intrathecal administration, intracerebroventricular administration, nasal administration, intravitreal administration, and administration by infusion. Still more preferable examples thereof include intrathecal administration, intracerebroventricular administration, and nasal administration. Particularly preferable examples thereof include intrathecal administration.


A formulation containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof and making intrathecal administration possible can be manufactured by a known conventional method. For example, a preparation obtained by adding an additive such as a buffer or an isotonizing agent to the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof is completely dissolved in water for injection, and then the resulting preparation solution is sterilized by filtration. A prefilled syringe formulation can be manufactured by filling the preparation solution into a sterilized syringe, a formulation for injection can be manufactured by filling the preparation solution into a sterilized vial, and a formulation for preparation at the time of use can be manufactured by filling the preparation solution into a sterilized vial and then freeze-drying the preparation solution. Instead of the filtration sterilization, terminal sterilization such as autoclaving or gamma irradiation may be performed.


Various mammalian diseases can be treated, prevented and/or ameliorated by the composition containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof. For example, diseases in mammals including but not limited to a human, a cow, a sheep, a goat, a horse, a dog, a cat, a gerbil, rat, a rabbit, a chimpanzee, a bovine, an ovine, an equine, a canine, a feline, and a rodent species such as a mouse can be treated, prevented and/or ameliorated. The mammal is particularly preferably a human.


When the composition containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof is administered to or ingested by a mammal including a human, a dose thereof or an intake thereof is preferably an effective amount. The effective amount means the sufficient amount of the compound to exhibit a desired pharmacological effect in an individual who needs a drug, changes depending on the age, weight, symptom, and health condition of an individual whose disease is treated, prevented, and/or ameliorated, blending in the composition, and the like, and is appropriately selected. The dose or the intake is preferably 0.0001 mg/kg/day to 100 mg/kg/day in terms of ASO.


Examples of a preferable method using the ASO of the present invention include those described below.


A method for controlling expression of an ATN1 gene, the method including a step of bringing a cell into contact with the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof.


A method for controlling expression of an ATN1 gene in a mammal, the method including a step of administering a pharmaceutical composition containing the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof to the mammal.


Use of the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof for controlling expression of an ATN1 gene in a mammal.


Use of the compound comprising the ASO of the present invention or a pharmacologically acceptable salt thereof for manufacturing a drug for controlling expression of an ATN1 gene in a mammal.


EXAMPLES

Hereinafter, the present invention will be described more specifically based on Examples, but the embodiments of the present invention are not limited to the following Examples.


In Tables (1 to 53) in Examples, “Cmpd No” means a compound number.


In the notation of a chemical structure of a sequence in Examples (chemical structures of Tables 1 to 10, 26 to 33, and 48 and 51), unless otherwise specified, “(L)” means LNA, “(V)” means 2′-O-MCE nucleoside, “(m)” means 2′-O-MOE nucleoside, a lower case alphabet (excluding “m” in the (m)) means deoxyribonucleoside, “{circumflex over ( )}” means a phosphorothioate bond, “5(x)” means that a nucleobase of the deoxyribonucleoside is 5-methylcytosine, and “5” in “5(m)”, “5(V)”, and, “5(L)” means that a nucleobase of the nucleoside is 5-methylcytosine.


Note that in the notation of a chemical structure (Tables 1 to 10, 26 to 33, 48, and 51) in Examples, when “{circumflex over ( )}” is not described between two adjacent nucleobases, the internucleoside bond between the two nucleobases is a phosphodiester bond. For example, in the notation “A(L)G(L)”, the internucleoside bond between A and G is a phosphodiester bond, and in the notation “G(L)a”, the internucleoside bond between G and a is a phosphodiester bond.


Manufacturing Example 1

Antisense oligonucleotides (compounds represented by chemical structures corresponding to compound numbers) described in Tables 1 to 10 were prepared using an automatic nucleic acid synthesizer nS-8II (manufactured by GeneDesign Inc.) or 3900 DNA Synthesizer (manufactured by Applied Biosystems Inc.). Note that the title rows in Tables 2 to 10 are the same as that in Table 1, and thus are omitted.










TABLE 1





Cmpd No
Chemical structure







M-0001
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0002
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0003
G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0004
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0005
5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0006
G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0007
A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0008
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x)a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0009
A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0010
A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0011
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0012
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0013
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0014
G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0015
5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0016
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x)a{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0017
5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0018
A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m)G{circumflex over ( )}(m){circumflex over ( )}T(m)


M-0019
5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0020
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0021
5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0022
5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0023
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0024
T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0025
T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0026
T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0027
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0028
T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0029
G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0030
T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0031
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0032
A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0033
5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0034
5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0035
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0036
T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0037
5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0038
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0039
A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0040
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0041
A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0042
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0043
T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0044
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0045
T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0046
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0047
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0048
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0049
G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}s{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0050
G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)

















TABLE 2







M-0051
A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0052
A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0053
G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0054
T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0055
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0056
A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0057
G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0058
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0059
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0060
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0061
5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0062
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0063
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0064
A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0065
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m)vA(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0066
5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0067
T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0068
G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0069
5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0070
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0071
A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0072
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0073
G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m)″A(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0074
A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0075
G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0076
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0077
A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0078
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0079
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0080
G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0081
G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0082
T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0083
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0084
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0085
A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0086
5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0087
5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0088
A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0089
G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0090
5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0091
5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0092
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0093
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0094
5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0095
5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0096
G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0097
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0098
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0099
5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0100
5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m)

















TABLE 3







M-0101
G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0102
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0103
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0104
T(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0105
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0106
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0107
G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0108
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0109
A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0110
T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0111
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0112
T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0113
A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0114
5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0115
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0116
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0117
5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0118
A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0119
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0120
A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0121
T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0122
5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0123
T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0124
A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0125
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0126
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0127
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0128
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0129
5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0130
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0131
A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0132
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0133
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0134
G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0135
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0136
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}T(m)


M-0137
A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0138
5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0139
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0140
A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0141
A(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0142
G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0143
A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0144
5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0145
T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0146
5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0147
5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0148
A(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0149
T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0150
5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)

















TABLE 4







M-0151
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0152
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0153
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0154
5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0155
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0156
5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0157
A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0158
G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0159
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0160
G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0161
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0162
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0163
A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0164
5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0165
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0166
5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0167
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0168
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0169
5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0170
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0171
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0172
T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0173
5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0174
G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0175
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0176
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0177
A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0178
A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0179
T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0180
G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0181
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0182
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0183
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0184
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0185
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0186
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0187
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0188
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0189
G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0190
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0191
G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0192
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0193
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0194
5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0195
5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0196
A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0197
A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0198
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0199
G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0200
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)

















TABLE 5







M-0201
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0202
A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0203
G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m)


M-0204
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0205
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0206
5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0207
5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0208
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0209
G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0210
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0211
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0212
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0213
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0214
T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0215
G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0216
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0217
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0218
T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}A(m)


M-0219
5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}A(m)


M-0220
G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0221
A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0222
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0223
5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}G(m)


M-0224
T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0225
T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0226
G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}T(m)


M-0227
A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0228
T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0229
T(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0230
G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0231
G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}T(m)


M-0232
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0233
G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0234
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0235
5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}5(m)


M-0236
A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0237
G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}A(m)


M-0238
G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}T(m){circumflex over ( )}G(m)


M-0239
A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0240
G(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}5(m)


M-0241
G(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}G(m)


M-0242
A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}A(m)


M-0243
A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m){circumflex over ( )}5(m){circumflex over ( )}5(m)


M-0244
A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}G(m){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m){circumflex over ( )}T(m)


M-0245
G(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(m){circumflex over ( )}5(m){circumflex over ( )}T(m){circumflex over ( )}G(m){circumflex over ( )}G(m)


M-0246
T(m){circumflex over ( )}G(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(m){circumflex over ( )}A(m){circumflex over ( )}5(m){circumflex over ( )}G(m){circumflex over ( )}G(m)

















TABLE 6







L-0001
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0002
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0003
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0004
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0005
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0006
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0007
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0008
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0009
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0010
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0011
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0012
G(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0013
A(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0014
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0015
5(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0016
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0017
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0018
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0019
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0020
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0021
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0022
5(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0023
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0024
T(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0025
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0026
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0027
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0028
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0029
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0030
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0031
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0032
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0033
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0034
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0035
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0036
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0037
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0038
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0039
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0040
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0041
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0042
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0043
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0044
T(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0045
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0046
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0047
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0048
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0049
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0050
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)

















TABLE 7







L-0051
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0052
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0053
G(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0054
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0055
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0056
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0057
T(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0058
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0059
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0060
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0061
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0062
G(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0063
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0064
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0065
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0066
A(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0067
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0068
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0069
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0070
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0071
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0072
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0073
G(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0074
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0075
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0076
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0077
A(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0078
G(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0079
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0080
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0081
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0082
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0083
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0084
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0085
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0086
T(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0087
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0088
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0089
G(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0090
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0091
T(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0092
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0093
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0094
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0095
G(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0096
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0097
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0098
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0099
A(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0100
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)

















TABLE 8







L-0101
G(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0102
5(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0103
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0104
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0105
G(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0106
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0107
5(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0108
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0109
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0110
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0111
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0112
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0113
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0114
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0115
5(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0116
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0117
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0118
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0119
5(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0120
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0121
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0122
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0123
A(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0124
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0125
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0126
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0127
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0128
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0129
T(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0130
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0131
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0132
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0133
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0134
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0135
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0136
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0137
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0138
G(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0139
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0140
A(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0141
A(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0142
G(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0143
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0144
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0145
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0146
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0147
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0148
A(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0149
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0150
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)

















TABLE 9







L-0151
5(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0152
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0153
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0154
A(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0155
5(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0156
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0157
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0158
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0159
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0160
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0161
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0162
G(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0163
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0164
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0165
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0166
A(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0167
G(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0168
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0169
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0170
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0171
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0172
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0173
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0174
G(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0175
T(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0176
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0177
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0178
T(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0179
G(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0180
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0181
T(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0182
T(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0183
A(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0184
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0185
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0186
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0187
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0188
G(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0189
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0190
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0191
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0192
G(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0193
T(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0194
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0195
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0196
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0197
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0198
G(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0199
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0200
T(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)

















TABLE 10







L-0201
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0202
G(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0203
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0204
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0205
5(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0206
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0207
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0208
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0209
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0210
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0211
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0212
G(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0213
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0214
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0215
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0216
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0217
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0218
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0219
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0220
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0221
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0222
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0223
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0224
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0225
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0226
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0227
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0228
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0229
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0230
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0231
T(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0232
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0233
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0234
T(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0235
T(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0236
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0237
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0238
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0239
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)









Positions in a sequence of human ATN1 mRNA or pre-mRNA targeted by the antisense oligonucleotides presented in Tables 1 to 10, and sequence numbers and nucleobase sequences corresponding to the antisense oligonucleotides are presented in Tables 11 to 20.


In the notation of a sequence in Tables 11 to 20, “SEQ1 START” means “SEQ ID NO: 1 start site” and represents the position number of a nucleoside on a side closest to a 5′ side targeted by an antisense oligonucleotide in the mRNA sequence of human ATN1 (SEQ ID NO: 1). “SEQ1 END” means “SEQ ID NO: 1 termination site” and represents the position number of a nucleoside on a side closest to a 3′ side targeted by an antisense oligonucleotide in the mRNA sequence of human ATN1 (SEQ ID NO: 1).


“SEQ2 START” means “SEQ ID NO: 2 start site” and represents the position number of a nucleoside on a side closest to a 5′ side targeted by an antisense oligonucleotide in the pre-mRNA sequence of human ATN1 (SEQ ID NO: 2). “SEQ2 END” means “SEQ ID NO: 2 termination site” and represents the position number of a nucleoside on a side closest to a 3′ side targeted by an antisense oligonucleotide in the pre-mRNA sequence of human ATN1 (SEQ ID NO: 2).


Each antisense oligonucleotide is targeted by human ATN1 mRNA designated herein as SEQ ID NO: 1 and/or human ATN1 pre-mRNA designated herein as SEQ ID NO: 2 or SEQ ID NO: 717.


“-” (Hyphen) indicates that an antisense oligonucleotide does not target a sequence of mRNA or pre-mRNA with 100% complementarity.


“SEQ No” represents a sequence number, and “BASE SEQUENCE” represents a nucleobase sequence of an antisense oligonucleotide.


Note that the title rows in Tables 12 to 20 are the same as that in Table 11, and thus are omitted.















