Targeted chromosomal genomic alterations with modified single stranded oligonucleotides

Abstract

Presented are methods and compositions for targeted chromosomal genomic alterations using modified single-stranded oligonucleotides of the invention have at least one modified nuclease-resistant terminal region comprising phosphorothioate linkages, LNA analogs or 2′-O-Me base analogs.

Description

FIELD OF THE INVENTION

[0001] The technical field of the invention is oligonucleotide-directed repair or alteration of genetic information using novel chemically modified oligonucleotides. Such genetic information is preferably from a eukaryotic organism, i.e. a plant, animal or fungus.

BACKGROUND OF THE INVENTION

[0002] A number of methods have been developed specifically to alter the sequence of an isolated DNA in addition to methods to alter directly the genomic information of various plants, fungi and animals, including humans (“gene therapy”). The latter methods generally include the use of viral or plasmid vectors carrying nucleic acid sequences encoding partial or complete portions of a particular protein which is expressed in a cell or tissue to effect the alteration. The expression of the particular protein then results in the desired phenotype. For example, retroviral vectors containing a transgenic DNA sequence allowing for the production of a normal CFTR protein when administered to defective cells are described in U.S. Pat. No. 5,240,846. Others have developed different “gene therapy vectors” which include, for example, portions of adenovirus (Ad) or adeno-associated virus (AAV), or other viruses. The virus portions used are often long terminal repeat sequences which are added to the ends of a transgene of choice along with other necessary control sequences which allow expression of the transgene. See U.S. Pat. Nos. 5,700,470 and 5,139,941. Similar methods have been developed for use in plants. See, for example, U.S. Pat. No. 4,459,355 which describes a method for transforming plants with a DNA vector and U.S. Pat. No. 5,188,642 which describes cloning or expression vectors containing a transgenic DNA sequence which when expressed in plants confers resistance to the herbicide glyphosate. The use of such transgene vectors in any eukaryotic organism adds one or more exogenous copies of a gene, which gene may be foreign to the host, in a usually random fashion at one or more integration sites of the organism's genome at some frequency. The gene which was originally present in the genome, which may be a normal allelic variant, mutated, defective, and/or functional, is retained in the genome of the host.

[0003] These methods of gene correction are problematic in that complications which can compromise the health of the recipient, or even lead to death, may result. One such problem is that insertion of exogenous nucleic acid at random location(s) in the genome can have deleterious effects. Another problem with such systems includes the addition of unnecessary and unwanted genetic material to the genome of the recipient, including, for example, viral or other vector remnants, control sequences required to allow production of the transgene protein, and reporter genes or resistance markers. Such remnants and added sequences may have presently unrecognized consequences, for example, involving genetic rearrangements of the recipient genomes. Other problems associated with these types of traditional gene therapy methods include autoimmune suppression of cells expressing an inserted gene due to the presence of foreign antigens. Concerns have also been raised with consumption, especially by humans, of plants containing exogenous genetic material.

[0004] More recently, simpler systems involving poly- or oligo-nucleotides have been described for use in the alteration of genomic DNA. These chimeric RNA-DNA oligonucleotides, requiring contiguous RNA and DNA bases in a double-stranded molecule folded by complementarity into a double hairpin conformation, have been shown to effect single basepair or frameshift alterations, for example, for mutation or repair of plant or animal genomes. See, for example, WO 99/07865 and U.S. Pat. No. 5,565,350. In the chimeric RNA-DNA oligonucleotide, an uninterrupted stretch of DNA bases within the molecule is required for sequence alteration of the targeted genome while the obligate RNA residues are involved in complex stability. Due to the length, backbone composition, and structural configuration of these chimeric RNA-DNA molecules, they are expensive to synthesize and difficult to purify. Moreover, if the RNA-containing strand of the chimeric RNA-DNA oligonucleotide is designed so as to direct gene conversion, a series of mutagenic reactions resulting in nonspecific base alteration can result. Such a result compromises the utility of such a molecule in methods designed to alter the genomes of plants and animals, including in human gene therapy applications.

[0005] Alternatively, other oligo- or poly-nucleotides have been used which require a triplex forming, usually polypurine or polypyrimidine, structural domain which binds to a DNA helical duplex through Hoogsteen interactions between the major groove of the DNA duplex and the oligonucleotide. Such oligonucleotides may have an additional DNA reactive moiety, such as psoralen, covalently linked to the oligonucleotide. These reactive moieties function as effective intercalation agents, stabilize the formation of a triplex and can be mutagenic. Such agents may be required in order to stabilize the triplex forming domain of the oligonucleotide with the DNA double helix if the Hoogsteen interactions from the oligonucleotide/target base composition are insufficient. See, e.g., U.S. Pat. No. 5,422,251. The utility of these oligonucleotides for directing gene conversion is compromised by a high frequency of nonspecific base changes.

[0006] In more recent work, the domain for altering a genome is linked or tethered to the triplex forming domain of the bi-functional oligonucleotide, adding an additional linking or tethering functional domain to the oligonucleotide. See, e.g., Culver et al., Nature Biotechnology 17: 989-93 (1999). Such chimeric or triplex forming molecules have distinct structural requirements for each of the different domains of the complete poly- or oligo-nucleotide in order to effect the desired genomic alteration in either episomal or chromosomal targets.

[0007] Other genes, e.g. CFTR, have been targeted by homologous recombination using duplex fragments having several hundred basepairs. See, e.g., Kunzelmann et al., Gene Ther. 3:859-867 (1996). Early experiments to mutagenize an antibiotic resistance indicator gene by homologous recombination used an unmodified DNA oligonucleotide with no functional domains other than a region of complementary sequence to the target See Campbell et al., New Biologist 1: 223-227 (1989). These experiments required large concentrations of the oligonucleotide, exhibited a very low frequency of episomal modification of a targeted exogenous plasmid gene not normally found in the cell and have not been reproduced. However, as shown in the examples herein, we have observed that an unmodified DNA oligonucleotide can convert a base at low frequency which is detectable using the assay systems described herein.

[0008] Artificial chromosomes can be useful for the screening purposed identified herein. These molecules are man-made linear or circular DNA molecules constructed from essential cis-acting DNA sequence elements that are responsible for the proper replication and partitioning of natural chromosomes (Murray et al., 1983). The essential elements are: (1) Autonomous Replication Sequences (ARS), (2) Centromeres, and (3) Telomeres.

[0009] Yeast artificial chromosomes (YACs) allow large genomic DNA to be modified and used for generating transgenic animals [Burke et al., Science 236:806; Peterson et al., Trends Genet. 13:61 (1997); Choi, et al., Nat. Genet, 4:117-223 (1993), Davies, et al., Biotechnology 11:911-914 (1993), Matsuura, et al., Hum. Mol. Genet., 5:451-459 (1996), Peterson et al., Proc. Natl. Acad. Sci., 93:6605-6609 (1996); and Schedl, et al., Cell, 86:71-82 (1996)]. Other vectors also have been developed for the cloning of large segments of mammalian DNA, including cosmids, and bacteriophage P1 [Sternberg et al., Proc. Natl. Acad. Sci. U.S.A., 87:103-107 (1990)]. YACs have certain advantages over these alternative large capacity cloning vectors [Burke et al., Science, 236:806-812 (1987)]. The maximum insert size is 35-30 kb for cosmids, and 100 kb for bacteriophage P1, both of which are much smaller than the maximal insert for a YAC.

[0010] An alternative to YACs are E. coli based cloning systems based on the E. coli fertility factor that have been developed to construct large genomic DNA insert libraries. They are bacterial artificial chromosomes (BACs) and P-1 derived artificial chromosomes (PACs) [Mejia et al., Genome Res. 7:179-186 (1997); Shizuya et al., Proc. Natl. Acad. Sci. 89:8794-8797 (1992); Ioannou et al., Nat. Genet., 6:84-89 (1994); Hosoda et al., Nucleic Acids Res. 18:3863 (1990)]. BACs are based on the E. coli fertility plasmid (F factor); and PACs are based on the bacteriophage P1. These vectors propagate at a very low copy number (1-2 per cell) enabling genomic inserts up to 300 kb in size to be stably maintained in recombination deficient hosts. Furthermore, the PACs and BACs are circular DNA molecules that are readily isolated from the host genomic background by classical alkaline lysis [Birnboim et al., Nucleic Acids Res. 7:1513-1523 (1979].

[0011] Oligonucleotides designed for use in the alteration of genetic information are significantly different from oligonucleotides designed for antisense approaches. For example, antisense oligonucleotides are perfectly complementary to and bind an mRNA strand in order to modify expression of a targeted mRNA and are used at high concentration. As a consequence, they are unable to produce a gene conversion event by either mutagenesis or repair of a defect in the chromosomal DNA of a host genome. Furthermore, the backbone chemical composition used in most oligonucleotides designed for use in antisense approaches renders them inactive as substrates for homologous pairing or mismatch repair enzymes and the high concentrations of oligonucleotide required for antisense applications can be toxic with some types of nucleotide modifications. In addition, antisense oligonucleotides must be complementary to the mRNA and therefore, may not be complementary to the other DNA strand or to genomic sequences that span the junction between intron sequence and exon sequence.

[0012] A need exists for simple, inexpensive oligonucleotides capable of producing targeted alteration of genetic material such as those described herein as well as methods to identify optimal oligonucleotides that accurately and efficiently alter target DNA.

SUMMARY OF THE INVENTION

[0013] Novel, modified single-stranded nucleic acid molecules that direct gene alteration in plants, fungi and animals are identified and the efficiency of alteration is analyzed both in vitro using a cell-free extract assay and in vivo using a yeast cell system. The alteration in an oligonucleotide of the invention may comprise an insertion, deletion, substitution, as well as any combination of these. Site specific alteration of DNA is not only useful for studying function of proteins in vivo, but it is also useful for creating animal models for human disease, and in gene therapy. As described herein, oligonucleotides of the invention target directed specific gene alterations in genomic double-stranded DNA cells. The target DNA can be normal, cellular chromosomal DNA, extrachromosomal DNA present in cells in different forms including, e.g., mammalian artificial chromosomes (MACs), PACs from P-1 vectors, yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), plant artificial chromosomes (PLACs), as well as episomal DNA, including episomal DNA from an exogenous source such as a plasmid or recombinant vector. Many of these artificial chromosome constructs containing human DNA can be obtained from a variety of sources, including, e.g., the Whitehead Institute, and are described, e.g., in Cohen et al., Nature 336:698-701 (1993) and Chumakov, et al., Nature 377:174-297 (1995). The target DNA may be transitionally silent or active. In a preferred embodiment, the target DNA to be altered is the non-transcribed strand of a genomic DNA duplex.

[0014] The low efficiency of gene alteration obtained using unmodified DNA oligonucleotides is believed to be largely the result of degradation by nucleases present in the reaction mixture or the target cell. Although different modifications are known to have different effects on the nuclease resistance of oligonucleotides or stability of duplexes formed by such oligonucleotides (see, e.g., Koshkin et al., J. Am. Chem. Soc., 120:13252-3), we have found that it is not possible to predict which of any particular known modification would be most useful for any given alteration event, including for the construction of gene conversion oligonucleotides, because of the interaction of different as yet unidentified proteins during the gene alteration event. Herein, a variety of nucleic acid analogs have been developed that increase the nuclease resistance of oligonucleotides that contain them, including, e.g., nucleotides containing phosphorothioate linkages or 2′-O-methyl analogs. We recently discovered that single-stranded DNA oligonucleotides modified to contain 2′-O-methyl RNA nucleotides or phosphorothioate linkages can enable specific alteration of genetic information at a higher level than either unmodified single-stranded DNA or a chimeric RNA/DNA molecule. See priority applications incorporated herein in their entirety; see also Gamper et al., Nucleic Acids Research 28: 4332-4339 (2000). We also found that additional nucleic acid analogs which increase the nuclease resistance of oligonucleotides that contain them, including, e.g., “locked nucleic acids” or “LNAs”, xylo-LNAs and L-ribo-LNAs; see, for example, Wengel & Nielsen, WO 99/14226; Wengel, WO 00/56748 and Wengel, WO 00/66604; also allow specific targeted alteration of genetic information.

[0015] The assay allows for determining the optimum length of the oligonucleotide, optimum sequence of the oligonucleotide, optimum position of the mismatched base or bases, optimum chemical modification or modifications, optimum strand targeted for identifying and selecting the most efficient oligonucleotide for a particular gene alteration event by comparing to a control oligonucleotide. Control oligonucleotides may include a chimeric RNA-DNA double hairpin oligonucleotide directing the same gene alteration event, an oligonucleotide that matches its target completely, an oligonucleotide in which all linkages are phosphorothiolated, an oligonucleotide fully substituted with 2′-O-methyl analogs or an RNA oligonucleotide. Such control oligonucleotides either fail to direct a targeted alteration or do so at a lower efficiency as compared to the oligonucleotides of the invention. The assay further allows for determining the optimum position of a gene alteration event within an oligonucleotide, optimum concentration of the selected oligonucleotide for maximum alteration efficiency by systematically testing a range of concentrations, as well as optimization of either the source of cell extract by testing different organisms or strains, or testing cells derived from different organisms or strains, or cell lines. Using a series of single-stranded oligonucleotides, comprising all RNA or DNA residues and various mixtures of the two, several new structures are identified as viable molecules in nucleotide conversion to direct or repair a genomic mutagenic event. When extracts from mammalian, plant and fungal cells are used and are analyzed using a genetic readout assay in bacteria, single-stranded oligonucleotides having one of several modifications are found to be more active than a control RNA-DNA double hairpin chimera structure when evaluated using an in vitro gene repair assay. Similar results are also observed in vivo using yeast, mammalian, rodent, monkey, human and embryonic cells, including stem cells. Molecules containing various lengths of modified bases were found to possess greater activity than unmodified single-stranded DNA molecules.

DETAILED DESCRIPTION OF THE INVENTION

[0016] The present invention provides oligonucleotides having chemically modified, nuclease resistant residues, preferably at or near the termini of the oligonucleotides, and methods for their identificaton and use in targeted alteration of genetic material, including gene mutation, targeted gene repair and gene knockout. The oligonucleotides are preferably used for mismatch repair or alteration by changing at least one nucleic acid base, or for frameshift repair or alteration by addition or deletion of at least one nucleic acid base. The oligonucleotides of the invention direct any such alteration, including gene correction, gene repair or gene mutation and can be used, for example, to introduce a polymorphism or haplotype or to eliminate (“knockout”) a particular protein activity.

[0017] The oligonucleotides of the invention are designed as substrates for homologous pairing and repair enzymes and as such have a unique backbone composition that differs from chimeric RNA-DNA double hairpin oligonucleotides, antsense oligonucleotides, and/or other poly- or oligo-nucleotides used for altering genomic DNA, such as triplex forming oligonucleotides. The single-stranded oligonucleotides described herein are inexpensive to synthesize and easy to purify. In side-by-side comparisons, an optimized single-stranded oligonucleotide comprising modified residues as described herein is significantly more efficient than a chimeric RNA-DNA double hairpin oligonucleotide in directing a base substitution or frameshift mutation in a cell-free extract assay.

[0018] We have discovered that single-stranded oligonucleotides having a DNA domain surrounding the targeted base, with the domain preferably central to the poly- or oligo-nucleotide, and having at least one modified end, preferably at the 3′ terminal region are able to alter a target genetic sequence and with an efficiency that is higher than chimeric RNA-DNA double hairpin oligonucleotides disclosed in U.S. Pat. No. 5,565,350. Oligonucleotides of the invention can efficiently be used to introduce targeted alterations in a genetic sequence of DNA in the presence of human, animal, plant, fungal (including yeast) proteins and in cultured cells of human liver, lung, colon, cervix, kidney, epethelium and cancer cells and in monkey, hamster, rat and mouse cells of different types, as well as embryonic stem cells. Cells for use in the invention include, e.g., fungi including S. cerevisiae, Ustillago maydis and Candida albicans, mammalian, mouse, hamster, rat, monkey, human and embryonic cells including stem cells. The DNA domain is preferably fully complementary to one strand of the gene target, except for the mismatch base or bases responsible for the gene alteration or conversion events. On either side of the preferably central DNA domain, the contiguous bases may be either RNA bases or, preferably, are primarily DNA bases. The central DNA domain is generally at least 8 nucleotides in length. The base(s) targeted for alteration in the most preferred embodiments are at least about 8, 9 or 10 bases from one end of the oligonucleotide.

[0019] According to certain embodiments, the termini of the oligonucleotides of the present invention comprise phosphorothioate modifications, LNA backbone modifications, or 2′-O-methyl base analogs, or any combination of these modifications. Oligonucleotides comprising 2′-O-methyl or LNA analogs are a mixed DNA/RNA polymer. These oligonucleotides are, however, single-stranded and are not designed to form a stable internal duplex structure within the oligonucleotide. The efficiency of gene alteration is surprisingly increased with oligonucleotides having internal complementary sequence comprising phosphorothioate modified bases as compared to 2′-O-methyl modifications. This result indicates that specific chemical interactions are involved between the converting oligonucleotide and the proteins involved in the conversion. The effect of other such chemical interactions to produce nuclease resistant termini using modifications other than LNA, phosphorothioate linkages, or 2′-O-methyl analog incorporation into an oligonucleotide can not yet be predicted because the proteins involved in the alteration process and their particular chemical interaction with the oligonucleotide substituents are not yet known and cannot be predicted.

[0020] In the examples, correcting oligonucleotides of defined sequence are provided for correction of genes mutated in human diseases. In the tables of these examples, the oligonucleotides of the invention are not limited to the particular sequences disclosed. The oligonucleotides of the invention include extensions of the appropriate sequence of the longer 120 base oligonucleotides which can be added base by base to the smallest disclosed oligonucleotides of 17 bases. Thus the oligonucleotides of the invention include for each correcting change, oligonucleotides of length 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, or 120 with further single-nucleotide additions up to the longest sequence disclosed. Moreover, the oligonucleotides of the invention do not require a symmetrical extension on either side of the central DNA domain. Similarly, the oligonucleotides of the invention as disclosed in the various tables for correction of human diseases contain phosphorothioate linkages, 2′-O-methyl analogs or LNAs or any combination of these modifications just as the assay oligonucleotides do.

[0021] The present invention, however, is not limited to oligonucleotides that contain any particular nuclease resistant modification. Oligonucleotides of the invention may be altered with any combination of additional LNAs, phosphorothioate linkages or 2′-O-methyl analogs to maximize conversion efficiency. For oligonucleotides of the invention that are longer than about 17 to about 25 bases in length, internal as well as terminal region segments of the backbone may be altered. Alternatively, simple fold-back structures at each end of a oligonucleotide or appended end groups may be used in addition to a modified backbone for conferring additional nuclease resistance.

[0022] The different oligonucleotides of the present invention preferably contain more than one of the aforementioned backbone modifications at each end. In some embodiments, the backbone modifications are adjacent to one another. However, the optimal number and placement of backbone modifications for any individual oligonucleotide will vary with the length of the oligonucleotide and the particular type of backbone modification(s) that are used. If constructs of identical sequence having phosphorothioate linkages are compared, 2, 3, 4, 5, or 6 phosphorothioate linkages at each end are preferred. If constructs of identical sequence having 2′-O-methyl base analogs are compared, 1, 2, 3 or 4 analogs are preferred. The optimal number and type of backbone modifications for any particular oligonucleotide useful for altering target DNA may be determined empirically by comparing the alteration efficiency of the oligonucleotide comprising any combination of the modifications to a control molecule of comparable sequence using any of the assays described herein. The optimal positon(s) for oligonucleotide modifications for a maximally efficient altering oligonucleotide can be determined by testing the various modifications as compared to control molecule of comparable sequence in one of the assays disclosed herein. In such assays, a control molecule includes, e.g., a completely 2′-O-methyl substituted molecule, a completely complementary oligonucleotide, or a chimeric RNA-DNA double hairpin.

[0023] Increasing the number of phosphorothioate linkages, LNAs or 2′-O-methyl bases beyond the preferred number generally decreases the gene repair activity of a 25 nucleotide long oligonucleotide. Based on analysis of the concentration of oligonucleotide present in the extract after different time periods of incubation, it is believed that the terminal modifications impart nuclease resistance to the oligonucleotide thereby allowing it to survive within the cellular environment. However, this may not be the only possible mechanism by which such modifications confer greater efficiency of conversion. For example, as disclosed herein, certain modifications to oligonucleotides confer a greater improvement to the efficiency of conversion than other modifications.

[0024] Efficiency of conversion is defined herein as the percentage of recovered substate molecules that have undergone a conversion event. Depending on the nature of the target genetic material, e.g. the genome of a cell, efficiency could be represented as the proportion of cells or clones containing an extrachromosomal element that exhibit a particular phenotype. Alternatively, representative samples of the target genetic material can be sequenced to determine the percentage that have acquired the desire change. The oligonucleotides of the invention in different embodiments can alter DNA one, two, three, four, five, six, seven, eight, nine, ten, twelve, fifteen, twenty, thirty, and fifty or more fold more than control oligonucleotides. Such control oligonucleotides are oligonucleotides with fully phosphorothiolated linkages, oligonucleotides that are fully substituted with 2′-O-methyl analogs, a perfectly matched oligonucleotide that is fully complementary to a target sequence or a chimeric DNA-RNA double hairpin oligonucleotide such as disclosed in U.S. Pat. No. 5,565,350.

[0025] In addition, for a given oligonucleotide length, additional modifications interfere with the ability of the oligonucleotide to act in concert with the cellular recombination or repair enzyme machinery which is necessary and required to mediate a targeted substitution, addition or deletion event in DNA. For example, fully phosphorothiolated or fully 2-O-methylated molecules are inefficient in targeted gene alteration.

[0026] The oligonucleotides of the invention as optimized for the purpose of targeted alteration of genetic material, including gene knockout or repair, are different in structure from antisense oligonucleotides that may possess a similar mixed chemical composition backbone. The oligonucleotides of the invention differ from such antisense oligonucleotides in chemical composition, structure, sequence, and in their ability to alter genomic DNA. Significantly, antisense oligonucleotides fail to direct targeted gene alteration. The oligonucleotides of the invention may target either the Watson or the Crick strand of DNA and can include any component of the genome including, for example, intron and exon sequences. The preferred embodiment of the invention is a modified oligonucleotide that binds to the non-transcribed strand of a genomic DNA duplex. In other words, the preferred oligonucleotides of the invention target the sense strand of the DNA, i.e. the oligonucleotides of the invention are complementary to the non-transcribed strand of the target duplex DNA. The sequence of the non-transcribed strand of a DNA duplex is found in the mRNA produced from that duplex, given that mRNA uses uracil-containing nucleotides in place of thymine-containing nucleotides.

[0027] Moreover, the initial observation that single-stranded oligonucleotides comprising these modifications and lacking any particular triplex forming domain have reproducibly enhanced gene repair activity in a variety of assay systems as compared to a chimeric RNA-DNA double-stranded hairpin control or single-stranded oligonucleotides comprising other backbone modifications was surprising. The single-stranded molecules of the invention totally lack the complementary RNA binding structure that stabilizes a normal chimeric double-stranded hairpin of the type disclosed in U.S. Pat. No. 5,565,350 yet is more effective in producing targeted base conversion as compared to such a chimeric RNA-DNA double-stranded hairpin. In addition, the molecules of the invention lack any particular triplex forming domain involved in Hoogsteen interactions with the DNA double helix and required by other known oligonucleotides in other oligonucleotide dependant gene conversion systems. Although the lack of these functional domains was expected to decrease the efficiency of an alteration in a sequence, just the opposite occurs: the efficiency of sequence alteration using the modified oligonucleotides of the invention is higher than the efficiency of sequence alteration using a chimeric RNA-DNA hairpin targeting the same sequence alteration. Moreover, the efficiency of sequence alteration or gene conversion directed by an unmodified oligonucleotide is many times lower as compared to a control chimeric RNA-DNA molecule or the modified oligonucleotides of the invention targeting the same sequence alteration. Similarly, molecules containing at least 3 2′-O-methyl base analogs are about four to five fold less efficient as compared to an oligonucleotide having the same number of phosphorothioate linkages.

[0028] The oligonucleotides of the present invention for alteration of a single base are about 17 to about 121 nucleotides in length, preferably about 17 to about 74 nucleotides in length. Most preferably, however, the oligonucleotides of the present invention are at least about 25 bases in length, unless there are self-dimerization structures within the oligonucleotide. If the oligonucleotide has such an unfavorable structure, lengths longer than 35 bases are preferred. Oligonucleotides with modified ends both shorter and longer than certain of the exemplified, modified oligonucleotides herein function as gene repair or gene knockout agents and are within the scope of the present invention.

[0029] Once an oligomer is chosen, it can be tested for its tendency to self-dimerize, since self-dimerization may result in reduced efficiency of alteration of genetic information. Checking for self-dimerization tendency can be accomplished manually or, more preferably, by using a software program. One such program is Oligo Analyzer 2.0, available through Integrated DNA Technologies (Coralville, Iowa 52241) (http://www.idtdna.com); this program is available for use on the world wide web at http://www.idtdna.com/program/oligoanalyzer/oligoanalyzer.asp. For each oligonucleotide sequence input into the program, Oligo Analyzer 2.0 reports possible self-dimerized duplex forms, which are usually only partially duplexed, along with the free energy change associated with such self-dimerization. Delta G-values that are negative and large in magnitude, indicating strong self-dimerization potential, are automatically flagged by the software as “bad”. Another software program that analyzes oligomers for pair dimer formation is Primer Select from DNASTAR, Inc., 1228 S. Park St, Madison, Wis. 53715, Phone: (608) 258-7420 (http://www.dnastar.com/products/PrimerSelect.html). If the sequence is subject to significant self-dimerization, the addition of further sequence flanking the “repair” nucleotide can improve gene correction frequency.

[0030] Generally, the oligonucleotides of the present invention are identical in sequence to one strand of the target DNA, which can be either strand of the target DNA, with the exception of one or more targeted bases positioned within the DNA domain of the oligonucleotide, and preferably toward the middle between the modified terminal regions. Preferably, the difference in sequence of the oligonucleotide as compared to the targeted genomic DNA is located at about the middle of the oligonucleotide sequence. In a preferred embodiment, the oligonucleotides of the invention are complementary to the non-transcribed strand of a duplex. In other words, the preferred oligonucleotides target the sense strand of the DNA, i.e. the oligonucleotides of the invention are preferably complementary to the strand of the target DNA the sequence of which is found in the mRNA.

[0031] The oligonucleotides of the invention can include more than a single base change. In an oligonucleotide that is about a 70-mer, with at least one modified residue incorporated on the ends, as disclosed herein, multiple bases can be simultaneously targeted for change. The target bases may be up to 27 nucleotides apart and may not be changed together in all resultant plasmids in all cases. There is a frequency distribution such that the closer the target bases are to each other in the central DNA domain within the oligonucleotides of the invention, the higher the frequency of change in a given cell. Target bases only two nucleotides apart are changed together in every case that has been analyzed. The farther apart the two target bases are, the less frequent the simultaneous change. Thus, oligonucleotides of the invention may be used to repair or alter multiple bases rather than just one single base. For example, in a 74-mer oligonucleotide having a central base targeted for change, a base change event up to about 27 nucleotides away can also be effected. The positions of the altering bases within the oligonucleotide can be optimized using any one of the assays described herein. Preferably, the altering bases are at least about 8 nucleotides from one end of the oligonucleotide.

[0032] The oligonucleotides of the present invention can be introduced into cells by any suitable means. According to certain preferred embodiments, the modified oligonucleotides may be used alone. Suitable means, however, include the use of polycations, cationic lipids, liposomes, polyethylenimine (PEI), electroporation, biolistics, microinjecton and other methods known in the art to facilitate cellular uptake. According to certain preferred embodiments of the present invention, the isolated cells are treated in culture according to the methods of the invention, to mutate or repair a target gene. Modified cells may then be reintroduced into the organism as, for example, in bone marrow having a targeted gene. Alternatively, modified cells may be used to regenerate the whole organism as, for example, in a plant having a desired targeted genomic change. In other instances, targeted genomic alteration, including repair or mutagenesis, may take place in vivo following direct administration of the modified, single-stranded oligonucleotides of the invention to a subject.

[0033] The single-stranded, modified oligonucleotides of the present invention have numerous applications as gene repair, gene modification, or gene knockout agents. Such oligonucleotides may be advantageously used, for example, to introduce or correct multiple point mutations. Each mutation leads to the addition, deletion or substitution of at least one base pair. The methods of the present invention offer distinct advantages over other methods of altering the genetic makeup of an organism, in that only the individually targeted bases are altered. No additional foreign DNA sequences are added to the genetic complement of the organism. Such agents may, for example, be used to develop plants or animals with improved traits by rationally changing the sequence of selected genes in cultured cells. Modified cells are then cloned into whole plants or animals having the altered gene. See, e.g., U.S. Pat. No. 6,046,380 and U.S. Pat. No. 5,905,185 incorporated herein by reference. Such plants or animals produced using the compositions of the invention lack additional undesirable selectable markers or other foreign DNA sequences. Targeted base pair substitution or frameshift mutations introduced by an oligonucleotide in the presence of a cell-free extract also provides a way to modify the sequence of extrachromosomal elements, including, for example, plasmids, cosmids and artificial chromosomes. The oligonucleotides of the invention also simplify the production of transgenic animals having particular modified or inactivated genes. Altered animal or plant model systems such as those produced using the methods and oligonucleotides of the invention are invaluable in determining the function of a gene and in evaluating drugs. The oligonucleotides and methods of the present invention may also be used for gene therapy to correct mutations causative of human diseases.

[0034] The purified oligonucleotide compositions may be formulated in accordance with routine procedures as a pharmaceutical composition adapted for bathing cells in culture, for microinjecton into cells in culture, and for intravenous administration to human beings or animals. Typically, compositions for cellular administration or for intravenous administration into animals, including humans, are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anaesthetic such as lignocaine to ease pain at the site of the injection. Generally, the ingredients will be supplied either separately or mixed together in unit dosage form, for example, as a dry, lyophilized powder or water-free concentrate. The composition may be stored in a hermetically sealed container such as an ampule or sachette indicating the quantity of active agent in activity units. Where the composition is administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade “water for injection” or saline. Where the composition is to be administered by injection, an ampule of sterile water for injection or saline may be provided so that the ingredients may be mixed prior to administration.

[0035] Pharmaceutical compositions of this invention comprise the compounds of the present invention and pharmaceutically acceptable salts thereof, with any pharmaceutically acceptable ingredient, excipient, carrier, adjuvant or vehicle.

[0036] The oligonucleotides of the invention are preferably administered to the subject in the form of an injectable composition. The composition is preferably administered parenterally, meaning intravenously, intraarterially, intrathecally, interstitially or intracavitarilly. Pharmaceutical compositions of this invention can be administered to mammals including humans in a manner similar to other diagnostic or therapeutic agents. The dosage to be administered, and the mode of administration will depend on a variety of factors including age, weight, sex, condition of the subject and genetic factors, and will ultimately be decided by medical personnel subsequent to experimental determinations of varying dosage as described herein. In general, dosage required for correction and therapeutic efficacy will range from about 0.001 to 50,000 μg/kg, preferably between 1 to 250 μg/kg of host cell or body mass, and most preferably at a concentration of between 30 and 60 micromolar.

[0037] For cell administration, direct injection into the nucleus, biolistic bombardment, electroporation, liposome transfer and calcium phosphate precipitation may be used. In yeast, lithium acetate or spheroplast transformation may also be used. In a preferred method, the administration is performed with a liposomal transfer compound, e.g., DOTAP (Boehringer-Mannheim) or an equivalent such as lipofectin. The amount of the oligonucleotide used is about 500 nanograms in 3 micrograms of DOTAP per 100,000 cells. For electroporation, between 20 and 2000 nanograms of oligonucleotide per million cells to be electroporated is an appropriate range of dosages which can be increased to improve efficiency of genetic alteration upon review of the appropriate sequence according to the methods described herein.