TABLE 11





Cmpd
SEQ1
SEQ1
SEQ2
SEQ2
SEQ



No
START
END
START
END
No
BASE SEQUENCE





















M-0001
59
78
— 
— 
242
TCAATGAAACCTGCTGGTAG





M-0002
65
84
— 
— 
243
CTGTTTTCAATGAAACCTGC





M-0003
68
87
5527
5546
244
GATCTGTTTTCAATGAAACC





M-0004
70
89
5529
5548
245
AGGATCTGTTTTCAATGAAA





M-0005
77
96
5536
5555
246
CTTTTGCAGGATCTGTTTTC





M-0006
109
128
5568
5587
247
GATCTCCAAGTTTCCAGTGT





M-0007
114
133
5573
5592
248
AGCAGGATCTCCAAGTTTCC





M-0008
118
137
5577
5596
249
GGGAAGCAGGATCTCCAAGT





M-0009
164
183
5623
5642
250
ACAGAAACTTCTCTGCTCCA





M-0010
166
185
5625
5644
251
ATACAGAAACTTCTCTGCTC





M-0011
169
188
5628
5647
252
TGAATACAGAAACTTCTCTG





M-0012
173
192
5632
5651
253
CAGCTGAATACAGAAACTTC





M-0013
207
226
5666
5685
254
CAGGCTGTGGAGACCCCATT





M-0014
219
238
5678
5697
255
GTCTTCATTCTTCAGGCTGT





M-0015
222
241
5681
5700
256
CGTGTCTTCATTCTTCAGGC





M-0016
226
245
5685
5704
257
CTGTCGTGTCTTCATTCTTC





M-0017
241
260
— 
— 
258
CATCGAGTCTTTATTCTGTC





M-0018
253
272

— 
259
ACTCCTCATTGACATCGAGT





M-0019
254
273
— 
— 
260
CACTCCTCATTGACATCGAG





M-0020
256
275
— 
— 
261
TCCACTCCTCATTGACATCG





M-0021
262
281
5868
5887
262
CTTCCGTCCACTCCTCATTG





M-0022
300
319
5906
5925
263
CTCGATCTCAGTTCTTCCCG





M-0023
353
372
5959
5978
264
CAGCTTTGCCATCACTGCTG





M-0024
356
375
5962
5981
265
TCTCAGCTTTGCCATCACTG





M-0025
357
376
5963
5982
266
TTCTCAGCTTTGCCATCACT





M-0026
366
385
5972
5991
267
TGCCTGGACTTCTCAGCTTT





M-0027
367
386
5973
5992
268
CTGCCTGGACTTCTCAGCTT





M-0028
417
436
6174
6193
269
TTGTTGACCTTTGGGGTGGA





M-0029
425
444
6182
6201
270
GACCCTGCTTGTTGACCTTT





M-0030
446
465
6203
6222
271
TCTCTGAGATCTCCTCACTC





M-0031
450
469
6207
6226
272
TCACTCTCTGAGATCTCCTC





M-0032
454
473
6211
6230
273
ACTTTCACTCTCTGAGATCT





M-0033
458
477
6215
6234
274
CCTCACTTTCACTCTCTGAG





M-0034
460
479
6217
6236
275
CTCCTCACTTTCACTCTCTG





M-0035
463
582
6220
6239
276
GGTCTCCTCACTTTCACTCT





M-0036
483
502
6240
6259
277
TTGGTCTTTTTTGGTGCATT





M-0037
490
509
6247
6266
278
CTCAGTTTTGGTCTTTTTTG





M-0038
495
514
— 
— 
279
TCCTGCTCAGTTTTGGTCTT





M-0039
523
542
7248
7267
280
ATCGGAGGGAGACTGTGGCC





M-0040
536
555
7261
7280
281
CCAAGCTATCCAGATCGGAG





M-0041
559
578
7284
7303
282
ATCATCATTAAGGCTCCGCC





M-0042
561
580
7286
7305
283
CCATCATCATTAAGGCTCCG





M-0043
563
582
7288
7307
284
TGCCATCATCATTAAGGCTC





M-0044
564
583
7289
7308
285
CTGCCATCATCATTAAGGCT





M-0045
566
585
7291
7310
286
TGCTGCCATCATCATTAAGG





M-0046
568
587
7293
7312
287
GCTGCTGCCATCATCATTAA





M-0047
627
646
7352
7371
288
CCAGGGCTGTAGATACTGGG





M-0048
642
661
7367
7386
289
TCATTCTCCACACTTCCAGG





M-0049
649
668
7374
7393
290
GTCAGAGTCATTCTCCACAC





M-0050
651
670
7376
7395
291
GAGTCAGAGTCATTCTCCAC






















TABLE 12







M-0051
653
672
7378
7397
292
ATGAGTCAGAGTCATTCTCC





M-0052
656
675
7381
7400
293
AAGATGAGTCAGAGTCATTC





M-0053
666
685
7391
7410
294
GACAGGCCAGAAGATGAGTC





M-0054
763
782
7488
7507
295
TTCAAAGCTAGCCTCTGGCT





M-0055
766
785
7491
7510
296
GGGTTCAAAGCTAGCCTCTG





M-0056
787
806
7512
7531
297
AGTGGGTGTCACAGAAGGAT





M-0057
800
819
7525
7544
298
GAGCATGATATCCAGTGGGT





M-0058
880
899
7605
7624
299
GCCCCCAGGATAGAGCTGTG





M-0059
899
918
7624
7643
300
CAGACAAAACTCCACCAGTG





M-0060
901
920
7626
7645
301
TCCAGACAAAACTCCACCAG





M-0061
924
943
7649
7668
302
CCCCCCTTGGGACCCATTGG





M-0062
970
989
7695
7714
303
GTGCTGCTTACCCCCATTAG





M-0063
995
1014
7720
7739
304
CTGAAATGGGAGTAGTGGGT





M-0064
998
1017
7723
7742
305
ATACTGAAATGGGAGTAGTG





M-0065
1007
1026
7732
7751
306
CAGAGCTTGATACTGAAATG





M-0066
1010
1029
7735
7754
307
CCCCAGAGCTTGATACTGAA





M-0067
1013
1032
7738
7757
308
TAGCCCCAGAGCTTGATACT





M-0068
1020
1039
7745
7764
309
GCACCACTAGCCCCAGAGCT





M-0069
1055
1074
7780
7799
310
CACCCACTGGAGTGGTAGGC





M-0070
1079
1098
7804
7823
311
GTGGAGCAGAAGGTAGGTTC





M-0071
1101
1120
7826
7845
312
ACATGGGGGAAGTTGGCTGG





M-0072
1157
1176
7882
7901
313
AGGCTGATGCATTGTTGAGG





M-0073
1196
1215
7921
7940
314
GATGACCAGGTAGTGGTTGG





M-0074
1204
1223
7929
7948
315
AGAGGGCAGATGACCAGGTA





M-0075
1310
1329
8035
8054
316
GAGCAGAAGAGGAAGCAGGA





M-0076
1339
1358
8064
8083
317
TGAATAAGGAAACCTCATGG





M-0077
1351
1370
8076
8095
318
ACTACTAGAGGATGAATAAG





M-0078
1354
1373
8079
8098
319
GCTACTACTAGAGGATGAAT





M-0079
1364
1383
8089
8108
320
CTGCTGCAGAGCTACTACTA





M-0080
1380
1399
8105
8124
321
GAACTGGAAGAGGAGGCTGC





M-0081
1392
1411
8117
8136
322
GAAGAGGAGGAAGAACTGGA





M-0082
1423
1442
8148
8167
323
TGCCTGGGAAGCTGGGAAGG





M-0083
1614
1633
8339
8358
324
GCCCCAGTAGAGGGAGGGAA





M-0084
1651
1670
8376
8395
325
GTGATGTGTTGAGACTGGTG





M-0085
1806
1825
8531
8550
326
ATGGCGTAAGGGTGTGCGTG





M-0086
1846
1865
8571
8590
327
CCCTGGTGGGTAGGGCCTCA





M-0087
1896
1915
8621
8640
328
CCTGCTTGGCTGTAGGACAC





M-0088
1924
1943
8649
8668
329
AGAGGAAGAGACTGGAGGGC





M-0089
1956
1975
8681
8700
330
GACCCTTGAGAAGTGGAAGA





M-0090
2023
2042
8748
8767
331
CACCGGTGGGAAAGGGTAGG





M-0091
2060
2079
8785
8804
332
CCGTGGAAAGGGTAGCCGAA





M-0092
2105
2124
8830
8849
333
AGGCCGTTTTGTAGCCTGCT





M-0093
2170
2189
8895
8914
334
GGTGGCTGTCTTGTAGGCCC





M-0094
2398
2417
9123
9142
335
CTCCTGTTTGATCTGCGTGG





M-0095
2427
2446
9152
9171
336
CTCTCGGGGGTCTCATACTC





M-0096
2480
2499
9205
9224
337
GTACATCTACCACCTTGGGA





M-0097
2484
2503
9209
9228
338
CTGGGTACATCTACCACCTT





M-0098
2501
2520
9226
9245
339
CAGACTGACTGGCATGGCTG





M-0099
2526
2545
9534
9553
340
CGATCCAGGTGTTTGTTGAA





M-0100
2543
2562
9551
9570
341
CGCACGAGTTGAAGCCGCGA






















TABLE 13







M-0101
2568
2587
9576
9595
342
GGCACGAAGTACAGGTCGCT





M-0102
2742
2761
— 
— 
343
TCCTGAGCCAACTTCACGCT





M-0103
2853
2872
10274
10293
344
GGAGTGTCAGGACCCAGGTA





M-0104
2877
2896
10298
10317
345
TATTCACTGAGAGTGCGCAA





M-0105
2903
2922
10324
10343
346
CAGGAGACATGACATGAGGC





M-0106
2904
2923
10325
10344
347
CCAGGAGACATGACATGAGG





M-0107
2931
2950
10352
10371
348
GGCACGTAGAATGGATGGTT





M-0108
2972
2991
10393
10412
349
GGACATTGTAACCCAGGAGC





M-0109
2992
3011
10413
10432
350
ATCACTGCTGTACAGGGCCG





M-0110
3069
3088
10490
10509
351
TTCACCTCAAAGCCAGGCTT





M-0111
3078
3097
10499
10518
352
TCACTAGGCTTCACCTCAAA





M-0112
3085
3104
10506
10525
353
TTCCAGCTCACTAGGCTTCA





M-0113
3094
3113
10515
10534
354
ATGTAGGGGTTCCAGCTCAC





M-0114
3109
3128
10530
10549
355
CGGCCCAGGGACCCCATGTA





M-0115
3193
3212
10614
10633
356
GCTCGGATGAAAGGGGAAAG





M-0116
3269
3288
10690
10709
357
GCTCAGCATAGGACATGTCA





M-0117
3333
3352
10754
10773
358
CGGGCCAGTGGGTCATTGCC





M-0118
3355
3374
10776
10795
359
AGTCACATTGAGCATCTGCA





M-0119
3358
3377
10779
10798
360
GGGAGTCACATTGAGCATCT





M-0120
3421
3440
10842
10861
361
ATGGATAGCATCTTGCTGGT





M-0121
3424
3443
10845
10864
362
TGCATGGATAGCATCTTGCT





M-0122
3452
3471
12575
12594
363
CAATGAGAGGGTGCACCGAG





M-0123
3479
3498
12602
12621
364
TAAGGTGAGACCCTGAGGCC





M-0124
3486
3505
12609
12628
365
ATCCGGGTAAGGTGAGACCC





M-0125
3516
3535
12639
12658
366
GGGTTAGGGAGAGTTCCAGC





M-0126
3538
3557
12661
12680
367
GTGCAGAGGGTGAGGAAGCA





M-0127
3754
3773
— 
— 
368
GTGACTGTAGTAGTCCTCCT





M-0128
3765
3784

— 
369
TCCTTCTTCAGGTGACTGTA





M-0129
3768
3787
13433
13452
370
CTTTCCTTCTTCAGGTGACT





M-0130
3789
3808
13454
13473
371
AGGTTCTACAGTGGCTTGTC





M-0131
3812
3831
13477
13496
372
AGCCATGGTGCTCTCTTGAT





M-0132
3826
3845
13491
13510
373
AGGTCCAATGTAGGAGCCAT





M-0133
3834
3853
13499
13518
374
GTGCTCCAAGGTCCAATGTA





M-0134
3888
3907
13553
13572
375
GCACCCTCTTGGCTCTGGGT





M-0135
3906
3925
13571
13590
376
AGGCCCTGCAACTGAGCAGC





M-0136
4022
4041
13687
13706
377
TCCAAGATTCTGTGCGCTTT





M-0137
4032
4051
13697
13716
378
AGAGACCTGGTCCAAGATTC





M-0138
4040
4059
13705
13724
379
CAAGGAAGAGAGACCTGGTC





M-0139
4043
4062
13708
13727
380
GGACAAGGAAGAGAGACCTG





M-0140
4117
4136
13782
13801
381
AATAATCACACCAACGGGGC





M-0141
4118
4137
13783
13802
382
AAATAATCACACCAACGGGG





M-0142
4122
4141
13787
13806
383
GATGAAATAATCACACCAAC





M-0143
4125
4144
13790
13809
384
ACAGATGAAATAATCACACC





M-0144
4128
4147
13793
13812
385
CTAACAGATGAAATAATCAC





M-0145
4129
4148
13794
13813
386
TCTAACAGATGAAATAATCA





M-0146
4131
4150
13796
13815
387
CATCTAACAGATGAAATAAT





M-0147
4133
4152
13798
13817
388
CACATCTAACAGATGAAATA





M-0148
4139
4158
13804
13823
389
AACAGCCACATCTAACAGAT





M-0149
4146
4165
13811
13830
390
TACGCAAAACAGCCACATCT





M-0150
4215
4234
13880
13899
391
CAAGGGGCATACATTGCAGA






















TABLE 14







M-0151
1362
1381
8087
8106
392
GCTGCAGAGCTACTACTAGA





M-0152
1365
1384
8090
8109
393
GCTGCTGCAGAGCTACTACT





M-0153
1844
1863
8569
8588
394
CTGGTGGGTAGGGCCTCAGA





M-0154
1845
1864
8570
8589
395
CCTGGTGGGTAGGGCCTCAG





M-0155
2058
2077
8783
8802
396
GTGGAAAGGGTAGCCGAAGA





M-0156
2059
2078
8784
8803
397
CGTGGAAAGGGTAGCCGAAG





M-0157
2061
2080
8786
8805
398
ACCGTGGAAAGGGTAGCCGA





M-0158
2062
2081
8787
8806
399
GACCGTGGAAAGGGTAGCCG





M-0159
2103
2122
8828
8847
400
GCCGTTTTGTAGCCTGCTGG





M-0160
2104
2123
8829
8848
401
GGCCGTTTTGTAGCCTGCTG





M-0161
2481
2500
9206
9225
402
GGTACATCTACCACCTTGGG





M-0162
2482
2501
9207
9226
403
GGGTACATCTACCACCTTGG





M-0163
2876
2895
10297
10316
404
ATTCACTGAGAGTGCGCAAG





M-0164
2879
2898
10300
10319
405
CATATTCACTGAGAGTGCGC





M-0165
2901
2920
10322
10341
406
GGAGACATGACATGAGGCCG





M-0166
2990
3009
10411
10430
407
CACTGCTGTACAGGGCCGGG





M-0167
2994
3013
10415
10434
408
GGATCACTGCTGTACAGGGC





M-0168
3267
3286
10688
10707
409
TCAGCATAGGACATGTCAGG





M-0169
3271
3290
10692
10711
410
CCGCTCAGCATAGGACATGT





M-0170
3335
3354
10756
10775
411
GCCGGGCCAGTGGGTCATTG





M-0171
3419
3438
10840
10859
412
GGATAGCATCTTGCTGGTGC





M-0172
3420
3439
10841
10860
413
TGGATAGCATCTTGCTGGTG





M-0173
3422
3441
10843
10862
414
CATGGATAGCATCTTGCTGG





M-0174
3423
3442
10844
10863
415
GCATGGATAGCATCTTGCTG





M-0175
3426
3445

— 
416
GCTGCATGGATAGCATCTTG





M-0176
3449
3468
12572
12591
417
TGAGAGGGTGCACCGAGGCA





M-0177
3450
3469
12573
12592
418
ATGAGAGGGTGCACCGAGGC





M-0178
3451
3470
12574
12593
419
AATGAGAGGGTGCACCGAGG





M-0179
3453
3472
12576
12595
420
TCAATGAGAGGGTGCACCGA





M-0180
3454
3473
12577
12596
421
GTCAATGAGAGGGTGCACCG





M-0181
3455
3474
12578
12597
422
GGTCAATGAGAGGGTGCACC





M-0182
3456
3475
12579
12598
423
GGGTCAATGAGAGGGTGCAC





M-0183
3457
3476
12580
12599
424
GGGGTCAATGAGAGGGTGCA





M-0184
3458
3477
12581
12600
425
GGGGGTCAATGAGAGGGTGC





M-0185
3459
3478
12582
12601
426
AGGGGGTCAATGAGAGGGTG





M-0186
3460
3479
12583
12602
427
CAGGGGGTCAATGAGAGGGT





M-0187
3461
3480
12584
12603
428
CCAGGGGGTCAATGAGAGGG





M-0188
3462
3481
12585
12604
429
GCCAGGGGGTCAATGAGAGG





M-0189
3463
3482
12586
12605
430
GGCCAGGGGGTCAATGAGAG





M-0190
3464
3483
12587
12606
431
AGGCCAGGGGGTCAATGAGA





M-0191
3465
3484
12588
12607
432
GAGGCCAGGGGGTCAATGAG





M-0192
3466
3485
12589
12608
433
TGAGGCCAGGGGGTCAATGA





M-0193
3467
3486
12590
12609
434
CTGAGGCCAGGGGGTCAATG





M-0194
3468
3487
12591
12610
435
CCTGAGGCCAGGGGGTCAAT





M-0195
3469
3488
12592
12611
436
CCCTGAGGCCAGGGGGTCAA





M-0196
3470
3489
12593
12612
437
ACCCTGAGGCCAGGGGGTCA





M-0197
3472
3491
12595
12614
438
AGACCCTGAGGCCAGGGGGT





M-0198
3474
3493
12597
12616
439
TGAGACCCTGAGGCCAGGGG





M-0199
3475
3494
12598
12617
440
GTGAGACCCTGAGGCCAGGG





M-0200
3476
3495
12599
12618
441
GGTGAGACCCTGAGGCCAGG






















TABLE 15







M-0201
3477
3496
12600
12619
442
AGGTGAGACCCTGAGGCCAG





M-0202
3478
3497
12601
12620
443
AAGGTGAGACCCTGAGGCCA





M-0203
3480
3499
12603
12622
444
GTAAGGTGAGACCCTGAGGC





M-0204
3481
3500
12604
12623
445
GGTAAGGTGAGACCCTGAGG





M-0205
3482
3501
12605
12624
446
GGGTAAGGTGAGACCCTGAG





M-0206
3483
3502
12606
12625
447
CGGGTAAGGTGAGACCCTGA





M-0207
3484
3503
12607
12626
448
CCGGGTAAGGTGAGACCCTG





M-0208
3485
3504
12608
12627
449
TCCGGGTAAGGTGAGACCCT





M-0209
3487
3506
12610
12629
450
GATCCGGGTAAGGTGAGACC





M-0210
3488
3507
12611
12630
451
GGATCCGGGTAAGGTGAGAC





M-0211
3489
3508
12612
12631
452
GGGATCCGGGTAAGGTGAGA





M-0212
3490
3509
12613
12632
453
GGGGATCCGGGTAAGGTGAG





M-0213
3491
3510
12614
12633
454
AGGGGATCCGGGTAAGGTGA





M-0214
3492
3511
12615
12634
455
TAGGGGATCCGGGTAAGGTG





M-0215
3493
3512
12616
12635
456
GTAGGGGATCCGGGTAAGGT





M-0216
3494
3513
12617
12636
457
GGTAGGGGATCCGGGTAAGG





M-0217
3495
3514
12618
12637
458
GGGTAGGGGATCCGGGTAAG





M-0218
3496
3515
12619
12638
459
TGGGTAGGGGATCCGGGTAA





M-0219
3497
3516
12620
12639
460
CTGGGTAGGGGATCCGGGTA





M-0220
3498
3517
12621
12640
461
GCTGGGTAGGGGATCCGGGT