[0038] Another aspect of the invention is a kit comprising at least one oligonucleotide of the invention. The kit may comprise an addition reagent or article of manufacture. The additional reagent or article of manufacture may comprise a cell extract, a cell, or a plasmid, such as one of those disclosed in the Figures herein, for use in an assay of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIG. 1. Flow diagram for the generation of modified single-stranded oligonucleotides. The upper strands of chimeric oligonucleotides I and II are separated into pathways resulting in the generation of single-stranded oligonucleotides that contain (A) 2′-O-methyl RNA nucleotides or (B) phosphorothioate linkages. Fold changes in repair activity for correction of kans in the HUH7 cell-free extract are presented in parenthesis. HUH7 cells are described in Nakabayashi et al., Cancer Research 42: 3858-3863 (1982). Each single-stranded oligonucleotide is 25 bases in length and contains a G residue mismatched to the complementary sequence of the kans gene. The numbers 3, 6, 8, 10, 12 and 12.5 respectively indicate how many phosphorothioate linkages (S) or 2′-O-methyl RNA nucleotides (R) are at each end of the molecule. Hence oligo 12S/25G contains an all phosphorothioate backbone, displayed as a dotted line. Smooth lines indicate DNA residues, wavy lines indicate 2′-O-methyl RNA residues and the carat indicates the mismatched base site (G). FIG. 1(C) provides a schematic plasmid indicating the sequence of the kan chimeric double-stranded hairpin oligonucleotide (left) and the sequence the tet chimeric double-stranded hairpin oligonucleotide used in other experiments. FIG. 1(D) provides a flow chart of a kan experiment in which a chimeric double-stranded hairpin oligonucleotide is used.

[0040] FIG. 2. Genetic readout system for correction of a point mutation in plasmid pKsm4021. A mutant kanamycin gene harbored in plasmid pKsm4021 is the target for correction by oligonucleotides. The mutant G is converted to a C by the action of the oligo. Corrected plasmids confer resistance to kanamycin in E.coli (DH10B) after electroporation leading to the genetic readout and colony counts.

[0041] FIG. 3: Target plasmid and sequence correction of a frameshift mutation by chimeric and single-stranded oligonucleotides. (A) Plasmid pTsΔ208 contains a single base deletion mutation at position 208 rendering it unable to confer tet resistance. The target sequence presented below indicates the insertion of a T directed by the oligonucleotides to re-establish the resistant phenotype. (B) DNA sequence confirming base insertion directed by Tet 3S/25G; the yellow highlight indicates the position of frameshift repair.

[0042] FIG. 4. DNA sequences of representative kanr colonies. Confirmation of sequence alteration directed by the indicated molecule is presented along with a table outlining codon distribution. Note that 10S/25G and 12S/25G elicit both mixed and unfaithful gene repair. The number of clones sequenced is listed in parentheses next to the designation for the single-stranded oligonucleotide. A plus (+) symbol indicates the codon identified while a figure after the (+) symbol indicates the number of colonies with a particular sequence. TAC/TAG indicates a mixed peak. Representative DNA sequences are presented below the table with yellow highlighting altered residues.

[0043] FIG. 5. Gene correction in HeLa cells. Representative oligonucleotides of the invention are co-transfected with the pCMVneo(−)FlAsH plasmid (shown in FIG. 9) into HeLa cells. Ligand is diffused into cells after co-transfection of plasmid and oligonucleotides. Green fluorescence indicates gene correction of the mutation in the antibiotic resistance gene. Correction of the mutation results in the expression of a fusion protein that carries a marker ligand binding site and when the fusion protein binds the ligand, a green fluorescence is emitted. The ligand is produced by Aurora Biosciences and can readily diffuse into cells enabling a measurement of corrected protein function; the protein must bind the ligand directly to induce fluorescence. Hence cells bearing the corrected plasmid gene appear green while “uncorrected” cells remain colorless.

[0044] FIG. 6. Z-series imaging of corrected cells. Serial cross-sections of the HeLa cell represented in FIG. 5 are produced by Zeiss 510 LSM confocal microscope revealing that the fusion protein is contained within the cell.

[0045] FIG. 7. Hygromycin-eGFP target plasmids. (A) Plasmid pAURHYG(ins)GFP contains a single base insertion mutation between nucleotides 136 and 137, at codon 46, of the Hygromycin B coding sequence (cds) which is transcribed from the constitutive ADH1 promoter. The target sequence presented below indicates the deletion of an A and the substitution of a C for a T directed by the oligonucleotides to re-establish the resistant phenotype. (B) Plasmid pAURHYG(rep)GFP contains a base substitution mutation introducing a G at nucleotide 137, at codon 46, of the Hygromycin B coding sequence (cds). The target sequence presented below the diagram indicates the amino acid conservative replacement of G with C, restoring gene function.

[0046] FIG. 8. Oligonucleotides for correction of hygromycin resistance gene. The sequence of the oligonucleotides used in experiments to assay correction of a hygromycin resistance gene are shown. DNA residues are shown in capital letters, RNA residues are shown in lowercase and nucleotides with a phosphorothioate backbone are capitalized and underlined.

[0047] FIG. 9. pAURNeo(−)FlAsH plasmid. This figure describes the plasmid structure, target sequence, oligonucleotides, and the basis for detection of the gene alteration event by fluorescence.

[0048] FIG. 10. pYESHyg(x)eGFP plasmid. This plasmid is a construct similar to the pAURHyg(x)eGFP construct shown in FIG. 7, except the promoter is the inducible GAL1 promoter. This promoter is inducible with galactose, leaky in the presence of raffinose, and repressed in the presence of dextrose.

[0049] The following examples are provided by way of illustration only, and are not intended to limit the scope of the invention disclosed herein.

EXAMPLE 1

Assay Method for Base Alteration and Preferred Oligonucleotide Selection

[0050] In this example, single-stranded and double-hairpin oligonucleotides with chimeric backbones (see FIG. 1 for structures (A and B) and sequences (C and D) of assay oligonucleotides) are used to correct a point mutation in the kanamycin gene of pKsm4021 (FIG. 2) or the tetracycline gene of pTsΔ208 (FIG. 3). All kan oligonucleotides share the same 25 base sequence surrounding the target base identified for change, just as all tet oligonucleotides do. The sequence is given in FIG. 1C and FIG. 1D. Each plasmid contains a functional ampicillin gene. Kanamycin gene function is restored when a G at position 4021 is converted to a C (via a substitution mutation); tetracycline gene function is restored when a deletion at position 208 is replaced by a C (via frameshift mutation). A separate plasmid, pAURNeo(−)FlAsH (FIG. 9), bearing the kans gene is used in the cell culture experiments. This plasmid was constructed by inserting a synthetic expression cassette containing a neomycin phosphotransferase (kanamycin resistance) gene and an extended reading frame that encodes a receptor for the FlAsH ligand into the pAUR123 shuttle vector (Panvera Corp., Madison, Wis.). The resulting construct replicates in S. cerevisiae at low copy number, confers resistance to aureobasidinA and constitutively expresses either the Neo+/FlAsH fusion product (after alteration) or the truncated Neo−/FlAsH product (before alteration) from the ADH1 promoter. By extending the reading frame of this gene to code for a unique peptide sequence capable of binding a small ligand to form a fluorescent complex, restoration of expression by correction of the stop codon can be detected in real time using confocal microscopy. Additional constructs can be made to test additional gene alteration events.

[0051] We also construct three mammalian expression vectors, pHyg(rep)eGFP, pHyg(Δ)eGFP, pHyg(ins)eGFP, that contain a substitution mutation at nucleotide 137 of the hygromycin-B coding sequence. (rep) indicates a T137→G replacement, (Δ) represents a deletion of the G137 and (ins) represents an A insertion between nucleotides 136 and 137. All point mutations create a nonsense termination codon at residue 46. We use pHygEGFP plasmid (Invitrogen, CA) DNA as a template to introduce the mutations into the hygromycin-eGFP fusion gene by a two step site-directed mutagenesis PCR protocol. First, we generate overlapping 5′ and a 3′ amplicons surrounding the mutation site by PCR for each of the point mutation sites. A 215 bp 5′ amplicon for the (rep), (Δ) or (ins) was generated by polymerization from oligonucleotide primer HygEGFPf (5′-AATACGACTCACTATAGG-3′) to primer Hygrepr (5′GACCTATCCACGCCCTCC-3′), HygΔr (5′-GACTATCCACGCCCTCC-3′), or Hyginsr (5′-GACATTATCCACGCCCTCC-3′), respectively. We generate a 300 bp 3′ amplicon for the (rep), (Δ) or (ins) by polymerization from oligonucleotide primers Hygrepf (5′-CTGGGATAGGTCCTGCGG-3′), HygΔf (5′-CGTGGATAGTCCTGCGG-3′), Hyginsf (5′-CGTGGATAATGTCCTGCGG-3′), respectively to primer HygEGFPr (5′-AAATCACGCCATGTAGTG-3′). We mix 20 ng of each of the resultant 5′ and 3′ overlapping amplicon mutation sets and use the mixture as a template to amplify a 523 bp fragment of the Hygromycin gene spanning the KpnI and RsrII restriction endonuclease sites. We use the Expand PCR system (Roche) to generate all amplicons with 25 cycles of denaturing at 94° C. for 10 seconds, annealing at 55° C. for 20 seconds and elongation at 68° C. for 1 minute. We digest 10 μg of vector pHygEGFP and 5 μg of the resulting fragments for each mutation with KpnI and RsrII (NEB) and gel purify the fragment for enzymatic ligation. We ligate each mutated insert into pHygEGFP vector at 3:1 molar ration using T4 DNA ligase (Roche). We screen clones by restriction digest, confirm the mutation by Sanger dideoxy chain termination sequencing and purify the plasmid using a Qiagen maxiprep kit.

[0052] Oligonucleotide synthesis and cells. Chimeric oligonucleotides and single-stranded oligonucleotides (including those with the indicated modifications) are synthesized using available phosphoramidites on controlled pore glass supports. After deprotecton and detachment from the solid support, each oligonucleotide is gel-purified using, for example, procedures such as those described in Gamper et al., Biochem. 39, 5808-5816 (2000) and the concentrations determined spectrophotometrically (33 or 40 μg/ml per A260 unit of single-stranded or hairpin oligomer). HUH7 cells are grown in DMEM, 10% FBS, 2 mM glutamine, 0.5% pen/strep. The E.coli strain, DH10B, is obtained from Life Technologies (Gaithersburg, Md.); DH10B cells contain a mutation in the RECA gene (recA).

[0053] Cell-free extracts. We prepare cell-free extracts from HUH7 cells or other mammalian cells, as follows. We employ this protocol with essentially any mammalian cell including, for example, H1299 cells (human epithelial carcinoma, non-small cell lung cancer), C127I (immortal murine mammary epithelial cells), MEF (mouse embryonic fibroblasts), HEC-1-A (human uterine carcinoma), HCT15 (human colon cancer), HCT116 (human colon carcinoma), LoVo (human colon adenocarcinoma), and HeLa (human cervical carcinoma). We harvest approximately 2×108 cells. We then wash the cells immediately in cold hypotonic buffer (20 mM HEPES, pH7.5; 5 mM KCl; 1.5 mM MgCl2; 1 mM DTT) with 250 mM sucrose. We then resuspend the cells in cold hypotonic buffer without sucrose and after 15 minutes we lyse the cells with 25 strokes of a Dounce homogenizer using a tight fitting pestle. We incubate the lysed cells for 60 minutes on ice and centrifuge the sample for 15 minutes at 12000×g. The cytoplasmic fraction is enriched with nuclear proteins due to the extended co-incubation of the fractions following cell breakage. We then immediately aliquote and freeze the supernatant at −80° C. We determine the protein concentration in the extract by the Bradford assay.

[0054] We also perform these experiments with cell-free extracts obtained from fungal cells, including, for example, S. cerevisiae (yeast), Ustilago maydis, and Candida albicans. For example, we grow yeast cells into log phase in 2L YPD medium for 3 days at 30° C. We then centrifuge the cultures at 5000×g, resuspend the pellets in a 10% sucrose, 50 mM Tris, 1 mM EDTA lysis solution and freeze them on dry ice. After thawing, we add KCl, spermidine and lyticase to final concentrations of 0.25 mM, 5 mM and 0.1 mg/ml, respectively. We incubate the suspension on ice for 60 minutes, add PMSF and Triton X100 to final concentrations of 0.1 mM and 0.1% and continue to incubate on ice for 20 minutes. We centrifuge the lysate at 3000×g for 10 minutes to remove larger debris. We then remove the supernatant and clarify it by centrifuging at 30000×g for 15 minutes. We then add glycerol to the clarified extract to a concentration of 10% (v/v) and freeze aliquots at −80° C. We determine the protein concentration of the extract by the Bradford assay.

[0055] Reaction mixtures of 50 μl are used, consisting of 10-30 μg protein of cell-free extract, which can be optionally substituted with purified proteins or enriched fractions, about 1.5 μg chimeric double-hairpin oligonucleotide or 0.55 μg single-stranded molecule (3S/25G or 6S/25G, see FIG. 1), and 1 μg of plasmid DNA (see FIGS. 2 and 3) in a reaction buffer of 20 mM Tris, pH 7.4, 15 mM MgCl2, 0.4 mM DTT, and 1.0 mM ATP. Reactions are initiated with extract and incubated at 30° C. for 45 min. The reaction is stopped by placing the tubes on ice and then immediately deproteinized by two phenol/chloroform (1:1) extractions. Samples are then ethanol precipitated. The nucleic acid is pelleted at 15,000 r.p.m. at 4° C. for 30 min., is washed with 70% ethanol, resuspended in 50 μl H2O, and is stored at −20° C. 5 μl of plasmid from the resuspension (˜100 ng) was transfected in 20 μl of DH10B cells by electroporation (400 V, 300 μF, 4 kΩ) in a Cell-Porator apparatus (Life Technologies). After electroporation, cells are transferred to a 14 ml Falcon snap-cap tube with 2 ml SOC and shaken at 37° C. for 1 h. Enhancement of final kan colony counts is achieved by then adding 3 ml SOC with 10 μg/ml kanamycin and the cell suspension is shaken for a further 2 h at 37° C. Cells are then spun down at 3750×g and the pellet is resuspended in 500 μl SOC. 200 μl is added undiluted to each of two kanamycin (50 μg/ml) agar plates and 200 μl of a 105 dilution is added to an ampicillin (100 μg/ml) plate. After overnight 37° C. incubation, bacterial colonies are counted using an Accucount 1000 (Biologics). Gene conversion effectiveness is measured as the ratio of the average of the kan colonies on both plates per amp colonies multiplied by 10−5 to correct for the amp dilution.

[0056] The following procedure can also be used. 5 μl of resuspended reaction mixtures (total volume 50 μl) are used to transform 20 μl aliquots of electro-competent ΔH10B bacteria using a Cell-Porator apparatus (Life Technologies). The mixtures are allowed to recover in 1 ml SOC at 37° C. for 1 hour at which time 50 μg/ml kanamycin or 12 μg/ml tetracycline is added for an additional 3 hours. Prior to plating, the bacteria are pelleted and resuspended in 200 μl of SOC. 100 μl aliquots are plated onto kan or tet agar plates and 100 μl of a 10−4 dilution of the cultures are concurrently plated on agar plates containing 100 μg/ml of ampicillin. Plating is performed in triplicate using sterile Pyrex beads. Colony counts are determined by an Accu-count 1000 plate reader (Biologics). Each plate contains 200-500 ampicillin resistant colonies or 0-500 tetracycline or kanamycin resistant colonies. Resistant colonies are selected for plasmid extraction and DNA sequencing using an ABI Prism kit on an ABI 310 capillary sequencer (PE Biosystems).

[0057] Chimeric single-stranded oligonucleotides. In FIG. 1 the upper strands of chimeric oligonucleotides I and II are separated into pathways resulting in the generation of single-stranded oligonucleotides that contain (FIG. 1A) 2′-O-methyl RNA nucleotides or (FIG. 1B) phosphorothioate linkages. Fold changes in repair activity for correction of kans in the HUH7 cell-free extract are presented in parenthesis. Each single-stranded oligonucleotide is 25 bases in length and contains a G residue mismatched to the complementary sequence of the kans gene.

[0058] Molecules bearing 3, 6, 8, 10 and 12 phosphorothioate linkages in the terminal regions at each end of a backbone with a total of 24 linkages (25 bases) are tested in the kans system. Alternatively, molecules bearing 2, 4, 5, 7, 9 and 11 in the terminal regions at each end are tested. The results of one such experiment, presented in Table 1 and FIG. 1B, illustrate an enhancement of correction activity directed by some of these modified structures. In this illustrative example, the most efficient molecules contained 3 or 6 phosphorothioate linkages at each end of the 25-mer; the activities are approximately equal (molecules IX and X with results of 3.09 and 3.7 respectively). A reduction in alteration activity may be observed as the number of modified linkages in the molecule is further increased. Interestingly, a single-strand molecule containing 24 phosphorothioate linkages is minimally active suggesting that this backbone modification when used throughout the molecule supports only a low level of targeted gene repair or alteration. Such a non-altering, completely modified molecule can provide a baseline control for determining efficiency of correction for a specific oligonucleotide molecule of known sequence in defining the optimum oligonucleotide for a particular alteration event.

[0059] The efficiency of gene repair directed by phosphorothioate-modified, single-stranded molecules, in a length dependent fashion, led us to examine the length of the RNA modification used in the original chimera as it relates to correction. Construct III represents the “RNA-containing” strand of chimera I and, as shown in Table 1 and FIG. 2A, it promotes inefficient gene repair. But, as shown in the same figure, reducing the RNA residues on each end from 10 to 3 increases the frequency of repair. At equal levels of modification, however, 25-mers with 2′-O-methyl ribonucleotides were less effective gene repair agents than the same oligomers with phosphorothioate linkages. These results reinforce the fact that an RNA containing oligonucleotide is not as effective in promoting gene repair or alteration as a modified DNA oligonucleotide.

[0060] Repair of the kanamycin mutation requires a G→C exchange. To confirm that the specific desired correction alteration was obtained, colonies selected at random from multiple experiments are processed and the isolated plasmid DNA is sequenced. As seen in FIG. 4, colonies generated through the action of the single-stranded molecules 3S/25G (IX), 6S/25G (X) and 8S/25G (XI) respectively contained plasmid molecules harboring the targeted base correction. While a few colonies appeared on plates derived from reaction mixtures containing 25-mers with 10 or 12 thioate linkages on both ends, the sequences of the plasmid molecules from these colonies contain nonspecific base changes. In these illustrative examples, the second base of the codon is changed (see FIG. 3). These results show that modified single-strands can direct gene repair, but that efficiency and specificity are reduced when the 25-mers contain 10 or more phosphorothioate linkages at each end.

[0061] In FIG. 1, the numbers 3, 6, 8, 10, 12 and 12.5 respectively indicate how many phosphorothioate linkages (S) or 2′-O-methyl RNA nucleotides (R) are at each end of the exemplified molecule although other molecules with 2, 4, 5, 7, 9 and 11 modifications at each end can also be tested. Hence oligo 12S/25G represents a 25-mer oligonucleotide which contains 12 phosphorothioate linkages on each side of the central G target mismatch base producing a fully phosphorothioate linked backbone, displayed as a dotted line. The dots are merely representative of a linkage in the figure and do not depict the actual number of linkages of the oligonucleotide. Smooth lines indicate DNA residues, wavy lines indicate 2′-O-methyl RNA residues and the carat indicates the mismatched base site (G).

[0062] Correction of a mutant kanamycin gene in cultured mammalian cells. The experiments are performed using different mammalian cells, including, for example, 293 cells (transformed human primary kidney cells), HeLa cells (human cervical carcinoma), and H1299 (human epithelial carcinoma, non-small cell lung cancer). HeLa cells are grown at 37° C. and 5% CO2 in a humidified incubator to a density of 2×105 cells/ml in an 8 chamber slide (Lab-Tek). After replacing the regular DMEM with Optimem, the cells are co-transfected with 10 μg of plasmid pAURNeo(−)FlAsH and 5 μg of modified single-stranded oligonucleotide (3S/25G) that is previously complexed with 10 μg lipofectamine, according to the manufacturer's directions (Life Technologies). The cells are treated with the liposome-DNA-oligo mix for 6 hrs at 37° C. Treated cells are washed with PBS and fresh DMEM is added. After a 16-18 hr recovery period, the culture is assayed for gene repair. The same oligonucleotide used in the cell-free extract experiments is used to target transfected plasmid bearing the kans gene. Correction of the point mutation in this gene eliminates a stop codon and restores full expression. This expression can be detected by adding a small non-fluorescent ligand that bound to a C-C-R-E-C-C sequence in the genetically modified carboxy terminus of the kan protein, to produce a highly fluorescent complex (FlAsH system, Aurora Biosciences Corporation). Following a 60 min incubation at room temperature with the ligand (FlAsH-EDT2), cells expressing full length kan product acquire an intense green fluorescence detectable by fluorescence microscopy using a fluorescein filter set. Similar experiments are performed using the HygeGFP target as described in Example 2 with a variety of mammalian cells, including, for example, COS-1 and COS-7 cells (African green monkey), and CHO-K1 cells (Chinese hamster ovary). The experiments are also performed with PG12 cells (rat pheochromocytoma) and ES cells (human embryonic stem cells).

[0063] Summary of experimental results. Tables 1, 2 and 3 respectively provide data on the efficiency of gene repair directed by single-stranded oligonucleotides. Table 1 presents data using a cell-free extract from human liver cells (HUH7) to catalyze repair of the point mutation in plasmid pkansm4021 (see FIG. 1). Table 2 illustrates that the oligomers are not dependent on MSH2 or MSH3 for optimal gene repair activity. Table 3 illustrates data from the repair of a frameshift mutation (FIG. 3) in the tet gene contained in plasmid pTetΔ208. Table 4 illustrates data from repair of the pkansm4021 point mutation catalyzed by plant cell extracts prepared from canola and musa (banana). Colony numbers are presented as kanr or tet and fold increases (single strand versus double hairpin) are presented for kanr in Table 1.

[0064] FIG. 5A is a confocal picture of HeLa cells expressing the corrected fusion protein from an episomal target. Gene repair is accomplished by the action of a modified single-stranded oligonucleotide containing 3 phosphorothioate linkages at each end (3S/25G). FIG. 5B represents a “Z-series” of HeLa cells bearing the corrected fusion gene. This series sections the cells from bottom to top and illustrates that the fluorescent signal is “inside the cells”.

[0065] Results. In summary, we have designed a novel class of single-stranded oligonucleotides with backbone modifications at the termini and demonstrate gene repair/conversion activity in mammalian and plant cell-free extracts. We confirm that the all DNA strand of the RNA-DNA double-stranded double hairpin chimera is the active component in the process of gene repair. In some cases, the relative frequency of repair by the novel oligonucleotides of the invention is elevated approximately 3-4-fold when compared to frequencies directed by chimeric RNA-DNA double hairpin oligonucleotides.

[0066] This strategy centers around the use of extracts from various sources to correct a mutation in a plasmid using a modified single-stranded or a chimeric RNA-DNA double hairpin oligonucleotide. A mutation is placed inside the coding region of a gene conferring antibiotic resistance in bacteria, here kanamycin or tetracycline. The appearance of resistance is measured by genetic readout in E.coli grown in the presence of the specified antibiotic. The importance of this system is that both phenotypic alteration and genetic inheritance can be measured. Plasmid pKsm4021 contains a mutation (T→G) at residue 4021 rendering it unable to confer antibiotic resistance in E.coli. This point mutation is targeted for repair by oligonucleotides designed to restore kanamycin resistance. To avoid concerns of plasmid contamination skewing the colony counts, the directed correction is from G→C rather than G→T (wild-type). After isolation, the plasmid is electroporated into the DH10B strain of E.coli, which contains inactive RecA protein. The number of kanamycin colonies is counted and normalized by ascertaining the number of ampicillin colonies, a process that controls for the influence of electroporation. The number of colonies generated from three to five independent reactions was averaged and is presented for each experiment. A fold increase number is recorded to aid in comparison.

[0067] The original RNA-DNA double hairpin chimera design, e.g., as disclosed in U.S. Pat. No. 5,565,350, consists of two hybridized regions of a single-stranded oligonucleotide folded into a double hairpin configuration. The double-stranded targeting region is made up of a 5 base pair DNA/DNA segment bracketed by 10 base pair RNA/DNA segments. The central base pair is mismatched to the corresponding base pair in the target gene. When a molecule of this design is used to correct the kans mutation, gene repair is observed (I in FIG. 1A). Chimera II (FIG. 1B) differs partly from chimera I in that only the DNA strand of the double hairpin is mismatched to the target sequence. When this chimera was used to correct the kans mutation, it was twice as active. In the same study, repair function could be further increased by making the targeting region of the chimera a continuous RNA/DNA hybrid.

[0068] Frame shift mutations are repaired. By using plasmid pTsΔ208, described in FIG. 1(C) and FIG. 3, the capacity of the modified single-stranded molecules that showed activity in correcting a point mutation, can be tested for repair of a frameshift. To determine efficiency of correction of the mutation, a chimeric oligonucleotide (Tet I), which is designed to insert a T residue at position 208, is used. A modified single-stranded oligonucleotide (Tet IX) directs the insertion of a T residue at this same site. FIG. 3 illustrates the plasmid and target bases designated for change in the experiments. When all reaction components are present (extract, plasmid, oligomer), tetracycline resistant colonies appear. The colony count increases with the amount of oligonucleotide used up to a point beyond which the count falls off (Table 3). No colonies above background are observed in the absence of either extract or oligonucleotide, nor when a modified single-stranded molecule bearing perfect complementarity is used. FIG. 3 represents the sequence surrounding the target site and shows that a T residue is inserted at the correct site. We have isolated plasmids from fifteen colonies obtained in three independent experiments and each analyzed sequence revealed the same precise nucleotide insertion. These data suggest that the single-stranded molecules used initially for point mutation correction can also repair nucleotide deletions.

[0069] Comparison of phosphorothioate oligonucleotides to 2′-O-methyl substituted oligonucleotides. From a comparison of molecules VII and XI, it is apparent that gene repair is more subject to inhibition by RNA residues than by phosphorothioate linkages. Thus, even though both of these oligonucleotides contain an equal number of modifications to impart nuclease resistance, XI (with 16 phosphorothioate linkages) has good gene repair activity while VII (with 16 2′-O-methyl RNA residues) is inactive. Hence, the original chimeric double hairpin oligonucleotide enabled correction directed, in large part, by the strand containing a large region of contiguous DNA residues.

[0070] Oligonucleotides can target multiple nucleotide alterations within the same template. The ability of individual single-stranded oligonucleotides to correct multiple mutations in a single target template is tested using the plasmid pKsm4021 and the following single-stranded oligonucleotides modified with 3 phosphorothioate linkages at each end (indicated as underlined nucleotides): Oligo1 is a 25-mer with the sequence TTCGATAAGCCTATGCTGACCCGTG corrects the original mutation present in the kanamycin resistance gene of pKsm4021 as well as directing another alteration 2 basepairs away in the target sequence (both indicated in boldface); Oligo2 is a 70-mer with the 5′-end sequence TTCGGCTACGACTGGGCACAACAGACAATTGGC with the remaining nucleotides being completely complementary to the kanamycin resistance gene and also ending in 3 phosphorothioate linkages at the 3′ end. Oligo2 directs correction of the mutation in pKsm4021 as well as directing another alteration 21 basepairs away in the target sequence (both indicated in boldface).

[0071] We also use additional oligonucleotides to assay the ability of individual oligonucleotides to correct multiple mutations in the pKsM4021 plasmid. These include, for example, a second 25-mer that alters two nucleotides that are three nucleotides apart with the sequence 5′-TTGTGCCCAGTCGTATCCGAATAGC-3′; a 70-mer that alters two nucleotides that are 21 nucleotides apart with the sequence 5′-CATCAGAGCAGCCAATTGTCTGTTGTGCCCAGTCGTAGCCGAA TAGCCTCTCCACCCAAGCGGCCGGAGA-3′; and another 70-mer that alters two nucleotides that are 21 nucleotides apart with the sequence 5′-GCTGACAGCCGGAACACGGCGGCATCAGAGCAGCCAATTGTCTGTTGTGCCCAGTCGTAGCCGAAT AGCCT-3′. The nucleotides in the oligonucleotides that direct alteration of the target sequence are underlined and in boldface. These oligonucleotides are modified in the same way as the other oligonucleotides of the invention.

[0072] We assay correction of the original mutation in pKsm4021 by monitoring kanamycin resistance (the second alterations which are directed by Oligo2 and Oligo3 are silent with respect to the kanamycin resistance phenotype). In addition, in experiments with Oligo2, we also monitor cleavage of the resulting plasmids using the restriction enzyme Tsp509I which cuts at a specific site present only when the second alteration has occurred (at ATT in Oligo2). We then sequence these clones to determine whether the additional, silent alteration has also been introduced. The results of an analysis are presented below:

	Oligo1 (25-mer)	Oligo2 (70-mer)
Clones with both sites changed	9	7
Clones with a single site changed	0	2
Clones that were not changed	4	1

[0073] Nuclease sensitivity of unmodified DNA oligonucleotide. Electrophoretic analysis of nucleic acid recovered from the cell-free extract reactions conducted here confirm that the unmodified single-stranded 25-mer did not survive incubation whereas greater than 90% of the terminally modified oligos did survive (as judged by photo-image analyses of agarose gels).

[0074] Plant extracts direct repair. The modified single-stranded constructs can be tested in plant cell extracts. We have observed gene alteration using extracts from multiple plant sources, including, for example, Arabidopsis, tobacco, banana, maize, soybean, canola, wheat, spinach as well as spinach chloroplast extract. We prepare the extracts by grinding plant tissue or cultured cells under liquid nitrogen with a mortar and pestle. We extract 3 ml of the ground plant tissue with 1.5 ml of extraction buffer (20 mM HEPES, pH7.5; 5 mM Kcl; 1.5 mM MgCl2; 10 mM DTT; 10% [v/v] glycerol; and 1% [w/v] PVP). We then homogenize the samples with 15 strokes of a Dounce homogenizer. Following homogenization, we incubate the samples on ice for 1 hour and centrifuge at 3000×g for 5 minutes to remove plant cell debris. We then determine the protein concentration in the supernatants (extracts) by Bradford assay. We dispense 100 μg (protein) aliquots of the extracts which we freeze in a dry ice-ethanol bath and store at −80° C.

[0075] We describe experiments using two sources here: a dicot (canola) and a monocot (banana, Musa acuminata cv. Rasthali). Each vector directs gene repair of the kanamycin mutation (Table 4); however, the level of correction is elevated 2-3 fold relative to the frequency observed with the chimeric oligonucleotide. These results are similar to those observed in the mammalian system wherein a significant improvement in gene repair occurred when modified single-stranded molecules were used.

[0076] Tables are attached hereto.

TABLE I
Gene repair activity is directed by single-stranded oligonucleotides.
Oligonucleotide	Plasmid	Extract (ug)	kanr colonies	Fold increase
I	pKSm4021	10	300
I	↓	20	418	1.0 ×
II	↓	10	537
II	↓	20	748	1.78 ×
III	↓	10	3
III	↓	20	5	0.01 ×
IV	↓	10	112
IV	↓	20	96	0.22 ×
V	↓	10	217
V	↓	20	342	0.81 ×
VI	↓	10	6
VI	↓	20	39	0.093 ×
VII	↓	10	0
VII	↓	20	0	0 ×
VIII	↓	10	3
VIII	↓	20	5	0.01 ×
IX	↓	10	936
IX	↓	20	1295	3.09 ×
X	↓	10	1140
X	↓	20	1588	3.7 ×
XI	↓	10	480
XI	↓	20	681	1.6 ×
XII	↓	10	18
XII	↓	20	25	0.059 ×
XIII	↓	10	0
XIII	↓	20	4	0.009 ×
—	↓	20	0
I	↓	—	0

[0077] Plasmid pKsm4021 (1 μg), the indicated oligonucleotide (1.5 μg chimeric oligonucleotide or 0.55 μg single-stranded oligonucleotide; molar ratio of oligo to plasmid of 360 to 1) and either 10 or 20 μg of HUH7 cell-free extract were incubated 45 min at 37° C. Isolated plasmid DNA was electroporated into E. coli (strain DH10B) and the number of kanr colonies counted. The data represent the number of kanamycin resistant colonies per 106 ampicillin resistant colonies generated from the same reaction and is the average of three experiments (standard deviation usually less than +/−15%). Fold increase is defined relative to 418 kanr colonies (second reaction) and in all reactions was calculated using the 20 μg sample.

TABLE II
Modified single-stranded oligomers are not dependent on MSH2
or MSH3 for optimal gene repair activity.
	A.	Oligonucleotide	Plasmid	Extract	kanr colonies
		TX (3S/25G)	↓	HUH7	637
		X (6S/25G)	↓	HUH7	836
		IX	↓	MEF2−/−	781
		X	↓	MEF2−/−	676
		IX	↓	MEF3−/−	582
		X	↓	MEF3−/−	530
		IX	↓	MEF+/+	332
		X	↓	MEF+/+	497
		—	↓	MEF2−/−	10
		—	↓	MEF3−/−	5
		—	↓	MEF+/+	14

[0078] Chimeric oligonucleotide (1.5 μg) or modified single-stranded oligonucleotide (0.55 μg) was incubated with 1 μg of plasmid pKsm4021 and 20 μg of the indicated extracts. MEF represents mouse embryonic fibroblasts with either MSH2 (2−/−) or MSH3 (3−/−) deleted. MEF+/+ indicates wild-type mouse embryonic fibroblasts. The other reaction components were then added and processed through the bacterial readout system. The data represent the number of kanamycin resistant colonies per 106 ampicillin resistant colonies.

TABLE III
Framesh1ft mutation repair is directed by
single-stranded oligonucleotides
Oligonucleotide	Plasmid	Extract	tetr colonies
Tet IX (3S/25A; 0.5 μg)	pTSΔ2O8 (1 μg)		—	0
—	↓	20 μg		0
Tet IX (0.5 μg)	↓	↓		48
Tet IX (1.5 μg)	↓	↓		130
Tet IX (2.0 μg)	↓	↓		68
Tet I (chimera; 1.5 μg)	↓	↓		48

[0079] Each reaction mixture contained the indicated amounts of plasmid and oligonucleotide. The extract used for these experiments came from HUH7 cells. The data represent the number of tetracycline resistant colonies per 106 ampicillin resistant colonies generated from the same reaction and is the average of 3 independent experiments. Tet I is a chimeric oligonucleotide and Tet IX is a modified single-stranded oligonucleotide that are designed to insert a T residue at position 208 of pTsΔ208. These oligonucleotides are equivalent to structures I and IX in FIG. 2.

TABLE IV
Plant cell-free extracts support gene repair by
single-stranded oligonucleotides
Oligonucleotide	Plasmid	Extract	kanr colonies
II (chimera)	pKSm402l	30 μg	Canola	337
IX (3S/25G)	↓	Canola	763
X (6S/25G)	↓	Canola	882
II	↓	Musa	203
IX	↓	Musa	343
X	↓	Musa	746
—	↓	Canola	0
—	↓	Musa	0
IX	↓	—	Canola	0
X	↓	—	Musa	0

[0080] Canola or Musa cell-free extracts were tested for gene repair activity on the kanamycin-sensitive gene as previously described in (18). Chimeric oligonucleotide II (1.5 μg) and modified single-stranded oligonucleotides IX and X (0.55 μg) were used to correct pKSm402 1. Total number of kanr colonies are present per 107 ampicillin resistant colonies and represent an average of four independent experiments.

TABLE V
Gene repair activity in cell-free extracts prepared from yeast
(Saccharomyces cerevisiae)
Cell-type	Plasmid	Chimeric Oligo	SS Oligo	kanr/ampr × 106
Wild type	pKansm4021	1 μg		0.36
Wild type	↓		1 μg	0.81
ΔRAD52	↓	1 μg		10.72
ΔRAD52	↓		1 μg	17.41
ΔPMS1	↓	1 μg		2.02
ΔPMS1	↓		1 μg	3.23
In this experiment, the kans gene in pKans4021 is corrected by either a chimeric double-hairpin oligonucleotide or a single-stranded oligonucleotide containing three thioate linkages at each end (3S/25G).

EXAMPLE 2

Yeast Cell Targeting Assay Method for Base Alteration and Preferred Oligonucleotide Selection

[0081] In this example, single-stranded oligonucleotides with modified backbones and double-hairpin oligonucleotides with chimeric, RNA-DNA backbones are used to measure gene repair using two episomal targets with a fusion between a hygromycin resistance gene and eGFP as a target for gene repair. These plasmids are pAURHYG(rep)GFP, which contains a point mutation in the hygromycin resistance gene (FIG. 7), pAURHYG(ins)GFP, which contains a single-base insertion in the hygromycin resistance gene (FIG. 7) and pAURHYG(Δ)GFP which has a single base deletion. We also use the plasmid containing a wild-type copy of the hygromycin-eGFP fusion gene, designated pAURHYG(wt)GFP, as a control. These plasmids also contain an aureobasidinA resistance gene. In pAURHYG(rep)GFP, hygromycin resistance gene function and green fluorescence from the eGFP protein are restored when a G at position 137, at codon 46 of the hygromycin B coding sequence, is converted to a C thus removing a premature stop codon in the hygromycin resistance gene coding region. In pAURHYG(ins)GFP, hygromycin resistance gene function and green fluorescence from the eGFP protein are restored when an A inserted between nucleotide positions 136 and 137, at codon 46 of the hygromycin B coding sequence, is deleted and a C is substituted for the T at position 137, thus correcting a frameshift mutation and restoring the reading frame of the hygromycin-eGFP fusion gene.

[0082] We synthesize the set of three yeast expression constructs pAURHYG(rep)eGFP, pAURHYG(Δ)eGFP, pAURHYG(ins)eGFP, that contain a point mutation at nucleotide 137 of the hygromycin-B coding sequence as follows. (rep) indicates a T137→G replacement, (Δ) represents a deletion of the G137 and (ins) represents an A insertion between nucleotides 136 and 137. We construct this set of plasmids by excising the respective expression cassettes by restriction digest from pHyg(x)EGFP and ligation into pAUR123 (Panvera, Calif.). We digest 10 μg pAUR123 vector DNA, as well as, 10 μg of each pHyg(x)EGFP construct with KpnI and SaII (NEB). We gel purify each of the DNA fragments and prepare them for enzymatic ligation. We ligate each mutated insert into pHygEGFP vector at 3:1 molar ration using T4 DNA ligase (Roche). We screen clones by restriction digest, confirm by Sanger dideoxy chain termination sequencing and purify using a Qiagen maxiprep kit.

[0083] We use this system to assay the ability of five oligonucleotides (shown in FIG. 8) to support correction under a variety of conditions. The oligonucleotides which direct correction of the mutation in pAURHYG(rep)GFP can also direct correction of the mutation in pAURHYG(ins)GFP. Three of the four oligonucleotides (HygE3T/25, HygE3T/74 and HygGG/Rev) share the same 25-base sequence surrounding the base targeted for alteration. HygGG/Rev is an RNA-DNA chimeric double hairpin oligonucleotide of the type described in the prior art. One of these oligonucleotides, HygE3T/74, is a 74-base oligonucleotide with the 25-base sequence centrally positioned. The fourth oligonucleotide, designated HygE3T/74α, is the reverse complement of HygE3T/74. The fifth oligonucleotide, designated Kan70T, is a non-specific, control oligonucleotide which is not complementary to the target sequence. Alternatively, an oligonucleotide of identical sequence but lacking a mismatch to the target or a completely thioate modified oligonucleotide or a completely 2-O-methylated modified oligonucleotide may be used as a control.

[0084] Oligonucleotide synthesis and cells. We synthesized and purified the chimeric, double-hairpin oligonucleotides and single-stranded oligonucleotides (including those with the indicated modifications) as described in Example 1. Plasmids used for assay were maintained stably in yeast (Saccharomyces cerevisiae) strain LSY678 MATα at low copy number under aureobasidin selection. Plasmids and oligonucleotides are introduced into yeast cells by electroporation as follows: to prepare electrocompetent yeast cells, we inoculate 10 ml of YPD media from a single colony and grow the cultures overnight with shaking at 300 rpm at 30° C. We then add 30 ml of fresh YPD media to the overnight cultures and continue shaking at 30° C. until the OD600 was between 0.5 and 1.0 (3-5 hours). We then wash the cells by centrifuging at 4° C. at 3000 rpm for 5 minutes and twice resuspending the cells in 25 ml ice-cold distilled water. We then centrifuge at 4° C. at 3000 rpm for 5 minutes and resuspend in 1 ml ice-cold 1M sorbitol and then finally centrifuge the cells at 4° C. at 5000 rpm for 5 minutes and resuspend the cells in 120 μl 1M sorbitol. To transform electrocompetent cells with plasmids or oligonucleotides, we mix 40 μl of cells with 5 μg of nucleic acid, unless otherwise stated, and incubate on ice for 5 minutes. We then transfer the mixture to a 0.2 cm electroporation cuvette and electroporate with a BIO-RAD Gene Pulser apparatus at 1.5 kV, 25 μF, 200 Ω for one five-second pulse. We then immediately resuspend the cells in 1 ml YPD supplemented with 1M sorbitol and incubate the cultures at 30° C. with shaking at 300 rpm for 6 hours. We then spread 200 μl of this culture on selective plates containing 300 μg/ml hygromycin and spread 200 μl of a 105 dilution of this culture on selective plates containing 500 ng/ml aureobasidinA and/or and incubate at 30° C. for 3 days to allow individual yeast colonies to grow. We then count the colonies on the plates and calculate the gene conversion efficiency by determining the number of hygromycin resistance colonies per 105 aureobasidinA resistant colonies.

[0085] Frameshift mutations are repaired in yeast cells. We test the ability of the oligonucleotides shown in FIG. 8 to correct a frameshift mutation in vivo using LSY678 yeast cells containing the plasmid pAURHYG(ins)GFP. These experiments, presented in Table 6, indicate that these oligonucleotides can support gene correction in yeast cells. These data reinforce the results described in Example 1 indicating that oligonucleotides comprising phosphorothioate linkages facilitate gene correction much more efficiently than control duplex, chimeric RNA-DNA oligonucleotides. This gene correction activity is also specific as transformation of cells with the control oligonucleotide Kan70T produced no hygromycin resistant colonies above background and thus Kan70T did not support gene correction in this system. In addition, we observe that the 74-base oligonucleotide (HygE3T/74) corrects the mutation in pAURHYG(ins)GFP approximately five-fold more efficiently than the 25-base oligonucleotide (HygE3T/25). We also perform control experiments with LSY678 yeast cells containing the plasmid pAURHYG(wt)GFP. With this strain we observed that even without added oligonucleotides, there are too many hygromycin resistant colonies to count.

[0086] We also use additional oligonucleotides to assay the ability of individual oligonucleotides to correct multiple mutations in the pAURHYG(x)eGFP plasmid. These include, for example, one that alters two basepairs that are 3 nucleotides apart is a 74-mer with the sequence 5′-CTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGGTACGTCCTGCGGGTAAATAGCTGCGCCGATG GTTTCTAC-3′; a 74-mer that alters two basepairs that are 15 nucleotides apart with the sequence 5′-CTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGATACGTCCTGCGGGTAAACAGCTGCGCCGATG GTTTCTAC-3′; and a 74-mer that alters two basepairs that are 27 nucleotides apart with the sequence 5′-CTCGTGCTTTCAGCTTCGATGTAGGAGGGCGTGGATACGTCCTGCGGGTAAATAGCTGCGCCGACG GTTTCTAC. The nucleotides in these oligonucleotides that direct alteration of the target sequence are underlined and in boldface. These oligonucleotides are modified in the same ways as the other oligonucleotides of the invention.

[0087] Oligonucleotides targeting the sense strand direct gene coffection more efficiently. We compare the ability of single-stranded oligonucleotides to target each of the two strands of the target sequence of both pAURHYG(ins)GFP and pAURHYG(rep)GFP. These experiments, presented in Tables 7 and 8, indicate that an oligonucleotide, HygE3T/74α, with sequence complementary to the sense strand (i.e. the strand of the target sequence that is identical to the mRNA) of the target sequence facilitates gene correction approximately ten-fold more efficiently than an oligonucleotide, HygE3T/74, with sequence complementary to the non-transcribed strand which serves as the template for the synthesis of RNA. As indicated in Table 7, this effect was observed over a range of oligonucleotide concentrations from 0-3.6 μg, although we did observe some variability in the difference between the two oligonucleotides (indicated in Table 7 as a fold difference between HygE3T/74α and HygE3T/74). Furthermore, as shown in Table 8, we observe increased efficiency of correction by HygE3T/74α relative to HygE3T/74 regardless of whether the oligonucleotides were used to correct the base substitution mutation in pAURHYG(rep)GFP or the insertion mutation in pAURHYG(ins)GFP. The data presented in Table 8 further indicate that the single-stranded oligonucleotides correct a base substitution mutation more efficiently than an insertion mutation. However, this last effect was much less pronounced and the oligonucleotides of the invention are clearly able efficiently to correct both types of mutations in yeast cells. In addition, the role of transcription is investigated using plasmids with inducible promoters such as that described in FIG. 10.

[0088] Optimization of oligonucleotide concentration. To determine the optimal concentration of oligonucleotide for the purpose of gene alteration, we test the ability of increasing concentrations of Hyg3T/74α to correct the mutation in pAURHYG(rep)GFP contained in yeast LSY678. We chose this assay system because our previous experiments indicated that it supports the highest level of correction. However, this same approach could be used to determine the optimal concentration of any given oligonucleotide. We test the ability of Hyg3T/74α to correct the mutation in pAURHYG(rep)GFP contained in yeast LSY678 over a range of oligonucleotide concentrations from 0-10.0 μg. As shown in Table 9, we observe that the correction efficiency initially increases with increasing oligonucleotide concentration, but then declines at the highest concentration tested.

[0089] Tables are attached hereto.

TABLE 6
Correction of an insertion mutation in pAURHYG(ins)GFP
by HygGG/Rev, HygE3T/25 and HygE3T/74
	Colonies on	Colonies on	Correction
Oligonucleotide Tested	Hygromycin	Aureobasidin (/105)	Efficiency
HygGG/Rev	3	157	0.02
HygE3T/25	64	147	0.44
HygE3T/74	280	174	1.61
Kan70T	0	—	—

[0090]

TABLE 7
An oligonucleotide targeting the sense strand
of the target sequence corrects more efficiently.
	Colonies per hygromycin plate
Amount of Oligonucleotide (μg)	HygE3T/74	HygE3T/74α
0	0	0
0.6	24	128 (8.4x)*
1.2	69	140 (7.5x)*
2.4	62	167 (3.8x)*
3.6	29	367 (15x)*
*The numbers in parentheses represent the fold increase in efficiency for targeting the non-transcribed strand as compared to the other strand of a DNA duplex that encodes a protein.

[0091]

TABLE 8
Correction of a base substitution mutation
is more efficient than correction of a frame shift mutation.
Oligonucleotide	Plasmid tested (contained in LSY678)
Tested (5 μg)	pAURHYG(ins)GFP	pAURHYG(rep)GFP
HygE3T/74	72	277
HygE3T/74α	1464	2248
Kan70T	0	0

[0092]

TABLE 9
Optimization of oligonucleotide concentration
in electroporated yeast cells.
	Colonies on	Colonies on
Amount (μg)	hygromycin	aureobasidin (/105)	Correction efficiency
0	0	67	0
1.0	5	64	0.08
2.5	47	30	1.57
5.0	199	33	6.08
7.5	383	39	9.79
10.0	191	33	5.79

EXAMPLE 3

Cultured Cell Manipulation

[0093] Mononuclear cells are isolated from human umbilical cord blood of normal donors using Ficoll Hypaque (Pharmacia Biotech, Uppsala, Sweden) density centrifugation. CD34+ cells are immunomagnetically purified from mononuclear cells using either the progenitor or Multisort Kits (Miltenyi Biotec, Auburn, Calif.). Lin−CD38− cells are purified from the mononuclear cells using negative selection with StemSep system according to the manufacturer's protocol (Stem Cell Technologies, Vancouver, Calif.). Cells used for microinjecton are either freshly isolated or cryopreserved and cultured in Stem Medium (S Medium) for 2 to 5 days prior to microinjecton. S Medium contains Iscoves' Modified Dulbecco's Medium without phenol red (IMDM) with 100 μg/ml glutamine/penicillin/streptomycin, 50 mg/ml bovine serum albumin, 50 μg/ml bovine pancreatic insulin, 1 mg/ml human transferrin, and IMDM; Stem Cell Technologies), 40 μg/ml low-density lipoprotein (LDL; Sigma, St. Louis, Mo.), 50 mM HEPEs buffer and 50 μM 2-mercaptoethanol, 20 ng/ml each of thrombopoietin, flt-3 ligand, stem cell factor and human IL-6 (Pepro Tech Inc., Rocky Hill, N.J.). After microinjection, cells are detached and transferred in bulk into wells of 48 well plates for culturing.

[0094] 35 mm dishes are coated overnight at 40° C. with 50 μg/ml Fibronectn (FN) fragment CH-296 (Retronectn; TaKaRa Biomedicals, Panvera, Madison, Wis.) in phosphate buffered saline and washed with IMDM containing glutamine/penicillin/streptomycin. 300 to 2000 cells are added to cloning rings and attached to the plates for 45 minutes at 37° C. prior to microinjecton. After incubation, cloning rings are removed and 2 ml of S Medium are added to each dish for microinjecton. Pulled injection needles with a range of 0.22μ to 0.3μ outer tip diameter are used. Cells are visualized with a microscope equipped with a temperature controlled stage set at 37° C. and injected using an electronically interfaced Eppendorf Micromanipulator and Transjector. Successfully injected cells are intact, alive and remain attached to the plate post injection. Molecules that are flourescently labeled allow determination of the amount of oligonucleotide delivered to the cells.

[0095] For in vitro erythropoiesis from Lin−CD38− cells, the procedure of Malik, 1998 can be used. Cells are cultured in ME Medium for 4 days and then cultured in E Medium for 3 weeks. Erythropoiesis is evident by glycophorin A expression as well as the presence of red color representing the presence of hemoglobin in the cultured cells. The injected cells are able to retain their proliferative capacity and the ability to generate myeloid and erythoid progeny. CD34+ cells can convert a normal A (βA) to sickle T (βS) mutation in the β-globin gene or can be altered using any of the oligonucleotides of the invention herein for correction or alteration of a normal gene to a mutant gene. Alternatively, stem cells can be isolated from blood of humans having genetic disease mutations and the oligonucleotides of the invention can be used to correct a defect or to modify genomes within those cells.

[0096] Alternatively, non-stem cell populations of cultured cells can be manipulated using any method known to those of skill in the art including, for example, the use of polycations, cationic lipids, liposomes, polyethylenimine (PEI), electroporaton, biolistcs, calcium phophate precipitation, or any other method known in the art.

[0097] Notes on the Tables Presented Below:

[0098] Each of the following tables presents, for the specified human gene, a plurality of mutations that are known to confer a clinically-relevant phenotype and, for each mutation, the oligonucleotides that can be used to correct the respective mutation site-specifically in the human genome according to the present invention.

[0099] The left-most column identifies each mutation and the clinical phenotype that the mutation confers.

[0100] For most entries, the mutation is identified at both the nucleic acid and protein level. At the amino acid level, mutations are presented according to the following standard nomenclature. The centered number identifies the position of the mutated codon in the protein sequence; to the left of the number is the wild type residue and to the right of the number is the mutant codon. Codon numbering is according to the Human Gene Mutation Database, Cardiff, Wales, UK (http://archive.uwcm.ac.uk/search/mg/allgenes). Terminator codons are shown as “TERM”. At the nucleic acid level, the entire triplet of the wild type and mutated codons is shown.

[0101] The middle column presents, for each mutation, four oligonucleotides capable of repairing the mutation site-specifically in the human genome or in cloned human DNA including human DNA in artificial chromosomes, episomes, plasmids, or other types of vectors. The oligonucleotides of the invention, however, may include any of the oligonucleotides sharing portions of the sequence of the 121 base sequence. Thus, oligonucleotides of the invention for each of the depicted targets may be 18, 19, 20 up to about 121 nucleotides in length. Sequence may be added non-symmetrically.

[0102] All oligonucleotides are presented, per convention, in the 5′ to 3′ orientation. The nucleotide that effects the change in the genome is underlined and presented in bold.

[0103] The first of the four oligonucleotides for each mutation is a 121 nt oligonucleotide centered about the repair nucleotide. The second oligonucleotide, its reverse complement, targets the opposite strand of the DNA duplex for repair. The third oligonucleotide is the minimal 17 nt domain of the first oligonucleotide, also centered about the repair nucleotide. The fourth oligonucleotide is the reverse complement of the third, and thus represents the minimal 17 nt domain of the second.

[0104] The third column of each table presents the SEQ ID NO: of the respective repair oligonucleotide.

EXAMPLE 4

Adenosine Deaminase (ADA)

[0105] Adenosine deaminase (ADA, EC 3.5.4.4) catalyses the deamination of adenosine and 2′-deoxyadenosine to inosine or 2′-deoxyinosine respectively. ADA deficiency has been identified as the metabolic basis for 20-30% of cases with recessively inherited severe combined immunodeficiency (SCID). Affected infants are subject to recurrent chronic viral, fungal, protozoal, and bacterial infections and frequently present with persistent diarrhea, failure to thrive and candidiasis. In patients homozygous for ADA deficiency, 2′-deoxyadenosine accumulating during the rapid turnover of cells rich in DNA is converted back to dATP, either by adenosine kinase or deoxycytidine kinase. Many hypotheses have been advanced to explain the specific toxicity to the immune system in ADA deficiency. The apparently selective accumulation of dATP in thymocytes and peripheral blood B cells, with resultant inhibition of ribonucleotide reductase and DNA synthesis is probably the principal mechanism.

[0106] The structural gene for ADA is encoded as a single 32 kb locus containing 12 exons. Studies of the molecular defect in ADA-deficient patients have shown that mRNA is usually detectable in normal or supranormal amounts. Specific base substitution mutations have been detected in the majority of cases with the complete deficiency. A C-to-T base substitution mutation in exon 11 accounts for a high proportion of these, whilst a few patents are homozygous for large deletions encompassing exon I. A common point mutation resulting in a heat-labile ADA has been characterised in some patients with partial ADA deficiency, a disorder with an apparently increased prevalence in the Caribbean.

[0107] As yet no totally effective therapy for ADA deficiency has been reported, except in those few cases where bone marrow from an HLA/MLR compatible sibling donor was available.

[0108] Two therapeutic approaches have provided long-term benefit in specific instances. First, reconstitution using T cell depleted mismatched sibling marrow has been encouraging, particularly in early presenters completely deficient in ADA. Secondly, therapy with polyethylene glycol-modified adenosine deaminase (PEG-ADA) for more than 5 years has produced a sustained increase in lymphocyte numbers and mitogen responses together with evidence of in vivo B cell function. Success has generally been achieved in late presenters with residual ADA activity in mononuclear cells.

[0109] ADA deficiency has been chosen as the candidate disease for gene replacement therapy and the first human experiment commenced in 1990. The clinical consequences of overexpression of ADA activity—one of the potential hazards of gene implant—are known and take the form of an hereditary haemolytic anaemia associated with a tissue-specific increase in ADA activity. The genetic basis for the latter autosomal dominant disorder seemingly relates to markedly increased levels of structurally normal ADA mRNA.