M-0221
3499
3518
12622
12641
462
AGCTGGGTAGGGGATCCGGG





M-0222
3500
3519
12623
12642
463
CAGCTGGGTAGGGGATCCGG





M-0223
3501
3520
12624
12643
464
CCAGCTGGGTAGGGGATCCG





M-0224
3502
3521
12625
12644
465
TCCAGCTGGGTAGGGGATCC





M-0225
3503
3522
12626
12645
466
TTCCAGCTGGGTAGGGGATC





M-0226
3504
3523
12627
12646
467
GTTCCAGCTGGGTAGGGGAT





M-0227
3505
3524
12628
12647
468
AGTTCCAGCTGGGTAGGGGA





M-0228
3512
3531
12635
12654
469
TAGGGAGAGTTCCAGCTGGG





M-0229
3513
3532
12636
12655
470
TTAGGGAGAGTTCCAGCTGG





M-0230
3514
3533
12637
12656
471
GTTAGGGAGAGTTCCAGCTG





M-0231
3515
3534
12638
12657
472
GGTTAGGGAGAGTTCCAGCT





M-0232
3517
3536
12640
12659
473
GGGGTTAGGGAGAGTTCCAG





M-0233
3518
3537
12641
12660
474
GGGGGTTAGGGAGAGTTCCA





M-0234
3519
3538
12642
12661
475
AGGGGGTTAGGGAGAGTTCC





M-0235
3520
3539
12643
12662
476
CAGGGGGTTAGGGAGAGTTC





M-0236
3522
3541
12645
12664
477
AGCAGGGGGTTAGGGAGAGT





M-0237
3524
3543
12647
12666
478
GAAGCAGGGGGTTAGGGAGA





M-0238
3814
3833
13479
13498
479
GGAGCCATGGTGCTCTCTTG





M-0239
3889
3908
13554
13573
480
AGCACCCTCTTGGCTCTGGG





M-0240
3904
3923
13569
13588
481
GCCCTGCAACTGAGCAGCAC





M-0241
3907
3926
13572
13591
482
GAGGCCCTGCAACTGAGCAG





M-0242
4038
4057
13703
13722
483
AGGAAGAGAGACCTGGTCCA





M-0243
4039
4058
13704
13723
484
AAGGAAGAGAGACCTGGTCC





M-0244
4041
4060
13706
13725
485
ACAAGGAAGAGAGACCTGGT





M-0245
4042
4061
13707
13726
486
GACAAGGAAGAGAGACCTGG





M-0246
4120
4139
13785
13804
487
TGAAATAATCACACCAACGG






















TABLE 16







L-0001
 63
 78


 3
TCAATGAAACCTGCTG





L-0002
 64
 79


 4
TTCAATGAAACCTGCT





L-0003
 67
 82
5526
5541
 5
GTTTTCAATGAAACCT





L-0004
 69
 84
5528
5543
 6
CTGTTTTCAATGAAAC





L-0005
 71
 86
5530
5545
 7
ATCTGTTTTCAATGAA





L-0006
 75
 90
5534
5549
 8
CAGGATCTGTTTTCAA





L-0007
 77
 92
5536
5551
 9
TGCAGGATCTGTTTTC





L-0008
 89
104
5548
5563
10
ACCTGGAACTTTTGCA





L-0009
 91
106
5550
5565
11
GCACCTGGAACTTTTG





L-0010
110
125
5569
5584
12
CTCCAAGTTTCCAGTG





L-0011
118
133
5577
5592
13
AGCAGGATCTCCAAGT





L-0012
120
135
5579
5594
14
GAAGCAGGATCTCCAA





L-0013
170
185
5629
5644
15
ATACAGAAACTTCTCT





L-0014
221
236
5680
5695
16
CTTCATTCTTCAGGCT





L-0015
226
241
5685
5700
17
CGTGTCTTCATTCTTC





L-0016
238
253
5697
5712
18
TCTTTATTCTGTCGTG





L-0017
239
254
5698
5713
19
GTCTTTATTCTGTCGT





L-0018
241
256
5700
5715
20
GAGTCTTTATTCTGTC





L-0019
244
259


21
ATCGAGTCTTTATTCT





L-0020
257
272
5863
5878
22
ACTCCTCATTGACATC





L-0021
300
315
5906
5921
23
ATCTCAGTTCTTCCCG





L-0022
302
317
5908
5923
24
CGATCTCAGTTCTTCC





L-0023
304
319
5910
5925
25
CTCGATCTCAGTTCTT





L-0024
353
368
5959
5974
26
TTTGCCATCACTGCTG





L-0025
354
369
5960
5975
27
CTTTGCCATCACTGCT





L-0026
371
386
5977
5992
28
CTGCCTGGACTTCTCA





L-0027
419
434
6176
6191
29
GTTGACCTTTGGGGTG





L-0028
428
443
6185
6200
30
ACCCTGCTTGTTGACC





L-0029
458
473
6215
6230
31
ACTTTCACTCTCTGAG





L-0030
464
479
6221
6236
32
CTCCTCACTTTCACTC





L-0031
465
480
6222
6237
33
TCTCCTCACTTTCACT





L-0032
473
488
6230
6245
34
TGCATTGGTGTCCTCA





L-0033
483
498
6240
6255
35
TCTTTTTTGGTGCATT





L-0034
497
512


36
CTGCTCAGTTTTGGTC





L-0035
538
553
7263
7278
37
AAGCTATCCAGATCGG





L-0036
539
554
7264
7279
38
CAAGCTATCCAGATCG





L-0037
540
555
7265
7280
39
CCAAGCTATCCAGATC





L-0038
544
559
7269
7284
40
CCGTCCAAGCTATCCA





L-0039
559
574
7284
7299
41
TCATTAAGGCTCCGCC





L-0040
562
577
7287
7302
42
TCATCATTAAGGCTCC





L-0041
568
583
7293
7308
43
CTGCCATCATCATTAA





L-0042
569
584
7294
7309
44
GCTGCCATCATCATTA





L-0043
570
585
7295
7310
45
TGCTGCCATCATCATT





L-0044
585
600
7310
7325
46
TATCCCTAGGGTCGCT





L-0045
587
602
7312
7327
47
GATATCCCTAGGGTCG





L-0046
603
618
7328
7343
48
TTCGGTTGTGCTGGTC





L-0047
626
641
7351
7366
49
GCTGTAGATACTGGGG





L-0048
630
645
7355
7370
50
CAGGGCTGTAGATACT





L-0049
642
657
7367
7382
51
TCTCCACACTTCCAGG





L-0050
643
658
7368
7383
52
TTCTCCACACTTCCAG






















TABLE 17







L-0051
 651
 666
 7376
 7391
 53
CAGAGTCATTCTCCAC





L-0052
 654
 669
 7379
 7394
 54
AGTCAGAGTGATTCTC





L-0053
 666
 681
 7391
 7406
 55
GGCCAGAAGATGAGTC





L-0054
 767
 782
 7492
 7507
 56
TTCAAAGCTAGCCTCT





L-0055
 768
 783
 7493
 7508
 57
GTTCAAAGCTAGCCTC





L-0056
 771
 786
 7496
 7511
 58
GGGGTTCAAAGCTAGC





L-0057
 789
 804
 7514
 7529
 59
TGGGTGTCACAGAAGG





L-0058
 804
 819
 7529
 7544
 60
GAGCATGATATCCAGT





L-0059
 838
 853
 7563
 7578
 61
GCCTGGAACATTCGAG





L-0060
 839
 854
 7564
 7579
 62
AGCCTGGAACATTCGA





L-0061
 880
 895
 7605
 7620
 63
CCAGGATAGAGCTGTG





L-0062
 901
 916
 7626
 7641
 64
GACAAAACTGGACCAG





L-0063
 904
 919
 7629
 7644
 65
CCAGACAAAACTCCAC





L-0064
 907
 922
 7632
 7647
 66
GGTCCAGACAAAACTC





L-0065
 972
 987
 7697
 7712
 67
GCTGCTTACCCCCATT





L-0066
 995
1010
 7720
 7735
 68
AATGGGAGTAGTGGGT





L-0067
 999
1014
 7724
 7739
 69
CTGAAATGGGAGTAGT





L-0068
1009
1024
 7734
 7749
 70
GAGCTTGATACTGAAA





L-0069
1014
1029
 7739
 7754
 71
CCCCAGAGCTTGATAC





L-0070
1080
1095
 7805
 7820
 72
GAGCAGAAGGTAGGTT





L-0071
1103
1118
 7828
 7843
 73
ATGGGGGAAGTTGGCT





L-0072
1158
1173
 7883
 7898
 74
CTGATGCATTGTTGAG





L-0073
1204
1219
 7929
 7944
 75
GGCAGATGACCAGGTA





L-0074
1238
1253
 7963
 7978
 76
TCCACCCATACCCTGT





L-0075
1245
1260
 7970
 7985
 77
GAGGAAGTCCACCCAT





L-0076
1313
1328
 8038
 8053
 78
AGCAGAAGAGGAAGCA





L-0077
1340
1355
 8065
 8080
 79
ATAAGGAAACCTCATG





L-0078
1342
1357
 8067
 8082
 80
GAATAAGGAAACCTCA





L-0079
1354
1369
 8079
 8094
 81
CTACTAGAGGATGAAT





L-0080
1362
1377
 8087
 8102
 82
CAGAGGTACTACTAGA





L-0081
1365
1380
 8090
 8105
 83
CTGCAGAGCTACTACT





L-0082
1382
1397
 8107
 8122
 84
ACTGGAAGAGGAGGCT





L-0083
1652
1667
 8377
 8392
 85
ATGTGTTGAGACTGGT





L-0084
1818
1833
 8543
 8558
 86
AGGGAGAGATGGCGTA





L-0085
1943
1958
 8668
 8683
 87
AGAGGAAGAGTTGGAA





L-0086
1955
1970
 8680
 8695
 88
TTGAGAAGTGGAAGAG





L-0087
1977
1992
 8702
 8717
 89
GGTGTGAACATGGGTA





L-0088
1980
1995
 8705
 8720
 90
AGGGGTGTGAACATGG





L-0089
2060
2075
 8785
 8800
 91
GGAAAGGGTAGCCGAA





L-0090
2106
2121
 8831
 8846
 92
CCGTTTTGTAGCCTGC





L-0091
2172
2187
 8897
 8912
 93
TGGCTGTCTTGTAGGC





L-0092
2400
2415
 9125
 9140
 94
CCTGTTTGATCTGCGT





L-0093
2402
2417
 9127
 9142
 95
CTCCTGTTTGATCTGC





L-0094
2423
2438
 9148
 9163
 96
GGTCTCATAGTCCTCA





L-0095
2484
2499
 9209
 9224
 97
GTACATCTACCACCTT





L-0096
2527
2542
 9535
 9550
 98
TCCAGGTGTTTGTTGA





L-0097
2570
2585
 9578
 9593
 99
CACGAAGTAGAGGTCG





L-0098
2743
2758


100
TGAGCCAACTTCACGC





L-0099
2880
2895
10301
10316
101
ATTCACTGAGAGTGCG





L-0100
2883
2898
10304
10319
102
CATATTCAGTGAGAGT






















TABLE 18







L-0101
2885
2900
10306
10321
103
GGCATATTCACTGAGA





L-0102
2887
2902
10308
10323
104
CGGGCATATTCACTGA





L-0103
2888
2903
10309
10324
105
CCGGGCATATTCACTG





L-0104
2903
2918
10324
10339
106
AGACATGACATGAGGC





L-0105
2905
2920
10326
10341
107
GGAGACATGACATGAG





L-0106
2908
2923
10329
10344
108
CCAGGAGACATGACAT





L-0107
2931
2946
10352
10367
109
CGTAGAATGGATGGTT





L-0108
2973
2988
10394
10409
110
CATTGTAACCCAGGAG





L-0109
2979
2994
10400
10415
111
CCGGGACATTGTAACC





L-0110
2995
3010
10416
10431
112
TCACTGCTGTACAGGG





L-0111
3000
3015
10421
10436
113
CTGGATCACTGCTGTA





L-0112
3001
3016
10422
10437
114
GCTGGATCACTGCTGT





L-0113
3072
3087
10493
10508
115
TCACCTCAAAGCCAGG





L-0114
3084
3099
10505
10520
116
GCTCACTAGGCTTCAC





L-0115
3194
3209
10615
10630
117
CGGATGAAAGGGGAAA





L-0116
3267
3282
10688
10703
118
CATAGGACATGTCAGG





L-0117
3271
3286
10692
10707
119
TCAGCATAGGACATGT





L-0118
3272
3287
10693
10708
120
CTCAGCATAGGACATG





L-0119
3274
3289
10695
10710
121
CGCTCAGCATAGGACA





L-0120
3356
3371
10777
10792
122
CACATTGAGCATCTGC





L-0121
3359
3374
10780
10795
123
AGTCACATTGAGCATC





L-0122
3362
3377
10783
10798
124
GGGAGTCACATTGAGC





L-0123
3421
3436
10842
10857
125
ATAGCATCTTGCTGGT





L-0124
3425
3440
10846
10861
126
ATGGATAGCATCTTGC





L-0125
3429
3444
10850
10865
127
CTGCATGGATAGCATC





L-0126
3489
3504
12612
12627
128
TCCGGGTAAGGTGAGA





L-0127
3754
3769
13227
13242
129
CTGTAGTAGTCCTCCT





L-0128
3765
3780


130
TCTTCAGGTGACTGTA





L-0129
3797
3812
13462
13477
131
TCGCAGGTTOTACAGT





L-0130
3798
3813
13463
13478
132
ATCGCAGGTTCTACAG





L-0131
3816
3831
13481
13496
133
AGCCATGGTGCTCTCT





L-0132
3826
3841
13491
13506
134
CCAATGTAGGAGCCAT





L-0133
3829
3844
13494
13509
135
GGTCCAATGTAGGAGC





L-0134
3835
3850
13500
13515
136
CTCCAAGGTCCAATGT





L-0135
3837
3852
13502
13517
137
TGCTCCAAGGTCCAAT





L-0136
4025
4040
13690
13705
138
CCAAGATTCTGTGCGC





L-0137
4032
4047
13697
13712
139
ACCTGGTCCAAGATTC





L-0138
4046
4061
13711
13726
140
GACAAGGAAGAGAGAC





L-0139
4119
4134
13784
13799
141
TAATCACACCAACGGG





L-0140
4121
4136
13786
13801
142
AATAATCACACCAACG





L-0141
4122
4137
13787
13802
143
AAATAATCACACCAAC





L-0142
4123
4138
13788
13803
144
GAAATAATCACACCAA





L-0143
4125
4140
13790
13805
145
ATGAAATAATCACACC





L-0144
4132
4147
13797
13812
146
CTAACAGATGAAATAA





L-0145
4138
4153
13803
13818
147
CCACATCTAACAGATG





L-0146
4141
4156
13806
13821
148
CAGCCACATCTAACAG





L-0147
4142
4157
13807
13822
149
ACAGCCACATCTAACA





L-0148
4149
4164
13814
13829
150
ACGCAAAACAGCCACA





L-0149
4218
4233
13883
13898
151
AAGGGGCATACATTGC





L-0150
4220
4235
13885
13900
152
GCAAGGGGCATACATT






















TABLE 19







L-0151
4266
4281
13931
13946
153
CGTCATATAGATATTT





L-0152
 537
 552
 7262
 7277
154
AGCTATCCAGATCGGA





L-0153
 541
 556
 7266
 7281
155
TCCAAGCTATCCAGAT





L-0154
 586
 601
 7311
 7326
156
ATATCCCTAGGGTCGC





L-0155
 588
 603
 7313
 7328
157
CGATATCCCTAGGGTC





L-0156
 664
 679
 7389
 7404
158
CCAGAAGATGAGTCAG





L-0157
 665
 680
 7390
 7405
159
GCCAGAAGATGAGTCA





L-0158
 667
 682
 7392
 7407
160
AGGCCAGAAGATGAGT





L-0159
 668
 683
 7393
 7408
161
CAGGCCAGAAGATGAG





L-0160
 787
 802
 7512
 7527
162
GGTGTCACAGAAGGAT





L-0161
 788
 803
 7513
 7528
163
GGGTGTCACAGAAGGA





L-0162
 790
 805
 7515
 7530
164
GTGGGTGTCACAGAAG





L-0163
 791
 806
 7516
 7531
165
AGTGGGTGTCACAGAA





L-0164
 840
 855
 7565
 7580
166
GAGCCTGGAACATTCG





L-0165
 994
1009
 7719
 7734
167
ATGGGAGTAGTGGGTG





L-0166
 996
1011
 7721
 7736
168
AAATGGGAGTAGTGGG





L-0167
 997
1012
 7722
 7737
169
GAAATGGGAGTAGTGG





L-0168
1007
1022
 7732
 7747
170
GCTTGATACTGAAATG





L-0169
1008
1023
 7733
 7748
171
AGCTTGATACTGAAAT





L-0170
1010
1025
 7735
 7750
172
AGAGCTTGATACTGAA





L-0171
1011
1026
 7736
 7751
173
CAGAGCTTGATACTGA





L-0172
1363
1378
 8088
 8103
174
GCAGAGGTACTACTAG





L-0173
1364
1379
 8089
 8104
175
TGCAGAGCTACTACTA





L-0174
1650
1665
 8375
 8390
176
GTGTTGAGACTGGTGG





L-0175
1651
1666
 8376
 8391
177
TGTGTTGAGACTGGTG





L-0176
1653
1668
 8378
 8393
178
GATGTGTTGAGACTGG





L-0177
1654
1669
 8379
 8394
179
TGATGTGTTGAGACTG





L-0178
1975
1990
 8700
 8715
180
TGTGAACATGGGTAGG





L-0179
1976
1991
 8701
 8716
181
GTGTGAACATGGGTAG





L-0180
1978
1993
 8703
 8718
182
GGGTGTGAAGATGGGT





L-0181
2061
2076
 8786
 8801
183
TGGAAAGGGTAGCCGA





L-0182
2881
2896
10302
10317
184
TATTCAOTGAGAGTGC





L-0183
2882
2897
10303
10318
185
ATATTCACTGAGAGTG





L-0184
2884
2899
10305
10320
186
GCATATTCACTGAGAG





L-0185
2886
2901
10307
10322
187
GGGCATATTGACTGAG





L-0186
2889
2904
10310
10325
188
GCCGGGCATATTCACT





L-0187
2901
2916
10322
10337
189
ACATGACATGAGGCCG





L-0188
2902
2917
10323
10338
190
GACATGACATGAGGCC





L-0189
2904
2919
10325
10340
191
GAGACATGACATGAGG





L-0190
2980
2995
10401
10416
192
GCCGGGAGATTGTAAC





L-0191
3192
3207
10613
10628
193
GATGAAAGGGGAAAGG





L-0192
3193
3208
10614
10629
194
GGATGAAAGGGGAAAG





L-0193
3195
3210
10616
10631
195
TCGGATGAAAGGGGAA





L-0194
3196
3211
10617
10632
196
CTCGGATGAAAGGGGA





L-0195
3270
3285
10691
10706
197
CAGCATAGGACATGTC





L-0196
3273
3288
10694
10709
198
GCTCAGCATAGGACAT





L-0197
3360
3375
10781
10796
199
GAGTCACATTGAGCAT





L-0198
3361
3376
10782
10797
200
GGAGTCACATTGAGCA





L-0199
3363
3378
10784
10799
201
GGGGAGTCACATTGAG





L-0200
3364
3379
10785
10800
202
TGGGGAGTCACATTGA






















TABLE 20







L-0201
3483
3498
12606
12621
203
TAAGGTGAGACCCTGA





L-0202
3484
3499
12607
12622
204
GTAAGGTGAGACCCTG





L-0203
3485
3500
12608
12623
205
GGTAAGGTGAGACCCT





L-0204
3486
3501
12609
12624
206
GGGTAAGGTGAGACCC





L-0205
3487
3502
12610
12625
207
CGGGTAAGGTGAGACC





L-0206
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0207
3490
3505
12613
12628
209
ATCCGGGTAAGGTGAG





L-0208
4024
4039
13689
13704
210
CAAGATTCTGTGCGCT





L-0209
4026
4041
13691
13706
211
TCCAAGATTCTGTGCG





L-0210
4027
4042
13692
13707
212
GTCGAAGATTCTGTGC





L-0211
4219
4234
13884
13899
213
CAAGGGGCATACATTG





L-0212
4221
4236
13886
13901
214
GGCAAGGGGCATACAT





L-0213
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0214
3453
3468
12576
12591
216
TGAGAGGGTGCACCGA





L-0215
3456
3471
12579
12594
217
CAATGAGAGGGTGCAC





L-0216
3457
3472
12580
12595
218
TCAATGAGAGGGTGCA





L-0217
3458
3473
12581
12596
219
GTCAATGAGAGGGTGC





L-0218
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0219
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0220
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0221
3462
3477
12585
12600
223
GGGGGTCAATGAGAGG





L-0222
3463
3478
12586
12601
224
AGGGGGTCAATGAGAG





L-0223
3464
3479
12587
12602
225
CAGGGGGTCAATGAGA





L-0224
3465
3480
12588
12603
226
CCAGGGGGTCAATGAG





L-0225
3466
3481
12589
12604
227
GCCAGGGGGTCAATGA





L-0226
3468
3483
12591
12606
228
AGGCCAGGGGGTCAAT





L-0227
3478
3493
12601
12616
229
TGAGACCCTGAGGCCA





L-0228
3481
3496
12604
12619
230
AGGTGAGACCCTGAGG





L-0229
3482
3497
12605
12620
231
AAGGTGAGACCCTGAG





L-0230
3491
3506
12614
12629
232
GATCCGGGTAAGGTGA





L-0231
3496
3511
12619
12634
233
TAGGGGATCCGGGTAA





L-0232
3503
3518
12626
12641
234
AGCTGGGTAGGGGATC





L-0233
3515
3530
12638
12653
235
AGGGAGAGTTCCAGCT





L-0234
3516
3531
12639
12654
236
TAGGGAGAGTTCCAGC





L-0235
3517
3532
12640
12655
237
TTAGGGAGAGTTCCAG





L-0236
3518
3533
12641
12656
238
GTTAGGGAGAGTTCCA





L-0237
3519
3534
12642
12657
239
GGTTAGGGAGAGTTCC





L-0238
3520
3535
12643
12658
240
GGGTTAGGGAGAGTTC





L-0239
3521
3536
12644
12659
241
GGGGTTAGGGAGAGTT









[Evaluation Example 1] Antisense Inhibition of Human ATN1 in SH-SY5Y Cells

An effect of an antisense oligonucleotide targeting ATN1 nucleic acid, which is a causative gene of DRPLA, on an ATN1 RNA transcript was tested in vitro. After approximately 24 hours, a 300 nM antisense oligonucleotide (manufactured in Manufacturing Example 1) was transfected into SH-SY5Y cells seeded in a 96 well plate at a density of 12,000 cells/well (ASO was added such that a final concentration thereof was 300 nM) using Lipofectamin (registered trademark) RNAiMAX Transfection Reagent (Thermo Fisher Scientific). After approximately 48 hours, RNA was isolated from the cells using RNeasy Micro Kit (QIAGEN), and then reverse-transcribed with High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific) to create cDNA. Using the created cDNA, an ATN1 gene expression level was measured by quantitative real-time PCR with TaqMan (registered trademark) Gene Expression Assays (Thermo Fisher Scientific). Results thereof are presented in Tables 21 to 24 as percent expression of ATN1 relative to untreated control cells. Note that the title rows in Tables 22 to 24 are the same as that in Table 21, and thus are omitted.












TABLE 21








ATN1




mRNA



Cmpd No
remain %



















M-0001
78.6



M-0006
73.5



M-0007
79.0



M-0012
57.8



M-0013
66.4



M-0014
75.0



M-0015
75.8



M-0017
65.8



M-0018
57.0



M-0022
70.3



M-0023
64.1



M-0033
75.3



M-0035
78.8



M-0036
73.5



M-0037
77.2



M-0039
79.0



M-0040
65.8



M-0042
79.7



M-0045
66.4



M-0046
74.0



M-0047
55.6



M-0050
72.5



M-0051
69.8



M-0052
77.4



M-0053
68.0



M-0055
78.8



M-0056
69.2



M-0057
60.4



M-0058
59.1



M-0059
75.8



M-0061
58.8



M-0062
64.2



M-0063
70.1



M-0064
73.9



M-0065
64.1



M-0066
70.9



M-0068
73.4



M-0069
62.9



M-0070
76.1



M-0072
67.2



M-0073
72.7



M-0074
66.0



M-0075
58.6



M-0076
74.9



M-0078
75.7



M-0079
55.4



M-0080
68.6



M-0082
64.0



M-0083
71.5



M-0084
75.0



M-0085
62.0



M-0086
45.1



M-0087
62.8



M-0088
77.4



M-0089
63.6



M-0090
74.5



M-0091
50.1



M-0092
49.9



M-0094
68.8



M-0096
44.9



M-0097
74.4



M-0098
66.1



M-0099
70.3



M-0100
66.8



M-0101
71.4



M-0103
67.2



M-0104
54.0



M-0105
58.5



M-0106
68.6



M-0107
73.9



M-0108
75.1



M-0109
53.6



M-0114
56.9



M-0116
58.3



M-0117
53.2



M-0118
76.6



M-0119
71.3



M-0120
52.8



M-0121
55.6



M-0122
23.8



M-0123
10.9



M-0124
28.5



M-0125
47.0



M-0126
65.6



M-0128
74.9



M-0130
77.2



M-0131
61.8



M-0132
75.7



M-0133
69.6



M-0134
62.1



M-0135
56.5



M-0136
69.6



M-0137
68.9



M-0138
52.2



M-0139
73.4



M-0141
62.9



M-0151
68.9



M-0152
70.7



M-0153
60.2




















TABLE 22









M-0154
50.1



M-0155
70.5



M-0156
55.3



M-0157
61.4



M-0158
73.0



M-0159
58.4



M-0160
40.2



M-0161
70.1



M-0162
63.3



M-0163
57.8



M-0164
66.7



M-0165
65.7



M-0166
58.8



M-0168
66.3



M-0169
48.4



M-0170
52.8



M-0171
33.2



M-0172
45.8



M-0173
38.7



M-0174
44.1



M-0175
39.7



M-0176
7.0



M-0177
13.6



M-0178
21.5



M-0179
49.3



M-0180
33.1



M-0181
26.2



M-0182
21.2



M-0183
16.9



M-0184
13.7



M-0185
21.8



M-0186
33.7



M-0187
25.4



M-0188
28.7



M-0189
28.6



M-0190
27.6



M-0191
13.5



M-0192
23.6



M-0193
23.9



M-0194
15.3



M-0195
22.5



M-0196
46.4



M-0197
54.8



M-0198
28.7



M-0199
20.1



M-0200
13.7



M-0201
20.1



M-0202
11.5



M-0203
27.1



M-0204
21.3



M-0205
35.2



M-0206
59.2



M-0207
60.9



M-0208
57.9



M-0209
21.7



M-0210
15.0



M-0211
14.0



M-0212
17.2



M-0213
13.2



M-0214
21.2



M-0215
29.1



M-0216
44.7



M-0217
46.0



M-0218
34.0



M-0219
19.4



M-0220
12.6



M-0221
19.3



M-0222
15.1



M-0223
11.4



M-0224
10.5



M-0225
17.3



M-0226
22.4



M-0227
27.7



M-0228
51.7



M-0229
65.1



M-0230
54.9



M-0231
49.9



M-0232
49.8



M-0233
68.4



M-0234
70.4



M-0235
73.2



M-0236
62.5



M-0237
67.9



M-0238
62.3



M-0239
57.1



M-0240
77.4



M-0241
52.8



M-0242
59.4



M-0243
58.5



M-0244
56.0



M-0245
65.0



M-0246
78.6




















TABLE 23









L-0001
74.6



L-0002
75.8



L-0007
69.4



L-0008
70.6



L-0010
78.6



L-0011
75.1



L-0016
74.5



L-0017
63.0



L-0018
63.7



L-0019
67.3



L-0024
76.8



L-0027
66.5



L-0032
66.2



L-0035
42.4



L-0036
56.7



L-0037
73.9



L-0038
74.4



L-0042
67.6



L-0043
77.3



L-0044
71.9



L-0045
48.0



L-0046
69.8



L-0047
79.6



L-0048
68.8



L-0050
78.9



L-0053
45.2



L-0057
60.2



L-0058
75.7



L-0059
56.7



L-0060
67.4



L-0061
70.7



L-0064
71.6



L-0065
68.8



L-0066
58.5



L-0067
73.9



L-0068
59.1



L-0070
67.4



L-0072
71.6



L-0073
74.6



L-0076
65.8



L-0077
78.4



L-0080
74.1



L-0081
58.6



L-0082
69.5



L-0083
65.0



L-0084
69.9



L-0085
79.8



L-0086
69.2



L-0087
64.5



L-0089
64.2



L-0090
76.0



L-0092
79.3



L-0093
76.9



L-0095
77.6



L-0097
75.0



L-0099
64.9



L-0100
54.4



L-0101
66.6



L-0102
62.7



L-0103
50.4



L-0104
58.3



L-0105
67.2



L-0106
75.1



L-0107
68.4



L-0108
78.3



L-0109
43.7



L-0110
69.5



L-0111
60.6



L-0112
64.5



L-0113
74.8



L-0114
76.2



L-0115
59.2



L-0116
73.9



L-0117
72.5



L-0118
58.2



L-0119
64.4



L-0120
68.8



L-0121
78.2



L-0122
61.4



L-0124
74.2



L-0125
66.6



L-0126
6.0



L-0129
77.6



L-0130
77.9



L-0131
77.4



L-0135
79.5



L-0136
59.4



L-0137
66.6



L-0146
74.7



L-0149
70.5



L-0150
56.4



L-0151
69.6



L-0152
48.4



L-0154
53.6



L-0155
50.2



L-0156
62.1



L-0157
54.3



L-0158
48.5



L-0159
48.5



L-0160
61.4




















TABLE 24









L-0161
49.3



L-0162
70.9



L-0163
74.4



L-0164
67.3



L-0165
61.9



L-0166
45.9



L-0167
49.5



L-0168
58.9



L-0169
54.7



L-0170
57.7



L-0171
61.2



L-0172
49.5



L-0173
59.0



L-0174
56.4



L-0175
71.3



L-0176
69.9



L-0177
72.9



L-0178
49.3



L-0179
61.2



L-0181
75.7



L-0182
65.9



L-0183
68.0



L-0184
60.7



L-0185
66.3



L-0186
58.9



L-0187
69.3



L-0188
62.5



L-0189
77.2



L-0190
65.1



L-0191
76.6



L-0192
65.8



L-0193
71.3



L-0194
61.7



L-0195
67.9



L-0196
68.2



L-0198
62.4



L-0199
65.8



L-0200
68.2



L-0201
63.5



L-0202
30.4



L-0203
52.4



L-0204
66.6



L-0205
15.1



L-0206
5.4



L-0207
19.1



L-0208
65.8



L-0209
69.4



L-0210
71.8



L-0211
65.6



L-0212
54.9



L-0213
3.5



L-0214
13.3



L-0215
60.7



L-0216
44.3



L-0217
26.8



L-0218
11.5



L-0219
7.9



L-0220
8.7



L-0221
7.0



L-0222
29.9



L-0223
37.1



L-0224
8.2



L-0225
4.9



L-0226
27.8



L-0227
19.9



L-0228
13.7



L-0229
42.3



L-0230
11.5



L-0231
32.8



L-0232
20.6



L-0233
56.5



L-0234
57.8



L-0236
70.5



L-0237
56.9



L-0238
47.6



L-0239
55.4










[Evaluation Example 2] Dose-Dependent Antisense Inhibition of Human ATN1 in SH-SY5Y Cells

The antisense oligonucleotide that exhibited inhibition of ATN1 in SH-SY5Y cells in Evaluation Example 1 was tested at various doses. After approximately 24 hours, antisense oligonucleotides at concentrations of 0.003 nM, 0.03 nM, 0.3 nM, 3 nM, 30 nM, and 300 nM were each transfected into SH-SY5Y cells seeded in a 96 well plate at a density of 12,000 cells/well (ASO was added such that final concentrations thereof were the above concentrations, respectively) using Lipofectamin (registered trademark) RNAiMAX Transfection Reagent (Thermo Fisher Scientific). After approximately 48 hours, RNA was isolated from the cells using RNeasy Micro Kit (QIAGEN), and then reverse-transcribed with High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific) to create cDNA. Using the created cDNA, an ATN1 gene expression level was measured by quantitative real-time PCR with TaqMan (registered trademark) Gene Expression Assays (Thermo Fisher Scientific). Results thereof were calculated as a concentration (IC50 value) at which an RNA transcript level was 50% relative to untreated control cells and are presented in Table 25.












TABLE 25








IC50



Cmpd No
(nM)



















M-0176
10.3



M-0177
13.7



M-0178
25.8



M-0182
6.5



M-0183
1.7



M-0184
0.5



M-0191
9.3



M-0194
13.3



M-0199
37.7



M-0200
8.3



M-0201
36.8



M-0202
11.6



M-0204
46.0



M-0209
15.3



M-0210
6.7



M-0211
3.7



M-0212
1.3



M-0213
1.7



M-0214
3.7



M-0219
7.0



M-0220
4.9



M-0221
5.8



M-0222
3.1



M-0223
2.6



M-0224
4.2



M-0225
9.6



M-0226
7.3



L-0126
8.7



L-0202
50.5



L-0205
3.4



L-0206
1.4



L-0207
26.6



L-0213
0.7



L-0214
5.2



L-0217
7.9



L-0218
1.2



L-0219
0.7



L-0220
0.7



L-0221
3.1



L-0224
19.4



L-0225
4.6



L-0226
28.5



L-0227
12.8



L-0228
9.1



L-0230
3.9



L-0231
4.1



L-0232
2.3










Manufacturing Example 2

Antisense oligonucleotides (compounds represented by chemical structures corresponding to compound numbers) described in Tables 26 to 33 were prepared using an automatic nucleic acid synthesizer nS-8II (manufactured by GeneDesign Inc.). Note that the title rows in Tables 28 to 33 are the same as that in Table 27, and thus are omitted.