TABLE 10
ADA Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Adenosine deaminase	AGAGACCCACCGAGCGGCGGCGGAGGGAGCAGCGCCGGGG	1
deficiency	CGCACGAGGGCACCATGGCCCAGACGCCCGCCTTCGACAAG
GLN3TERM	CCCAAAGTGAGCGCGCGCGGGGGCTCCGGGGACGGGGGTC
CAG to TAG
	GACCCCCGTCCCCGGAGCCCCCGCGCGCGCTCACTTTGGG	2
	CTTGTCGAAGGCGGGCGTCTGGGCCATGGTGCCCTCGTGCG
	CCCCGGCGCTGCTCCCTCCGCCGCCGCTCGGTGGGTCTCT
	CCATGGCCCAGACGCCC	3
	GGGCGTCTGGGCCATGG	4
Adenosine deaminase	TATTTGTTCTCTCTCTCCCTTTCTCTCTCTCTTCCCCCTGCCC	5
deficiency	CCTTGCAGGTRAGAACTGCATGTCCACCTAGACGGATCCATCA
HIS15ASP	AGCCTGAAACCATCTTATACTATGGCAGGTAAGTCC
CAT to GAT
	GGACTTACCTGCCATAGTATAAGATGGTTTCAGGCTTGATGGA	6
	TCCGTCTAGGTGGACATGCAGTTCTACCTGCAAGGGGGCAG
	GGGGAAGAGAGAGAGAAAGGGAGAGAGAGAACAAATA
	TAGAACTGCATGTCCAC	7
	GTGGACATGCAGTTCTA	8
Adenosine deaminase	TCCCTTTCTCTCTCTCTTCCCCCTGCCCCCTTGCAGGTAGAA	9
deficiency	CTGCATGTCCACCTAGACGGATCCATCAAGCCTGAAACCATC
GLY20ARG	TTATACTATGGCAGGTAAGTCCATACAGAAGAGCCCT
GGA to AGA
	AGGGCTCTTCTGTATGGACTTACCTGCCATAGTATAAGATGGT	10
	TTCAGGCTTGATGGATCCGTCTAGGTGGACATGCAGTTCTAC
	CTGCAAGGGGGCAGGGGGAAGAGAGAGAGAAAGGGA
	ACCTAGACGGATCCATC	11
	GATGGATCCGTCTAGGT	12
Adenosine deaminase	CCTGGAGCTCCCAAGGGACTTGGGGAAGGTTGTTCCCAACC	13
deficiency	CCTTTCTTCCCTTCCCAGGGGCTGCCGGGAGGCTATCAAAAG
GLY74CYS	GATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGG
GGC to GGC
	CCTCTTTGGCCTTCATCTCTACAAACTCATAGGCGATCCTTTT	14
	GATAGCCTCCCGGCAGCCCCTGGGAAGGGAAGAAAGGGGTT
	GGGAACAACCTTCCCCAAGTCCCTTGGGAGCTCCAGG
	CTATCGCGGGCTGCCGG	15
	CCGGCAGCCCGCGATAG	16
Adenosine Deaminase	GCTCCCAAGGGACTTGGGGAAGGTTGTTCCCAACCCCTTTCT	17
Deficiency	TCCCTTCCCAGGGGCTGCCGGGAGGCTATCAAAAGGATCGC
ARG76TRP	CTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCGTGG
CGG to TGG
	CCACGCCCTCTTTGGCCTTCATCTCTACAAACTCATAGGCGAT	18
	CCTTTTGATAGCCTCCCGGCAGCCCCTGGGAAGGGAAGAAA
	GGGGTTGGGAACAACCTTCCCCAAGTCCCTTGGGAGC
	GGGGCTGCCGGGAGGCT	19
	AGCCTCCCGGCAGCCCC	20
Adenosine Deaminase	TTGGGGAAGGTTGTTCCCAACCCCTTTCTTCCCTTCCCAGGG	21
Deficiency	GCTGCCGGGAGGCTATCAAAAGGATCGCCTATGAGTTTGTAG
LYS80ARG	AGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAGGT
AAA to AGA
	ACCTCCACATACACCACGCCCTCTTTGGCCTTCATCTCTACAA	22
	ACTCATAGGCGATCCTTTTGATAGCCTCCCGGCAGCCCCTGG
	GAAGGGAAGAAAGGGGTTGGGAACAACCTTCCCCAA
	GGCTATCAAAAGGATCG	23
	CGATCCTTTTGATAGCC	24
Adenosine deaminase	GTTGTTCCCAACCCCTTTCTTCCCTTCCCAGGGGCTGCCGGG	25
deficiency	AGGCTATCAAAAGGATCGCCTATGAGTTTGTAGAGATGAAGG
ALA83ASP	CCAAAGAGGGCGTGGTGTATGTGGAGGTGCGGTACAG
GCC to GAC
	CTGTACCGCACCTCCACATACACCACGCCCTCTTTGGCCTTC	26
	ATCTCTACAAACTCATAGGCGATCCTTTTGATAGCCTCCCGGC
	AGCCCCTGGGAAGGGAAGAAAGGGGTTGGGAACAAC
	AAGGATCGCCTATGAGT	27
	ACTCATAGGCGATCCTT	28
Adenosine deaminase	AGGCTATCAAAAGGATCGCCTATGAGTTTGTAGAGATGAAGG	29
deficiency	CCAAAGAGGGCGTGGTGTATGTGGAGGTGCGGTACAGTCCG
TYR97CYS	CACCTGCTGGCCAACTCCAAAGTGGAGCCAATCCCCTG
TAT to TGT
	CAGGGGATTGGCTCCACTTTGGAGTTGGCCAGCAGGTGCGG	30
	ACTGTACCGCACCTCCACATACACCACGCCCTCTTTGGCCTT
	CATCTCTACAAACTCATAGGCGATCCTTTTGATAGCCT
	CGTGGTGTATGTGGAGG	31
	CCTCCACATACACCACG	32
Adenosine deaminase	GGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCG	33
deficiency	TGGTGTATGTGGAGGTGCGGTACAGTCCGCACCTGCTGGCC
ARG101GLN	AACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCTGA
CGG to CAG
	TCAGCCTGGTTCCAGGGGATTGGCTCCACTTTGGAGTTGGCC	34
	AGCAGGTGCGGACTGTACCGCACCTCCACATACACCACGCC
	CTCTTTGGCCTTCATCTCTACAAACTCATAGGCGATCC
	GGAGGTGCGGTACAGTC	35
	GACTGTACCGCACCTCC	36
Adenosine deaminase	GGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCG	37
deficiency	TGGTGTATGTGGAGGTGCGGTACAGTCCGCACCTGCTGGCC
ARG101LEU	AACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCTGA
CGG to CTG
	TCAGCCTGGTTCCAGGGGATTGGCTCCACTTTGGAGTTGGCC	38
	AGCAGGTGCGGACTGTACCGCACCTCCACATACACCACGCC
	CTCTTTGGCCTTCATCTCTACAAACTCATAGGCGATCC
	GGAGGTGCGGTACAGTC	39
	GACTGTACCGCACCTCC	40
Adenosine deaminase	AGGATCGCCTATGAGTTTGTAGAGATGAAGGCCAAAGAGGGC	41
deficiency	GTGGTGTATGTGGAGGTGCGGTACAGTCCGCACCTGCTGGC
ARG101TRP	CAACTCCAAAGTGGAGCCAATCCCCTGGAACCAGGCTG
CGG to TGG
	CAGCCTGGTTCCAGGGGATTGGCTCCACTTTGGAGTTGGCCA	42
	GCAGGTGCGGACTGTACCGCACCTCCACATACACCACGCCC
	TCTTTGGCCTTCATCTCTACAAACTCATAGGCGATCCT
	TGGAGGTGCGGTACAGT	43
	ACTGTACCGCACCTCCA	44
Adenosine deaminase	ATGAGTTTGTAGAGATGAAGGCCAAAGAGGGCGTGGTGTATG	45
deficiency	TGGAGGTGCGGTACAGTCCGCACCTGCTGGCCAACTCCAAA
PRO104LEU	GTGGAGCCAATCCCCTGGAACCAGGCTGAGTGAGTGAT
CCG to CTG
	ATCACTCACTCAGCCTGGTTCCAGGGGATTGGCTCCACTTTG	46
	GAGTTGGCCAGCAGGTGCGGACTGTACCGCACCTCCACATA
	CACCACGCCCTCTTTGGCCTTCATCTCTACAAACTCAT
	GTACAGTCCGCACCTGC	47
	GCAGGTGCGGACTGTAC	48
Adenosine deaminase	TTTGTAGAGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAG	49
deficiency	GTGCGGTACAGTCCGCACCTGCTGGCCAACTCCAAAGTGGA
LEU106VAL	GCCAATCCCCTGGAACCAGGCTGAGTGAGTGATGGGCC
CTG to GTG
	GGCCCATCACTCACTCAGCCTGGTTCCAGGGGATTGGCTCCA	50
	CTTTGGAGTTGGCCAGCAGGTGCGGACTGTACCGCACCTCC
	ACATACACCACGCCCTCTTTGGCCTTCATCTCTACAAA
	GTCCGCACCTGCTGGCC	51
	GGCCAGCAGGTGCGGAC	52
Adenosine deaminase	TAGAGATGAAGGCCAAAGAGGGCGTGGTGTATGTGGAGGTG	53
deficiency	CGGTACAGTCCGCACCTGCTGGCCAACTCCAAAGTGGAGCC
LEU107PRO	AATCCCCTGGAACCAGGCTGAGTGAGTGATGGGCCTGGA
CTG to CCG
	TCCAGGCCCATCACTCACTCAGCCTGGTTCCAGGGGATTGGC	54
	TCCACTTTGGAGTTGGCCAGCAGGTGCGGACTGTACCGCAC
	CTCCACATACACCACGCCCTCTTTGGCCTTCATCTCTA
	GCACCTGCTGGCCAACT	55
	AGTTGGCCAGCAGGTGC	56
Adenosine deaminase	GCCTTCCTTTTGCCTCAGGCCCATCCCTACTCCTCTCCTCAC	57
deficiency	ACAGAGGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTG
PRO126GLN	GGCCAGGGCCTGCAGGAGGGGGAGCGAGACTTCGGGGT
CCA to CAA
	ACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCCCTGGCCCAC	58
	TAGGGCCACCACCTCGTCTGGGGTGAGGTCCCCTCTGTGTG
	AGGAGAGGAGTAGGGATGGGCCTGAGGCAAAAGGAAGGC
	CCTCACCCCAGACGAGG	59
	CCTCGTCTGGGGTGAGG	60
Adenosine deaminase	TTTGCCTCAGGCCCATCCCTACTCCTCTCCTCACACAGAGGG	61
deficiency	GACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCAGGG
TAL129MET	CCTGCAGGAGGGGGAGCGAGACTTCGGGGTCAAGGCCC
GTG to ATG
	GGGCCTTGACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCCC	62
	TGGCCCACTAGGGCCACCACCTCGTCTGGGGTGAGGTCCCC
	TCTGTGTGAGGAGAGGAGTAGGGATGGGCCTGAGGCAAA
	CAGACGAGGTGGTGGCC	63
	GGCCACCACCTCGTCTG	64
Adenosine deaminase	ACAGAGGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTG	65
deficiency	GGCCAGGGCCTGCAGGAGGGGGAGCGAGACTTCGGGGTCA
GLY140GLU	AGGCCCGGTCCATCCTGTGCTGCATGCGCCACCAGCCCAG
GGG to GAG
	CTGGGCTGGTGGCGCATGCAGCACAGGATGGACCGGGCCTT	66
	GACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCCCTGGCCCA
	CTAGGGCCACCACCTCGTCTGGGGTGAGGTCCCCTCTGT
	GCAGGAGGGGGAGCGAG	67
	CTCGCTCCCCCTCCTGC	68
Adenosine deaminase	GGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCAG	69
deficiency	GGCCTGCAGGAGGGGGAGCGAGACTTCGGGGTCAAGGCCC
ARG142GLN	GGTCCATCCTGTGCTGCATGCGCCACCAGCCCAGTGAGTA
CGA to CAA
	TACTCACTGGGCTGGTGGCGCATGCAGCACAGGATGGACCG	70
	GGCCTTGACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCCCT
	GGCCCACTAGGGCCACCACCTCGTCTGGGGTGAGGTCCC
	GGGGGAGCGAGACTTCG	71
	CGAAGTCTCGCTCCCCC	72
Adenosine deaminase	GGGGACCTCACCCCAGACGAGGTGGTGGCCCTAGTGGGCCA	73
deficiency	GGGCCTGCAGGAGGGGGAGCGAGACTTCGGGGTCAAGGCC
ARG142TERM	CGGTCCATCCTGTGCTGCATGCGCCACCAGCCCAGTGAGT
CGA to TGA
	ACTCACTGGGCTGGTGGCGCATGCAGCACAGGATGGACCGG	74
	GCCTTGACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCCCTG
	GCCCACTAGGGCCACCACCTCGTCTGGGGTGAGGTCCCC
	AGGGGGAGCGAGACTTC	75
	GAAGTCTCGCTCCCCCT	76
Adenosine deaminase	TGGTGGCCCTAGTGGGCCAGGGCCTGCAGGAGGGGGAGCG	77
deficiency	AGACTTCGGGGTCAAGGCCCGGTCCATCCTGTGCTGCATGC
ARG149GLN	GCCACCAGCCCAGTGAGTAGGATCACCGCCCTGCCCAGGG
CGG to CAG
	CCCTGGGCAGGGCGGTGATCCTACTCACTGGGCTGGTGGCG	78
	CATGCAGCACAGGATGGACCGGGCCTTGACCCCGAAGTCTC
	GCTCCCCCTCCTGCAGGCCCTGGCCCACTAGGGCCACCA
	CAAGGCCCGGTCCATCC	79
	GGATGGACCGGGCCTTG	80
Adenosine deaminase	GTGGTGGCCCTAGTGGGCCAGGGCCTGCAGGAGGGGGAGC	81
deficiency	GAGACTTCGGGGTCAAGGCCCGGTCCATCCTGTGCTGCATG
ARG149TRP	CGCCACCAGCCCAGTGAGTAGGATCACCGCCCTGCCCAGG
CGG to TGG
	CCTGGGCAGGGCGGTGATCCTACTCACTGGGCTGGTGGCGC	82
	ATGCAGCACAGGATGGACCGGGCCTTGACCCCGAAGTCTCG
	CTCCCCCTCCTGCAGGCCCTGGCCCACTAGGGCCACCAC
	TCAAGGCCCGGTCCATC	83
	GATGGACCGGGCCTTGA	84
Adenosine deaminase	CTAGTGGGCCAGGGCCTGCAGGAGGGGGAGCGAGACTTCG	85
deficiency	GGGTCAAGGCCCGGTCCATCCTGTGCTGCATGCGCCACCAG
LEU152MET	CCCAGTGAGTAGGATCACCGCCCTGCCCAGGGCCGCCCGT
CTG to ATG
	ACGGGCGGCCCTGGGCAGGGCGGTGATCCTACTCACTGGG	86
	CTGGTGGCGCATGCAGCACAGGATGGACCGGGCCTTGACCC
	CGAAGTCTCGCTCCCCCTCCTGCAGGCCCTGGCCCACTAG
	GGTCCATCCTGTGCTGC	87
	GCAGCACAGGATGGACC	88
Adenosine deaminase	GGCCTGCAGGAGGGGGAGCGAGACTTCGGGGTCAAGGCCC	89
deficiency	GGTCCATCCTGTGCTGCATGCGCCACCAGCCCAGTGAGTAG
ARG156CYS	GATCACCGCCCTGCCCAGGGCCGCCCGTCTCACCCTGGCC
CGC to TGC
	GGCCAGGGTGAGACGGGCGGCCCTGGGCAGGGCGGTGATC	90
	CTACTCACTGGGCTGGTGGCGCATGCAGCACAGGATGGACC
	GGGCCTTGACCCCGAAGTCTCGCTCCCCCTCCTGCAGGCC
	GCTGCATGCGCCACCAG	91
	CTGGTGGCGCATGCAGC	92
Adenosine deaminase	GCCTGCAGGAGGGGGAGCGAGACTTCGGGGTCAAGGCCCG	93
deficiency	GTCCATCCTGTGCTGCATGCGCCACCAGCCCAGTGAGTAGG
ARG156H1S	ATCACCGCCCTGCCCAGGGCCGCCCGTCTCACCCTGGCCC
CGC to CAC
	GGGCCAGGGTGAGACGGGCGGCCCTGGGCAGGGCGGTGAT	94
	CCTACTCACTGGGCTGGTGGCGCATGCAGCACAGGATGGAC
	CGGGCCTTGACCCCGAAGTCTCGCTCCCCCTCCTGCAGGC
	CTGCATGCGCCACCAGC	95
	GCTGGTGGCGCATGCAG	96
Adenosine deaminase	CTGCCCACAGACTGGTCCCCCAAGGTGGTGGAGCTGTGTAA	97
deficiency	GAAGTACCAGCAGCAGACCGTGGTAGCCATTGACCTGGCTG
VAL177MET	GAGATGAGACCATCCCAGGAAGCAGCCTCTTGCCTGGAC
GTG to ATG
	GTCCAGGCAAGAGGCTGCTTCCTGGGATGGTCTCATCTCCAG	98
	CCAGGTCAATGGCTACCACGGTCTGCTGCTGGTACTTCTTAC
	ACAGCTCCACCACCTTGGGGGACCAGTCTGTGGGCAG
	AGCAGACCGTGGTAGCC	99
	GGCTACCACGGTCTGCT	100
Adenosine deaminase	CAGACTGGTCCCCCAAGGTGGTGGAGCTGTGTAAGAAGTAC	101
deficiency	CAGCAGCAGACCGTGGTAGCCATTGACCTGGCTGGAGATGA
ALA179ASP	GACCATCCCAGGAAGCAGCCTCTTGCCTGGACATGTCCA
GCC to GAC
	TGGACATGTCCAGGCAAGAGGCTGCTTCCTGGGATGGTCTCA	102
	TCTCCAGCCAGGTCAATGGCTACCACGGTCTGCTGCTGGTAC
	TTCTTACACAGCTCCACCACCTTGGGGGACCAGTCTG
	CGTGGTAGCCATTGACC	103
	GGTCAATGGCTACCACG	104
Adenosine deaminase	CCATTGACCTGGCTGGAGATGAGACCATCCCAGGAAGCAGC	105
deficiency	CTCTTGCCTGGACATGTCCAGGCCTACCAGGTGGGTCCTGT
GLN199PRO	GAGAAGGAATGGAGAGGCTGGCCCTGGGTGAGCTTGTCT
CAG to CCG
	AGACAAGCTCACCCAGGGCCAGCCTCTCCATTCCTTCTCACA	106
	GGACCCACCTGGTAGGCCTGGACATGTCCAGGCAAGAGGCT
	GCTTCCTGGGATGGTCTCATCTCCAGCCAGGTCAATGG
	ACATGTCCAGGCCTACC	107
	GGTAGGCCTGGACATGT	108
Adenosine deaminase	GCTAGGGCACCCATGACCTGGCTCTCCCCCTTCCAGGAGGC	109
deficiency	TGTGAAGAGCGGCATTCACCGTACTGTCCACGCCGGGGAGG
ARG211CYS	TGGGCTCGGCCGAAGTAGTAAAAGAGGTGAGGGCCTGGG
CGT to TGT
	CCCAGGCCCTCACCTCTTTTACTACTTCGGCCGAGCCCACCT	110
	CCCCGGCGTGGACAGTACGGTGAATGCCGCTCTTCACAGCC
	TCCTGGAAGGGGGAGAGCCAGGTCATGGGTGCCCTAGC
	GCATTCACCGTACTGTC	111
	GACAGTACGGTGAATGC	112
Adenosine deaminase	CTAGGGCACCCATGACCTGGCTCTCCCCCTTCCAGGAGGCT	113
deficiency	GTGAAGAGCGGCATTCACCGTACTGTCCACGCCGGGGAGGT
ARG211HIS	GGGCTCGGCCGAAGTAGTAAAAGAGGTGAGGGCCTGGGC
CGT to CAT
	GCCCAGGCCCTCACCTCTTTTACTACTTCGGCCGAGCCCACC	114
	TCCCCGGCGTGGACAGTACGGTGAATGCCGCTCTTCACAGC
	CTCCTGGAAGGGGGAGAGCCAGGTCATGGGTGCCCTAG
	CATTCACCGTACTGTGC	115
	GGACAGTACGGTGAATG	116
Adenosine deaminase	ATGACCTGGCTCTCCCCCTTCCAGGAGGCTGTGAAGAGCGG	117
deficiency	CATTCACCGTACTGTCCACGCCGGGGAGGTGGGCTCGGCCG
ALA215THR	AAGTAGTAAAAGAGGTGAGGGCCTGGGCTGGCCATGGGG
GCC to ACC
	CCCCATGGCCAGCGCAGGCCCTCACCTCTTTTACTACTTCGG	118
	CCGAGCCCACCTCCCCGGCGTGGACAGTACGGTGAATGCCG
	CTCTTCACAGCCTCCTGGAAGGGGGAGAGCCAGGTCAT
	CTGTCCACGCCGGGGAG	119
	CTCCCCGGCGTGGACAG	120
Adenosine deaminase	ACCTGGCTCTCCCCCTTCCAGGAGGCTGTGAAGAGCGGCAT	121
deficiency	TCACCGTACTGTCCACGCCGGGGAGGTGGGCTCGGCCGAAG
GLY216ARG	TAGTAAAAGAGGTGAGGGCCTGGGCTGGCCATGGGGTCC
GGG to AGG
	GGACCCCATGGCCAGCCCAGGCCCTCACCTCTTTTACTACTT	122
	CGGCCGAGCCCACCTCCCCGGCGTGGACAGTACGGTGAATG
	CCGCTCTTCACAGCCTCCTGGAAGGGGGAGAGCCAGGT
	TCCACGCCGGGGAGGTG	123
	CACCTCCCCGGCGTGGA	124
Adenosine deaminase	TGGCTCTCCCCCTTCCAGGAGGCTGTGAAGAGCGGCATTCA	125
deficiency	CCGTACTGTCCACGCCGGGGAGGTGGGCTCGGCCGAAGTAG
GLU217LYS	TAAAAGAGGTGAGGGCCTGGGCTGGCCATGGGGTCCCTC
GAG to AAG
	GAGGGACCCCATGGCCAGCCCAGGCCCTCACCTCTTTTACTA	126
	CTTCGGCCGAGCCCACCTCCCCGGCGTGGACAGTACGGTGA
	ATGCCGCTCTTCACAGCCTCCTGGAAGGGGGAGAGCCA
	ACGCCGGGGAGGTGGGC	127
	GCCCACCTCCCCGGCGT	128
Adenosine deaminase	CTGCCTCCTCCCATACTTGGCTCTATTCTGCTTCTCTACAGGC	129
deficiency	TGTGGACATACTCAAGACAGAGCGGCTGGGACACGGCTACC
THR233ILE	ACACCCTGGAAGACCAGGCCCTTTATAACAGGCTGCG
ACA to ATA
	CGCAGCCTGTTATAAAGGGCCTGGTCTTCCAGGGTGTGGTAG	130
	CCGTGTCCCAGCCGCTCTGTCTTGAGTATGTCCACAGCCTGT
	AGAGAAGCAGAATAGAGCCAAGTATGGGAGGAGGCAG
	ACTCAAGACAGAGCGGC	131
	GCCGCTCTGTCTTGAGT	132
Adenosine deaminase	CAGAGCGGCTGGGACACGGCTACCACACCCTGGAAGACCAG	133
deficiency	GCCCTTTATAACAGGCTGCGGCAGGAAAACATGCACTTCGAG
ARG253PRO	GTAAGCGGGCCAGGGAGTGGGGAGGAACCATCCCCGGC
CGG to CCG
	GCCGGGGATGGTTCCTCCCCACTCCCTGGCCCGCTTACCTC	134
	GAAGTGCATGTTTTCCTGCCGCAGCCTGTTATAAAGGGCCTG
	GTCTTCCAGGGTGTGGTAGCCGTGTCCCAGCCGCTCTG
	CAGGCTGCGGCAGGAAA	135
	TTTCCTGCCGCAGCCTG	136
Adenosine deaminase	GAGCGGCTGGGACACGGCTACCACACCCTGGAAGACCAGGC	137
deficiency	CCTTTATAACAGGCTGCGGCAGGAAAACATGCACTTCGAGGT
GLN254TERM	AAGCGGGCCAGGGAGTGGGGAGGAACCATCCCCGGCTG
CAG to TAG
	CAGCCGGGGATGGTTCCTCCCCACTCCCTGGCCCGCTTACC	138
	TCGAAGTGCATGTTTTCCTGCCGCAGCCTGTTATAAAGGGCC
	TGGTCTTCCAGGGTGTGGTAGCCGTGTCCCAGCCGCTC
	GGCTGCGGCAGGAAAAC	139
	GTTTTCCTGCCGCAGCC	140
Adenosine deaminase	CCACACACCTGCTCTTCCAGATCTGCCCCTGGTCCAGCTACC	141
deficiency	TCACTGGTGCCTGGAAGCCGGACACGGAGCATGCAGTCATT
PRO274LEU	CGGTGAGCTCTGTTCCCCTGGGCCTGTTCAATTTTGTT
CCG to CTG
	AACAAAATTGAACAGGCCCAGGGGAACAGAGCTCACCGAATG	142
	ACTGCATGCTCCGTGTCCGGCTTCCAGGCACCAGTGAGGTA
	GCTGGACCAGGGGCAGATCTGGAAGAGCAGGTGTGTGG
	CTGGAAGCCGGACACGG	143
	CCGTGTCCGGCTTCCAG	144
Adenosine deaminase	GGAGGCTGATTCTCTCCTCCTCCCTCTTCTGCAGGCTCAAAA	145
deficiency	ATGACCAGGCTAACTACTCGCTCAACACAGATGACCCGCTCA
SER291LEU	TCTTCAAGTCCACCCTGGACACTGATTACCAGATGAC
TCG to TTG
	GTCATCTGGTAATCAGTGTCCAGGGTGGACTTGAAGATGAGC	146
	GGGTCATCTGTGTTGAGCGAGTAGTTAGCCTGGTCATTTTTGA
	GCCTGCAGAAGAGGGAGGAGGAGAGAATCAGCCTCC
	TAACTACTCGCTCAACA	147
	TGTTGAGCGAGTAGTTA	148
Adenosine deaminase	CCTCCCTCTTCTGCAGGCTCAAAAATGACCAGGCTAACTACT	149
deficiency	CGCTCAACACAGATGACCCGCTCATCTTCAAGTCCACCCTGG
PRO297GLN	ACACTGATTACCAGATGACCAAACGGGACATGGGCTT
CCG to CAG
	AAGCCCATGTCCCGTTTGGTCATCTGGTAATCAGTGTCCAGG	150
	GTGGACTTGAAGATGAGCGGGTCATCTGTGTTGAGCGAGTAG
	TTAGCCTGGTCATTTTTGAGCCTGCAGAAGAGGGAGG
	AGATGACCCGCTCATCT	151
	AGATGAGCGGGTCATCT	152
Adenosine deaminase	AAAATGACCAGGCTAACTACTCGCTCAACACAGATGACCCGC	153
deficiency	TCATCTTCAAGTCCACCCTGGACACTGATTACCAGATGACCAA
LEU304ARG	ACGGGACATGGGCTTTACTGAAGAGGAGTTTAAAAG
CTG to CGG
	CTTTTAAACTCCTCTTCAGTAAAGCCCATGTCCCGTTTGGTCA	154
	TCTGGTAATCAGTGTCCAGGGTGGACTTGAAGATGAGCGGGT
	CATCTGTGTTGAGCGAGTAGTTAGCCTGGTCATTTT
	GTCCACCCTGGACACTG	155
	CAGTGTCCAGGGTGGAC	156
Adenosine deaminase	GCCTTCTTTGTTCTCTGGTTCCATGTTGTCTGCCATTCTGGCC	157
deficiency	TTTCCAGAACATCAATGCGGCCAAATCTAGTTTCCTCCCAGAA
ALA329TAL	GATGAAAAGAGGGAGCTTCTCGACCTGCTCTATAA
C-to-T at base 1081
	TTATAGAGCAGGTCGAGAAGCTCCCTCTTTTCATCTTCTGGGA	158
	GGAAACTAGATTTGGCCGCATTGATGTTCTGGAAAGGCCAGA
	ATGGCAGACAACATGGAACCAGAGAACAAAGAAGGC
	CATCAATGCGGCCAAAT	159
	ATTTGGCCGCATTGATG	160

EXAMPLE 5

P53 Mutations

[0110] The p53 gene codes for a protein that acts as a transcription factor and serves as a key regulator of the cell cycle. Mutation in this gene is probably the most significant genetic change characterizing the transformation of cells from normalcy to malignancy.

[0111] Inactivation of p53 by mutation disrupts the cell cycle which, in turn, sets the stage for tumor formation. Mutations in the p53 gene are among the most commonly diagnosed genetic disorders, occuring in as many as 50% of cancer patients. For some types of cancer, most notably of the breast, lung and colon, p53 mutations are the predominant genetic alternations found thus far. These mutations are associated with genomic instability and thus an increased susceptibility to cancer. Some p53 lesions result in malignancies that are resistant to the most widely used therapeutic regimens and therefore demand more aggressive treatment.

[0112] That p53 is associated with different malignant tumors is illustrated in the Li-Fraumeni autosomal dominant hereditary disorder characterized by familial multiple tumors due to mutation in the p53 gene. Affected individuals can develop one or more tumors, including: brain (12%); soft-tissue sarcoma (12%); breast cancer (25%); adrenal tumors (1%); bone cancer (osteosarcoma) (6%); cancer of the lung, prostate, pancreas, and colon as well as lymphoma and melanoma can also occur.

[0113] Certain of the most frequently mutated codons are codons 175, 248 and 273, however a variety of oligonucleotides are described below in the atttached table.