TABLE 26





Cmpd No
Chemical structure







M-0248
A(V){circumflex over ( )}A(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}G(V)


M-0249
G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}5(V){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}5(V){circumflex over ( )}A(V){circumflex over ( )}5(V)


M-0250
5(V){circumflex over ( )}5(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(V){circumflex over ( )}5(V){circumflex over ( )}A(V){circumflex over ( )}A(V){circumflex over ( )}T(V)


M-0251
G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}G(V)


M-0252
A(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V){circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}A(V){circumflex over ( )}G(V)


M-0253
A(V){circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}A(V)


M-0254
G(V){circumflex over ( )}A(V){circumflex over ( )}T(V){circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}5(V){circumflex over ( )}5(V)


M-0255
G(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}T(V){circumflex over ( )}5(V){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}5(V)


M-0256
G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}T(V){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}G(V){circumflex over ( )}A(V)


M-0257
G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}G(V)


M-0258
A(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}A(V)


M-0259
5(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}T(V){circumflex over ( )}A(V)


M-0260
A(V){circumflex over ( )}G(V){circumflex over ( )}5(V){circumflex over ( )}T(V){circumflex over ( )}G(V){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V)


M-0261
G(V){circumflex over ( )}T(V){circumflex over ( )}T(V){circumflex over ( )}5(V){circumflex over ( )}5(V){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}G(V){circumflex over ( )}A(V){circumflex over ( )}T(V)

















TABLE 27





Cmpd No
Chemical structure







L-0240
G(V){circumflex over ( )}T(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0241
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}5(V)


L-0242
G(L){circumflex over ( )}T(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}5(L)


L-0243
G(V){circumflex over ( )}G(L){circumflex over ( )}T(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0244
G(V){circumflex over ( )}G(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0245
G(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(V){circumflex over ( )}G(V)


L-0246
G(L){circumflex over ( )}G(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(V){circumflex over ( )}G(L)


L-0247
G(V){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(V){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0248
G(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0249
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(V)


L-0250
G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L)


L-0251
G(V){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0252
T(V){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0253
T(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}A(V)


L-0254
T(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}A(L)


L-0255
G(V){circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0256
A(V){circumflex over ( )}G(V){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0257
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(V){circumflex over ( )}5(V)


L-0258
A(L){circumflex over ( )}G(V){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(V){circumflex over ( )}5(L)


L-0259
5(V){circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}T(V){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0260
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0261
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0262
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0263
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0264
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0265
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0266
5(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0267
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0268
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0269
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0270
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0271
A(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0272
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0273
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0274
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0275
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0276
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0277
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0278
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0279
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0280
T(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0281
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0282
G(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0283
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0284
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0285
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0286
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0287
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0288
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0289
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)

















TABLE 28







L-0290
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0291
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0292
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0293
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0294
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0295
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0296
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0297
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0298
A(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0299
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0300
A(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0301
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0302
5(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0303
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0304
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0305
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0306
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0307
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0308
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0309
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0310
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0311
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0312
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0313
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0314
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0315
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0316
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0317
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0318
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0319
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0320
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0321
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0322
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0323
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0324
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0325
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0326
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0327
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0328
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0329
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0330
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0331
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0332
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0333
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0334
A(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0335
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0336
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0337
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0338
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0339
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)

















TABLE 29







L-0340
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0341
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0342
A(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0343
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0344
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0345
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0346
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0347
G(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0348
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0349
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0350
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0351
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0352
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0353
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0354
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0355
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0356
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0357
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0358
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0359
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0360
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0361
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0362
A(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0363
T(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0364
T(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0365
T(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0366
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0367
T(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0368
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0369
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0370
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0371
A(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0372
T(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0373
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0374
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0375
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0376
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0377
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0378
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0379
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0380
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0381
T(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0382
T(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0383
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0384
A(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0385
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0386
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0387
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0388
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0389
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)

















TABLE 30







L-0390
G(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0391
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0392
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0393
T(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0394
T(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0395
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0396
G(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0397
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0398
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0399
A(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0400
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0401
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0402
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0403
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0404
A(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0405
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0406
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0407
T(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0408
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0409
5(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0410
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0411
T(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0412
5(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0413
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0414
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0415
A(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0416
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0417
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0418
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0419
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}G(V)


L-0420
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0421
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0422
T(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0423
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0424
5(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0425
A(V){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(V)


L-0426
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0427
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0428
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0429
G(V){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0430
G(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}G(V)


L-0431
G(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}G(L)


L-0432
T(V){circumflex over ( )}G(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0433
5(V){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0434
5(V){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0435
5(L){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(V){circumflex over ( )}G(L)


L-0436
G(V){circumflex over ( )}5(L){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(V){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0437
G(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0438
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(V){circumflex over ( )}5(V)


L-0439
G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(V){circumflex over ( )}5(L)

















TABLE 31







L-0440
G(V){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(V){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0441
T(V){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0442
T(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(V){circumflex over ( )}A(V)


L-0443
T(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(V){circumflex over ( )}A(L)


L-0444
A(V){circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0445
T(V){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0446
T(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(V){circumflex over ( )}A(V)


L-0447
T(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(V){circumflex over ( )}A(L)


L-0448
G(V){circumflex over ( )}T(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0449
G(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0450
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(V)


L-0451
G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L)


L-0452
A(V){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0453
A(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0454
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(V)


L-0455
A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L)


L-0456
5(V){circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0457
5(V){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0458
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}A(V)


L-0459
5(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}A(L)


L-0460
5(V){circumflex over ( )}5(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0461
5(V){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0462
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(V)


L-0463
5(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L)


L-0464
G(V){circumflex over ( )}5(L){circumflex over ( )}5(V){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0465
G(V){circumflex over ( )}5(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0466
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(V)


L-0467
G(L){circumflex over ( )}5(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(L)


L-0468
G(V){circumflex over ( )}G(L){circumflex over ( )}5(V){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0469
A(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0470
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(V){circumflex over ( )}T(V)


L-0471
A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(V){circumflex over ( )}T(L)


L-0472
G(V){circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(V){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0473
5(V){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0474
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}5(V)


L-0475
5(L){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}5(L)


L-0476
T(V){circumflex over ( )}5(L){circumflex over ( )}5(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0477
G(V){circumflex over ( )}A(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0478
G(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(V)


L-0479
G(L){circumflex over ( )}A(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(L)


L-0480
G(V){circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0481
A(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0482
A(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(V)


L-0483
A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L)


L-0484
A(V){circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}5(V)


L-0485
G(V){circumflex over ( )}T(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0486
G(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(V){circumflex over ( )}G(V)


L-0487
G(L){circumflex over ( )}T(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(V){circumflex over ( )}G(L)


L-0488
G(V){circumflex over ( )}G(L){circumflex over ( )}T(V){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(V){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0489
A(V){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)

















TABLE 32







L-0490
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(V)


L-0491
A(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L)


L-0492
T(V){circumflex over ( )}A(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0498
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0499
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}A(V)


L-0500
5(V){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}T(V)


L-0501
T(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0502
5(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0503
5(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0504
5(V){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0505
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0506
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0507
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0508
T(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0509
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0510
5(V){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0511
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0512
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0513
G(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0514
5(V){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0515
5(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(V)


L-0516
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0517
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0518
A(V){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0519
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0520
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0521
5(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0522
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0523
T(V){circumflex over ( )}T(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}A(V)


L-0524
A(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0525
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}A(V)


L-0526
G(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0527
A(V){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0528
5(V){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0529
T(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(V)


L-0530
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0531
G(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0532
A(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0533
G(V){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0534
5(V){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}T(V)


L-0535
G(V){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(V)


L-0536
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(V)


L-0537
G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L)


L-0538
T(V){circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}A(V){circumflex over ( )}G(L){circumflex over ( )}G(V)


L-0539
G(L){circumflex over ( )}A(L){circumflex over ( )}G(V){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(V){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0540
G(V){circumflex over ( )}A(L)G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(L){circumflex over ( )}G(V)


L-0541
G(V){circumflex over ( )}A(L)G(L)a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(L){circumflex over ( )}G(V)


L-0542
G(V){circumflex over ( )}A(L)G(L)A(V){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(L){circumflex over ( )}G(V)


L-0543
G(V){circumflex over ( )}A(L)G(L)a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(V)G(L)A(L){circumflex over ( )}G(V)

















TABLE 33







L-0544
G(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}gg{circumflex over ( )}g{circumflex over ( )}tg{circumflex over ( )}5(x){circumflex over ( )}a5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(L){circumflex over ( )}G(V)


L-0545
G(V){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(V)


L-0546
G(V){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}T(V)


L-0547
G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}T(L)


L-0548
G(V){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}T(L){circumflex over ( )}G(V)


L-0549
G(L){circumflex over ( )}G(L){circumflex over ( )}G(V){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V){circumflex over ( )}G(L){circumflex over ( )}T(L)









Positions in a sequence of human ATN1 mRNA or pre-mRNA targeted by the antisense oligonucleotides presented in Tables 26 to 33, and sequence numbers and nucleobase sequences corresponding to the antisense oligonucleotides are presented in Tables 34 to 41. The notations in Tables 34 to 41 are the same as those in Tables 11 to 20.


Note that the title rows in Tables 36 to 41 are the same as that in Table 35, and thus are omitted.















TABLE 34






SEQ1
SEQ1
SEQ2
SEQ2
SEQ



Cmpd No
START
END
START
END
No
BASE SEQUENCE







M-0248
3451
3470
12574
12593
419
AATGAGAGGGTGCACCGAGG





M-0249
3456
3475
12579
12598
423
GGGTCAATGAGAGGGTGCAC





M-0250
3468
3487
12591
12610
435
CCTGAGGCCAGGGGGTCAAT





M-0251
3476
3495
12599
12618
441
GGTGAGACCCTGAGGCCAGG





M-0252
3477
3496
12600
12619
442
AGGTGAGACCCTGAGGCCAG





M-0253
3478
3497
12601
12620
443
AAGGTGAGACCCTGAGGCCA





M-0254
3487
3506
12610
12629
450
GATCCGGGTAAGGTGAGACC





M-0255
3488
3507
12611
12630
451
GGATCCGGGTAAGGTGAGAC





M-0256
3489
3508
12612
12631
452
GGGATCCGGGTAAGGTGAGA





M-0257
3490
3509
12613
12632
453
GGGGATCCGGGTAAGGTGAG





M-0258
3491
3510
12614
12633
454
AGGGGATCCGGGTAAGGTGA





M-0259
3497
3516
12620
12639
460
CTGGGTAGGGGATCCGGGTA





M-0260
3499
3518
12622
12641
462
AGCTGGGTAGGGGATCCGGG





M-0261
3504
3523
12627
12646
467
GTTCCAGCTGGGTAGGGGAT






















TABLE 35






SEQ1
SEQ1
SEQ2
SEQ2
SEQ



Cmpd No
START
END
START
END
No
BASE SEQUENCE







L-0240
3458
3473
12581
12596
219
GTCAATGAGAGGGTGC





L-0241
3458
3473
12581
12596
219
GTCAATGAGAGGGTGC





L-0242
3458
3473
12581
12596
219
GTCAATGAGAGGGTGC





L-0243
3457
3474
12580
12597
488
GGTCAATGAGAGGGTGCA





L-0244
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0245
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0246
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0247
3458
3475
12581
12598
489
GGGTCAATGAGAGGGTGC





L-0248
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0249
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0250
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0251
3460
3477
12583
12600
490
GGGGGTCAATGAGAGGGT





L-0252
3496
3511
12619
12634
233
TAGGGGATCCGGGTAA





L-0253
3496
3511
12619
12634
233
TAGGGGATCCGGGTAA





L-0254
3496
3511
12619
12634
233
TAGGGGATCCGGGTAA





L-0255
3495
3512
12618
12635
491
GTAGGGGATCCGGGTAAG





L-0256
3503
3518
12626
12641
234
AGCTGGGTAGGGGATC





L-0257
3503
3518
12626
12641
234
AGCTGGGTAGGGGATC





L-0258
3503
3518
12626
12641
234
AGCTGGGTAGGGGATC





L-0259
3502
3519
12625
12642
492
CAGCTGGGTAGGGGATCC





L-0260


 373
 388
493
CTCCTCTTTTGAGTCT





L-0261


 383
 398
494
CTCGATGTTCCTCCTC





L-0262


 426
 441
495
ACCCCACTCACAGCAT





L-0263


 450
 465
496
CTATCCATTCTGCCTT





L-0264


 456
 471
497
TCTCTCCTATCCATTC





L-0265


 546
 561
498
TTCCTAAAGCCCCCAA





L-0266


 552
 567
499
CGTCTATTCCTAAAGC





L-0267


 589
 604
500
TTCCACCTACCACACC





L-0268


 603
 618
501
GCCACAATCCCTCTTT





L-0269


 644
 659
502
ACCTCTCTTTGCCCAA





L-0270


 653
 668
503
CAAAAATGGACCTCTC





L-0271


 678
 693
504
ACGCTGGAAAACCTCC





L-0272


 709
 724
505
ACCGTCACAAAGACAT





L-0273


 780
 795
506
CTCTCCAAGAAATAAC





L-0274


 828
 843
507
TCCTCCTCACTAGTTT





L-0275


 838
 853
508
GTTCCTGTTTTCCTCC





L-0276


 847
 862
509
CCCTTCTGTGTTCCTG





L-0277


 874
 889
510
TCCCAGAACCCCTTTC





L-0278


 889
 904
511
TCTCCATTTCCATCCT





L-0279


 899
 914
512
GTTGCTCAATTCTCCA





L-0280


 986
1001
513
TATAGATCACAGCTCC





L-0281


 993
1008
514
CTCCCTATATAGATCA





L-0282


1004
1019
515
GTAACTAAGGCCTCCC





L-0283


1043
1058
516
TAAGCCCATGCACAAA





L-0284


1048
1063
517
CAAAATAAGCCCATGC





L-0285


1059
1074
518
CCTACCCTAGTCAAAA





L-0286


1098
1113
519
ACCCTCCTATAGCACC





L-0287


1108
1123
520
AGCAACTCCTACCCTC





L-0288


1120
1135
521
CCCAGTTGCCAAAGCA





L-0289


1163
1178
522
TCAAGAGACCATCCCA






















TABLE 36







L-0290


1194
1209
523
ACCATAGCAACACAGT





L-0291


1210
1225
524
ATCCCACTGGATCACT





L-0292


1217
1232
525
ATCTGACATCCCACTG





L-0293


1225
1240
526
CCCAACCAATCTGACA





L-0294


1246
1261
527
CCAATAAACATTCGAA





L-0295


1294
1309
528
ACCTCCAAAACCCAGC





L-0296


1304
1319
529
TCCAGAAACAACCTCC





L-0297


1315
1330
530
CCACCAACAGATCCAG





L-0298


1324
1339
531
AACTCCCAACCACCAA





L-0299


1363
1378
532
CCAACAGACTTCAACA





L-0300


1378
1393
533
ACGTATCTACCTGTTC





L-0301


1398
1413
534
ACACCTATGATCTGCA





L-0302


1442
1457
535
CGTTTTCATCCTCCCA





L-0303


1482
1497
536
CAGAACCAACTGGCAA





L-0304


1529
1544
537
CAAAAAGACAACTCTA





L-0305


1658
1673
538
CCCAGCCATTTCTACA





L-0306


1713
1728
539
AGCTGTTTCACAGCCC





L-0307


1735
1750
540
CTATAGTATTTCCCCT





L-0308


1762
1777
541
CTAGACACAGGTCTCC





L-0309


1827
1842
542
CTTAACAATGAAGCCC





L-0310


1847
1862
543
CTCATCTATAGCCCCT





L-0311


1853
1868
544
GATCATCTCATCTATA





L-0312


1902
1917
545
CACTGGCCTAAGCCTT





L-0313


1944
1959
546
ACTCCTAGATAACAAT





L-0314


1953
1968
547
TCCAAAGTGACTCCTA





L-0315


1965
1980
548
CTAACAAACCAGTCCA





L-0316


1993
2008
549
CCCCCAACATCATTCT





L-0317


2114
2129
550
CCCCTAAGTAAGAACA





L-0318


2189
2204
551
GCCATTACCTTACTTT





L-0319


2522
2537
552
CTTCATTACCTTGCTT





L-0320


2532
2547
553
GCACATTCACCTTCAT





L-0321


2562
2577
554
GCACCTACTCTGTATC





L-0322


2587
2602
555
CAATCACTGTAACTAA





L-0323


2600
2615
556
CACTCCTAGCAGGCAA





L-0324


2789
2804
557
CAATCATAGTATGCCC





L-0325


2863
2878
558
CCTGTTCACCAAGTCA





L-0326


2878
2893
559
TTCCCCATCACAGAAC





L-0327


2989
3004
560
ACCCACCATAGCAAAA





L-0328


2997
3012
561
AGAACAACACCCACCA





L-0329


3002
3017
562
TCCGAAGAACAACACC





L-0330


3066
3081
563
CCCACATTTTTTAGTT





L-0331


3082
3097
564
CAACTACAGCTATTTT





L-0332


3380
3395
565
TCTTTGCTCTTGTTCC





L-0333


3662
3677
566
TGATCTCACTCACTGC





L-0334


3762
3777
567
AACTGATGCTCTGCCC





L-0335


3774
3789
568
TTCTGAACTTTCAACT





L-0336


3821
3836
569
CTTCACAATTTACTTA





L-0337


3829
3844
570
CCAGGAAACTTCACAA





L-0338


3841
3856
571
AGTCTAACCTTTCCAG





L-0339


3908
3923
572
TTCCCAAGAAACACAG






















TABLE 37







L-0340


3978
3993
573
ACCCATGTATTCTATT





L-0341


3987
4002
574
ACTAAGCTTACCCATG





L-0342


4061
4076
575
ATTGACCTTTAAACCC





L-0343


4108
4123
576
CTTACTGTTTTCTTCC





L-0344


4157
4172
577
CCTCCAAATTACTGAT





L-0345


4168
4183
578
AGTGTCAAGTCCCTCC





L-0346


4227
4242
579
CTTTATCCAAATCCCT





L-0347


4235
4250
580
GTATCTATCTTTATCC





L-0348


4255
4270
581
CCGTATCTGTCTATCA





L-0349


4266
4281
582
AGCCAATCCATCCGTA





L-0350


4280
4295
583
ACACAGTTTCTCACAG





L-0351


4314
4329
584
TAAGCCTATCCTCCTA





L-0352


4335
4350
585
CAACACAGATGTACCA





L-0353


4360
4375
586
AAGACTCAAAATATCC





L-0354


4425
4440
587
CCATTCTCTAGTACTT





L-0355


4468
4483
588
CCCCAAATTGTAGAAC





L-0356


4477
4492
589
CCTAGGTAGCCCCAAA





L-0357


4504
4519
590
CACAGCCCTACCAATC





L-0358


4525
4540
591
CCATTCTATAATACAA





L-0359


4562
4577
592
TCTTTTCTCACATCAG





L-0360


4636
4651
593
TGCTGTATTCTCCTCA





L-0361


4649
4664
594
TTCTTCTATACTTTGC





L-0362


4687
4702
595
AATCAAACCCATGTCG





L-0363


4734
4749
596
TGTGACTAGCCCAACC





L-0364


4780
4795
597
TACCCTCATTATATAG





L-0365


4809
4824
598
TACAACCAACCCTGAA





L-0366


4835
4850
599
TCACATACATGATTTC





L-0367


4857
4872
600
TACCTTCTTTATATCA





L-0368


5205
5220
601
ACACACATTCCACGGA





L-0369


5235
5250
602
CTTCATGATCCCTAAA





L-0370


5246
5261
603
CACAGTTTACCOTTCA





L-0371


5277
5292
604
ATGTACCTACAAGCCC





L-0372


5316
5331
605
TATAATCTCTTTCATC





L-0373


5354
5369
606
CCTTAGOTATCTAAAA





L-0374


5393
5408
607
CAGATACCACAAGACA





L-0375


5421
5436
608
CAACCCTAAGCCTTTG





L-0376


5497
5512
609
CATCAGAGTCTCCAAC





L-0377


5716
5731
610
CTCATTTTAACTCACC





L-0378


5728
5743
611
TCTTTCATGTCTCTCA





L-0379


5733
5748
612
CCTCATCTTTCATGTC





L-0380


5758
5773
613
TTCCTCCTAGCTTGCC





L-0381


5779
5794
614
TTGTTCTTCTTCTCTA





L-0382


5807
5822
615
TTGCACCTAACTTTAT





L-0383


5824
5839
616
TAACACTGTTCTTTAC





L-0384


6069
6084
617
AACAGGAAGTTCCCCC





L-0385


6115
6130
618
TCCTGTCTTTTCCCTA





L-0386


6356
6371
619
TTCTCTTATGTCCCAG





L-0387


6382
6397
620
CTCTCATAAGCACTAT





L-0388


6420
6435
621
GCTCTAAGAATCTCTC





L-0389


6478
6493
622
ATCCCCCAACTCTTCT






















TABLE 38







L-0390


 6506
 6521
623
GACTAAGACTTCTCAC





L-0391


 6540
 6555
624
TTGTGCATTTTCCTTA





L-0392


 6548
 6563
625
AAGACCACTTCTGCAT





L-0393


 6875
 6890
626
TTTTATACCACTTGTG





L-0394


 6907
 6922
627
TTTAACCATCCTCCAT





L-0395


 6924
 6939
628
CATCTCATAACCACCA





L-0396


 6947
 6962
629
GACTCCAACTCCCTGT





L-0397


 6969
 6984
630
CACCTTGTCTCTACCC





L-0398


 6989
 7004
631
CCTCAAGGATCCATCT





L-0399


 7002
 7017
632
AACCCTATTCCTTCCT





L-0400


 7023
 7038
633
AGTCTTGTTTCCCGCC





L-0401


 7055
 7070
634
TTCCTCACATTCTTGG





L-0402


 7066
 7081
635
GATTTCTCACTTTCCT





L-0403


 7083
 7098
636
ACCTCTTACCATCTGG





L-0404


 7147
 7162
637
AAAATCATTTCCCCTC





L-0405


 9336
 9351
638
ACACTACACCAGCGCA





L-0406


 9923
 9938
639
CTCGCTGAAAACCTTT





L-0407


 9951
 9966
640
TTTTCCCAACCCAGGA





L-0408


 9966
 9981
641
CCATCTGAGCATGCCT





L-0409


10001
10016
642
CGAATATTTGCCCTTC





L-0410


10031
10046
643
CACCTGGAACTTAACT





L-0411


10056
10071
644
TGCCTCAACTCATTGA





L-0412


11122
11137
645
CTTCAAAAGCTCCCGT





L-0413


11621
11636
646
ACACCCAAACCCAAAG





L-0414


11631
11646
647
ATCGCCTATGACACCC





L-0415


11641
11656
648
AAAGCTCATTATCGCC





L-0416


12705
12720
649
CATCCTTACCAAAGAG





L-0417


12758
12773
650
CCCAAATACCTCCTTT





L-0418


12835
12850
651
AGCTCTCCTATTCCCA





L-0419


12873
12888
652
CTGACACTAAAACTCG





L-0420


12931
12946
653
ACACCCAGTTCTGTAA





L-0421


12974
12989
654
GCTCCTTTACATACAA





L-0422


13008
13023
655
TAACAAGTACCTGCTC





L-0423


12442
12457
656
TCCAAAGTGGAACAAA





L-0424


12456
12471
657
CAAACACAAGGAGGTC





L-0425


12463
12478
658
AGTCAGACAAACACAA





L-0426


12467
12482
659
ACTGAGTCAGACAAAC





L-0427


12506
12521
660
GCAAACCATGCATTTG





L-0428


12508
12523
661
GGGCAAACCATGCATT





L-0429
1363
1378
 8088
 8103
174
GCAGAGCTACTACTAG





L-0430
1363
1378
 8088
 8103
174
GCAGAGCTACTACTAG





L-0431
1363
1378
 8088
 8103
174
GCAGAGCTACTACTAG





L-0432
1362
1379
 8087
 8104
662
TGCAGAGCTACTACTAGA





L-0433
2888
2903
10309
10324
105
CCGGGCATATTCACTG





L-0434
2888
2903
10309
10324
105
CCGGGCATATTCACTG





L-0435
2888
2903
10309
10324
105
CCGGGCATATTCACTG





L-0436
2887
2904
10308
10325
663
GCCGGGCATATTCACTGA





L-0437
3520
3535
12643
12658
240
GGGTTAGGGAGAGTTC





L-0438
3520
3535
12643
12658
240
GGGTTAGGGAGAGTTC





L-0439
3520
3535
12643
12658
240
GGGTTAGGGAGAGTTC






















TABLE 39







L-0440
3519
3536
12642
12659
664
GGGGTTAGGGAGAGTTCC





L-0441
3453
3468
12576
12591
216
TGAGAGGGTGCACGGA





L-0442
3453
3468
12576
12591
216
TGAGAGGGTGCACCGA





L-0443
3453
3468
12576
12591
216
TGAGAGGGTGCACGGA





L-0444
3452
3469
12575
12592
665
ATGAGAGGGTGCACCGAG





L-0445
3457
3472
12580
12595
218
TCAATGAGAGGGTGCA





L-0446
3457
3472
12580
12595
218
TCAATGAGAGGGTGCA





L-0447
3457
3472
12580
12595
218
TCAATGAGAGGGTGCA





L-0448
3456
3473
12579
12596
666
GTCAATGAGAGGGTGCAC





L-0449
3462
3477
12585
12600
223
GGGGGTCAATGAGAGG





L-0450
3462
3477
12585
12600
223
GGGGGTCAATGAGAGG





L-0451
3462
3477
12585
12600
223
GGGGGTCAATGAGAGG





L-0452
3461
3478
12584
12601
667
AGGGGGTCAATGAGAGGG





L-0453
3463
3478
12586
12601
224
AGGGGGTCAATGAGAG





L-0454
3463
3478
12586
12601
224
AGGGGGTCAATGAGAG





L-0455
3463
3478
12586
12601
224
AGGGGGTCAATGAGAG





L-0456
3462
3479
12585
12602
668
CAGGGGGTCAATGAGAGG





L-0457
3464
3479
12587
12602
225
CAGGGGGTCAATGAGA





L-0458
3464
3479
12587
12602
225
CAGGGGGTCAATGAGA





L-0459
3464
3479
12587
12602
225
CAGGGGGTCAATGAGA





L-0460
3463
3480
12586
12603
669
CCAGGGGGTCAATGAGAG





L-0461
3465
3480
12588
12603
226
CCAGGGGGTCAATGAG





L-0462
3465
3480
12588
12603
226
CCAGGGGGTCAATGAG





L-0463
3465
3480
12588
12603
226
CCAGGGGGTCAATGAG





L-0464
3464
3481
12587
12604
670
GCCAGGGGGTCAATGAGA





L-0465
3466
3481
12589
12604
227
GCCAGGGGGTCAATGA





L-0466
3466
3481
12589
12604
227
GCCAGGGGGTCAATGA





L-0467
3466
3481
12589
12604
227
GCCAGGGGGTCAATGA





L-0468
3465
3482
12588
12605
671
GGCCAGGGGGTCAATGAG





L-0469
3468
3483
12591
12606
228
AGGCCAGGGGGTCAAT





L-0470
3468
3483
12591
12606
228
AGGCCAGGGGGTCAAT





L-0471
3468
3483
12591
12606
228
AGGCCAGGGGGTCAAT





L-0472
3467
3484
12590
12607
672
GAGGCCAGGGGGTCAATG





L-0473
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0474
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0475
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0476
3487
3504
12610
12627
673
TCCGGGTAAGGTGAGACC





L-0477
3491
3506
12614
12629
232
GATCCGGGTAAGGTGA





L-0478
3491
3506
12614
12629
232
GATCCGGGTAAGGTGA





L-0479
3491
3506
12614
12629
232
GATCCGGGTAAGGTGA





L-0480
3490
3507
12613
12630
674
GGATCCGGGTAAGGTGAG





L-0481
3481
3496
12604
12619
230
AGGTGAGACCCTGAGG





L-0482
3481
3496
12604
12619
230
AGGTGAGACCCTGAGG





L-0483
3481
3496
12604
12619
230
AGGTGAGACCCTGAGG





L-0484
3480
3497
12603
12620
675
AAGGTGAGACCCTGAGGC





L-0485
3484
3499
12607
12622
204
GTAAGGTGAGACCCTG





L-0486
3484
3499
12607
12622
204
GTAAGGTGAGACCCTG





L-0487
3484
3499
12607
12622
204
GTAAGGTGAGACCCTG





L-0488
3483
3500
12606
12623
676
GGTAAGGTGAGACCCTGA





L-0489
3482
3497
12605
12620
231
AAGGTGAGACCCTGAG






















TABLE 40







L-0490
3482
3497
12605
12620
231
AAGGTGAGACCCTGAG





L-0491
3482
3497
12605
12620
231
AAGGTGAGACCCTGAG





L-0492
3481
3498
12604
12621
677
TAAGGTGAGACCCTGAGG





L-0498




678
GCCCTACCCATACAGA





L-0499




679
GCCCACACTGAAACTA





L-0500




680
CTAGCTGTAACCCAAT





L-0501




681
TTCCAAATCCCTTCCA





L-0502




682
CAGTTCAGTCTCCCAC





L-0503




683
CTCAGTTCAGTCTCCC





L-0504




684
CTGTACCACTCAGTTC





L-0505




685
CCCCATGGCATTTCCT





L-0506




686
CCCCTGACTTTGTTCC





L-0507




687
CACCCCTGACTTTGTT





L-0508




688
TCCAAGCACACCTTCC





L-0509




689
ACCACTCCAAGCACAC





L-0510




690
CATCACTCTGAAGTCC





L-0511




691
GTCTCACAATTCCTTG





L-0512




692
CACCACCAGTTCCTTC





L-0513




693
GTTGCTCAATCCCACT





L-0514




694
CACTAAAGATCCCCTG





L-0515




695
CCTTCTCAAATCTGTT





L-0516


 1971
 1986
696
GCCAGACTAACAAACC





L-0517


 4217
 4232
697
ATCCCTATAGCCAGCT





L-0518


 4501
 4516
698
AGCCCTACCAATCCCA





L-0519


 4840
 4855
699
GCCCTTCACATACATG





L-0520


 5424
 5439
700
GCCCAACCCTAAGCCT





L-0521
 151
 166
 5610
 5625
701
CCACCCCAAGTTCCCC





L-0522


 5769
 5784
702
TCTCTAGACCCTTCCT





L-0523


 6107
 6122
703
TTTCCCTACCTCCCGA





L-0524
 452
 467
 6209
 6224
704
ACTCTCTGAGATCTCC





L-0525


 6486
 6501
705
AGACTAGAATCCCCCA





L-0526


 6963
 6978
706
GTCTCTACCCACAGCT





L-0527


 6981
 6996
707
ATCCATCTCAAGCACC





L-0528


 7012
 7027
708
CCGCCTGTAAAACCCT





L-0529


 7097
 7112
709
TCTTGCTCAAGCCCAC





L-0530


 9312
 9327
710
CCCTGCTACTCCCTCT





L-0531


 9425
9440
711
GCCTCAAAACCACCCC





L-0532


12716
12731
712
ACCCCAACTTCCATCC





L-0533


12723
12738
713
GCTGCCTACCCCAACT





L-0534


12763
12778
714
CCCCACCCAAATACCT





L-0535
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0536
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0537
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0538
3451
3468
12574
12591
715
TGAGAGGGTGCACCGAGG





L-0539
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0540
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0541
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0542
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0543
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0544
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG






















TABLE 41







L-0545
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0546
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0547
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0548
3459
3476
12582
12599
716
GGGGTCAATGAGAGGGTG





L-0549
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT









Positions in a sequence of human ATN1 pre-mRNA targeted by L-0498 to 0515 presented in Table 40, and sequence numbers and nucleobase sequences corresponding to the antisense oligonucleotides are presented in Table 42.


“SEQ717 START” means “SEQ ID NO: 717 start site” and represents the position number of a nucleoside on a side closest to a 5′ side targeted by an antisense oligonucleotide in the pre-mRNA sequence of human ATN1 (SEQ ID NO: 717). “SEQ717 END” means “SEQ ID NO: 717 termination site” and represents the position number of a nucleoside on a side closest to a 3′ side targeted by an antisense oligonucleotide in the pre-mRNA sequence of human ATN1 (SEQ ID NO: 717). The notations in Table 42 are similar to those in Tables 11 to 20.


Note that SEQ ID NO: 2 corresponds to position number 4451 to 18401 of nucleobases of SEQ ID NO: 717.













TABLE 42






SEQ717
SEQ717
SEQ



Cmpd No
START
END
No
BASE SEQUENCE







L-0498
 735
 750
678
GGCCTACCCATACAGA





L-0499
 845
 860
679
GGCCACACTGAAACTA





L-0500
1106
1121
680
CTAGCTGTAACCCAAT





L-0501
1479
1494
681
TTCCAAATCCCTTCCA





L-0502
1515
1530
682
CAGTTCAGTGTCCCAC





L-0503
1517
1532
683
CTCAGTTCAGTCTCCC





L-0504
1525
1540
684
CTGTACCACTCAGTTC





L-0505
1547
1562
685
CCCCATGGCATTTCCT





L-0506
1593
1608
686
CGCCTGACTTTGTTCC





L-0507
1595
1610
687
CACCCCTGAGTTTGTT





L-0508
1703
1718
688
TCCAAGCACACCTTCC





L-0509
1708
1723
689
ACCACTCCAAGCACAC





L-0510
1748
1763
690
CATCACTCTGAAGTCC





L-0511
1873
1888
691
GTCTCACAATTCCTTG





L-0512
2193
2208
692
CACCACCAGTTCCTTC





L-0513
2341
2356
693
GTTGCTCAATCCCACT





L-0514
2421
2436
694
CACTAAAGATCCCCTG





L-0515
2446
2461
695
CCTTCTCAAATCTGTT









[Evaluation Example 3] Antisense Inhibition of Human ATN1 in SH-SYSY Cells

An effect of an antisense oligonucleotide on an ATN1 RNA transcript was tested in vitro using the same evaluation method as in Evaluation Example 1. Results thereof are presented in Tables 43 and 44 as percent expression of ATN1 relative to untreated control cells.