TABLE 11
p53 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
In 2 families with	GACTGTACCACCATCCACTACAACTACATGTGTAACAGTTCCT	161
Li-Fraumeni	GCATGGGCGGCATGAACCGGAGGCCCATCCTCACCATCATC
syndrome, there was a	ACACTGGAAGACTCCAGGTCAGGAGCCACTTGCCACC
C-to-T mutation at the
first nucleotide of	GGTGGCAAGTGGCTCCTGACCTGGAGTCTTCCAGTGTGATGA	162
codon 248 which	TGGTGAGGATGGGCCTCCGGTTCATGCCGCCCATGCAGGAA
changed arginine to	CTGTTACACATGTAGTTGTAGTGGATGGTGGTACAGTC
tryptophan.	GCATGAACCGGAGGCCC	163
	GGGCCTCCGGTTCATGC	164
In a family with the	TGTAACAGTTCCTGCATGGGCGGCATGAACCGGAGGCCCAT	165
Li-Fraumeni	CCTCACCATCATCACACTGGAAGACTCCAGGTCAGGAGCCAC
syndrome, a G-to-A	TTGCCACCCTGCACACTGGCCTGCTGTGCCCCAGCCTC
mutation at the first
nucleotide of codon	GAGGCTGGGGCACAGCAGGCCAGTGTGCAGGGTGGCAAGT	166
258 resulting in the	GGCTCCTGACCTGGAGTCTTCCAGTGTGATGATGGTGAGGAT
substitution of lysine	GGGCCTCCGGTTCATGCCGCCCATGCAGGAACTGTTACA
for glutamic acid.
	TCACACTGGAAGACTCC	167
	GGAGTCTTCCAGTGTGA	168
In a family with the	GTTGGCTCTGACTGTACCACCATCCACTACAACTACATGTGTA	169
Li-Fraumeni	ACAGTTCCTGCATGGGCGGCATGAACCGGAGGCCCATCCTC
syndrome, a G-to-T	ACCATCATCACACTGGAAGACTCCAGGTCAGGAGCCA
mutation at
the first nucleotide of
codon 245 resulting in
the substitution of
cysteine for glycine.
A gly245-to-ser,	TGGCTCCTGACCTGGAGTCTTCCAGTGTGATGATGGTGAGGA	170
GGC-to-AGC,	TGGGCCTCCGGTTCATGCCGCCCATGCAGGAACTGTTACACA
mutation was found in	TGTAGTTGTAGTGGATGGTGGTACAGTCAGAGCCAAC
a patient in whom
osteosarcoma was	GCATGGGCGGCATGAAC	171
diagnosed at the age
of 18 years.	GTTCATGCCGCCCATGC	172
In a family with the	TCCACTACAACTACATGTGTAACAGTTCCTGCATGGGCGGCA	173
Li-Fraumeni	TGAACCGGAGGCCCATCCTCACCATCATCACACTGGAAGACT
syndrome, a germline	CCAGGTCAGGAGCCACTTGCCACCCTGCACACTGGCC
mutation at codon 252:
a T-to-C change at the	GGCCAGTGTGCAGGGTGGCAAGTGGCTCCTGACCTGGAGTC	174
second position	TTCCAGTGTGATGATGGTGAGGATGGGCCTCCGGTTCATGCC
resulted in substitution	GCCCATGCAGGAACTGTTACACATGTAGTTGTAGTGGA
of proline for leucine.
	GCCCATCCTCACCATCA	175
	TGATGGTGAGGATGGGC	176
Researchers analyzed	TACCACCATCCACTACAACTACATGTGTAACAGTTCCTGCATG	177
for mutations in p53	GGCGGCATGAACCGGAGGCCCATCCTCACCATCATCACACT
hepatocellular	GGAAGACTCCAGGTCAGGAGCCACTTGCCACCCTGCA
carcinomas from
patents in Qidong, an	TGCAGGGTGGCAAGTGGCTCCTGACCTGGAGTCTTCCAGTG	178
area of high incidence	TGATGATGGTGAGGATGGGCCTCCGGTTCATGCCGCCCATG
in China, in which both	CAGGAACTGTTACACATGTAGTTGTAGTGGATGGTGGTA
hepatitis B virus and
aflatoxin B1 are risk	AACCGGAGGCCCATCCT	179
factors. Eight of 16
tumors had a point	AGGATGGGCCTCCGGTT	180
mutation at the third
base position of codon
249. The G-to-T
mutation at codon 249
led to a change from
arginine to serine
(AGG to AGT).
In cases of	CTGGCCAAGACCTGCCCTGTGCAGCTGTGGGTTGATTCCACA	181
hepatocellular	CCCCCGCCCGGCACCCGCGTCCGCGCCATGGCCATCTACAA
carcinoma in southern	GCAGTCACAGCACATGACGGAGGTTGTGAGGCGCTGCC
Africa, a G-to-T
substitution in codon	GGCAGCGCCTCACAACCTCCGTCATGTGCTGTGACTGCTTGT	182
157 resulting in a	AGATGGCCATGGCGCGGACGCGGGTGCCGGGCGGGGGTGT
change from valine to	GGAATCAACCCACAGCTGCACAGGGCAGGTCTTGGCCAG
phenylahanine.
	GCACCCGCGTCCGCGCC	183
	GGCGCGGACGCGGGTGC	184
In a family with	TTGGCTCTGACTGTACCACCATCCACTACAACTACATGTGTAA	185
Li-Fraumeni in which	CAGTTCCTGCATGGGCGGCATGAACCGGAGGCCCATCCTCA
noncancerous skin	CCATCATCACACTGGAAGACTCCAGGTCAGGAGCCAC
fibroblasts from
affected individuals	GTGGCTCCTGACCTGGAGTCTTCCAGTGTGATGATGGTGAGG	186
showed an unusual	ATGGGCCTCCGGTTCATGCCGCCCATGCAGGAACTGTTACAC
radiation-resistant	ATGTAGTTGTAGTGGATGGTGGTACAGTCAGAGCCAA
phenotype, a point
mutation in codon 245	CATGGGCGGCATGAACC	187
of the P53 gene. A
change from GGC to	GGTTCATGCCGCCCATG	188
GAC predicted
substitution of aspartic
acid for glycine.
In 2 of 8 families with	ACTGTACCACCATCCACTACAACTACATGTGTAACAGTTCCTG	189
Li-Fraumeni	CATGGGCGGCATGAACCGGAGGCCCATCCTCACCATCATCA
syndrome, a mutation	CACTGGAAGACTCCAGGTCAGGAGCCACTTGCCACCC
in codon 248: a	GGGTGGCAAGTGGCTCCTGACCTGGAGTCTTCCAGTGTGAT	190
CGG-to-CAG change	GATGGTGAGGATGGGCCTCCGGTTCATGCCGCCCATGCAGG
resulting in substitution	AACTGTTACACATGTAGTTGTAGTGGATGGTGGTACAGT
of glutamine for	CATGAACCGGAGGCCCA	191
arginine.	TGGGCCTCCGGTTCATG	192
In 9 members of an	CCCTGACTTTCAACTCTGTCTCCTTCCTCTTCCTACAGTACTC	193
extended family with	CCCTGCCCTCAACAAGATGTTTTGCCAACTGGCCAAGACCTG
Li-Fraumeni	CCCTGTGCAGCTGTGGGTTGATTCCACACCCCCGCC
syndrome, a germline
mutation at codon 133	GGCGGGGGTGTGGAATCAACCCACAGCTGCACAGGGCAGGT	194
(ATG-to-ACG),	CTTGGCCAGTTGGCAAAACATCTTGTTGAGGGCAGGGGAGTA
resulted in the	CTGTAGGAAGAGGAAGGAGACAGAGTTGAAAGTCAGGG
substitution of
threonine for	CAACAAGATGTTTTGCC	195
methionine (M133T),
and completely	GGCAAAACATCTTGTTG	196
cosegregated with the
cancer syndrome.
In 1 pedigree	TCTTGCTTCTCTTTTCCTATCCTGAGTAGTGGTAATCTACTGG	197
consistent with the	GACGGAACAGCTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGA
Li-Fraumeni	GAGACCGGCGCACAGAGGAAGAGAATCTCCGCAAGA
syndrome, a germline
G-to-T transversion at	TCTTGCGGAGATTCTCTTCCTCTGTGCGCCGGTCTCTCCCAG	198
codon 272 (valine to	GACAGGCACAAACACGCACCTCAAAGCTGTTCCGTCCCAGTA
leucine) was found.	GATTACCACTACTCAGGATAGGAAAAGAGAAGCAAGA
	GCTTTGAGGTGCGTGTT	199
	AACACGCACCTCAAAGC	200
A ser241-to-phe	TTATCTCCTAGGTTGGCTCTGACTGTACCACCATCCACTACAA	201
mutation due to a	CTACATGTGTAACAGTTCCTGCATGGGCGGCATGAACCGGAG
TCC-to-TTC change	GCCCATCCTCACCATCATCACACTGGAAGACTCCAG
was found in a patient
with hepatoblastoma	CTGGAGTCTTCCAGTGTGATGATGGTGAGGATGGGCCTCCG	202
and multiple foci of	GTTCATGCCGCCCATGCAGGAACTGTTACACATGTAGTTGTA
osteosarcoma.	GTGGATGGTGGTACAGTCAGAGCCAACCTAGGAGATAA
	TAACAGTTCCTGCATGG	203
	CCATGCAGGAACTGTTA	204
An AAG-to-TAG	CAGAAAACCTACCAGGGCAGCTACGGTTTCCGTCTGGGCTTC	205
change of codon 120,	TTGCATTCTGGGACAGCCAAGTCTGTGACTTGCACGGTCAGT
resulting in conversion	TGCCCTGAGGGGCTGGCTTCCATGAGACTTCAATGCC
from lysine to a stop
codon, was found in a	GGCATTGAAGTCTCATGGAAGCCAGCCCCTCAGGGCAACTG	206
patient with	ACCGTGCAAGTCACAGACTTGGCTGTCCCAGAATGCAAGAAG
osteosarcoma and	CCCAGACGGAAACCGTAGCTGCCCTGGTAGGTTTTCTG
adenocarcinoma of
the lung at age 18 and	GGACAGCCAAGTCTGTG	207
brain tumor (glioma) at
the age of 27.	CACAGACTTGGCTGTCC	208
A CGG-to-TGG	GGTAATCTACTGGGACGGAACAGCTTTGAGGTGCGTGTTTGT	209
change at codon 282,	GCCTGTCCTGGGAGAGACCGGCGCACAGAGGAAGAGAATCT
resulting in the	CCGCAAGAAAGGGGAGCCTCACCACGAGCTGCCCCCAG
substitution of
tryptophan for arginine,	CTGGGGGCAGCTCGTGGTGAGGCTCCCCTTTCTTGCGGAGA	210
was found in a	TTCTCTTCCTCTGTGCGCCGGTCTCTCCCAGGACAGGCACAA
patient who developed	ACACGCACCTCAAAGCTGTTCCGTCCCAGTAGATTACC
osteosarcoma at the
age of 10 years.	GGAGAGACCGGCGCACA	211
	TGTGCGCCGGTCTCTCC	212
In 5 of 6 anaplastic	GCTTCTCTTTTCCTATCCTGAGTAGTGGTAATCTACTGGGACG	213
carcinomas of the	GAACAGCTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGAGAGA
thyroid and in an	CCGGCGCACAGAGGAAGAGAATCTCCGCAAGAAAGG
anaplastic carcinoma
thyroid cell line ARO, a	CCTTTCTTGCGGAGATTCTCTTCCTCTGTGCGCCGGTCTCTC	214
CGT-to-CAT mutation	CCAGGACAGGCACAAACACGCACCTCAAAGCTGTTCCGTCCC
converted	AGTAGATTACCACTACTCAGGATAGGAAAAGAGAAGC
arginine-273 to
histidine.	TGAGGTGCGTGTTTGTG	215
	CACAAACACGCACCTCA	216
A germline	TCCTAGCACTGCCCAACAACACCAGCTCCTCTCCCCAGCCAA	217
GGA-to-GTA mutation	AGAAGAAACCACTGGATGGAGAATATTTCACCCWTCAGGTACT
resulting in a change	AAGTCTTGGGACCTCTTATCAAGTGGAAAGTTTCCA
of
glycine-325 to valine	TGGAAACTTTCCACTTGATAAGAGGTCCCAAGACTTAGTACCT	218
was found in a patient	GAAGGGTGAAATATTCTCCATCCAGTGGTTTCTTCTTTGGCTG
who had non-Hodgkin	GGGAGAGGAGCTGGTGTTGTTGGGCAGTGCTAGGAA
lymphoma diagnosed
at age 17 and colon	ACTGGATGGAGAATATT	219
carcinoma at age 26.
	AATATTCTCCATCCAGT	220
CGC-CCC	AATGGTTCACTGAAGACCCAGGTCCAGATGAAGCTCCCAGAA	221
Arg-72 to Pro	TGCCAGAGGCTGCTCCCCGCGTGGCCCCTGCACCAGCAGCT
association with Lung	CCTACACCGGCGGCCCCTGCACCAGCCCCCTCCTGGCC
cancer
	GGCCAGGAGGGGGCTGGTGCAGGGGCCGCCGGTGTAGGAG	222
	CTGCTGGTGCAGGGGCCACGCGGGGAGCAGCCTCTGGCATT
	CTGGGAGCTTCATCTGGACCTGGGTCTTCAGTGAACCATT
	TGCTCCCCGCGTGGCCC	223
	GGGCCACGCGGGGAGCA	224
CCG-CTG	AAGCTCCCAGAATGCCAGAGGCTGCTCCCCGCGTGGCCCCT	225
Pro-82 to Leu	GCACCAGCAGCTCCTACACCGGCGGCCCCTGCACCAGCCCC
Breast cancer	CTCCTGGCCCCTGTCATCTTCTGTCCCTTCCCAGAAAAC
	GTTTTCTGGGAAGGGACAGAAGATGACAGGGGCCAGGAGGG	226
	GGCTGGTGCAGGGGCCGCCGGTGTAGGAGCTGCTGGTGCA
	GGGGCCACGCGGGGAGCAGCCTCTGGCATTCTGGGAGCTT
	TCCTACACCGGCGGCCC	227
	GGGCCGCCGGTGTAGGA	228
cCAA-TAA	TTCAACTCTGTCTCCTTCCTCTTCCTACAGTACTCCCCTGCCC	229
Gln-136 to Term	TCAACAAGATGTTTTGCCAACTGGCCAAGACCTGCCCTGTGC
Li-Fraumeni syndrome	AGCTGTGGGTTGATTCCACACCCCCGCCCGGCACCC
	GGGTGCCGGGCGGGGGTGTGGAATCAACCCACAGCTGCACA	230
	GGGCAGGTCTTGGCCAGTTGGCAAAACATCTTGTTGAGGGCA
	GGGGAGTACTGTAGGAAGAGGAAGGAGACAGAGTTGAA
	TGTTTTGCCAACTGGCC	231
	GGCCAGTTGGCAAAACA	232
TGC-TAC	TCCTCTTCCTACAGTACTCCCCTGCCCTCAACAAGATGTTTTG	233
Cys-141 to Tyr	CCAACTGGCCAAGACCTGCCCTGTGCAGCTGTGGGTTGATTC
Li-Fraumeni syndrome	CACACCCCCGCCCGGCACCCGCGTCCGCGCCATGGC
	GCCATGGCGCGGACGCGGGTGCCGGGCGGGGGTGTGGAAT	234
	CAACCCACAGCTGCACAGGGCAGGTCTTGGCCAGTTGGCAA
	AACATCTTGTTGAGGGCAGGGGAGTACTGTAGGAAGAGGA
	CAAGACCTGCCCTGTGC	235
	GCACAGGGCAGGTCTTG	236
aCCC-TCC	AACAAGATGTTTTGCCAACTGGCCAAGACCTGCCCTGTGCAG	237
Pro-151 to Ser	CTGTGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCG
Li-Fraumeni syndrome	CGCCATGGCCATCTACAAGCAGTCACAGCACATGACGG
	CCGTCATGTGCTGTGACTGCTTGTAGATGGCCATGGCGCGG	238
	ACGCGGGTGCCGGGCGGGGGTGTGGAATCAACCCACAGCT
	GCACAGGGCAGGTCTTGGCCAGTTGGCAAAACATCTTGTT
	ATTCCACACCCCCGCCC	239
	GGGCGGGGGTGTGGAAT	240
CCG-CTG	AGATGTTTTGCCAACTGGCCAAGACCTGCCCTGTGCAGCTGT	241
Pro-152 to Leu	GGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCGCGCC
Adrenocortical	ATGGCCATCTACAAGCAGTCACAGCACATGACGGAGGT
carcinoma
	ACCTCCGTCATGTGCTGTGACTGCTTGTAGATGGCCATGGCG	242
	CGGACGCGGGTGCCGGGCGGGGGTGTGGAATCAACCCACA
	GCTGCACAGGGCAGGTCTTGGCCAGTTGGCAAAACATCT
	CACACCCCCGCCCGGCA	243
	TGCCGGGCGGGGGTGTG	244
GGC-GTC	TTTGCCAACTGGCCAAGACCTGCCCTGTGCAGCTGTGGGTTG	245
Gly-154 to Val	ATTCCACACCCCCGCCCGGCACCCGCGTCCGCGCCATGGCC
Glioblastoma	ATCTACAAGCAGTCACAGCACATGACGGAGGTTGTGAG
	CTCACAACCTCCGTCATGTGCTGTGACTGCTTGTAGATGGCC	246
	ATGGCGCGGACGCGGGTGCCGGGCGGGGGTGTGGAATCAA
	CCCACAGCTGCACAGGGCAGGTCTTGGCCAGTTGGCAAA
	CCCGCCCGGCACCCGCG	247
	CGCGGGTGCCGGGCGGG	248
CGC-CAC	CCCGCGTCCGCGCCATGGCCATCTACAAGCAGTCACAGCAC	249
Arg-175 to His	ATGACGGAGGTTGTGAGGCGCTGCCCCCACCATGAGCGCTG
Li-Fraumeni syndrome	CTCAGATAGCGATGGTGAGCAGCTGGGGCTGGAGAGACG
	CGTCTCTCCAGCCCCAGCTGCTCACCATCGCTATCTGAGCAG	250
	CGCTCATGGTGGGGGCAGCGCCTCACAACCTCCGTCATGTG
	CTGTGACTGCTTGTAGATGGCCATGGCGCGGACGCGGG
	TGTGAGGCGCTGCCCCC	251
	GGGGGCAGCGCCTCACA	252
tGAG-AAG	ATGGCCATCTACAAGCAGTCACAGCACATGACGGAGGTTGTG	253
GTu-180 to Lys	AGGCGCTGCCCCCACCATGAGCGCTGCTCAGATAGCGATGG
Li-Fraumeni syndrome	TGAGCAGCTGGGGCTGGAGAGACGACAGGGCTGGTTGC
	GCAACCAGCCCTGTCGTCTCTCCAGCCCCAGCTGCTCACCAT	254
	CGCTATCTGAGCAGCGCTCATGGTGGGGGCAGCGCCTCACA
	ACCTCCGTCATGTGCTGTGACTGCTTGTAGATGGCCAT
	CCCACCATGAGCGCTGC	255
	GCAGCGCTCATGGTGGG	256
gCGC-TGC	GCCATCTACAAGCAGTCACAGCACATGACGGAGGTTGTGAGG	257
Arg-181 to Cys	CGCTGCCCCCACCATGAGCGCTGCTCAGATAGCGATGGTGA
Breast cancer	GCAGCTGGGGCTGGAGAGACGACAGGGCTGGTTGCCCA
	TGGGCAACCAGCCCTGTCGTCTCTCCAGCCCCAGCTGCTCA	258
	CCATCGCTATCTGAGCAGCGCTCATGGTGGGGGCAGCGCCT
	CACAACCTCCGTCATGTGCTGTGACTGCTTGTAGATGGC
	ACCATGAGCGCTGCTCA	259
	TGAGCAGCGCTCATGGT	260
CGC-CAC	CCATCTACAAGCAGTCACAGCACATGACGGAGGTTGTGAGGC	261
Arg-81 to His	GCTGCCCCCACCATGAGCGCTGCTCAGATAGCGATGGTGAG
Breast cancer	CAGCTGGGGCTGGAGAGACGACAGGGCTGGTTGCCCAG
	CTGGGCAACCAGCCCTGTCGTCTCTCCAGCCCCAGCTGCTC	262
	ACCATCGCTATCTGAGCAGCGCTCATGGTGGGGGCAGCGCC
	TCACAACCTCCGTCATGTGCTGTGACTGCTTGTAGATGG
	CCATGAGCGCTGCTCAG	263
	CTGAGCAGCGCTCATGG	264
0
CAT-CGT	CCAGGGTCCCCAGGCCTCTGATTCCTCACTGATTGCTCTTAG	265
His-193 to Arg	GTCTGGCCCCTCCTCAGCATCTTATCCGAGTGGAAGGAAATT
Li-Fraumeni syndrome	TGCGTGTGGAGTATTTGGATGACAGAAACACTTTTCG
	CGAAAAGTGTTTCTGTCATCCAAATACTCCACACGCAAATTTC	266
	CTTCCACTCGGATAAGATGCTGAGGAGGGGCCAGACCTAAGA
	GCAATCAGTGAGGAATCAGAGGCCTGGGGACCCTGG
	TCCTCAGCATCTTATCC	267
	GGATAAGATGCTGAGGA	268
cCGA-TGA	CCCAGGCCTCTGATTCCTCACTGATTGCTCTTAGGTCTGGCC	269
Arg-196 to Term	CCTCCTCAGCATCTTATCCGAGTGGAAGGAAATTTGCGTGTG
Adrenocortical	GAGTATTTGGATGACAGAAACACTTTTCGACATAGTG
carcinoma
	CACTATGTCGAAAAGTGTTTCTGTCATCCAAATACTCCACACG	270
	CAAATTTCCTTCCACTCGGATAAGATGCTGAGGAGGGGCCAG
	ACCTAAGAGCAATCAGTGAGGAATCAGAGGCCTGGG
	ATCTTATCCGAGTGGAA	271
	TTCCACTCGGATAAGAT	272
cAGA-TGA	GCCCCTCCTCAGCATCTTATCCGAGTGGAAGGAAATTTGCGT	273
Arg-209 to Term	GTGGAGTATTTGGATGACAGAAACACTTTTCGACATAGTGTG
Li-Fraumeni syndrome	GTGGTGCCCTATGAGCCGCCTGAGGTCTGGTTTGCAA
	TTGCAAACCAGACCTCAGGCGGCTCATAGGGCACCACCACA	274
	CTATGTCGAAAAGTGTTTCTGTCATCCAAATACTCCACACGCA
	AATTTCCTTCCACTCGGATAAGATGCTGAGGAGGGGC
	TGGATGACAGAAACACT	275
	AGTGTTTCTGTCATCCA	276
tCGA-TGA	CATCTTATCCGAGTGGAAGGAAATTTGCGTGTGGAGTATTTG	277
Arg-213 to Term	GATGACAGAAACACTTTTCGACATAGTGTGGTGGTGCCCTAT
Li-Fraumeni syndrome	GAGCCGCCTGAGGTCTGGTTTGCAACTGGGGTCTCTG
	CAGAGACCCCAGTTGCAAACCAGACCTCAGGCGGCTCATAG	278
	GGCACCACCACACTATGTCGAAAAGTGTTTCTGTCATCCAAAT
	ACTCCACACGCAAATTTCCTTCCACTCGGATAAGATG
	ACACTTTTCGACATAGT	279
	ACTATGTCGAAAAGTGT	280
gCCC-TCC	GGAAATTTGCGTGTGGAGTATTTGGATGACAGAAACACTTTTC	281
Pro-219 to Ser	GACATAGTGTGGTGGTGCCCTATGAGCCGCCTGAGGTCTGG
Adrenocortical	TTTGCAACTGGGGTCTCTGGGAGGAGGGGTTAAGGGT
carcinoma
	ACCCTTAACCCCTCCTCCCAGAGACCCCAGTTGCAAACCAGA	282
	CCTCAGGCGGCTCATAGGGCACCACCACACTATGTCGAAAAG
	TGTTTCTGTCATCCAAATACTCCACACGCAAATTTCC
	TGGTGGTGCCCTATGAG	283
	CTCATAGGGCACCACCA	284
TAT-TGT	ATTTGCGTGTGGAGTATTTGGATGACAGAAACACTTTTCGACA	285
Tyr-220 to Cys	TAGTGTGGTGGTGCCCTATGAGCCGCCTGAGGTCTGGTTTG
Li-Fraumeni syndrome	CAACTGGGGTCTCTGGGAGGAGGGGTTAAGGGTGGTT
	AACCACCCTTAACCCCTCCTCCCAGAGACCCCAGTTGCAAAC	286
	CAGACCTCAGGCGGCTCATAGGGCACCACCACACTATGTCG
	AAAAGTGTTTCTGTCATCCAAATACTCCACACGCAAAT
	GGTGCCCTATGAGCCGC	287
	GCGGCTCATAGGGCACC	288
cTCT-ACT	CACAGGTCTCCCCAAGGCGCACTGGCCTCATCTTTGGGCCTG	289
Ser-227 to Thr	TGTTATCTCCTAGGTTGGCTCTGACTGTACCACCATCCACTAC
Rhabdomyosarcoma	AACTACATGTGTAACAGTTCCTGCATGGGCGGCATGA
	TCATGCCGCCCATGCAGGAACTGTTACACATGTAGTTGTAGT	290
	GGATGGTGGTACAGTCAGAGCCAACCTAGGAGATAACACAG
	GCCCAAGATGAGGCCAGTGCGCCTTGGGGAGACCTGTG
	AGGTTGGCTCTGACTGT	291
	ACAGTCAGAGCCAACCT	292
cCAC-AAC	GCACTGGCCTCATCTTGGGCCTGTGTTATCTCCTAGGTTGGC	293
His-233 to Asn	TCTGACTGTACCACCATCCACTACAACTACATGTGTAACAGTT
Glioma	CCTGCATGGGCGGCATGAACCGGAGGCCCATCCTCA
	TGAGGATGGGCCTCCGGTTCATGCCGCCCATGCAGGAACTG	294
	TTACACATGTAGTTGTAGTGGATGGTGGTACAGTCAGAGCCA
	ACCTAGGAGATAACACAGGCCCAAGATGAGGCCAGTGC
	CCACCATCCACTACAAC	295
	GTTGTAGTGGATGGTGG	296
cAAC-GAC	GCCTCATCTTGGGCCTGTGTTATCTCCTAGGTTGGCTCTGAC	297
Asn-235 to Asp	TGTACCACCATCCACTACAACTACATGTGTAACAGTTCCTGCA
Adrenocortical	TGGGCGGCATGAACCGGAGGCCCATCCTCACCATCA
carcinoma
	TGATGGTGAGGATGGGCCTCCGGTTCATGCCGCCCATGCAG	298
	GAACTGTTACACATGTAGTTGTAGTGGATGGTGGTACAGTCA
	GAGCCAACCTAGGAGATAACACAGGCCCAAGATGAGGC
	TCCACTACAACTACATG	299
	CATGTAGTTGTAGTGGA	300
AAC-AGC	CCTCATCTTGGGCCTGTGTTATCTCCTAGGTTGGCTCTGACT	301
Asn-235 to Ser	GTACCACCATCCACTACAACTACATGTGTAACAGTTCCTGCAT
Rhabdomyosarcoma	GGGCGGCATGAACCGGAGGCCCATCCTCACCATCAT
	ATGATGGTGAGGATGGGCCTCCGGTTTCATGCCGCCCATGCA	302
	GGAACTGTTACACATGTAGTTGTAGTGGATGGTGGTACAGTC
	AGAGCCAACCTAGGAGATAACACAGGCCCAAGATGAGG
	CCACTACAACTACATGT	303
	ACATGTAGTTGTAGTGG	304
ATCc-ATG	CATCCACTACAACTACATGTGTAACAGTTCCTGCATGGGCGG	305
Ile-251 to Met	CATGAACCGGAGGCCCATCCTCACCATCATCACACTGGAAGA
Glioma	CTCCAGGTCAGGAGCCACTTGCCACCCTGCACACTGG
	CCAGTGTGCAGGGTGGCAAGTGGCTCCTGACGTGGAGTCTT	306
	CCAGTGTGATGATGGTGAGGATGGGCCTCCGGTTCATGCCG
	CCCATGCAGGAACTGTTACACATGTAGTTGTAGTGGATG
	AGGCCCATCCTCACCAT	307
	ATGGTGAGGATGGGCCT	308
ACA-ATA	ACATGTGTAACAGTTCCTGCATGGGCGGCATGAACCGGAGG	309
Thr-256 to Ile	CCCATCCTCACCATCATCACACTGGAAGACTCCAGGTCAGGA
Glioblastoma	GCCACTTGCCACCCTGCACACTGGCCTGCTGTGCCCCA
	TGGGGCACAGCAGGCCAGTGTGCAGGGTGGCAAGTGGCTCC	310
	TGACCTGGAGTCTTCCAGTGTGATGATGGTGAGGATGGGCCT
	CCGGTTCATGCCGCCCATGCAGGAACTGTTACACATGT
	CATCATCACACTGGAAG	311
	CTTCCAGTGTGATGATG	312
CTG-CAG	TGTGTAACAGTTCCTGCATGGGCGGCATGAACCGGAGGCCC	313
Leu-257 to Gln	ATCCTCACCATCATCACACTGGAAGACTCCAGGTCAGGAGCC
Li-Fraumeni syndrome	ACTTGCCACCCTGCACACTGGCCTGCTGTGCCCCAGCC
	GGCTGGGGCACAGCAGGCCAGTGTGCAGGGTGGCAAGTGG	314
	CTCCTGACCTGGAGTCTTCCAGTGTGATGATGGTGAGGATGG
	GCCTCCGGTTCATGCCGCCCATGCAGGAACTGTTACACA
	CATCACACTGGAAGACT	315
	AGTCTTCCAGTGTGATG	316
CTG-CCG	GACCTGATTTCCTTACTGCCTCTTGCTTCTCTTTTCCTATCCT	317
Leu-265 to Pro	GAGTAGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCG
Li-Fraumeni syndrome	TGTTTGTGCCTGTCCTGGGAGAGACCGGCGCACAGA
	TCTGTGCGCCGGTCTCTCCCAGGACAGGCACAAACACGCAC	318
	CTCAAAGCTGTTCCGTCCCAGTAGATTACCACTACTCAGGAT
	AGGAAAAGAGAAGCAAGAGGCAGTAAGGAAATCAGGTC
	TAATCTACTGGGACGGA	319
	TCCGTCCCAGTAGATTA	320
gCGT-TGT	TGCTTCTCTTTTCCTATCCTGAGTAGTGGTAATCTACTGGGAC	321
Arg-273 to Cys	GGAACAGCTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGAGA
Li-Fraumeni syndrome	GACCGGCGCACAGAGGAAGAGAATCTCCGCAAGAAAG
	cmCTrGCGGAGATTCTCTTCCTCTGTGCGCCGGTCTCTCC	322
	CAGGACAGGCACAAACACGCACCTCAAAGCTGTTCCGTCCCA
	GTAGATTACCACTACTCAOGATAGGAAAAGAGAAGCA
	TTGAGGTGCGTGTTTGT	323
	ACAAACACGCACCTCAA	324
TGT-TAT	CTTTTCCTATCCTGAGTAGTGGTAATCTACTGGGACGGAACA	325
Cys-275 to Tyr	GCTTTGAGGTGCGTGTTTGTGCCTGTCCTGGGAGAGACCGG
Li-Fraumeni syndrome	CGCACAGAGGAAGAGAATCTCCGCAAGAAAGGGGAGCC
	GGCTCCCCTTTCTTGCGGAGATTCTCTTCCTCTGTGCGCCGG	326
	TCTCTCCCAGGACAGGCACAAACACGCACCTCAAAGCTGTTC
	CGTCCCAGTAGATTACCACTACTCAGGATAGGAAAAG
	GCGTGTTTGTGCCTGTC	327
	GACAGGCACAAACACGC	328
CCT-CTT	TCCTGAGTAGTGGTAATCTACTGGGACGGAACAGCTTTGAGG	329
Pro-278 to Leu	TGCGTGTTTGTGCCTGTCCTGGGAGAGACCGGCGCACAGAG
Breast cancer	GAAGAGAATCTCCGCAAGAAAGGGGAGCCTCACCACGA
	TCGTGGTGAGGCTCCCCTTTCTTGCGGAGATTCTCTTCCTCT	330
	GTGCGCCGGTCTCTCCCAGGACAGGCACAAACACGCACCTC
	AAAGCTGTTCCGTCCCAGTAGATTACCACTACTCAGGA
	TGCCTGTCCTGGGAGAG	331
	CTCTCCCAGGACAGGCA	332
AGA-AAA	GTAGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCGTG	333
Arg-280 to Lys	TTTGTGCCTGTCCTGGGAGAGACCGGCGCACAGAGGAAGAG
Glioma	AATCTCCGCAAGAAAGGGGAGCCTCACCACGAGCTGCC
	GGCAGCTCGTGGTGAGGCTCCCCTTTCTTGCGGAGATTCTCT	334
	TCCTCTGTGCGCCGGTCTCTCCCAGGACAGGCACAAACACG
	CACCTCAAAGCTGTTCCGTCCCAGTAGATTACCACTAC
	TCCTGGGAGAGACCGGC	335
	GCCGGTCTCTCCCAGGA	336
GAA-GCA	GGAACAGCTTTGAGGTGCGTGWTTGTGCCTGTCCTGGGAGA	337
GTu-286 to Ala	GACCGGCGCACAGAGGAAGAGAATCTCCGCAAGAATTAGGGGA
Adrenocortical	GCCTCACCACGAGCTGCCCCCAGGGAGCACTAAGCGAGG
carcinoma
	CCTCGCTTAGTGCTCCCTGGGGGCAGCTCGTGGTGAGGCTC	338
	CCCTTTCTTGCGGAGATTCTCTTCCTCTGTGCGCCGGTCTCT
	CCCAGGACAGGCACAAACACGCACCTCAAAGCTGTTCC
	AGAGGAAGAGAATCTCC	339
	GGAGATTCTCTTCCTCT	340
CGA-CCA	AAGAGAATCTCCGCAAGAAAGGGGAGCCTCACCACGAGCTG	341
Arg-306 to Pro	CCCCCAGGGAGCACTAAGCGAGGTAAGCAAGCAGGACAAGA
Rhabdomyosarcoma	AGCGGTGGAGGAGACCAAGGGTGCAGTTATGCCTCAGAT
	ATCTGAGGCATAACTGCACCCTTGGTCTCCTCCACCGCTTCT	342
	TGTCCTGCTTGCTTACCTCGCTTAGTGCTCCCTGGGGGCAGC
	TCGTGGTGAGGCTCCCCTTTCTTGCGGAGATTCTCTT
	CACTAAGCGAGGTAAGC	343
	GCTTACCTCGCTTAGTG	344
gCGA-TGA	GAAGAGAATCTCCGCAAGAAAGGGGAGCCTCACCACGAGCT	345
Arg-306 to Term	GCCCCCAGGGAGCACTAAGCGAGGTAAGCAAGCAGGACAAG
Li-Fraumeni syndrome	AAGCGGTGGAGGAGACCAAGGGTGCAGTTATGCCTCAGA
	TCTGAGGCATAACTGCACCCTTGGTCTCCTCCACCGCTTCTT	346
	GTCCTGCTTGCTTACCTCGCTTAGTGCTCCCTGGGGGCAGCT
	CGTGGTGAGGCTCCCCTTTCTTGCGGAGATTCTCTTC
	GCACTAAGCGAGGTAAG	347
	CTTACCTCGCTTAGTGC	348
gCGC-TGC	GGTACTGTGAATATACTTACTTCTCCCCCTCCTCTGTTGCTGC	349
Arg-337 to Cys	AGATCCGTGGGCGTGAGCGCTTCGAGATGTTCCGAGAGCTG
Osteosarcoma	AATGAGGCCTTGGAACTCAAGGATGCCCAGGCTGGGA
	TCCCAGCCTGGGCATCCTTGAGTTCCAAGGCCTCATTCAGCT	350
	CTCGGAACATCTCGAAGCGCTCACGCCCACGGATCTGCAGC
	AACAGAGGAGGGGGAGAAGTAAGTATATTCACAGTACC
	GGCGTGAGCGCTTCGAG	351
	CTCGAAGCGCTCACGCC	352
CTG-CCG	CTCTCCCCCTCCTCTGTTGCTGCAGATCCGTGGGCGTGAGCGC	353
Leu-344 to Pro	TTCGAGATGTTCCGAGAGCTGAATGAGGCCTTGGAACTCAAG
Li-Fraumeni syndrome	GATGCCCAGGCTGGGAAGGAGCCAGGGGGGAGCAGGGC
	GCCCTGCTCCCCCCTGGCTCCTTCCCAGCCTGGGCATCCTT	354
	GAGTTCCAAGGCCTCATTCAGCTCTCGGAACATCTCGAAGCG
	CTCACGCCCACGGATCTGCAGCAACAGAGGAGGGGGAG
	CCGAGAGCTGAATGAGG	355
	CCTCATTCAGCTCTCGG	356

EXAMPLE 6

Beta Globin

[0114] Hemoglobin, the major protein in the red blood cell, binds oxygen reversibly and is responsible for the cells' capacity to transport oxygen to the tissues. In adults, the major hemoglobin is hemoglobin A, a tetrameric protein consisting of two identical alpha globin chains and two beta globin chains. Disorders involving hemoglobin are among the most common genetic disorders worldwide, with approximately 5% of the world's population being carriers for clinically important hemoglobin mutations. Approximately 300,000 severely affected homozygotes or compound heterozygotes are born each year.

[0115] Mutation of the glutamic acid at position 7 in beta globin to valine causes sickle cell anemia, the clinical manifestations of which are well known. Mutations that cause absence of beta chain cause beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic). Patients with thalassemia major present in the first year of life with severe anemia; they are unable to maintain a hemoglobin level about 5 gm/dl.

[0116] The beta-thalassemias were among the first human genetic diseases to be examined by means of recombinant DNA analysis. Baysal et al., Hemoglobin 19(3-4):213-36 (1995) and others provide a compendium of mutations that result in beta-thalassemia.

[0117] Hemoglobin disorders were among the first to be considered for gene therapy. Transcriptional silencing of genes transferred into hematopoietic stem cells, however, poses one of the most significant challenges to its success. If the transferred gene is not completely silenced, a progressive decline in gene expression is often observed. Position effect variegation (PEV) and silencing mechanisms may act on a transferred globin gene residing in chromatin outside of the normal globin locus during the important terminal phases of erythroblast development when globin transcripts normally accumulate rapidly despite heterochromatization and shutdown of the rest of the genome. The attached table discloses the correcting oligonucleotide base sequences for the beta globin oligonucleotides of the invention.