TABLE 43








ATN1 mRNA



Cmpd No
remain %



















M-0248
39.3



M-0249
9.6



M-0250
26.5



M-0251
7.6



M-0252
17.2



M-0253
17.8



M-0254
39.5



M-0255
16.7



M-0256
5.9



M-0257
5.5



M-0258
5.5



M-0259
15.5



M-0260
18.8



M-0261
16.9



L-0240
45.2



L-0241
21.1



L-0242
21.1



L-0243
9.4



L-0244
18.8



L-0245
13.9



L-0246
7.1



L-0247
3.9



L-0248
31.2



L-0249
8.7



L-0250
6.9



L-0251
7.8



L-0252
59.7



L-0253
23.0



L-0254
13.7



L-0255
9.4



L-0256
18.9



L-0257
20.9



L-0258
23.7



L-0259
22.0



L-0261
66.0



L-0280
60.2



L-0282
61.9



L-0300
69.2



L-0301
77.0



L-0311
61.3



L-0318
70.3



L-0319
79.9



L-0321
74.1



L-0333
69.5



L-0341
72.0



L-0349
73.2



L-0352
73.0



L-0353
66.0



L-0356
61.4



L-0359
75.6



L-0360
72.4



L-0362
76.1



L-0363
63.0



L-0405
65.0



L-0406
77.6



L-0409
77.7



L-0411
79.0



L-0428
73.7



L-0429
51.1



L-0430
48.9



L-0431
58.8



L-0432
56.3



L-0433
45.4




















TABLE 44









L-0434
48.2



L-0435
50.3



L-0436
43.0



L-0437
40.7



L-0438
49.4



L-0439
48.5



L-0440
48.6



L-0441
19.1



L-0442
8.7



L-0443
2.8



L-0444
1.5



L-0445
45.3



L-0446
53.8



L-0447
31.2



L-0448
12.4



L-0449
16.8



L-0450
16.4



L-0451
6.1



L-0452
6.9



L-0453
42



L-0454
19.6



L-0455
11.8



L-0456
5.7



L-0457
63.7



L-0458
45.8



L-0459
31.4



L-0460
2.5



L-0461
24.3



L-0462
12.5



L-0463
5.8



L-0464
3.6



L-0465
14.8



L-0466
5.1



L-0467
4.9



L-0468
3.7



L-0469
38.4



L-0470
43.7



L-0471
34.7



L-0472
3.1



L-0473
7.8



L-0474
11.0



L-0475
7.2



L-0476
5.3



L-0477
36.5



L-0478
10.6



L-0479
8.7



L-0480
3.2



L-0481
26.8



L-0482
45.3



L-0483
12.2



L-0484
9.5



L-0485
64.3



L-0486
46.6



L-0487
43.4



L-0488
23.0



L-0489
76.8



L-0490
56.2



L-0491
43.2



L-0492
5.3



L-0516
79.3



L-0517
62.4



L-0519
64.5



L-0526
74.9



L-0533
74.2



L-0535
13.8



L-0536
5.4



L-0537
1.6



L-0538
1.0



L-0539
2.5



L-0540
2.6



L-0541
3.1



L-0542
1.6



L-0543
2.6



L-0544
8.2



L-0545
25.3



L-0546
9.5



L-0547
6.5



L-0548
15.1



L-0549
6.1










[Evaluation Example 4] Dose-Dependent Antisense Inhibition of Human ATN1 in SH-SY5Y Cells

The antisense oligonucleotide that exhibited inhibition of ATN1 in SH-SY5Y cells in Evaluation Examples 1 and 3 was tested at various doses using the same evaluation method as in Evaluation Example 2. Results thereof were calculated as a concentration (IC50 value) at which an RNA transcript level was 50% relative to untreated control cells and are presented in Table 45.












TABLE 45








IC50



Cmpd No
(nM)









L-0238
61.8



L-0441
95.3



L-0443
36.0



L-0450
64.6










[Evaluation Example 5] Antisense Inhibition of Human ATN1 in GM13716 Cells [DRPLA Patient-Derived Cells]

An effect of an antisense oligonucleotide targeting ATN1 nucleic acid, which is a causative gene of DRPLA, on an ATN1 RNA transcript was tested in vitro. An antisense oligonucleotide (manufactured in Manufacturing Example 1) was added to GM13716 cells cultured at a density of 7,500 cells/well such that a final concentration thereof was 100 nM using Lipofectamin (registered trademark) RNAiMAX Transfection Reagent (Thermo Fisher Scientific). After approximately 48 hours, RNA was isolated from the cells using RNeasy Micro Kit (QIAGEN), and then reverse-transcribed with High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific) to create cDNA. An ATN1 RNA transcript level was measured by quantitative real-time PCR with TaqMan (registered trademark) Gene Expression Assays (Thermo Fisher Scientific). Results thereof are presented in Table 46 as percent expression of ATN1 relative to untreated control cells.












TABLE 46








ATN1 mRNA



Cmpd No
remain %



















L-0044
19.3



L-0057
14.7



L-0103
10.4



L-0126
2.3



L-0155
28.8



L-0172
20.1



L-0205
4.3



L-0207
31.1



L-0219
2.2



L-0238
12.1



M-0053
70.1



M-0092
71.2



M-0121
70.4



M-0124
50.5



M-0174
66.0



M-0175
50.2



M-0184
10.5



M-0187
28.3



M-0204
29.8



M-0220
10.7










[Evaluation Example 6] Antisense Inhibition of Human ATN1 in GM13716 Cells [DRPLA Patient-Derived Cells] (Free-Uptake)

An effect of an antisense oligonucleotide targeting ATN1 nucleic acid, which is a causative gene of DRPLA, on an ATN1 RNA transcript was tested in vitro. An antisense oligonucleotide (manufactured in Manufacturing Example 1) was added to GM13716 cells cultured at a density of 7,500 cells/well such that a final concentration thereof was 100 nM (Free-Uptake). After approximately 48 hours, RNA was isolated from the cells using RNeasy Micro Kit (QIAGEN), and then reverse-transcribed with High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific) to create cDNA. An ATN1 RNA transcript level was measured by quantitative real-time PCR with TaqMan (registered trademark) Gene Expression Assays (Thermo Fisher Scientific). Results thereof are presented in Table 47 as percent expression of ATN1 relative to untreated control cells.












TABLE 47








ATN1 mRNA



Cmpd No
remain %



















L-0126
26.2



L-0205
43.4



L-0207
54.0



L-0219
12.7



L-0238
69.9



M-0092
88.7



M-0175
73.7



M-0184
12.5



M-0187
29.8



M-0204
50.4



M-0220
25.2










Manufacturing Example 3

Antisense oligonucleotides (compounds represented by chemical structures corresponding to compound numbers) described in Table 48 were prepared using an automatic nucleic acid synthesizer nS-8II (manufactured by GeneDesign Inc.).










TABLE 48





Cmpd No
Chemical structure







L-0565
A(V){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0566
A(V){circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0567
A(V){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0568
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(V)


L-0569
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0570
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0571
A(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(V)


L-0572
A(V){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0573
A(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0574
G(L){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(L)


L-0575
G(L){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0576
A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0577
A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(L)


L-0578
A(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(L)


L-0579
G(L){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}A(L)


L-0580
5(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(L)


L-0581
5(L){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0582
A(L){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}G(L)


L-0583
5(L){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}T(L)


L-0584
G(L){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(L)


L-0585
T(L){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0586
G(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0587
G(L){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}A(L)


L-0588
G(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0589
A(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}A(L)


L-0590
G(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(L)


L-0591
A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0592
A(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}G(L)


L-0593
A(L){circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0594
G(L){circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}T(L){circumflex over ( )}G(L)


L-0595
G(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}A(L)


L-0596
T(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}A(L)


L-0597
5(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}5(L)


L-0598
5(L){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(L)


L-0599
5(L){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0600
A(L){circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0601
G(L){circumflex over ( )}A(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0602
A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0603
G(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0604
G(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0605
G(L){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}5(L)


L-0606
G(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}G(L)


L-0607
G(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(L)


L-0608
G(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0609
A(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}A(L){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0610
G(L){circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}A(L)


L-0611
G(L){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(L)


L-0612
G(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0613
T(L){circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0614
5(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}5(L){circumflex over ( )}5(L){circumflex over ( )}G(L)


L-0615
G(L){circumflex over ( )}5(L){circumflex over ( )}T(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(L)


L-0616
5(L){circumflex over ( )}5(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(L)


L-0617
T(L){circumflex over ( )}T(L){circumflex over ( )}5(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0618
A(L){circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}T(L){circumflex over ( )}A(L){circumflex over ( )}G(L)


L-0619
A(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}T(L)


L-0620
G(L){circumflex over ( )}G(L){circumflex over ( )}A(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}G(L)


L-0621
G(L){circumflex over ( )}A(L){circumflex over ( )}G(L){circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L){circumflex over ( )}T(L){circumflex over ( )}T(L)


L-0622
G(L){circumflex over ( )}T(L){circumflex over ( )}G(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L){circumflex over ( )}G(L){circumflex over ( )}A(L)









Positions in a sequence of human ATN1 mRNA or pre-mRNA targeted by the antisense oligonucleotides presented in Table 48, and sequence numbers and nucleobase sequences corresponding to the antisense oligonucleotides are presented in Table 49. The notations in Table 49 are the same as those in Tables 11 to 20.















TABLE 49





Cmpd
SEQ1
SEQ1
SEQ2
SEQ2
SEQ



No
START
END
START
END
No
BASE SEQUENCE





















L-0565


4336
4351
718
ACAACACAGATGTACC





L-0566


4361
4376
719
AAAGACTCAAAATATC





L-0567


4360
4374
720
AGACTCAAAATATCC





L-0568


4361
4375
721
AAGACTCAAAATATC





L-0569


4360
4375
586
AAGACTCAAAATATCC





L-0570


4360
4375
586
AAGACTCAAAATATCC





L-0571


4360
4375
586
AAGACTCAAAATATCC





L-0572


4360
4375
586
AAGACTCAAAATATCC





L-0573


4360
4375
586
AAGACTCAAAATATCC





L-0574


12518
12533
722
TTGCCCCAAACCTGCC





L-0575


12528
12543
723
CCTGCCTTCTGGTGAC





L-0576


12538
12553
724
GGTGACACCTTCCTCT





L-0577


12543
12558
725
CACCTTCCTCTTCTCT





L-0578


12548
12563
726
TCCTCTTCTCTGCCCT





L-0579


12553
12568
727
TTCTCTGCCCTCCAGC





L-0580


12558
12573
728
TGCCCTCCAGCCTCTG





L-0581


12564
12579
729
CCAGOCTCTGCCTOGG





L-0582
3442
3457
12565
12580
730
CAGCCTCTGCCTCGGT





L-0583
3443
3458
12566
12581
731
AGCCTCTGCCTCGGTG





L-0584
3444
3459
12567
12582
732
GCCTCTGCCTCGGTGC





L-0585
3445
3460
12568
12583
733
GGTCTGGCTCGGTGCA





L-0586
3446
3461
12569
12584
734
CTCTGCCTCGGTGCAC





L-0587
3447
3462
12570
12585
735
TCTGCCTCGGTGCACC





L-0588
3448
3463
12571
12586
736
CTGCCTCGGTGCACCC





L-0589
3449
3464
12572
12587
737
TGCCTCGGTGCACCCT





L-0590
3450
3465
12573
12588
738
GCCTCGGTGCACCCTC





L-0591
3451
3466
12574
12589
739
GGTCGGTGCACCCTCT





L-0592
3454
3469
12577
12592
740
CGGTGCACCCTCTCAT





L-0593
3455
3470
12578
12593
741
GGTGCACCCTCTCATT





L-0594
3467
3482
12590
12605
742
CATTGACCCCCTGGCC





L-0595
3469
3484
12592
12607
743
TTGACCCCCTGGCCTC





L-0596
3470
3485
12593
12608
744
TGACOCCCTGGCCTCA





L-0597
3471
3486
12594
12609
745
GACCCCCTGGCCTCAG





L-0588
3472
3487
12595
12610
746
ACCCCCTGGCCTCAGG





L-0599
3473
3488
12596
12611
747
CCCCCTGGCCTCAGGG





L-0600
3474
3489
12597
12612
748
GCCCTGGCCTCAGGGT





L-0601
3475
3480
12598
12613
749
GCCTGGCCTCAGGGTG





L-0602
3476
3491
12599
12614
750
CCTGGCCTCAGGGTCT





L-0603
3477
3492
12600
12615
751
CTGGCCTCAGGGTCTC





L-0604
3479
3494
12602
12617
752
GGCCTGAGGGTCTCAC





L-0605
3480
3495
12603
12618
753
GCCTCAGGGTCTCACC





L-0606
3492
3507
12615
12630
754
CACCTTACCCGGATCC





L-0607
3493
3508
12618
12631
755
ACCTTACCCGGATCCC





L-0608
3494
3509
12617
12632
756
GCTTACGCGGATCGCC





L-0609
3495
3510
12618
12633
757
CTTAOCCGGATCCCCT





L-0610
3497
3512
12620
12635
758
TACCCGGATCCCCTAC





L-0611
3498
3513
12621
12636
759
ACCCGGATCCCCTACC





L-0612
3499
3514
12622
12637
760
GGGGGATCCCCTACCC





L-0613
3500
3515
12623
12638
761
CCGGATCCCCTACCCA





L-0614
3501
3516
12624
12639
762
CGGATCCCCTACCCAG





L-0615
3502
3517
12625
12640
763
GGATCCCCTACCCAGC





L-0616
3505
3520
12628
12643
764
TCGCCTACCCAGCTGG





L-0617
3507
3522
12630
12645
765
CCCTACCCAGCTGGAA





L-0618
3509
3524
12632
12647
766
CTACCGAGCTGGAACT





L-0619
3511
3526
12634
12649
767
ACCCAGCTGGAAGTCT





L-0620
3513
3528
12636
12651
768
CCAGCTGGAACTCTCC





L-0621
3531
3546
12654
12669
769
AACCCCCTGCTTCCTC





L-0622
3542
3557
12665
12680
770
TCCTCACCCTCTGCAC









[Evaluation Example 7] Antisense Inhibition of Human ATN1 in SH-SY5Y Cells

An effect of an antisense oligonucleotide on an ATN1 RNA transcript was tested in vitro using the same evaluation method as in Evaluation Example 1. Results thereof are presented in Table 50 as percent expression of ATN1 relative to untreated control cells.












TABLE 50








ATN1 mRNA



Cmpd No
remain %



















L-0574
77.2



L-0575
40.5



L-0576
68.6



L-0579
56.0



L-0580
71.0



L-0581
27.5



L-0582
11.2



L-0583
33.6



L-0584
79.5



L-0585
16.5



L-0586
14.6



L-0587
22.0



L-0588
1.8



L-0589
2.7



L-0590
0.7



L-0591
1.2



L-0592
11.7



L-0593
29.0



L-0594
26.6



L-0595
4.5



L-0596
3.2



L-0597
2.1



L-0598
15.8



L-0600
74.6



L-0602
24.8



L-0603
7.4



L-0604
2.7



L-0605
5.0



L-0606
11.2



L-0607
17.4



L-0608
27.6



L-0609
30.6



L-0610
49.2



L-0611
33.7



L-0612
42.1



L-0613
31.7



L-0614
36.1



L-0615
24.0



L-0616
46.6



L-0617
47.5



L-0618
45.0



L-0619
34.9



L-0620
56.9



L-0621
30.2



L-0622
46.4










Manufacturing Example 4

Antisense oligonucleotides (compounds represented by chemical structures corresponding to compound numbers) described in Table 51 were prepared using an automatic nucleic acid synthesizer nS-8II (manufactured by GeneDesign Inc.).