TABLE 12
Beta Globin Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Sickle Cell Anemia	TCTGACACAACTGTGTTCACTAGCAACCTCAAACAGACACCA	357
GLU-7-VAL	TGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCC
GAG to GTG	CTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGA
	TCACCACCAACTTCATCCACGTTCACCTTGCCCCACAGGGCA	358
	GTAACGGCAGACTTCTCCTCAGGAGTCAGGTGCACCATGGT
	GTCTGTTTGAGGTTGCTAGTGAACACAGTTGTGTCAGA
	GACTCCTGAGGAGAAGT	359
	ACTTCTCCTCAGGAGTC	360
Thalassaemia Beta	CTATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCA	361
MET-0-ARG	ACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGA
ATG to AGG	AGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGT
	ACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCTC	362
	CTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGCT
	AGTGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATAG
	AGACACCATGGTGCACC	363
	GGTGCACCATGGTGTCT	364
Thalassaemia Beta	TATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCAA	365
MET-0-ILE	CCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAA
ATG to ATA	GTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTG
	CACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCT	366
	CCTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGC
	TAGTGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATA
	GACACCATGGTGCACCT	367
	AGGTGCACCATGGTGTC	368
Thalassaemia Beta	TATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCAA	369
MET-0-ILE	CCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAT
ATG to ATT	GTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTG
	CACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCT	370
	CCTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGC
	TAGTGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATA
	GACACCATGGTGCACCT	371
	AGGTGCACCATGGTGTC	372
Thalassaemia Beta	CTATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCA	373
MET-0-LYS	ACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGA
ATG to AAG	AGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGT
	ACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCTC	374
	CTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGCT
	AGTGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATAG
	AGACACCATGGTGCACC	375
	GGTGCACCATGGTGTCT	376
Thalassaemia Beta	CTATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCA	377
MET-0-THR	ACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGA
ATG to ACG	AGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGT
	ACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCTC	378
	CTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGCT
	AGTGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATAG
	AGACACCATGGTGCACC	379
	GGTGCACCATGGTGTCT	380
Thalassaemia Beta	TCTATTGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGC	381
MET-0-VAL	AACCTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAG
ATG to GTG	AAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACG
	CGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTTCTCC	382
	TCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAGGTTGCTAG
	TGAACACAGTTGTGTCAGAAGCAAATGTAAGCAATAGA
	CAGACACCATGGTGCAC	383
	GTGCACCATGGTGTCTG	384
Thalassaemia Beta	TCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGT	385
TRP-16-Term	CTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAA
TGG to TGA	GTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTA
	TAACCTTGATACCAACCTGCCCAGGGCCTCACCACCAACTTC	386
	ATCCACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACT
	TCTCCTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGA
	GCCCTGTGGGGCAAGGT	387
	ACCTTGCCCCACAGGGC	388
Thalassaemia Beta	CTCAAACAGACACCATGGTGCACCTGACTCCTGAGGAGAAG	389
TRP-16-Term	TCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGA
TGG to TAG	AGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTT
	AACCTTGATACCAACCTGCCCAGGGCCTCACCACCAACTTCA	390
	TCCACGTTCACCTTGCCCCACAGGGCAGTAACGGCAGACTT
	CTCCTCAGGAGTCAGGTGCACCATGGTGTCTGTTTGAG
	TGCCCTGTGGGGCAAGG	391
	CCTTGCCCCACAGGGCA	392
Thalassaemia Beta	ACAGACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGC	393
LYS-18-Term	CGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTG
AAG to TAG	GTGGTGAGGCCCTGGGCAGGTTGGTATCAAGGTTACAAG
	CTTGTAACCTTGATACCAACCTGCCCAGGGCCTCACCACCAA	394
	CTTCATCCACGTTCACCTTGCCCCACAGGGCAGTAACGGCA
	GACTTCTCCTCAGGAGTCAGGTGCACCATGGTGTCTGT
	TGTGGGGCAAGGTGAAC	395
	GTTCACCTTGCCCCACA	396
Thalassaemia Beta	CCATGGTGCACCTGACTCGTGAGGAGAAGTCTGCCGTTACT	397
ASN-20-SER	GCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGA
AAC to AGC	GGCCCTGGGCAGGTTGGTATCAAGGTTACAAGACAGGTT
	AACCTGTCTTGTAACCTTGATACCAACCTGCCCAGGGCCTCA	398
	CCACCAACTTCATCCACGTTCACCTTGCCCCACAGGGCAGTA
	ACGGCAGACTTCTCCTCAGGAGTCAGGTGCACCATGG
	CAAGGTGAACGTGGATG	399
	CATCCACGTTCACCTTG	400
Thalassaemia Beta	ACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGG	401
GLU-23-ALA	GGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGG
GAA to GCA	GCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGAC
	GTCTCCTTAAACCTGTCTTGTAACCTTGATACCAACCTGCCC	402
	AGGGCCTCACCACCAACTTCATCCACGTTCACCTTGCCCCAC
	AGGGCAGTAACGGCAGACTTCTCCTCAGGAGTCAGGT
	CGTGGATGAAGTTGGTG	403
	CACCAACTTCATCCACG	404
Thalassaemia Beta	CACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTG	405
GLU-23-term	GGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTG
GAA to TAA	GGCAGGTTGGTATCAAGGTTACAAGACAGGTTTAAGGAGA
	TCTCCTTAAACCTGTCTTGTAACCTTGATACCAACCTGCCCA	406
	GGGCCTCACCACCAACTTCATCCACGTTCACCTTGCCCCACA
	GGGCAGTAACGGCAGACTTCTCCTCAGGAGTCAGGTG
	ACGTGGATGAAGTTGGT	407
	ACCAACTTCATCCACGT	408
Thalassaemia Beta	GAGGAGAAGACTGCTGTCAATGCCCTGTGGGGCAAAGTGAA	409
GLU-27-LYS	CGTGGATGCAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTAT
GAG to AAG	CAAGGTTATAAGAGAGGCTCAAGGAGGCAAATGGAAACT
	AGTTTCCATTTGCCTCCTTGAGCCTCTCTTATAACCTTGATAC	410
	CAACCTGCCCAGGGCCTCACCACCAACTGCATCCACGTTCA
	CTTTGCCCCACAGGGCATTGACAGCAGTCTTCTCCTC
	TTGGTGGTGAGGCCCTG	411
	CAGGGCCTCACCACCAA	412
Thalassaemia Beta	GAGGAGAAGACTGCTGTCAATGCCCTGTGGGGCAAAGTGAA	413
GLU-27-Term	CGTGGATGCAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTAT
GAG to TAG	CAAGGTTATAAGAGAGGCTCAAGGAGGCAAATGGAAACT
	AGTTTCCATTTGCCTCCTTGAGCCTCTCTTATAACCTTGATAC	414
	CAACCTGCCCAGGGCCTCACCACCAACTGCATCCACGTTCA
	CTTTGCCCCACAGGGCATTGACAGCAGTCTTCTCCTC
	TTGGTGGTGAGGCCCTG	415
	CAGGGCCTCACCACCAA	416
Thalassaemia Beta	GAGAAGACTGCTGTCAATGCCCTGTGGGGCAAAGTGAACGT	417
ALA-28-SER	GGATGCAGTTGGTGGTGAGGCCCTGGGCAGGTTGGTATCAA
GCC to TCC	GGTTATAAGAGAGGCTCAAGGAGGCAAATGGAAACTGGG
	CCCAGTTTCCATTTGCCTCCTTGAGCCTCTCTTATAACCTTGA	418
	TACCAACCTGCCCAGGGCCTCACCACCAACTGCATCCACGT
	TCACTTTGCCCCACAGGGCATTGACAGCAGTCTTCTC
	GTGGTGAGGCCCTGGGC	419
	GCCCAGGGCCTCACCAC	420
Thalassaemia Beta	CTGTCAATGCCCTGTGGGGCAAAGTGAACGTGGATGCAGTT	421
ARG-31-THR	GGTGGTGAGGCCCTGGGCAGGTTGGTATGAAGGTTATAAGA
AGG to ACG	GAGGCTCAAGGAGGCAAATGGAAACTGGGCATGTGTAGA
	TCTACACATGCCCAGTTTCCATTTGCCTCCTTGAGCCTCTCTT	422
	ATAACCTTGATACCAACCTGCCCAGGGCCTCACCACCAACTG
	CATCCACGTTCACTTTGCCCCACAGGGCATTGACAG
	CCTGGGCAGGTTGGTAT	423
	ATACCAACCTGCCCAGG	424
Thalassaemia Beta	TGGGTTTCTGATAGGCACTGACTCTCTGTCCCTTGGGCTGTT	425
Leu-33-GLN	TTCCTACCCTCAGATTACTGGTGGTCTACCCTTGGACCCAGA
CTG to CAG	GGTTCTTTGAGTCCTTTGGGGATCTGTCCTCTCCTGA
	TCAGGAGAGGAGAGATCCCCAAAGGACTCAAAGAACCTCTG	426
	GGTCCAAGGGTAGACCACCAGTAATCTGAGGGTAGGAAAAC
	AGCCCAAGGGACAGAGAGTCAGTGCCTATCAGAAACCCA
	CAGATTACTGGTGGTCT	427
	AGACCACCAGTAATCTG	428
Thalassaemia Beta	ATAGGCACTGACTCTCTGTCCCTTGGGCTGTTTTCCTACCCT	429
TYR-36-Term	CAGATTACTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGA
TAC to TAA	GTCCTTTGGGGATCTGTCCTCTCCTGATGCTGTTATG
	CATAACAGCATCAGGAGAGGACAGATCCCCAAAGGACTCAAA	430
	GAACCTCTGGGTCCAAGGGTAGACCACCAGTAATCTGAGGG
	TAGGAAAACAGCCCAAGGGACAGAGAGTCAGTGCCTAT
	GTGGTCTACCCTTGGAC	431
	GTCCAAGGGTAGACCAC	432
Thalassaemia Beta	ACTGACTCTCTGTCCCTTGGGCTGTTTTCCTACCCTCAGATT	433
TRP-38-Term	ACTGGTGGTCTACCCGTTGGACCCAGAGGTTCTTTGAGTCCTT
TGG to TGA	TGGGGATCTGTCCTCTCCTGATGCTGTTATGGGCAAC
	GTTGCCCATAACAGCATCAGGAGAGGACAGATCCCCAAAGG	434
	ACTCAAAGAACCTCTGGGTCCAAGGGTAGACCACCAGTAATC
	TGAGGGTAGGAAAACAGCCCAAGGGACAGAGAGTCAGT
	TACCCTTGGACCCAGAG	435
	CTCTGGGTCCAAGGGTA	436
Thalassaemia Beta	CACTGACTCTCTGTCCCTTGGGCTGTTTTCCTACCCTCAGAT	437
TRP-38-Term	TACTGGTGGTCTACCCTTGGACCCAGAGGTTCTTGAGTCCT
TGG to TAG	TTGGGGATCTGTCCTCTCCTGATGCTGTTATGGGCAA
	TTGCCCATAACAGCATCAGGAGAGGACAGATCCCCAAAGGA	438
	CTCAAAGAACCTCTGGGTCCAAGGGTAGACCACCAGTAATCT
	GAGGGTAGGAAAACAGCCCAAGGGACAGAGAGTCAGTG
	CTACCCTTGGACCCAGA	439
	TCTGGGTCCAAGGGTAG	440
Thalassaemia Beta	ACTCTCTGTCCCTTGGGCTGTTTTCCTACCCTCAGATTACTG	441
GLN-40-Term	GTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGG
CAG-TAG	GATCTGTCCTCTCCTGATGCTGTTATGGGCAACCCTA
	TAGGGTTGCCCATAACAGCATCAGGAGAGGACAGATCCCCA	442
	AAGGACTCAAAGAACCTCTGGGTCCAAGGGTAGACCACCAG
	TAATCTGAGGGTAGGAAAACAGCCCAAGGGAGAGAGAGT
	CTTGGACCCAGAGGTTC	443
	GAACCTCTGGGTCCAAG	444
Thalassaemia Beta	TTGGGCTGTTTTCCTACCCTCAGATTACTGGTGGTCTACCCT	445
GLU-44-Term	TGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCTCT
GAG to TAG	CCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTC
	GAGCCTTCACCTTAGGGTTGCCCATAACAGCATCAGGAGAG	446
	GACAGATCCCCAAAGGACTCAAAGAACCTGTGGGTCCAAGG
	GTAGACCACCAGTAATCTGAGGGTAGGAAAACAGCCCAA
	GGTTCTTTGAGTCCTTT	447
	AAAGGACTCAAAGAACC	448
Thalassaemia Beta	TTCTTTGAGTCCTTTGGGGATCTGTCCTCTCCTGATGCTGTTA	449
LYS-62-Term	TGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAGGTGCTA
AAG to TAG	GGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACC
	GGTTGTCCAGGTGAGCCAGGCCATCACTAAAGGCACCTAGC	450
	ACCTTCTTGCCATGAGCCTTCACCTTAGGGTTGCCCATAACA
	GCATCAGGAGAGGACAGATCCCCAAAGGACTCAAAGAA
	CTAAGGTGAAGGCTCAT	451
	ATGAGCCTTCACCTTAG	452
Thalassaemia Beta	TGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGA	453
SER-73-ARG	AGGTGCTAGGTGCCTTTAGTGATGGCCTGGCTCACCTGGAC
AGT to AGA	AACCTCAAGGGCACTTTTTCTCAGCTGAGTGAGCTGCAC
	GTGCAGCTCACTCAGCTGAGAAAAAGTGCCCTTGAGGTTGTC	454
	CAGGTGAGCCAGGCCATCACTAAAGGCACCTAGCACCTTCT
	TGCCATGAGCCTTCACCTTAGGGTTGCCCATAACAGCA
	GCCTTTAGTGATGGCCT	455
	AGGCCATCACTAAAGGC	456
Haemolylic Anaemia	TTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAGGTG	457
GLY-75-VAL	CTAGGTGCCTTTTAGTGATGGCCTGGCTCACCTGGACAACCT
GGC to GTC	CAAGGGCACTTTTTCTCAGCTGAGTGAGCTGCACTGTGA
	TCACAGTGCAGCTCACTCAGCTGAGAAAAAGTGCCCTTGAG	458
	GTTGTCCAGGTGAGCCAGGCCATCACTAAAGGCACCTAGCA
	CCTTCTTGCCATGAGCCTTCACCTTAGGGTTGCCCATAA
	TAGTGATGGCCTGGCTC	459
	GAGCCAGGCCATCACTA	460
Thalassaemia Beta	GCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGG	461
GLU-91-Term	CACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGC
GAG to TAG	ACGTGGATCCTGAGAACTTCAGGGTGAGTCTATGGGACC
	GGTCCCATAGACTCACCCTGAAGTTCTCAGGATCCACGTGCA	462
	GCTTGTCACAGTGCAGCTCACTCAGTGTGGCAAAGGTGCCC
	TTGAGGTTGTCCAGGTGAGCCAGGCCATCACTAAAGGC
	CACTGAGTGAGCTGCAC	463
	GTGCAGCTCACTCAGTG	464
Thalassaemia Beta	CTGGACAACCTCAAGGGCACTTTTTCTCAGCTGAGTGAGCTG	465
VAL-99-MET	CACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGGT
GTG to ATG	GAGTCCAGGAGATGCTTCACTTTTCTCTTTTTACTTTC
	GAAAGTAAAAAGAGAAAAGTGAAGCATCTCCTGGACTCACCC	466
	TGAAGTTCTCAGGATCCACGTGCAGCTTGTCACAGTGCAGCT
	CACTCAGCTGAGAAAAAGTGCCCTTGAGGTTGTCCAG
	AGCTGCACGTGGATCCT	467
	AGGATCCACGTGCAGCT	468
Thalassaemia Beta	CCCTTTTGCTAATCATGTTCATACCTCTTATCTTCCTCCCACA	469
LEU-111-PRO	GCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACT
CTG-CCG	TTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTA
	TAGGCAGCCTGCACTGGTGGGGTGAATTCTTTGCCAAAGTG	470
	ATGGGCCAGCACACAGACCAGCACGTTGCCCAGGAGCTGTG
	GGAGGAAGATAAGAGGTATGAACATGATTAGCAAAAGGG
	CAACGTGCTGGTCTGTG	471
	CACAGACCAGCACGTTG	472
Thalassaemia Beta	GCTAATCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTG	473
CYS-113-Term	GGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAA
TGT to TGA	AGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAA
	TTTCTGATAGGCAGCCTGCACTGGTGGGGTGAATTCTTTGCC	474
	AAAGTGATGGGCCAGCACACAGACCAGCACGTTGCCCAGGA
	GCTGTGGGAGGAAGATAAGAGGTATGAACATGATTAGC
	CTGGTCTGTGTGCTGGC	475
	GCCAGCACACAGACCAG	476
Thalassaemia Beta	TCATGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCA	477
LEU-115-PRO	ACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAAT
CTG to CCG	TCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGT
	ACCACTTTCTGATAGGCAGCCTGCACTGGTGGGGTGAATTCT	478
	TTGCCAAAGTGATGGGCCAGCACACAGACCAGCACGTTGCC
	CAGGAGCTGTGGGAGGAAGATAAGAGGTATGAACATGA
	CTGTGTGCTGGCCCATC	479
	GATGGGCCAGCACACAG	480
Thalassaemia Beta	TGTTCATACCTCTTATCTTCCTCCCACAGCTCCTGGGCAACG	481
ALA-116-ASP	TGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCA
GCC to GAC	CCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGC
	GCCACCACTTTCTGATAGGCAGCCTGCACTGGTGGGGTGAA	482
	TTCTTTGCCAAAGTGATGGGCCAGCACACAGACCAGCACGTT
	GCCCAGGAGCTGTGGGAGGAAGATAAGAGGTATGAACA
	TGTGCTGGCCCATCACT	483
	AGTGATGGGCCAGCACA	484
Thalassaemia Beta	TTCCTCCCACAGCTCCTGGGCAACGTGCTGGTCTGTGTGCT	485
GLU-122-Term	GGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGG
GAA to TAA	CTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCC
	GGGCATTAGCCACACCAGCCACCACTTTCTGATAGGCAGCC	486
	TGCACTGGTGGGGTGAATTCTTTGCCAAAGTGATGGGCCAG
	CACACAGACCAGCACGTTGCCCAGGAGCTGTGGGAGGAA
	TTGGCAAAGAATTCACC	487
	GGTGAATTCTTTGCCAA	488
Thalassaemia Beta	GCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAA	489
GLN-128-PRO	GAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGT
CAG to CCG	GGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTA
	TAGTGATACTTGTGGGCCAGGGCATTAGCCACACCAGCCAC	490
	CACTTTCTGATAGGCAGCCTGCACTGGTGGGGTGAATTCTTT
	GCCAAAGTGATGGGCCAGCACACAGACCAGCACGTTGC
	ACCAGTGCAGGCTGCCT	491
	AGGCAGCCTGCACTGGT	492
Thalassaemia Beta	GGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAA	493
GLN-128-Term	AGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGT
CAG to TAG	GGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACT
	AGTGATACTTGTGGGCCAGGGCATTAGCCACACCAGCCACC	494
	ACTTTCTGATAGGCAGCCTGCACTGGTGGGGTGAATTCTTTG
	CCAAAGTGATGGGCCAGCACACAGACCAGCACGTTGCC
	CACCAGTGCAGGCTGCC	495
	GGCAGCCTGCACTGGTG	496
Thalassaemia Beta	GTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCA	497
GLN-132-LYS	CCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGC
CAG to AAG	TAATGCCCTGGCCCACAAGTATCACTAAGCTCGCTTTC
	GAAAGCGAGCTTAGTGATACTTGTGGGCCAGGGCATTAGCC	498
	ACACCAGCCACCACTTTCTGATAGGCAGCCTGCACTGGTGG
	GGTGAATTCTTTGCCAAAGTGATGGGCCAGCACACAGAC
	CTGCCTATCAGAAAGTG	499
	CACTTTCTGATAGGCAG	500

EXAMPLE 7

Retinoblastoma

[0118] Retinoblastoma (RB) is an embryonic neoplasm of retinal origin. It almost always presents in early childhood and is often bilateral. The risk of osteogenic sarcoma is increased 500-fold in bilateral retinoblastoma patients, the bone malignancy being at sites removed from those exposed to radiation treatment of the eye tumor.

[0119] The retinoblastoma susceptibility gene (pRB; pRb) plays a pivotal role in the regulation of the cell cycle. pRB restrains cell cycle progression by maintaining a checkpoint in late G1 that controls commitment of cells to enter S phase. The critical role that pRB plays in cell cycle regulation explains its status as archetypal tumor suppressor: loss of pRB function results in an inability to maintain control of the G1 checkpoint; unchecked progression through the cell cycle is, in turn, a hallmark of neoplasia.

[0120] Blanquet et al., Hum. Molec. Genet. 4: 383-388 (1995) performed a mutation survey of the RB1 gene in 232 patients with hereditary or nonhereditary retinoblastoma. They systematically explored all 27 exons and flanking sequences, as well as the promoter. All types of point mutations were represented and found to be unequally distributed along the RB1 gene sequence. In the population studied, exons 3, 8, 18, and 19 were preferentially altered. The attached table discloses the correcting oligonucleotide base sequences for the retinoblastoma oligonucleotides of the invention.

TABLE 13
pRB Mutations and Genome-Correcting Oligos
Clinical Phenotype		SEQ ID
Mutation	Correcting Oligos	NO:
Retinoblastoma	AATATTTGATCTTTATTTTTTGTTCCCAGGGAGGTTATATTCAA	501
Trp99Term	AAGAAAAAGGAACTGTGGGGAATCTGTATCTTTATTGCAGCA
TGG-TAG	GTTGACCTAGATGAGATGTCGTTCACTTTTACTGA
	TCAGTAAAAGTGAACGACATCTCATCTAGGTCAACTGCTGCA	502
	ATAAAGATACAGATTCCCCACAGTTCCTTTTTCTTTTGAAIATA
	ACCTCCCTGGGAACAAAAAATAAAGATCAAATATT
	GGAACTGTGGGGAATCT	503
	AGATTCCCCACAGTTCC	504
Retinoblastoma	ATTTACTTTTTTCTATTCTTTCCTTTGTAGTGTCCATAAATTCTT	505
Glu137Asp	TAACTTACTAAAAGAAATTGATACCAGTACCAAAGTTGATAAT
GAA-GAT	GCTATGTCAAGACTGTTGAAGAAGTATGAIGTA
	TACATCATACTTCTTCAACAGTCTTGACATAGCATTATCAACTT	506
	TGGTACTGGTATCAATTTCTTTTAGTAAGTTAAAGAATTTATGG
	ACACTACAAAGGAAAGAATAGAAAAAAGTAAAT
	CTAAAAGAAATTGATAC	507
	GTATCAATTTCTTTTAG	508
Retinoblastoma	TGATTTACTTTTTTTCTATTCTTTCCTTTGTAGTGTCCATAAATT	509
Glu137Term	CTTTAACTTACTAAAAGAAATTGATACCAGTACCAAAGTTGAT
GAA-TAA	AATGCTATGTCAAGACTGTTGAAGAAGTATGATG
	CATCATACTTCTTCAACAGTCTTGACATAGCATTATCAACTTT	510
	GGTACTGGTATCAATTTCTTTTAGTAAGTTAAAGAATTTATGG
	ACACTACAAAGGAAAGAATAGAAAAAAGTAAATCA
	TACTAAAAGAAATTGAT	511
	ATCAATTTCTTTTAGTA	512
Retinoblastoma	AAAATGTTAAAAAGTCATAATGTTTTTCTTTTCAGGACATGTGA	513
Gln176Term	ACTTATATATTTGACACAACCCAGCAGTTCGTAAGTAGTTCAC
CAA-TAA	AGAATGTTATTTTTCACTTAAAAAAAAAGATTTT
	AAAATCTTTTTTTTTAAGTGAAAAATAACATTCTGTGAACTACT	514
	TACGAACTGCTGGGTTGTGTCAAATATATAAGTTCACATGTCC
	TGAAAAGAAAAACATTATGACTTTTTAACATTTT
	ATTTGACACAACCCAGC	515
	GCTGGGTTGTGTCAAAT	516
Relinoblastoma	TGATACATTTTTCCTGTTTTTTTTCTGCTTTCTATTTGTTTAATA	517
lle185Thr	GGATATCTACTGAAATAAATTCTGCATTGGTGCTAAAAGTTTC
ATA-ACA	TTGGATCACATTTTTATTAGCTAAAGGTAAGTT
	AACTTACCTTTAGCTAATAAAAATGTGATCCAAGAAACTTTTA	518
	GCACCAATGCAGAATTTATTTCAGTAGATATCCTATTAAACAA
	ATAGAAAGCAGAAAAAAAACAGGAAAAATGTATCA
	TACTGAAATAAATTCTG	519
	CAGAATTTATTTCAGTA	520
Retinoblastoma	AAAGATCTGAATCTCTAACTTTCTTTAAAAATGTACATTTTTTT	521
Gln207Term	TTCAGGGGAAGTATTACAAATGGAAGATGATCTGGTGATTTC
CAA-TAA	ATTTCAGTTAATGCTATGTGTCCTTGACTATTTTA
	TAAAATAGTCAAGGACACATAGCATTAACTGAAATGAAATCAC	522
	CAGATCATCTTCCATTTGTAATACTTCCCCTGAAAAAAAAAATG
	TACATTTTTAAAGAAAGTTAGAGATTCAGATCTTT
	AAGTATTACAAATGGAA	523
	TTCCATTTGTAATACTT	524
Retinoblastoma	GTTCTTATCTAATTTACCACTTTTACAGAAACAGCTGTTATACC	525
Arg251Term	CATTAATGGTTCACCTCGAACACCCAGGCGAGGTCAGAACA
CGA to TGA	GGAGTGCACGGATAGCAAAACAACTAGAAAATGATA
	TATCATTTTCTAGTTGTTTTGCTATCCGTGCACTCCTGTTCTG	526
	ACCTCGCCTGGGTGTTCGAGGTGAACCATTAATGGGTATAAC
	AGCTGTTTCTGTAAAAGTGGTAAATTAGATAAGAAC
	GTTCACCTCGAACACCC	527
	GGGTGTTCGAGGTGAAC	528
Retinoblastoma	TTTACCACTTTTACAGAAACAGCTGTTATACCCATTAATGGTT	529
Arg255Term	CACCTCGAACACCCAGGCGAGGTCAGAACAGGAGTGCACG
CGA to TGA	GATAGCAAAACAACTAGAAAATGATACAAGAATTATTG
	CAATAATTCTTGTATCATTTTCTAGTTGTTTTGCTATCCGTGCA	530
	CTCCTGTTCTGACCTCGCCTGGGTGTTCGAGGTGAACCATTA
	ATGGGTATAACAGCTGTTTCTGTAAAAGTGGTAAA
	CACCCAGGCGAGGTCAG	531
	CTGACCTCGCCTGGGTG	532
Retinoblastoma	ATTAATGGTTCACCTCGAACACCCAGGCGAGGTCAGAACAG	533
Gln266Term	GAGTGCACGGATAGCAAAACAACTAGAAAATGATACAAGAAT
CAA to TAA	TATTGAAGTTCTCTGTAAAGAACATGAATGTAATATAG
	CTATATTACATTCATGTTCTTTACAGAGAACTTCAATAATTCTT	534
	GTATCATTTTCTAGTTGTTTTGCTATCCGTGCACTCCTGTTCT
	GACCTCGCCTGGGTGTTCGAGGTGAACCATTAAT
	TAGCAAAACAACTAGAA	535
	TTCTAGTTGTTTTGCTA	536
Retinoblastoma	TGACATGTAAAGGATAATTGTCAGTGACTTTTTTCTTTCAAGG	537
Arg320Term	TTGAAAATCTTTCTAAACGATACGAAGAAATTTATCTTAAAAAT
CGA to TGA	AAAGATCTAGATGCAAGATTATTTTTGGATCATG
	CATGATCCAAAAATAATCTTGCATCTAGATCTTTATTTTTAAGA	538
	TAAATTTCTTCGTATCGTTTAGAAAGATTTTCAACCTTGAAAGA
	AAAAAGTCACTGACAATTATCCTTTACATGTCA
	TTTCTAAACGATACGAA	539
	TTCGTATCGTTTAGAAA	540
Retinoblastoma	ACAAATTGTAAATTTTCAGTATGAAGACTTGACTTCACTTATTGTT	541
Gln354Term	ATTTAGTTTTGAAACACAGAGAACACCACGAAAAAGTAACCTT
CAG to TAG	GATGAAGAGGTGAATGTAATTCCTCCACACACTC
	GAGTGTGTGGAGGAATTACATTCACCTCTTCATCAAGGTTAC	542
	TTTTTCGTGGTGTTCTCTGTGTTTCAAAACTAAATAACAATAA
	GTGAAGTCATTCACATACTGAAAATTTACAATTTGT
	TTGAAACACAGAGAACA	543
	TGTTCTCTGTGTTTCAA	544
Retinoblastoma	TTTTCAGTATGIGAATGACTTCACTTATTGTTATTTAGTTTTGA	545
Arg358Gly	AACACAGAGAACACCACGAAAAAGTAACCTTGATGAAGAGGT
CGA to GGA	GAATGTAATTCCTCCACACACTCCAGTTAGGTATG
	CATACCTAACTGGAGTGTGTGGAGGAATTACATTCACCTCTT	546
	CATCAAGGTTACTTTTTCGTGGTGTTCTCTGTGTTTCAAAACT
	AAATAACAATAAGTGAAGTCATTCACATACTGAAAA
	GAACACCACGAAAAAGT	547
	ACTTTTTCGTGGTGTTC	548
Retinoblastoma	TTTTCAGTATGTGAATGACTTCACTTATTGTTATTTATTTTTGA	549
Arg358Term	AACACAGAGAACACCACGAAAAAGTAACCTTGATGAAGAGGT
CGA to TGA	GAATGTAATTCCTCCACACACTCCAGTTAGGTATG
	CATACCTAACTGGAGTGTGTGGAGGAATTACATTCACCTCTT	550
	CATCAAGGTTACTTTTTCGTGGTGTTCTCTGTGTTTCAAAACT
	AAATAACAATAAGTGAAGTCATTCACATACTGAAAA
	GAACACCACGAAAAAGT	551
	ACTTTTTCGTGGTGTTC	552
Retinoblastoma	CTGTTATGAACACTATCCAACAATTAATGATGATTTTAAATTCA	553
Ser397Term	GCAAGIGATCAACCTTCAGAAAATCTGATTTCCTATTTTAACG
TCA to TAA	TAAGCCATATATGAAACATTATTTATTGTAATAT
	ATATTACAATAAATAATGTTTCATATATGGCTTACGTTAAAATA	554
	GGAAATCAGATTTTCTGAAGGTTGATCACTTGCTGAATTTAAA
	ATCATCATTAATTGTTGGATAGTGTTCATAACAG
	TCAACCTTCAGAAAATC	555
	GATTTTCTGAAGGTTGA	556
Retinoblastoma	TTTCATAATTGTGATTTTCTAAAATAGCAGGCTCTTATTTTTCT	557
Arg445Term	TTTTGTTTGTTTGTAGCGATACAAACTTGGAGTTCGCTTGTAT
CGA to TGA	TACCGAGTAATGGAATCCATGCTTAAATCAGTAA
	TTACTGATTTAAGCATGGATTCCATTACTCGGTAATACAAGCG	558
	AACTCCAAGTTTGTATCGCTACAAACAAACAAAAAGAAAAATA
	AGAGCCTGCTATTTTAGAAAATCACAATTATGAAA
	GTTTGTAGCGATACAAA	559
	TTTGTATCGCTACAAAC	560
Retinoblastoma	GCTCTTATTTTTCTTTTTGTTTGTTTGTAGCGATACAAACTTGG	561
Arg455Term	AGTTCGCTTGTATTACCGAGTAATGGAATCCATGCTTAAATCA
CGA to TGA	GTAAGTAAAAACAATATAAAAAAATTTCAGCCG
	CGGCTGAAATTTTTTTATATTGTTTTTAACTTACTGATTTAAGC	562
	ATGGATTCCATTACTCGGTAATACAAGCGAACTCCAAGTTTGT
	ATCGCTACAAACAAACAAAAAGAAAAATAAGAGC
	TGTATTACCGAGTAATG	563
	CATTACTCGGTAATACA	564
Retinoblastoma	ATCGAAAGTTTTATCAAAGCAGAAGGCAACTTGACAAGAGAA	565
Arg552Term	ATGATAAAACATTTAGAACGATGTGAACATCGAATCATGGAAT
CGA to TGA	CCCTTGCATGGCTCTCAGTAAGTAGCTAAATAATTG
	CAATTATTTAGCTACTTACTGAGAGCCATGCAAGGGATTCCAT	566
	GATTCGATGTTCACATCGTTCTAAATGTTTTATCATTTCTCTTG
	TCAAGTTGCCTTCTGCTTTGATAAAACTTTCGAT
	ATTTAGAACGATGTGAA	567
	TTCACATCGTTCAAAT	568
Retinoblastoma	AAGTTTTATCAAAGCAGAAGGCAACTTGACAAGAGAAATGATA	569
Cys553Term	AAACATTTAGAACGATGTGAACATCGAATCATGGAATCCCTTG
TGT to TGA	CATGGCTCTCAGTAAGTAGCTAAATAATTGAAGAA
	TTCTTCAATTATTTAGCTACTTACTGAGAGCCATGCAAGGGAT	570
	TCCATGATTCGATGTTCACATCGTTCTAAATGTTTTATCATTTC
	TCTTGTCAAGTTGCCTTCTGCTTTGATAAAACTT
	GAACGATGTGAACATCG	571
	CGATGTTCACATCGTTC	572
Retinoblastoma	AGTTTTATCAAAGCAGAAGGCAACTTGACAAGAGAAATGATAA	573
Glu554Term	AACATTTAGAACGATGTGAACATCGAATCATGGAATCCCTTG
GAA to TAA	CATGGCTCTCAGTAAGTAGCTAAATAATTGAAGAAA
	TTTCTTCAATTATTTAGCTACTTACTGAGAGCCATGCAAGGGA	574
	TTCCATGATTCGATGTTCACATCGTTCTAAATGTTTTATCATTT
	CTCTTGTCAAGTTGCCTTCTGCTTTGATAAAACT
	AACGATGTGAACATCGA	575
	TCGATGTTCACATCGTT	576
Retinoblastoma	TACCTGGGAAAATTATGCTTACTAATGTGGTTTTAATTTCATC	577
Ser567Leu	ATGTTTCATATAGGATTCACCTTTATTTGATCTTATTAAACAAT
TCA to TTA	CAAAGGACCGAGAAGGACCAACTGATCACCTTGA
	TCAAGGTGATCAGTTGGTCCTTCTCGGTCCTTTGATTGTTTAA	578
	TAAGATCAAATAAAGGTGAATCCTATATGAAACATGATGAAAT
	TAAAACCACATTAGTAAGCATAATTTTCCCAGGTA
	ATAGGATTCACCTTTAT	579
	ATAAAGGTGAATCCTAT	580
Retinoblastoma	AATGTGGTTTTAATTTCATCATGTTTFCATATAGGATTCACCTTT	581
Gln575Term	ATTTGATCTTATTAAACAATCAAAGGACCGAGAAGGACCAACT
CAA to TAA	GATCACCTTGAATCTGCTTGTCCTCTTAATCTTC
	GAAGATTAAGAGGACAAGCAGATTCAAGGTGATCAGTTGGTC	582
	CTTCTCGGTCCTTTGATTGTTTAATAAGATCAAATAAAGGTGA
	ATCCTATATGAAACATGATGAAATTAAAACCACATT
	TTATTAAACAATCAAAG	583
	CTTTGATTGTTTAATAA	584
Retinoblastoma	ATTTCATCATGTTTCATATAGGATTCACCTTTATTTGATCTTAT	585
Arg579Term	TAAACAATCAAAGGACCGAGAAGGACCAACTGATCACCTTGA
CGA to TGA	ATCTGCTTGTCCTCTTAATCTTCCTCTCCAGAATA
	TATTCTGGAGAGGAAGATTAAGAGGACAAGCAGATTCAAGGT	586
	GATCAGTTGGTCCTTCTCGGTCCTTTGATTGTTTAATAAGATC
	AAATAAAGGTGAATCCTATATGAAACATGATGAAAT
	CAAAGGACCGAGAAGGA	587
	TCCTTCTCGGTCCTTTG	588
Retinoblastoma	TCATCATGTTTCATATAGGATTCACCTTTATTTGATCTTATTAA	589
Glu580Term	ACAATCAAAGGACCGAGAAGGACCAACTGATCACCTTGAATC
GAA to TAA	TGCTTGTCCTCTTAATCTTCCTCTCCAGAATAATC
	GATTATTCTGGAGAGGAAGATTAAGAGGACAAGCAGATTCAA	590
	GGTGATCAGTTGGTCCTTCTCGGTCCTTTGATTGTTTAATAAG
	ATCAAATAAAGGTGAATCCTATATGAAACATGATGA
	AGGACCGAGAAGGACCA	591
	TGGTCCTTCTCGGTCCT	592
Retinoblastoma	AGAAAAAAGGTTCAACTACGCGTGTAAATTCTACTGCAAATG	593
Ser634Term	CAGAGACACAAGCAACCTCAGCCTTCCAGACCCAGAAGCCA
TCA to TGA	TTGAAATCTACCTCTCTTTCACTGTTTTATAAAAAAGG
	CCTTTTTTATAAAACAGTGAAAGAGAGGTAGATTTCAATGGCT	594
	TCTGGGTCTGGAAGGCTGAGGTTGCTTGTGTCTCTGCATTTG
	CAGTAGAATTTACACGCGTAGTTGAACCTTTTTTCT
	AGCAACCTCAGCCTTCC	595
	GGAAGGCTGAGGTTGCT	596
Retinoblastoma	AAAAAAGGTTCAACTACGCGTGTAAATTCTACTGCAAATGCA	597
Ala635Pro	GAGACACAAGCAACCTCAGCCTTCCAGACCCAGAAGCCATT
GCC to CCC	GAAATCTACCTCTCTTTCACTGTTTTATAAAAAAGGTT
	AACCTTTTTTATAAAACAGTGAAAGAGAGGTAGATTTCAATGG	598
	CTTCTGGGTCTGGAAGGCTGAGGTTGCTTGTGTCTCTGCATT
	TGCAGTAGAATTTACACGCGTAGTTGAACCTTTTTT
	CAACCTCAGCCTTCCAG	599
	CTGGAAGGCTGAGGTTG	600
Retinoblastoma	ACTACGCGTGTAAATTCTACTGCAAATGCAGAGACACAAGCA	601
Gln639Term	ACCTCAGCCTTCCAGACCCAGAAGCCATTGAAATCTACCTCT
CAG to TAG	CTTTCACTGTTTTATAAAAAAGGTTAGTAGATGATTA
	TAATCATCTACTAACCTTTTTTATAAAACAGTGAAAGAGAGGT	602
	AGATTTCAATGGCTTCTGGGTCTGGAAGGCTGAGGTTGCTTG
	TGTCTCTGCATTTGCAGTAGAATTTACACGCGTAGT
	TCCAGACCCAGAAGCCA	603
	TGGCTTCTGGGTCTGGA	604
Retinoblastoma	TTGTAATTCAAAATGAACAGTAAAAATGACTAATTTTTCTTATT	605
Leu657Pro	CCCACAGTGTATCGGCTAGCCTATCTCCGGCTAAATACACTT
CTA to CCA	TGTGAACGCCTTCTGTCTGAGCACCCAGAATTAGA
	TCTAATTCTGGGTGCTCAGACAGAAGGCGTTCACAAAGTGTA	606
	TTTAGCCGGAGATAGGCTAGCCGATACACTGTGGGAATAAG
	AAAAATTAGTCATTTTTACTGTTCATTTTGAATTACAA
	GTATCGGCTAGCCTATC	607
	GATAGGCTAGCCGATAC	608
Retinoblastoma	AATGAACAGTAAAAATGACTAATTTTTCTTATTCCCACAGTGTA	609
Arg661Trp	TCGGCTAGCCTATCTCCGGCTAAATACACTTTGTGAACGCCT
CGG to TGG	TCTGTCTGAGCACCCAGAATTAGAACATATCATCT
	AGATGATATGTTCTAATTCTGGGTGCTCAGACAGAAGGCGTT	610
	CACAAAGTGTATTTAGCCGGAGATAGGCTAGCCGATACACTG
	TGGGAATAAGAAAAATTAGTCATTTTTACTGTTCATT
	CCTATCTCCGGCTAAAT	611
	ATTTAGCCGGAGATAGG	612
Retinoblastoma	AACAGTAAAAATGACTAATTTTTCTTATTCCCACAGTGTATCG	613
Leu662Pro	GCTAGCCTATCTCCGGCTAAATACACTTTGTGAACGCCTTCT
CTA to CCA	GTCTGAGCACCCAGAATTAGAACATATCATCTGGAC
	GTCCAGATGATATGTTCTAATTCTGGGTGCTCAGACAGAAGG	614
	CGTTCACAAAGTGTATTTAGCCGGAGATAGGCTAGCCGATAC
	ACTGTGGGAATAAGAAAAATTAGTCATTTTTACTGTT
	TCTCCGGCTAAATACAC	615
	GTGTATTTAGCCGGAGA	616
Retinoblastoma	TATCGGCTAGCCTATCTCCGGCTAAATACACTTTGTGAACGC	617
Glu675Term	CTTCTGTCTGAGCACCCAGAATTAGAACATATCATCTGGACC
GAA to TAA	CTTTTCCAGCACACCCTGCAGAATGAGTATGAACTCA
	TGAGTTCATACTCATTCTGCAGGGTGTGCTGGAAAAGGGTCC	618
	AGATGATATGTTCTAATTCTGGGTGCTCAGACAGAAGGCGTT
	CACAAAGTGTATTTAGCCGGAGATAGGCTAGCCGATA
	AGCACCCAGAATTAGAA	619
	TTCTAATTCTGGGTGCT	620
Retinoblastoma	TTTGTGAACGCCTTCTGTCTGAGCACCCAGAATTAGAACATA	621
Gln685Pro	TCATCTGGACCCTTTTCCAGCACACCCTGCAGAATGAGTATG
CAG to CCG	AACTCATGAGAGACAGGCATTTGGACCAAGTAAGAAA
	TTTCTTACTTGGTCCAAATGCCTGTCTCTCATGAGTTCATACT	622
	CATTCTGCAGGGTGTGCTGGAAAAGGGTCCAGATGATATGTT
	CTAATTCTGGGTGCTCAGACAGAAGGCGTTCACAAA
	CCTTTTCCAGCACACCC	623
	GGGTGTGCTGGAAAAGG	624
Retinoblastoma	AAAACCATGTAATAAAATTCTGACTACTTTTACATCAATTTATT	625
Cys706Tyr	TACTAGATTATGATGTGTTCCATGTATGGCATATGCAAAGTGA
TGT to TAT	AGAATATAGACCTTAAATTCAAAATCATTGTAAC
	GTTACAATGATTTTGAATTTAAGGTCTATATTCTTCACTTTGCA	626
	TATGCCATACATGGAACACATCATAATCTAGTAAATAAATTGA
	TGTAAAAGTAGTCAGAATTTTATTACATGGTTTT
	TATGATGTGTTCCATGT	627
	ACATGGAACACATCATA	628
Retinoblastoma	TTCTGACTACTTTTACATCAATTTATTTACTAGATTATGATGTG	629
Cys712Arg	TTCCATGTATGGCATATGCAAAGTGAAGAATATAGACCTTAAA
TGC to CGC	TTCAAAATCATTGTAACAGCATACAAGGATCTTC
	GAAGATCCTTGTATGCTGTTACAATGATTTTGAATTTAAGGTC	630
	TATATTCTTCACTTTGCATATGCCATACATGGAACACATCATA
	ATCTAGTAAATAAATTGATGTAAAAGTAGTCAGAA
	ATGGCATATGCAAAGTG	631
	CACTTTGCATATGCCAT	632
Retinoblastoma	GTATGGCATATGCAAAGTGAAGAATATAGACCTTAAATTCAAA	633
Tyr728Term	ATCATTGTAACAGCATACAAGGATCTTCCTCATGCTGTTCAG
TAC to TAA	GAGGTAGGTAATTTTCCATAGTAAGTTTTTTTGATA
	TATCAAAAAAACTTACTATGGAAAATTACCTACCTCCTGAACA	634
	GGATGAGGAAGATCCTTGTATGCTGTTACAATGATTTTGAATT
	TAAGGTCTATATTCTTCACTTTGCATATGCCATAC
	ACAGCATACAAGGATCT	635
	AGATGCTTGTATGCTGT	636
Retinoblastoma	TTTTTTTTTTTTTTTACTGTTGTTCCTCAGACATTCAAACGTGT	637
Glu748Term	TTTGATCAAAGAAGAGGAGTATGATTCTATTATAGTATTCTATA
GAG to TAG	ACTCGGTCTTCATGCAGAGACTGAAAACAAATA
	TATTTGTTTTCAGTCTCTGCATGAAGACCGAGTTATAGAATAC	638
	TATAATAGAATCATACTCCTCTTCTTTGATCAAAACACGTTTGA
	ATGTCTGAGGAAGAACAGTAAAAAAAAAAAAAAA
	AAGAAGAGGAGTATGAT	639
	ATCATACTCCTCTTCTT	640
Retinoblastoma	GTTTTGATCAAAGAAGAGGAGTATGATTCTATTATAGTATTCT	641
Gln762Term	ATAACTCGGTCTTCATGCAGAGACTGAAAACAAATATTTTGCA
CAG to TAG	GTATGCTTCCACCAGGGTAGGTGAAAAGTATCCTT
	AAGGATACTTTTGACCTACCCTGGTGGAAGCATACTGCAAAA	642
	TATTTGTTTTCAGTCTCTGCATGAAGACCGAGTTATAGAATAC
	TATAATAGAATCATACTCCTCTTCTTTGATCAAAAC
	TCTTCATGCAGAGACTG	643
	CAGTCTCTGCATGAAGA	644
Retinoblastoma	TAATCTACTTTTTTGTTTTTGCTCTAGCCCCCTACCTTGTCAC	645
Arg787Term	CAATACCTCACATTCCTCGAAGCCCTTACAAGTTTCCTAGTTC
CGA-TGA	ACCCTTACGGATTCCTGGAGGGAACATCTATATTT
	AAATATAGATGTTCCCTCCAGGAATCCGTAAGGGTGAACTAG	646
	GAAACTTGTAAGGGGCTTCGAGGAATGTGAGGTATTGGTGACA
	AGGTAGGGGGCTAGAGCAAAAACAAAAAAGTAGATTA
	ACATTCCTCGAAGCCCT	647
	AGGGCTTCGAGGAATGT	648
Retinoblastoma	CCTTACGGATTCCTGGAGGGAACATCTATATTTCACCCCTGA	649
Ser816Term	AGAGTCCATATAAAATTTCAGAAGGTCTGCCAACACCAACAA
TCA to TGA	AAATGACTCCAAGATCAAGGTGTGTGTTTTCTCTTTA
	TAAAGAGAAAACACACACCTTGATCTTGGAGTCATTTTTGTTG	650
	GTGTTGGCAGACCTTCTGAAATTTTATATGGACTCTTCAGGG
	GTGAAATATAGATGTTCCCTCCAGGAATCCGTAAGG
	TAAAATTTCAGAAGGTC	651
	GACCTTCTGAAATTTTA	652

EXAMPLE 8

BRCA1 and BRCA2

[0121] Breast cancer is the second major cause of cancer death in American women, with an estimated 44,190 lives lost (290 men and 43,900 women) in the US in 1997. While ovarian cancer accounts for fewer deaths than breast cancer, it still represents 4% of all female cancers. In 1994, two breast cancer susceptibility genes were identified: BRCA1 on chromosome 17 and BRCA2 on chromosome 13. When a woman carries a mutation in either BRCA1 or BRCA2, she is at increased risk of being diagnosed with breast or ovarian cancer at some point in her life.

[0122] Ford et al., Am. J. Hum. Genet 62: 676-689 (1998) assessed the contribution of BRCA1 and BRCA2 to inherited breast cancer by linkage and mutation analysis in 237 families, each with at least 4 cases of breast cancer. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16%, suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority (76%) of families with both male and female breast cancer were due to BRCA2. The largest proportion (67%) of families due to other genes were families with 4 or 5 cases of female breast cancer only.

[0123] More than 75% of the reported mutations in the BRCA1 gene result in truncated proteins. Couch et al., Hum. Mutat. 8: 8-18, 1996. (1996) reported a total of 254 BRCA1 mutations, 132 (52%) of which were unique. A total of 221 (87%) of all mutations or 107 (81%) of the unique mutations are small deletions, insertions, nonsense point mutations, splice variants, and regulatory mutations that result in truncation or absence of the BRCA1 protein. A total of 11 disease-associated missense mutations (5 unique) and 21 variants (19 unique) as yet unclassified as missense mutations or polymorphisms had been detected. Thirty-five independent benign polymorphisms had been described. The most common mutations were 185delAG and 5382insC, which accounted for 30 (11.7%) and 26 (10.1%), respectively, of all the mutations.

[0124] Most BRCA2 mutations are predicted to result in a truncated protein product. The smallest known cancer-associated deletion removes from the C terminus only 224 of the 3,418 residues constituting BRCA2, suggesting that these terminal amino acids are critical for BRCA2 function. Studies (Spain et al., Proc. Natl. Acad. Sci. 96:13920-13925 (1999)) suggest that such truncations eliminate or interfere with 2 nuclear localization signals that reside within the final 156 residues of BRCA2, suggesting that the vast majority of BRCA2 mutants are nonfunctional because they are not translocated into the nucleus.

[0125] The attached table discloses the correcting oligonucleotide base sequences for the BRACA1 and BRACA2 oligonucleotides of the invention.