TABLE 51





Cmpd No
Chemical structure







L-0623
G(L){circumflex over ( )}A(L)G(L)a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(L){circumflex over ( )}G(L)


L-0624
G(L){circumflex over ( )}A(V)G(L){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(V){circumflex over ( )}G(L)


L-0625
G(L){circumflex over ( )}A(V)G(L)a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(V){circumflex over ( )}G(L)


L-0626
G(L){circumflex over ( )}A(V)G(L)A(V)g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(L)A(V){circumflex over ( )}G(L)


L-0627
G(L){circumflex over ( )}A(L)G(V){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(V)A(L){circumflex over ( )}G(L)


L-0628
G(L){circumflex over ( )}A(L)G(V){circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(V)A(L){circumflex over ( )}G(L)


L-0629
G(L){circumflex over ( )}A(L)G(V)A(V)g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(V)A(L){circumflex over ( )}G(L)


L-0630
G(V){circumflex over ( )}A(L)G(L)A(V)g{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}5(x){circumflex over ( )}5(x){circumflex over ( )}G(D)A(L){circumflex over ( )}G(V)


L-0631
G(L){circumflex over ( )}G(L)G(L)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(L){circumflex over ( )}T(L)


L-0632
G(L){circumflex over ( )}G(V)G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(V){circumflex over ( )}T(L)


L-0633
G(L){circumflex over ( )}G(V)G(L)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(V){circumflex over ( )}T(L)


L-0634
G(L){circumflex over ( )}G(V)G(L)T(V)5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(V){circumflex over ( )}T(L)


L-0635
G(L){circumflex over ( )}G(L)G(V){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V)G(L){circumflex over ( )}T(L)


L-0636
G(L){circumflex over ( )}G(L)G(V)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V)G(L){circumflex over ( )}T(L)


L-0637
G(L){circumflex over ( )}G(L)G(V)T(V)5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(V)G(L){circumflex over ( )}T(L)


L-0638
G(V){circumflex over ( )}G(L)G(L){circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(L){circumflex over ( )}T(V)


L-0639
G(V){circumflex over ( )}G(L)G(L)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(L){circumflex over ( )}T(V)


L-0640
G(V){circumflex over ( )}G(L)G(L)T(V)5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}G(L)G(L){circumflex over ( )}T(V)


L-0641
G(V){circumflex over ( )}G(L)G(L)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(V)G(L)G(L){circumflex over ( )}T(V)


L-0642
G(V){circumflex over ( )}G(L)T(L){circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L)T(L){circumflex over ( )}G(V)


L-0643
G(V){circumflex over ( )}G(L)T(L)5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L)T(L){circumflex over ( )}G(V)


L-0644
G(V){circumflex over ( )}G(L)T(L)5(V)a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L)T(L){circumflex over ( )}G(V)


L-0645
G(L){circumflex over ( )}G(L)T(L)5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}G(L)T(L){circumflex over ( )}G(L)


L-0646
G(V){circumflex over ( )}G(L)G(L){circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)G(L){circumflex over ( )}G(V)


L-0647
G(V){circumflex over ( )}G(L)G(L)g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)G(L){circumflex over ( )}G(V)


L-0648
G(V){circumflex over ( )}G(L)G(L)G(V)t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)G(L){circumflex over ( )}G(V)


L-0649
G(L){circumflex over ( )}G(L)G(L)g{circumflex over ( )}t{circumflex over ( )}5(x){circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)G(L){circumflex over ( )}G(L)


L-0650
5(V){circumflex over ( )}5(L)G(L){circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)A(L){circumflex over ( )}5(V)


L-0651
5(V){circumflex over ( )}5(L)G(L)g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)A(L){circumflex over ( )}5(V)


L-0652
5(V){circumflex over ( )}5(L)G(L)G(V)g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)A(L){circumflex over ( )}5(V)


L-0653
5(L){circumflex over ( )}5(L)G(L)g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}a{circumflex over ( )}a{circumflex over ( )}g{circumflex over ( )}g{circumflex over ( )}t{circumflex over ( )}g{circumflex over ( )}a{circumflex over ( )}G(L)A(L){circumflex over ( )}5(L)









Positions in a sequence of human ATN1 mRNA or pre-mRNA targeted by the antisense oligonucleotides presented in Table 51, and sequence numbers and nucleobase sequences corresponding to the antisense oligonucleotides are presented in Table 52. The notations in Table 52 are the same as those in Tables 11 to 20.















TABLE 52






SEQ1
SEQ1
SEQ2
SEQ2
SEQ



Cmpd No
START
END
START
END
No
BASE SEQUENCE







L-0623
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0624
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0625
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0626
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0627
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0628
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0629
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0630
3452
3467
12575
12590
215
GAGAGGGTGCACCGAG





L-0631
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0632
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0633
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0634
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0635
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0636
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0637
3460
3475
12583
12598
221
ACATAAATAACAAAAT





L-0638
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0639
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0640
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0641
3460
3475
12583
12598
221
GGGTCAATGAGAGGGT





L-0642
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0643
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0644
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0645
3459
3474
12582
12597
220
GGTCAATGAGAGGGTG





L-0646
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0647
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0648
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0649
3461
3476
12584
12599
222
GGGGTCAATGAGAGGG





L-0650
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0651
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0652
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC





L-0653
3488
3503
12611
12626
208
CCGGGTAAGGTGAGAC









[Evaluation Example 8] Antisense Inhibition of Human ATN1 in SH-SY5Y Cells

An effect of an antisense oligonucleotide on an ATN1 RNA transcript was tested in vitro using the same evaluation method as in Evaluation Example 1. Results thereof are presented in Table 53 as percent expression of ATN1 relative to untreated control cells.












TABLE 53








ATN1 mRNA



Cmpd No
remain %



















L-0623
7.2



L-0624
6.7



L-0625
13.0



L-0626
23.9



L-0627
8.6



L-0628
25.1



L-0629
14.2



L-0630
19.8



L-0631
1.0



L-0632
4.6



L-0633
3.8



L-0634
3.3



L-0635
4.4



L-0636
3.9



L-0637
2.3



L-0638
4.9



L-0639
4.0



L-0640
2.6



L-0641
2.4



L-0642
7.9



L-0643
7.0



L-0644
6.7



L-0645
1.7



L-0646
7.2



L-0647
5.1



L-0648
5.7



L-0649
4.5



L-0650
17.9



L-0651
31.5



L-0652
42.4



L-0653
16.9










All publications or parts thereof, patents, and patent applications cited herein are hereby incorporated by reference in their entirety.


INDUSTRIAL APPLICABILITY

The antisense oligonucleotide of the present invention inhibits expression of an ATN1 gene, and therefore is useful for treating, preventing, and/or ameliorating a disease to which inhibition of expression of an ATN1 gene is effective, particularly dentatorubral-pallidoluysian atrophy.

Claims
  • 1. A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770, or a pharmacologically acceptable salt thereof.
  • 2. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which has a nucleobase sequence including any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770.
  • 3. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which has any one of nucleobase sequences of SEQ ID NOs: 3 to 716 and 718 to 770.
  • 4. A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 59 to 104, 109 to 133, 173 to 192, 207 to 272, 300 to 319, 353 to 372, 419 to 434, 458 to 509, 523 to 559, 561 to 618, 626 to 685, 766 to 785, 787 to 819, 838 to 855, 880 to 922, 924 to 943, 970 to 989, 994 to 1039, 1055 to 1074, 1079 to 1098, 1157 to 1176, 1196 to 1223, 1310 to 1329, 1339 to 1399, 1423 to 1442, 1614 to 1633, 1650 to 1670, 1806 to 1833, 1844 to 1865, 1896 to 1915, 1924 to 1992, 2023 to 2042, 2058 to 2081, 2103 to 2124, 2398 to 2417, 2480 to 2520, 2526 to 2562, 2568 to 2587, 2853 to 2872, 2876 to 2923, 2931 to 2950, 2972 to 3016, 3072 to 3099, 3109 to 3128, 3192 to 3211, 3267 to 3290, 3333 to 3379, 3419 to 3557, 3765 to 3784, 3789 to 3853, 3888 to 3926, 4022 to 4062, 4118 to 4139, 4141 to 4156, 4218 to 4236, and 4266 to 4281 of nucleobases of SEQ ID NO: 1, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 1, or a pharmacologically acceptable salt thereof.
  • 5. The compound or pharmacologically acceptable salt thereof according to claim 4, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence represented by position numbers 3419 to 3557 of nucleobases of SEQ ID NO: 1, wherein the modified oligonucleotide is at least 80% complementary to the part in the nucleobase sequence represented by position numbers 3419 to 3557 of the nucleobases of SEQ ID NO: 1.
  • 6. A compound comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 383 to 398, 986 to 1001, 1004 to 1019, 1378 to 1393, 1398 to 1413, 1853 to 1868, 1971 to 1986, 2189 to 2204, 2522 to 2537, 2562 to 2577, 3662 to 3677, 3987 to 4002, 4217 to 4232, 4266 to 4281, 4335 to 4350, 4360 to 4375, 4477 to 4492, 4562 to 4577, 4636 to 4651, 4687 to 4702, 4734 to 4749, 4840 to 4855, 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 6963 to 6978, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9336 to 9351, 9534 to 9570, 9576 to 9595, 9923 to 9938, 10001 to 10016, 10056 to 10071, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12508 to 12680, 12723 to 12738, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of SEQ ID NO: 2, or complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 4320 to 4390 and 12508 to 12680 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2, or a pharmacologically acceptable salt thereof.
  • 7. The compound or pharmacologically acceptable salt thereof according to claim 6, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 5536 to 5563, 5568 to 5592, 5632 to 5651, 5666 to 5715, 5906 to 5925, 5959 to 5978, 6176 to 6191, 6215 to 6266, 7248 to 7284, 7286 to 7343, 7351 to 7410, 7491 to 7510, 7512 to 7544, 7563 to 7580, 7605 to 7647, 7649 to 7668, 7695 to 7714, 7719 to 7764, 7780 to 7799, 7804 to 7823, 7882 to 7901, 7921 to 7948, 8035 to 8054, 8064 to 8124, 8148 to 8167, 8339 to 8358, 8375 to 8395, 8531 to 8558, 8569 to 8590, 8621 to 8640, 8649 to 8717, 8748 to 8767, 8783 to 8806, 8828 to 8849, 9123 to 9142, 9205 to 9245, 9534 to 9570, 9576 to 9595, 10274 to 10293, 10297 to 10344, 10352 to 10371, 10393 to 10437, 10493 to 10520, 10530 to 10549, 10613 to 10632, 10688 to 10711, 10754 to 10800, 10840 to 10865, 12572 to 12680, 13454 to 13518, 13553 to 13591, 13687 to 13727, 13783 to 13804, 13806 to 13821, 13883 to 13901, and 13931 to 13946 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2.
  • 8. The compound or pharmacologically acceptable salt thereof according to claim 6, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 4320 to 4390 and 12508 to 12680 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2.
  • 9. The compound or pharmacologically acceptable salt thereof according to claim 6, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides complementary to a part in a nucleobase sequence selected from the group consisting of nucleobase sequences represented by position numbers 10840 to 10865 and 12572 to 12680 of nucleobases of SEQ ID NO: 2, wherein the modified oligonucleotide is at least 80% complementary to the part in the selected nucleobase sequence of SEQ ID NO: 2.
  • 10. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 696, 697, 699, 706, 713, 715, 716, 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.
  • 11. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which consists of 8 to 80 nucleosides and has a nucleobase sequence including at least 8 contiguous nucleobases of any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.
  • 12. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which consists of 12 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, 241, 488, 489, 490, 491, 492, 494, 513, 515, 533, 534, 544, 551, 552, 554, 566, 574, 582, 585, 586, 589, 592, 593, 595, 596, 638, 639, 642, 644, 661, 662, 663, 664, 665, 666, 667, 668, 669,670, 671, 672, 673, 674, 675, 676, 677, 696, 697, 699, 706, 713, 715, 716, 722, 723, 724, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 748, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, and 770.
  • 13. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which consists of 12 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 3, 4, 9, 10, 12, 13, 18, 19, 20, 21, 26, 29, 34, 37, 38, 39, 40, 44, 45, 46, 47, 48, 49, 50, 52, 55, 59, 60, 61, 62, 63, 66, 67, 68, 69, 70, 72, 74, 75, 78, 79, 82, 83, 84, 85, 86, 87, 88, 89, 91, 92, 94, 95, 97, 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 126, 127, 128, 131, 132, 133, 137, 138, 139, 148, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 238, 239, 240, and 241.
  • 14. The compound or pharmacologically acceptable salt thereof according to claim 1, comprising a modified oligonucleotide which consists of 16 to 80 nucleosides and has a nucleobase sequence including any one of nucleobase sequences selected from the group consisting of SEQ ID NOs: 242, 247, 248, 253, 254, 255, 256, 258, 259, 263, 264, 274, 276, 277, 278, 280, 281, 283, 286, 287, 288, 291, 292, 293, 294, 296, 297, 298, 299, 300, 302, 303, 304, 305, 306, 307, 309, 310, 311, 313, 314, 315, 316, 317, 319, 320, 321, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 335, 337, 338, 339, 340, 341, 342, 344, 345, 346, 347, 348, 349, 350, 355, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 369, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 382, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, and 487.
  • 15. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide includes a phosphorothioate bond.
  • 16. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide includes at least one nucleoside selected from the group consisting of a 2′-modified nucleoside and a 2′-4′-bridged nucleoside.
  • 17. The compound or pharmacologically acceptable salt thereof according to claim 16, wherein the 2′-4′-bridged nucleoside is at least one selected from the group consisting of LNA, ENA, cEt, AmNA, scpBNA, and GuNA.
  • 18. The compound or pharmacologically acceptable salt thereof according to claim 17, wherein the 2′-4′-bridged nucleoside is LNA.
  • 19. The compound or pharmacologically acceptable salt thereof according to claim 16, wherein the 2′-modified nucleoside is at least one selected from the group consisting of a 2′-O-MCE nucleoside, a 2′-O-MOE nucleoside, a 2′-O-NMA nucleoside, and a 2′-O-Me nucleoside.
  • 20. The compound or pharmacologically acceptable salt thereof according to claim 19, wherein the 2′-modified nucleoside is at least one selected from the group consisting of a 2′-O-MCE nucleoside and a 2′-O-MOE nucleoside.
  • 21. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide includes 5-methylcytosine.
  • 22. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide includes a gap segment, a 5′ wing segment, and a 3′ wing segment,the gap segment includes at least two deoxyribonucleosides, and a 5′-terminal and a 3′-terminal of the gap segment are deoxyribonucleosides,the nucleoside at the 3′-terminal of the 5′ wing segment is a sugar-modified nucleoside and is linked to the 5′-terminal of the gap segment, andthe nucleoside at the 5′-terminal of the 3′ wing segment is a sugar-modified nucleoside and is linked to the 3′-terminal of the gap segment.
  • 23. The compound or pharmacologically acceptable salt thereof according to claim 22, wherein the gap segment consists of 5 to 30 deoxyribonucleosides,the 5′ wing segment and the 3′ wing segment each independently consist of 1 to 10 sugar-modified nucleosides independently selected from the group consisting of LNA, a 2′ MCE nucleoside, and a 2′-O-MOE nucleoside,each of the wing segments includes at least one phosphorothioate bond, andeach of cytosines of the gap segment and each wing segment is replaced with 5-methylcytosine.
  • 24. The compound or pharmacologically acceptable salt thereof according to claim 23, wherein the gap segment consists of 8 to 12 deoxyribonucleosides,the 5′ wing segment and the 3′ wing segment each independently consist of 2 to 5 sugar-modified nucleosides independently selected from the group consisting of LNA and a 2′-O-MCE nucleoside, and include at least one 2′-O-MCE nucleoside, andthe gap segment includes at least one phosphorothioate bond.
  • 25. The compound or pharmacologically acceptable salt thereof according to claim 23, wherein the gap segment consists of 8 to 12 deoxyribonucleosides,the 5′ wing segment and the 3′ wing segment each independently consist of 3 to 6 sugar-modified nucleosides selected from the group consisting of a 2′-O-MOE nucleoside and a 2′-O-MCE nucleoside, andthe gap segment includes at least one phosphorothioate bond.
  • 26. The compound or pharmacologically acceptable salt thereof according to claim 25, wherein the 5′ wing segment and the 3′ wing segment each independently consist of five 2′-O-MOE nucleosides.
  • 27. The compound or pharmacologically acceptable salt thereof according to claim 25, wherein the 5′ wing segment and the 3′ wing segment each independently consist of five 2′-O-MCE nucleosides.
  • 28. The compound or pharmacologically acceptable salt thereof according to claim 24, wherein the 5′ wing segment and the 3′ wing segment are each independently selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, LLL, VVLL, VLVL, VLLV, LVLV, LLVV, LVVL, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL, in which L represents LNA, and V represents a 2′-O-MCE nucleoside.
  • 29. The compound or pharmacologically acceptable salt thereof according to claim 24, wherein the 5′ wing segment and the 3′ wing segment are each independently selected from the group consisting of VLL, LVL, LLV, LVV, VLV, VVL, VVLL, VLVL, LVLV, LLVV, VLLL, LVLL, LLVL, LLLV, LVVV, VLVV, VVLV, and VVVL, in which L represents LNA, and V represents a 2′-O-MCE nucleoside.
  • 30. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide consists of 15 to 25 nucleosides.
  • 31. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the modified oligonucleotide is an antisense oligonucleotide.
  • 32. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the compound including the modified oligonucleotide includes a prodrug moiety.
  • 33. The compound or pharmacologically acceptable salt thereof according to claim 1, wherein the compound including the modified oligonucleotide includes a functional molecule.
  • 34. The compound or pharmacologically acceptable salt thereof according to claim 1, consisting of the modified oligonucleotide.
  • 35. The salt according to claim 1, wherein the pharmacologically acceptable salt is a sodium salt.
  • 36. A medicinal drug comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to claim 1.
  • 37. A drug for treating, preventing, and/or ameliorating a disease or a condition to which an ATN1 gene expression inhibitory action is effective, the drug comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to claim 1.
  • 38. An ATN1 gene expression inhibitor comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to claim 1.
  • 39. A drug for treating, preventing, and/or ameliorating dentatorubral-pallidoluysian atrophy, the drug comprising, as an active ingredient, the compound or pharmacologically acceptable salt according to claim 1.
Priority Claims (2)
Number Date Country Kind
2020-015521 Jan 2020 JP national
2020-183718 Nov 2020 JP national
PCT Information
Filing Document Filing Date Country Kind
PCT/JP2021/003293 1/29/2021 WO