TABLE 14
BRCA1 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Breast Cancer	CTGCGCTCAGGAGGCCTTCACCCTCTGCTCTGGGTAAAGTT	653
Met-1-Ile	CATTGGAACAGAAAGAAATGGATTTATCTGCTCTTCGCGTTG
ATG to ATT	AAGAAGTACAAAATGTCATTAATGCTATGCAGAAAATC
	GATTTTCTGCATAGCATTAATGACATTTTGTACTTCTTCAACG
	CGAAGAGCAGATAAATCCATTTCTTTCTGTTCCAATGAACTTT
	ACCCAGAGCAGAGGGTGAAGGCCTCCTGAGCGCAG
	AAAGAAATGGATTTATC	655
	GATAAATCCATTTCTTT	656
Breast Cancer	CTGGGTAAAGTTCATTGGAACAGAAAGAAATGGATTTATCTG	657
Val-11-Ala	CTCTTCGCGTTGAAGAAGTACAAAATGTCATTAATGCTATGCA
GTA to GCA	GAAAATCTTAGAGTGTCCCATCTGTCTGGAGTTGAT
	ATCAACTCCAGACAGATGGGACACTCTAAGATTTTCTGCATA	658
	GCATTAATGACATTTTGTACTTCTTCAACGCGAAGAGCAGATA
	AATCCATTTCTTTCTGTTCCAATGAACTTTACCCAG
	TGAAGAAGTACAAAATG	659
	CATTTTGTACTTCTTCA	660
Breast Cancer	ATGGATTTATCTCTCTTCGCGTTGAAGAAGTACAAAATGTCA	661
Ile-21-Val	TTAATGCTATGCAGAAAATCTTAGAGTGTCCCATCTGTCTGG
ATC to GTC	AGTTGATCAAGGAACCTGTCTCCACAAAGTGTGACC
	GGTCACACTTTGTGGAGACAGGTTCCTTGATCAACTCCAGAC	662
	AGATGGGACACTCTAAGATTTTCTGCATAGCATTAATGACATT
	TTGTACTTCTTCAACGCGAAGAGCAGATAAATCCAT
	TGCAGAAAATCTTAGAG	663
	CTCTAAGATTTTCTGCA	664
Breast Cancer	ATTTATCTGCTCTTCGCGTTGAAGAAGTACAAAATGTCATTAA	665
Leu-22-Ser	TGCTATGCAGAAAATCTTAGAGTGTCCCATCTGTCTGGAGTT
TTA to TCA	GATCAAGGAACCTGTCTCCACAAAGTGTGACCACAT
	ATGTGGTCACACTTTGTGGAGACAGGTTCCTTGATCAACTCC	666
	AGACAGATGGGACACTCTAAGATTTTCTGCATAGCATTAATG
	ACATTTTGTACTTCTTCAACGCGAAGAGCAGATAAAT
	GAAAATCTTAGAGTGTC	667
	GACACTCTAAGATTTTC	668
Breast Cancer	AGAAAATCTTAGAGTGTCCCATCTGTCTGGAGTTGATCAAGG	669
Cys-39-Tyr	AACCTGTCTCCACAAAGTGTGACCACATATTTTGCAAATTTTG
TGT to TAT	CATGCTGAAACTTCTCAACCAGAAGAAAGGGCCTTC
	GAAGGCCCTTTCTTCTGGTTGAGAAGTTTCAGCATGCAAAAT	670
	TTGCAAAATATGTGGTCACACTTTGTGGAGACAGGTTCCTTG
	ATCAACTCCAGACAGATGGGACACTCTAAGATTTTCT
	CACAAAGTGTGACCACA	671
	TGTGGTCACACTTTGTG	672
Breast Cancer	CACATATTTTGCAAATTTTGCATGCTGAAACTTCTCAACCAGA	673
Cys-61-Gly	AGAAAGGGCCTTCACAGTGTCCTTTATGTAAGAATGATATAAC
TGT to GGT	CAAAAGGAGCCTACAAGAAAGTACGAGATTTAGTC
	GACTAAATCTCGTACTTTCTTGTAGGCTCCTTTTGGTTATATC	674
	ATTCTTACATAAAGGACACTGTGAAGGCCCTTTCTTCTGGTT
	GAGAAGTTTCAGCATGCAAAATTTGCAAAATATGTG
	CTTCACAGTGTCCTTTA	675
	TAAAGGACACTGTGAAG	676
Breast Cancer	TTTGCAAATTTTGCATGCTGAAACTTCTCAACCAGAAGAAAGG	677
Leu-63-Stop	GCCTTCACAGTGTCCTTTATGTAAGAATGATATAACCAAAAGG
TTA to TAA	AGCCTACAAGAAAGTACGAGATTTAGTCAACTTGT
	ACAAGTTGACTAAATCTCGTACTTTCTTGTAGGCTCCTTTTGG	678
	TTATATCATTCTTACATAAAGGACACTGTGAAGGCCCTTTCTT
	CTGGTTGAGAAGTTTCAGCATGCAAAATTTGCAAA
	GTGTCCTTTATGTAAGA	679
	TCTTACATAAAGGACAC	680
Breast Cancer	TGCAAATTTTGCATGCTGAAACTTCTCAACCAGAAGAAAGGG	681
Cys-64-Arg	CCTTCACAGTGTCCTTTATGTAAGAATGATATAACCAAAAGGA
TGT to CGT	GCCTACAAGAAAGTACGAGATTTAGTCAACTTGTTG
Breast Cancer	CAACAAGTTGACTAAATCTCGTACTTTCTTGTAGGCTCCTTTT	682
Cys-64-Gly	GGTTATATCATTCTTACATAAAGGACACTGTGAAGGCCCTTTC
TGT to GGT	TTCTGGTTGAGAAGTTTCAGCATGCAAAATTTGCA
	GTCCTTTATGTAAGAAT	683
	ATTCTTACATAAAGGAC	684
Breast Cancer	GCAAATTTTGCATGCTGAAACTTCTCAACCAGAAGAAAGGGC	685
Cys-64-Tyr	CTTCACAGTGTCCTTTATGTAAGAATGATATAACCAAAAGGAG
TGT to TAT	CCTACAAGAAAGTACGAGATTTAGTCAACTTGTTGA
	TCAACAAGTTGACTAAATCTCGTACTTTCTTGTAGGCTCCTTT	686
	TGGTTATATCATTCTTACATAAAGGACACTGTGAAGGCCCTTT
	CTTCTGGTTGAGAAGTTTCAGCATGCAAAATTTGC
	TCCTTTATGTAAGAATG	687
	CATTCTTACATAAAGGA	688
Breast Cancer	CAGAAGAAAGGGCCTTCACAGTGTCCTTTATGTAAGAATGAT	689
Gln-74-Stop	ATAACCAAAAGGAGCCTACAAGAAAGTACGAGATTTAGTCAA
CAA to TAA	CTTGTTGAAGAGCTATTGAAAATCATTTGTGCTTTTC
	GAAAAGCACAAATGATTTTCAATAGCTCTTCAACAAGTTGACT	690
	AAATCTCGTACTTTCTTGTAGGCTCCTTTTGGTTATATCATTCT
	TACATAAAGGACACTGTGAAGGCCCTTTCTTCTG
	GGAGCCTACAAGAAAGT	691
	ACTTTCTTGTAGGCTCC	692
Breast Cancer	AGCTATTGAAAATCATTTGTGCTTTTCAGCTTGACACAGGTTT	693
Tyr-105-Cys	GGAGTATGCAAACAGCTATAATTTTGCAAAAAAGGAAAATAAC
TAT to TGT	TCTCCTGAACATCTAAAAGATGAAGTTTCTATCAT
	ATGATAGAAACTTCATCTTTTAGATGTTCAGGAGAGTTATTTT	694
	CCTTTTTTGCAAAATTATAGCTGTTTGCATACTCCAAACCTGT
	GTCAAGCTGAAAAGCACAAATGATTTTCAATAGCT
	AAACAGCTATAATTTTG	695
	CAAAATTATAGCTGTTT	696
Breast Cancer	CTACAGAGTGAACCCGAAAATCCTTCCTTGCAGGAAACCAGT	697
Asn-158-Tyr	CTCAGTGTCCAACTCTCTAACCTTGGAACTGTGAGAACTCTG
AAC to TAC	AGGACAAAGCAGCGGATACAACCTCAAAAGACGTCTG
	CAGACGTCTTTTGAGGTTGTATCCGCTGCTTTGTCCTCAGAG	698
	TTCTCACAGTTCCAAGGTTAGAGAGTTGGACACTGAGACTGG
	TTTCCTGCAAGGAAGGATTTTCGGGTTCACTCTGTAG
	AACTCTCTAACCTTGGA	699
	TCCAAGGTTAGAGAGTT	700
Breast Cancer	GAAACCAGTCTCAGTGTCCAACTCTCTAACCTTGGAACTGTG	701
Gln-169-Stop	AGAACTCTGAGGACAAAGCAGCGGATACAACCTCAAAAGAC
CAG to TAG	GTCTGTCTACATTGAATTGGGATCTGATTCTTCTGAAG
	CTTCAGAAGAATCAGATCCCAATTCAATGTAGACAGACGTCTT	702
	TTGAGGTTGTATCCGCTGCTTTGTCCTCAGAGTTCTCACAGT
	TCCAAGGTTAGAGAGTTGGACACTGAGACTGGTTTC
	GGACAAAGCAGCGGATA	703
	TATCCGCTGCTTTGTCC	704
Breast Cancer	CTCCCAGCACAGAAAAAAAGGTAGATCTGAATGCTGATCCCC	705
Trp-353-Stop	TGTGTGAGAGAAAAGAATGGAATAAGCAGAAACTGCCATGCT
TGG to TAG	CAGAGAATCCTAGAGATACTGAAGATGTTCCTTGGAT
	ATCCAAGGAACATCTTCAGTATCTCTAGGATTCTCTGAGCAT	706
	GGCAGTTTCTGCTTATTCCATTCTTTTCTCTCACACAGGGGAT
	CAGCATTCAGATCTACCTTTTTTTCTGTGCTGGGAG
	AAAAGAATGGAATAAGC	707
	GCTTATTCCATTCTTTT	708
Breast Cancer	ATGCTCAGAGAATCCTAGAGATACTGAAGATGTTCCTTGGAT	709
Ile-379-Met	AACACTAAATAGCAGCATTCAGAAAGTTAATGAGTGGTTTTCC
ATT to ATG	AGAAGTGATGAACTGTTAGGTTCTGATGACTCACAT
	ATGTGAGTCATCAGAACCTAACAGTTCATCACTTCTGGAAAAC	710
	CACTCATTAACTTTCTGAATGCTGCTATTTAGTGTTATCCAAG
	GAACATCTTCAGTATCTCTAGGATTCTCTGAGCAT
	AGCAGCATTCAGAAAGT	711
	ACTTTCTGAATGCTGCT	712
Breast Cancer	GGGAGTCTGAATCAAATGCCAAAGTAGCTGATGTATTGGACG	713
Glu-421-Gly	TTCTAAATGAGGTAGATGAATATTCTGGTTCTTCAGAGAAAAT
GAA to GGA	AGACTTACTGGCCAGTGATCCTCATGAGGCTTTAAT
	ATTAAAGCCTCATGAGGATCACTGGCCAGTAAGTCTATTTTCT	714
	CTGAAGAACCAGAATATTCATCTACCTCATTTAGAACGTCCAA
	TACATCAGCTACTTTGGCATTTGATTCAGACTCCC
	GGTAGATGAATATTCTG	715
	CAGAATATTCATCTACC	716
Breast Cancer	ATATGTAAAAGTGAAAGAGTTCACTCCAAATCAGTAGAGAGTA	717
Phe-461-Leu	ATATTGAAGACAAAATATTTGGGAAAACCTATCGGAAGAAGG
TTT to CTT	CAAGCCTCCCCAACTTAAGCCATGTAACTGAAAATC
	GATTTTCAGTTACATGGCTTAAGTTGGGGAGGCTTGCCTTCT	718
	TCCGATAGGTTTTCCCAAATATTTTGTCTTCAATATTACTCTCT
	ACTGATTTGGAGTGAACTCTTTCACTTTTACATAT
	ACAAAATATTTGGGAAA	719
	TTTCCCAAATATTTTGT	720
Breast Cancer	GAAAGAGTTCACTCCAAATCAGTAGAGAGTAATATTGAAGAC	721
Tyr-465-Leu	AAAATATTTGGGAAAACCTATCGGAAGAAGGCAAGCCTCCCC
TAT to GAT	AACTTAAGCCATGTAACTGAAAATCTAATTATAGGAG
	CTCCTATAATTAGATTTTCAGTTACATGGCTTAAGTTGGGGAG	722
	GCTTGCCTTCTTCCGATAGGTTTTCCCAAATATTTTGTCTTCA
	ATATTACTCTCTACTGATTTGGAGTGAACTCTTTC
	GGAAAACCTATCGGAAG	723
	CTTCCGATAGGTTTTCC	724
Breast Cancer	ACCTATCGGAAGAAGGCAAGCCTCCCCAACTTAAGCCATGTA	725
Gly-484-Stop	ACTGAAAATCTAATTATAGGAGCATTTGTTACTGAGCCACAGA
GGA to TGA	TAATACAAGAGCGTCCCCTCACAAATAAATTAAAGC
	GCTTTAATTTATTTGTGAGGGGACGCTCTTGTATTATCTGTGG	726
	CTCAGTAACAAATGCTCCTATAATTAGATTTTCAGTTACATGG
	CTTAAGTTGGGGAGGCTTGCCTTCTTCCGATAGGT
	TAATTATAGGAGCATTT	727
	AAATGCTCCTATAATTA	728
Breast Cancer	TTACTGAGCCACAGATAATACAAGAGCGTCCCCTCACAAATA	729
Arg-507-Ile	AATTAAAGCGTAAAAGGAGACCTACATCAGGCCTTCATCCTG
AGA to ATA	AGGATTTTATCAAGAAAGCAGATTTGGCAGTTCAAAA
	TTTTGAACTGCCAAATCTGCTTTCTTGATAAAATCCTCAGGAT	730
	GAAGGCCTGATGTAGGTCTCCTTTTACGCTTTAATTTATTTGT
	GAGGGGACGCTCTTGTATTATCTGTGGCTCAGTAA
	TAAAAGGAGACCTACAT	731
	ATGTAGGTCTCCTTTTA	732
Breast Cancer	CACAGATAATACAAGAGCGTCCCCTCACAAATAAATTAAAGC	733
Ser-510-Stop	GTAAAAGGAGACCTACATCAGGCCTTCATCCTGAGGATTTTA
TCA to TGA	TCAAGAAAGCAGATTTGGCAGTTCAAAAGACTCCTGA	Q
	TCAGGAGTCTTTTGAACTGCCAAATCTGCTTTCTTGATAAAAT	734
	CCTCAGGATGAAGGCCTGATGTAGGTCTCCTTTTACGCTTTA
	ATTTATTTGTGAGGGGACGCTCTTGTATTATCTGTG
	ACCTACATCAGGCCTTC	735
	GAAGGCCTGATGTAGGT	736
Breast Cancer	AGGAGACCTACATCAGGCCTTCATCCTGAGGATTTTATCAAG	737
Gln-526-Stop	AAAGCAGATTTGGCAGTTCAAAAGACTCCTGAAATGATAAATC
CAA to TAA	AGGGAACTAACCAAACGGAGCAGAATGGTCAAGTGA
	TCACTTGACCATTCTGCTCCGTTTGGTTAGTTCCCTGATTTAT	738
	CATTTCAGGAGTCTTTTGAACTGCCAAATCTGCTTTCTTGATA
	AAATCCTCAGGATGAAGGCCTGATGTAGGTCTCCT
	TGGCAGTTCAAAAGACT	739
	AGTCTTTTGAACTGCCA	740
Breast Cancer	AGGAGACCTACATCAGGCCTTCATCCTGAGGATTTTATCAAG	741
Gln-541-Stop	AAAGCAGATTTGGCAGTTCAAAAGACTCCTGAAATGATAAATC
CAG to TAG	AGGGAACTAACCAAACGGAGCAGAATGGTCAAGTGA
	TCACTTGACCATTCTGCTCCGTTTGGTTAGTTCCCTGATTTAT	742
	CATTTCAGGAGTCTTTTGAACTGCCAAATCTGCTTTCTTGATA
	AAATCCTCAGGATGAAGGCCTGATGTAGGTCTCCT
	AAACGGAGCAGAATGGT	743
	ACCATTCTGCTCCGTTT	744
Breast Cancer	TAAATCAGGGAACTAACCAAACGGAGCAGAATGGTCAAGTGA	745
Gly-552-Val	TGAATATTACTAATAGTGGTCATGAGAATAAAACAAAAGGTGA
GGT to GTT	TTCTATTCAGAATGAGAAAAATCCTAACCCAATAGA
	TCTATTGGGTTAGGATTTTTCTCATTCTGAATAGAATCACCTTT	746
	TGTTTTATTCTCATGACCACTATTAGTAATATTCATCACTTGAC
	CATTCTGCTCCGTTTGGTTAGTTCCCTGATTTA
	TAATAGTGGTCATGAGA	747
	TCTCATGACCACTATTA	748
Breast Cancer	GGTCAAGTGATGAATATTACTAATAGTGGTCATGAGAATAAAA	749
Gln-563-Stop	CAAAAGGTGATTCTATTCAGAATGAGAAAAATCCTAACCCAAT
CAT to TAG	AGAATCACTCGAAAAAGAATCTGCTTTCAAAACGA
	TCGTTTTGAAAGCAGATTCTTTTTCGAGTGATTCTATTGGGTT	750
	AGGATTTTTCTCATTCTGAATAGAATCACCTTTTGTTTTATTCT
	CATGACCACTATTAGTAATATTCATCACTTGACC
	ATTCTATTCAGAATGAG	751
	CTCATTCTGAATAGAAT	752
Ovarian Cancer	ATAAGCAGCAGTATAAGCAATATGGAACTCGAATTAAATATCC	753
Lys-607-Stop	ACAATTCAAAAGCACCTAAAAAGAATAGGCTGAGGAGGAAGT
AAA to TAA	CTTCTACCAGGCATATTCATGCGCTTGAACTAGTAG
	CTACTAGTTCAAGCGCATGAATATGCCTGGTAGAAGACTTCC	754
	TCCTCAGCCTATTCTTTTTAGGTGCTTTTGAATTGTGGATATT
	TAATTCGAGTTCCATATTGCTTATACTGCTGCTTAT
	AAGCACCTAAAAAGAAT	755
	ATTCTTTTTAGGTGCTT	756
Breast Cancer	ATATTCATGCGCTTGAACTAGTAGTCAGTAGAAATCTAAGCCC	757
Leu-639-Stop	ACCTAATTGTACTGAATTGCAAATTGATAGTTGTTCTAGCAGT
TTG to TAG	GAAGAGATAAAGAAAAAAAAGTACAACCAAATGCC
	GGCATTTGGTTGTACTTTTTTTTCTTTATCTCTTCACTGCTAGA	758
	ACAACTATCAATTTGCAATTCAGTACAATTAGGTGGGCTTAGA
	TTTCTACTGACTACTAGTTCAAGCGCATGAATAT
	TACTGAATTGCAAATTG	759
	CAATTTGCAATTCAGTA	760
Breast Cancer	GAACCTGCAACTGGAGCCAAGAAGAGTAACAAGCCAAATGAA	761
Asp-693-Asn	CAGACAAGTAAAAGACATGACAGCGATACTTTCCCAGAGCTG
GAC to AAC	AAGTTAACAAATGCACCTGGTTCTTTTACTAAGTGTT
	AACACTTAGTAAAAGAACCAGGTGCATTTGTTAACTTCAGCTC	762
	TGGGAAAGTATCGCTGTCATGTCTTTTACTTGTCTGTTCATTT
	GGCTTGTTACTCTTCTTGGCTCCAGTTGCAGGTTC
	AAAGACATGACAGCGAT	763
	ATCGCTGTCATGTCTTT	764
Ovarian Cancer	CTGAAGTTAACAAATGCACCTGGTTCTTTTACTAAGTGTTCAA	765
Glu-720-Stop	ATACCAGTGAACTTAAAGAATTTGTCAATCCTAGCCTTCCAAG
GAA to TAA	AGAAGAAAAAGAAGAGAAACTAGAAACAGTTAAAG
	CTTTAACTGTTTCTAGTTTCTCTTCTTTTTCTTCTCTTGGAAGG	766
	CTAGGATTGACAAATTCTTTAAGTTCACTGGTATTTGAACACT
	TAGTAAAAGAACCAGGTGCATTTGTTAACTTCAG
	AACTTAAAGAATTTGTC	767
	GACAAATTCTTTAAGTT	768
Breast Cancer	CTAGAAACAGTTAAAGTGTCTAATAATGCTGAAGACCCCAAA	769
Glu-755-Stop	GATCTCATGTTAAGTGGAGAAAGGGTTTTGCAAACTGAAAGA
GAA to TAA	TCTGTAGAGAGTAGCAGTATTTCATTGGTACCTGGTA
	TACCAGGTACCAATGAAATACTGCTACTCTCTACAGATCTTTC	770
	AGTTTGCAAAACCCTTTCTCCACTTAACATGAGATCTTTGGGG
	TCTTCAGCATTATTAGACACTTTAACTGTTTCTAG
	TAAGTGGAGAAAGGGTT	771
	AACCCTTTCTCCACTTA	772
Breast Cancer	TCATGTTAAGTGGAGAAAGGGTTTTGCAAACTGAAAGATCTG	773
Ser-770-Stop	TAGAGAGTAGCAGTATTTCATTGGTACCTGGTACTGATTATG
TCA to TAA	GCACTCAGGAAAGTATCTCGTTACTGGAAGTTAGCAC
	GTGCTAACTTCCAGTAACGAGATACTTTCCTGAGTGCCATAA	774
	TCAGTACCAGGTACCAATGAAATACTGCTACTCTCTACAGAT
	CTTTCAGTTTGCAAAACCCTTTCTCCACTTAACATGA
	CAGTATTTCATTGGTAC	775
	GTACCAATGAAATACTG	776
Breast Cancer	TAAGTGGAGAAAGGGTTTTGCAAACTGAAAGATCTGTAGAGA	777
Val-772-Ala	GTAGCAGTATTTCATTGGTACCTGGTACTGATTATGGCACTC
GTA to GCA	AGGAAAGTATCTCGTTACTGGAAGTTAGCACTCTAGG
	CCTAGAGTGCTAACTTCCAGTAACGAGATACTTTCCTGAGTG	778
	CCATAATCAGTACCAGGTACCAATGAAATACTGCTACTCTCTA
	CAGATCTTTCAGTTTGCAAAACCCTTTCTCCACTTA
	TTCATTGGTACCTGGTA	779
	TACCAGGTACCAATGAA	780
Breast Cancer	ACTGAAAGATCTGTAGAGAGTAGCAGTATTTCATTGGTACCT	781
Gln-780-Stop	GGTACTGATTATGGCACTCAGGAAAGTATCTCGTTACTGGAA
CAG to TAG	GTTAGCACTCTAGGGAAGGCAAAAACAGAACCAAATA
	TATTTGGTTCTGTTTTTGCCTTCCCTAGAGTGCTAACTTCCAG	782
	TAACGAGATACTTTCCTGAGTGCCATAATCAGTACCAGGTAC
	CAATGAAATACTGCTACTCTCTACAGATCTTTCAGT
	ATGGCACTCAGGAAAGT	783
	ACTTTCCTGAGTGCCAT	784
Breast Cancer	TATGGCACTCAGGAAAGTATCTCGTTACTGGAAGTTAGCACT	785
Glu-797-Stop	CTAGGGAAGGCAAAAACAGAACCAAATAAATGTGTGAGTCAG
GAA to TAA	TGTGCAGCATTTGAAAACCCCAAGGGACTAATTCATG
	CATGAATTAGTCCCTTGGGGTTTTCAAATGCTGCACACTGAC	786
	TCACACATTTATTTGGTTCTGTTTTTGCCTTCCCTAGAGTGCT
	AACTTCCAGTAACGAGATACTTTCCTGAGTGCCATA
	CAAAAACAGAACCAAAT	787
	ATTTGGTTCTGTTTTTG	788
Breast Cancer	AAATGTGTGAGTCAGTGTGCAGCATTTGAAAACCCCAAGGGA	789
Lys-820-Glu	CTAATTCATGGTTGTTCCAAAGATAATAGAAATGACACAGAAG
AAA to GAA	GCTTTAAGTATCCATTGGGACATGAAGTTAACCACA
	TGTGGTTAACTTCATGTCCCAATGGATACTTAAAGCCTTCTGT	790
	GTCATTTCTATTATCTTTGGAACAACCATGAATTAGTCCCTTG
	GGGTTTTCAAATGCTGCACACTGACTCACACATTT
	GTTGTTCCAAAGATAAT	791
	ATTATCTTTGGAACAAC	792
Breast Cancer	CAGCATTTGAAAACCCCAAGGGACTAATTCATGGTTGTTCCA	793
Thr-826-Lys	AAGATAATAGAAATGACACAGAAGGCTTTAAGTATCCATTGG
ACA to AAA	GACATGAAGTTAACCACAGTCGGGAAACAAGCATAGA
	TCTATGCTTGTTTCCCGACTGTGGTTAACTTCATGTCCCAATG	794
	GATACTTAAAGCCTTCTGTGTCATTTCTATTATCTTTGGAACA
	ACCATGAATTAGTCCCTTGGGGTTTTCAAATGCTG
	AAATGACACAGAAGGCT	795
	AGCCTTCTGGTCATTT	796
Breast Cancer	GATAATAGAAATGACACAGAAGGCTTTAAGTATCCATTGGGA	797
Arg-841-Trp	CATGAAGTTAACCACAGTTGGGAAACAAGCATAGAAATGGAA
CGG to TGG	GAAAGTGAACTTGATGCTCAGTATTTGCAGAATACAT	798
	ATGTATTCTGCAAATACTGAGCATCAAGTTCACTTTCTTCCAT
	GGATACTTAAAGCCTTCTGTGTCATTTCTATTATC
	ACCACAGTCGGGAAACA	799
	TGTTTCCCGACTGTGGT	800
Breast Cancer	AACTTGATGCTCAGTATTTGCAGAATACATTCAAGGTTTCAAA	801
Pro-871-Leu	GCGCCAGTCATTTGCTCCGTTTTCAAATCCAGGAAATGCAGA
CCG to CTG	AGAGGAATGTGCAACATTCTCTGCCCACTCTGGGTC
	GACCCAGAGTGGGCAGAGAATGTTGCACATTCCTCTTCTGCA	802
	TTTCCTGGATTTGAAAACGGAGCAAATGACTGGCGCTTTGAA
	ACCTTGAATGTATTCTGCAAATACTGAGCATCAAGTT
	ATTTGCTCCGTTTTCAA	803
	TTGAAAACGGAGCAAAT	804
Breast Cancer	TTTCAAATCCAGGAAATGCAGAAGAGGAATGTGCAACATTCT
Leu-892-Ser	CTGCCCACTCTGGGTCCTTAAAGAAACAAAGTCCAAAAGTCA
TTA to TCA	CTTTTGAATGTGAACAAAAGGAAGAAAATCAAGGAAA
	TTTCCTTGATTTTCTTCCTTTTGTTCACATTCAAAAGTGACTTT	806
	TGGACTTTGTTTCTTTAAGGACCCAGAGTGGGCAGAGAATGT
	TGCACATTCCTCTTCTGCATTTCCTGGATTTGAAA
	TGGGTCCTTAAAGAAAC	807
	GTTTCTTTAAGGACCCA	808
Breast Cancer	CACTCTGGGTCCTTAAAGAAACAAAGTCCAAAAGTCACTTTTG	809
Glu-908-Stop	AATGTGAACAAAAGGAAGAAAATCAAGGAAAGAATGAGTCTA
GAA to TAA	ATATCAAGCCTGTACAGACAGTTAATATCACTGCAG
	CTGCAGTGATATTAACTGTCTGTACAGGCTTGATATTAGACTC	810
	ATTCTTTCCTTGATTTTCTTCCTTTTGTTCACATTCAAAAGTGA
	CTTTTGGACTTTGTTTCTTTAAGGACCCAGAGTG
	AAAAGGAAGAAAATCAA	811
	TTGATTTTCTTCCTTTT	812
Breast Cancer	ATAATGCCAAATGTAGTATCAAAGGAGGCTCTAGGTTTTGTCT	813
Gly-960-Asp	ATCATCTCAGTTCAGAGGCAACGAAACTGGACTCATTACTCC
GGC to GAC	AAATAAACATGGACTTTTACAAAACCCATATCGTAT
	ATACGATATGGGTTTTGTAAAAGTCCATGTTTATTTGGAGTAA	814
	TGAGTCCAGTTTCGTTGCCTCTGAACTGAGATGATAGACAAA
	ACCTAGAGCCTCCTTTGATACTACATTTGGCATTAT
	GTTCAGAGGCAACGAAA	815
	TTTCGTTGCCTCTGAAC	816
Breast Cancer	ATTTGTTAAAACTAAATGTAAGAAAAATCTGCTAGAGGAAAAC	817
Met-1008-Ile	TTTGAGGAACATTCAATGTCACCTGAAAGAGAAATGGGAAAT
ATG to ATA	GAGAACATTCCAAGTACAGTGAGCACAATTAGCCGT
	ACGGCTAATTGTGCTCACTGTACTTGGAATGTTCTCATTTCCC	818
	ATTTCTCTTTCAGGTGACATTGAATGTTCCTCAAAGTTTTCCT
	CTAGCAGATTTTTCTTACATTTAGTTTTAACAAAT
	CATTCAATGTCACCTGA	819
	TCAGGTGACATTGAATG	820
Breast Cancer	ACTTTGAGGAACATTCAATGTCACCTGAAAGAGAAATGGGAA	821
Thr-1025-Ile	ATGAGAACATTCCAAGTACAGTGAGCACAATTAGCCGTAATA
ACA to ATA	ACATTAGAGAAAATGTTTTTAAAGAAGCCAGCTCAAG
	CTTGAGCTGGCTTCTTTAAAAACATTTTCTCTAATGTTATTACG	822
	GCTAATTGTGCTCACTGTACTTGGAATGTTCTCATTTCCCATT
	TCTCTTTCAGGTGACATTGAATGTTCCTCAAAGT
	TCCAAGTACAGTGAGCA	823
	TGCTCACTGTACTTGGA	824
Breast Cancer	ACATTCCAAGTACAGTGAGCACAATTAGCCGTAATAACATTAG	825
Glu-1038-Gly	AGAAAATGTTTTTAAAGAAGCCAGCTCAAGCAATATTAATGAA
GAA to GGA	GTAGGTTCCAGTACTAATGAAGTGGGCTCCAGTAT
	ATACTGGAGCCCACTTCATTAGTACTGGAACCTACTTCATTAA	826
	TATTGCTTGAGCTGGCTTCTTTAAAAACATTTTCTCTAATGTTA
	TTACGGCTAATTGTGCTCACTGTACTTGGAATGT
	TTTTAAAGAAGCCAGCT	827
	AGCTGGCTTCTTTAAAA	828
Breast Cancer	CAAGTACAGTGAGCACAATTAGCCGTAATAACATTAGAGAAA	829
Ser-1040-Asn	ATGTTTTTAAAGAAGCCAGCTCAAGCAATATTAATGAAGTAGG
AGC to AAC	TTCCAGTACTAATGAAGTGGGCTCCAGTATTAATGA
	TCATTAATACTGGAGCCCACTTCATTAGTACTGGAACCTACTT	830
	CATTAATATTGCTTGAGCTGGCTTCTTTAAAAACATTTTCTCTA
	ATGTTATTACGGCTAATTGTGCTCACTGTACTTG
	AGAAGCCAGCTCAAGCA	831
	TGCTTGAGCTGGCTTCT	832
Breast Cancer	GCCGTAATAACATTAGAGAAAATGTTTTTAAAGAAGCCAGCTC	833
Val-1047-Ala	AAGCAATATTAATGAAGTAGGTTCCAGTACTAATGAAGTGGG
GTA to GCA	CTCCAGTATTAATGAAATAGGTTCCAGTGATGAAAA
	TTTTCATCACTGGAACCTATTTCATTAATACTGGAGCCCACTT	834
	CATTAGTACTGGAACCTACTTCATTAATATTGCTTGAGCTGGC
	TTCTTTAAAAACATTTTCTCTAATGTTATTACGGC
	TAATGAAGTAGGTTCCA	835
	TGGAACCTACTTCATTA	836
Breast Cancer	AAATAGGTTCCAGTGATGAAAACATTCAAGCAGAACTAGGTA	837
Leu-1080-Stop	GAAACAGAGGGCCAAAATTGAATGCTATGCTTAGATTAGGGG
TTG to TAG	TTTTGCAACCTGAGGTCTATAAACAAAGTCTTCCTGG
	CCAGGAAGACTTTGTTTATAGACCTCAGGTTGCAAAACCCCT	838
	AATCTAAGCATAGCATTCAATTTTGGCCCTCTGTTTCTACCTA
	GTTCTGCTTGAATGTTTTCATCACTGGAACCTATTT
	GCCAAAATTGAATGCTA	839
	TAGCATTCAATTTTGGC	840
Breast Cancer	AAAACATTCAAGCAGAACTAGGTAGAAACAGAGGGCCAAAAT	841
Leu-1086-Stop	TGAATGCTATGCTTAGATTAGGGGTTTTGCAACCTGAGGTCT
TTA to TGA	ATAAACAAAGTCTTCCTGGAAGTAATTGTAAGCATCC
	GGATGCTTACAATTACTTCCAGGAAGACTTTGTTTATAGACCT	842
	CAGGTTGCAAAACCCCTAATCTAAGCATAGCATTCAATTTTG
	GCCCTCTGTTTCTACCTAGTTCTGCTTGAATGTTTT
	GCTTAGATTAGGGGTTT	843
	AAACCCCTAATCTAAGC	844
Breast Cancer	AGCAAGAATATGAAGAAGTAGTTCAGACTGTTAATACAGATTT	845
Ser-1130-Stop	CTCTCCATATCTGATTTCAGATAACTTAGAACAGCCTATGGGA
TCA to TGA	AGTAGTCATGCATCTCAGGTTTGTTCTGAGACACC
	GGTGTCTCAGAACAAACCTGAGATGCATGACTACTTCCCATA	846
	GGCTGTTCTAAGTTATCTGAAATCAGATATGGAGAGAAATCT
	GTATTAACAGTCTGAACTACTTCTTCATATTCTTGCT
	TCTGATTTCAGATAACT	847
	AGTTATCTGAAATCAGA	848
Breast Cancer	CTAGTTTTGCTGAAAATGACATTAAGGAAAGTTCTGCTGTTTT	849
Lys-1183-Arg	TAGCAAAAGCGTCCAGAAAGGAGAGCTTAGCAGGAGTCCTA
AAA to AGA	GCCCTTTCACCCATACACATTTGGCTCAGGGTTACCG
	CGGTAACCCTGAGCCAAATGTGTATGGGTGAAAGGGCTAGG	850
	ACTCCTGCTAAGCTCTCCTTTCTGGACGCTTTTGCTAAAAACA
	GCAGAACTTTCCTTAATGTCATTTTCAGCAAAACTAG
	CGTCCAGAAAGGAGAGC	851
	GCTCTCCTTTCTGGACG	852
Breast Cancer	AGCGTCCAGAAAGGAGAGCTTAGCAGGAGTCCTAGCCCTTT	853
Gln-1200-Stop	CACCCATACACATTTGGCTCAGGGTTACCGAAGAGGGGCCA
CAG to TAG	AGAAATTAGAGTCCTCAGAAGAGAACTTATCTAGTGAGG
	CCTCACTAGATAAGTTCTCTTCTGAGGACTCTAATTTCTTGGC	854
	CCCTCTTCGGTAACCCTGAGCCAAATGTGTATGGGTGAAAGG
	GCTAGGACTCCTGCTAAGCTCTCCTTTCTGGACGCT
	ATTTGGCTCAGGGTTAC	855
	GTAACCCTGAGCCAAAT	856
Breast Cancer	AAAGGAGAGCTTAGCAGGAGTCCTAGCCCTTTCACCCATACA	857
Arg-1203-Stop	CATTTGGCTCAGGGTTACC AGGGTTACCGAAGAGGGGCCA
CAG to TAG	GCTGTGTTAGAACAGCATGGGAGCCAGCCTTCTAACA
	TGTTAGAAGGCTGGCTCCCATGCTGTTCTAACACAGCTTCTA	906
	GTTCAGCCATTTCCTGCTGGAGCTTTATCAGGTTATGTTGCAT
	GGTATCCCTCTGCTTCAAAAACGATAAATGGCACCA
	TAAAGCTCCAGCAGGAA	907
	TTCCTGCTGGAGCTTTA	908
Breast Cancer	AGCCAGCCTTCTAACAGCTACCCTTCCATCATAAGTGACTCT	909
Arg-1443-Gly	TCTGCCCTTGAGGACCTGCGAAATCCAGAACAAAGCACATCA
CGA to GGA	GAAAAAGGTGTGTATTGTTGGCCAAACACTGATATCT
Arg-1443-Stop	AGATATCAGTGTTTGGCCAACAATACACACCTTTTTCTGATGT	910
CGA to TGA	GCTTTGTTCTGGATTTCGCAGGTCCTCAAGGGCAGAAGAGTC
	ACTTATGATGGAAGGGTAGCTGTTAGAAGGCTGGCT
	AGGACCTGCGAAATCCA	911
	TGGATTTCGCAGGTCCT	912
Breast Cancer	CAGAATAGAAACTACCCATCTCAAGAGGAGCTCATTAAGGTT	913
Ser-1512-Ile	GTTGATGTGGAGGAGCAACAGCTGGAAGAGTCTGGGCCACA
AGT to ATT	CGATTTGACGGAAACATCTTACTTGCCAAGGCAAGATC
	GATCTTGCCTTGGCAAGTAAGATGTTTCCGTCAAATCGTGTG	914
	GCCCAGACTCTTCCAGCTGTTGCTCCTCCACATCAACAACCT
	TAATGAGCTCCTCTTGAGATGGGTAGTTTCTATTCTG
	AGGAGCAACAGCTGGAA	915
	TTCCAGCTGTTGCTCCT	916
Breast Cancer	ATCTTTCTAGGTCATCCCCTTCTAAATGCCCATCATTAGATGA	917
Gln-1538-Stop	TAGGTGGTACATGCACAGTTGCTCTGGGAGTCTTCAGAATAG
CAG to TAG	AAACTACCCATCTCAAGAGGAGCTCATTAAGGTTGT
	ACAACCTTAATGAGCTCCTCTTGAGATGGGTAGTTTCTATTCT	918
	GAAGACTCCCAGAGCAACTGTGCATGTACCACCTATCATCAT
	ATGATGGGCATTTAGAAGGGGATGACCTAGAAAGAT
	CATGCACAGTTGCTCTG	919
	CAGAGCAACTGTGCATG	920
Breast Cancer	CAGAATAGAAACTACCCATCTCAAGAGGAGCTCATTAAGGTT	921
Glu-1541-Stop	GTTGATGTGGAGGAGCAACAGCTGGAAGAGTCTGGGCCACA
GAG to TAG	CGATTTGACGGAAACATCTTACTTGCCAAGGCAAGATC
	GATCTTGCCTTGGCAAGTAAGATGTTTCCGTCAAATCGTGTG	922
	GCCCAGACTCTTCCAGCTGTTGCTCCTCCACATCAACAACCT
	TAATGAGCTCCTCTTGAGATGGGTAGTTTCTATTCTG
	AGGAGCAACAGCTGGAA	923
	TTCCAGCTGTTGCTCCT	924
Breast Cancer	AACTACCCATCTCAAGAGGAGCTCATTAAGGTTGTTGATGTG	925
Thr-1561-Ile	GAGGAGCAACAGCTGGAAGAGTCTGGGCCACACGATTTGAC
ACC to ATC	GGAAACATCTTACTTGCCAAGGCAAGATCTAGGTAATA
	TATTACCTAGATCTTGCCTTGGCAAGTAAGATGTTTCCGTCAA	926
	ATCGTGTGGCCCAGACTCTTCCAGCTGTTGCTCCTCCACATC
	AACAACCTTAATGAGCTCCTCTTGAGATGGGTAGTT
	AGCTGGAAGAGTCTGGG	927
	CCCAGACTCTTCCAGCT	928
Breast Cancer	TTTGTAATTCAACATTCATCGTTGTGTAAATTAAACTTCTCCCA	929
Tyr-1563-Stop	TTCCTTTCAGAGGGGAACCCCTTACCTGGAATCTGGAATCAGC
TAC to TAG	CTCTTCTCTGATGACCCTGAATCTGATCCTTCTGA
	TCAGAAGGATCAGATTCAGGGTCATCAGAGAAGAGGCTGATT	930
	CCAGATTCCAGGTAAGGGGTTCCCTCTGAAAGGAATGGGAG
	AAGTTTAATTTACACAACGATGAATGTTGAATTACAAA
	AGAGGGAACCCCTTACC	931
	GGTAAGGGGTTCCCTCT	932
Breast Cancer	CAACATTCATCGTTGTGTAAATTAAACTTCTCCCATTCCTTTC	933
Leu-1564-Pro	AGAGGGAACCCCTTACCTGGAATCTGGAATCAGCCTCTTCTC
CTG to CCG	TGATGACCCTGAATCTGATCCTTCTGAAGACAGAGC
	GCTCTGTCTTCAGAAGGATCAGATTCAGGGTCATCAGAGAAG	934
	AGGCTGATTCCAGATTCCAGGTAAGGGGTTCCCTCTGAAAG
	GAATGGGAGAAGTTTAATTTACACAACGATGAATGTTG
	CCCTTACCTGGAATCTG	935
	CAGATTCCAGGTAAGGG	936
Breast Cancer	GCCCCAGAGTCAGCTCGTGTTGGCAACATACCATCTTCAACC	937
Gln-1604-Stop	TCTGCATTGAAAGTTCCCCAATTGAAAGTTGCAGAATCTGCC
CAA to TAA	CAGAGTCCAGCTGCTGCTCATACTACTGATACTGCTG
	CAGCAGTATCAGTAGTATGAGCAGCAGCTGGACTCTGGGCA	938
	GATTCTGCAACTTTCAATTGGGGAACTTTCAATGCAGAGGTT
	GAAGATGGTATGTTGCCAACACGAGCTGACTCTGGGGC
	AAGTTCCCCAATTGAAA	939
	TTTCAATTGGGGAACTT	940
Breast Cancer	GAGTCAGCTCGTGTTGGCAACATACCATCTTCAACCTCTGCA	941
Lys-1606-Glu	TTGAAAGTTCCCCAATTGAAAGTTGCAGAATCTGCCCAGAGT
AAA to GAA	CCAGCTGCTGCTCATACTACTGATACTGCTGGGTATA
	TATACCCAGCAGTATCAGTAGTATGAGCAGCAGCTGGACTCT	942
	GGGCAGATTCTGCAACTTTCAATTGGGGAACTTTCAATGCAG
	AGGTTGAAGATGGTATGTTGCCAACACGAGCTGACTC
	CCCAATTGAAAGTTGCA	943
	TGCAACTTTCAATTGGG	944
Breast Cancer	CAGAATCTGCCCAGAGTCCAGCTGCTGCTCATACTACTGATA	945
Met-1628-Thr	CTGCTGGGTATAATGCAATGGAAGAAAGTGTGAGCAGGGAG
ATG to ACG	AAGCCAGAATTGACAGCTTCAACAGAAAGGGTCAACAA
	TTGTTGACCCTTTCTGTTGAAGCTGTCAATTCTGGCTTCTCCC	946
	TGCTCACACTTTCTTCCATTGCATTATACCCAGCAGTATCAGT
	AGTATGAGCAGCAGCTGGACTCTGGGCAGATTCTG
	TAATGCAATGGAAGAAA	947
	TTTCTTCCAee TtGCATTA	948
Breast Cancer	GCAGAATCTGCCCAGAGTCCAGCTGCTGCTCATACTACTGAT	949
Met-1628-Val	ACTGCTGGGTATAATGCAATGGAAGAAAGTGTGAGCAGGGA
ATG to GTG	GAAGCCAGAATTGACAGCTTCAACAGAAAGGGTCAACA
	TGTTGACCCTTTCTGTTGAAGCTGTCAATTCTGGCTTCTCCCT	950
	GCTCACACTTTCTTCCATTGCATTATACCCAGCAGTATCAGTA
	GTATGAGCAGCAGCTGGACTCTGGGCAGATTCTGC
	ATAATGCAATGGAAGAA	951
	TTCTTCCATTGCATTAT	952
Breast Cancer	CTCATACTACTGATACTGCTGGGTATAATGCAATGGAAGAAA	953
Pro-1637-Leu	GTGTGAGCAGGGAGAAGCCAGAATTGACAGCTTCAACAGAA
CCA to CTA	AGGGTCAACAAAAGAATGTCCATGGTGGTGTCTGGCCT
	AGGCCAGACACCACCATGGACATTCTTTTGTTGACCCTTTCT	954
	GTTGAAGCTGTCAATTCTGGCTTCTCCCTGCTCACACTTTCTT
	CCATTGCATTATACCCAGCAGTATCAGTAGTATGAG
	GGAGAAGCCAGAATTGA	955
	TCAATTCTGGCTTCTCC	956
Breast Cancer	GAGCAGGGAGAAGCCAGAAtTGACAGCTTCAACAGAAAGGG	957
Met-1652-Ile	TCAACAAAAGAATGTCCATGGTGGTGTCTGGCCTGACCCCAG
ATG to ATA	AAGAATTTGTGAGTGTATCCATATGTATCTCCCTAATG
	CATTAGGGAGATACATATGGATACACTCACAAATTCTTCTGG	958
	GGTCAGGCCAGACACCACCATGGACATTCTTTTGTTGACCCT
	TTCTGTTGAAGCTGTCAATTCTGGCTTCTCCCTGCTC
	ATGTCCATGGTGGTGTC	959
	GACACCACCATGGACAT	960	960
Breast Cancer	CACTTCCTGATTTTGTTTTCAACTTCTAATCCTTTGAGTGTTTT	961
Glu-1694-Stop	TCATTCTGCAGATGCTGAGTTTGTGTGTGAACGGACACTAA
GAG to TAG	ATATTTTCTAGGAATTGCGGGAGGAAAATGGGTAG
	CTACCCATTTTCCTCCCGCAATTCCTAGAAAATATTTCAGTGT	962
	CCGTTCACACACAAACTCAGCATCTGCAGAATGAAAAACACT
	CAAAGGATTAGAAGTTGAAAACAAAATCAGGAAGTG
	CAGATGCTGAGTTTGTG	963
	CACAAACTCAGCATCTG	964
Breast Cancer	GTGTTTTTTCATTCTGCAGATGCTGAGTTTGTGTGTGAACGGA	965
Gly-1706-Glu	CACTGAAATATTTTCTAGGAATTGCGGGAGGAAAATGGGTAG
GGA to GAA	TTAGCTATTTCTGTAAGTATAATACTATTTCTCCCCT
	AGGGGAGAAATAGTATTATACTTACAGAAATAGCTAACTACCC	966
	ATTTTCCTCCCGCAATTCCTAGAAAATATTTCAGTGTCCGTTC
	ACACACAAACTCAGCATCIGCAGAATGAAAAACAC
	TTTTCTAGGAATTGCGG	967
	CCGCAATTCCTAGAAAA	968
Breast Cancer	TTCATTCTGCAGATGCTGAGTTTGTGTGTGAACGGACACTGA	969
Ala-1708-Glu	AATATTTTCTAGGAATTGCGGGAGGAAAATGGGTAGTTAGCT
GCG to GAG	ATTTCTGTAAGTATAATACTATTTCTCCCCTCCTCCC
	GGGAGGAGGGGAGAAATAGTATTATACTTACAGAAATAGCTA	970
	ACTACCCATTTTCCTCCCGCAATTCCTAGAAAATATTTCAGTG
	TCCGTTCACACACAAACTCAGCATCTGCAGAATGAA
	AGGAATTGCGGGAGGAA	971
	TTCCTCCCGCAATTCCT	972
Breast Cancer	CTGAGTTTGTGTGTGAACGGACACTGAAATATTTTCTAGGAAT	973
Val-1713-Ala	TGCGGGAGGAAAATGGGTAGTTAGCTATTTCTGTAAGTATAA
GTA to GCA	TACTATTTCTCCCCTCCTCCCTTTAACACCTCAGAA
	TTCTGAGGTGTTAAAGGGAGGAGGGGAGAAATAGTATTATAC	974
	TTACAGAAATAGCTAACTACCCATTTTCCTCCCGCAATTCCTA
	GAAAATATTTCAGTGTCCGTTCACACACAAACTCAG
	AAAATGGGTAGTTAGCT	975
	AGCTAACTACCCATTTT	976
Breast Cancer	AACGGACACTGAAATATTTTCTAGGAATTGCGGGAGGAAAAT	977
Trp-1718-Stop	GGGTAGTTAGCTATTTCTGTAAGTATAATACTATTTCTCCCCT
TGG to TAG	CCTCCCTTTAACACCTCAGAATTGCATTTTTACACC
	GGTGTAAAAATGCAATTCTGAGGTGTTAAAGGGAGGAGGGG	978
	AGAAATAGTATTATACTTACAGAAATAGCTAACTACCCATTTTC
	CTCCCGCAATTCCTAGAAAATATTTCAGTGTCCGTT
	CTATTTCTGTAAGTATA	979
	TATACTTACAGAAATAG	980
Breast Cancer	TTCTGCTGTATGTAACCTGTCTTTTCTATGATCTCTTTAGGGG	981
Glu-1725-Stop	TGACCCAGTCTATTAAAGAAAGAAAAATGCTGAATGAGGTAA
GAA to TAA	GTACTTGATGTTACAAACTAACCAGAGATATTCATT
	AATGAATATCTCTGGTTAGTTTGTAACATCAAGTACTTACCTC	982
	ATTCAGCATTTTTCTTTCTTTAATAGACTGGGTCACCCCTAAA
	GAGATCATAGAAAAGACAGGTTACATACAGCAGAA
	CTATTAAAGAAAGAAAA	983
	TTTTCTTTCTTTAATAG	984
Breast Cancer	TGTATGTAACCTGTCTTTTCTATGATCTCTTTAGGGGTGACCC	985
Lys-1727-Stop	AGTCTATTAAAGAAAGAAAAATGCTGAATGAGGTAAGTACTTG
AAA to TAA	ATGTTACAAACTAACCAGAGATATTCATTCAGTCA
	TGACTGAATGAATATCTCTGGTTAGTTTGTAACATCAAGTACT	986
	TACCTCATTCAGCATTTTTCTTTCTTTAATAGACTGGGTCACC
	CCTAAAGAGATCATAGAAAAGACAGGTTACATACA
	AAGAAAGAAAAATGCTG	987
	CAGCATTTTTCTTTCTT	988
Breast Cancer	TCTTTCAGCATGATTTTGAAGTCAGAGGAGATGTGGTCAATG	989
Pro-1749-Arg	GAAGAAACCACCAAGGTCCAAAGCGAGCAAGAGAATCCCAG
CCA to CGA	GACAGAAAGGTAAAGCTCCCTCCCTCAAGTTGACAAAA
	TTTTGTCAACTTGAGGGAGGGAGCTTTACCTTTCTGTCCTGG	990
	GATTCTCTTGCTCGCTTTGGACCTTGGTGGTTTCTTCCATTGA
	CCACATCTCCTCTGACTTCAAAATCATGCTGAAAGA
	CCAAGGTCCAAAGCGAG	991
	CTCGCTTTGGACCTTGG	992
Breast Cancer	CAGCATGATTTTGAAGTCAGAGGAGATGTGGTCAATGGAAGA	993
Arg-1751-Stop	AACCACCAAGGTCCAAAGCGAGCAAGAGAATCCCAGGACAG
CGA to TGA	AAAGGTAAAGCTCCCTCCCTCAAGTTGACAAAAATCTC
	GAGATTTTGTCAACTTGAGGGAGGGAGCTTTACCTTTCTGT	994
	CCTGGGATTCTCTTGCTCGCTTTGGACCTTGGTGGTTTCTTC
	CATTGACCACATCTCCTCTGACTTCAAAATCATGCTG
	GTCCAAAGCGAGCAAGA	995
	TCTTGCTCGCTTTGGAC	996
Breast Cancer	GTCAGAGGAGATGTGGTCAATGGAAGAAACCACCAAGGTCC	997
Gln-1756-Stop	AAAGCGAGCAAGAGAATCCCAGGACAGAAAGGTAAAGCTCC
CAG to TAG	CTCCCTCAAGTTGACAAAAATCICACCCCACCACTCTGT
	ACAGAGTGGTGGGGTGAGATTTTTGTCAACTTGAGGGAGGG	998
	AGCTTTACCTTTCTGTCCTGGGATTCTCTTGCTCGCTTTGGA
	CCTTGGTGGTTTCTTCCATTGACCACATCTCCTCTGAC
	GAGAATCCCAGGACAGA	999
	TCTGTCCTGGGATTCTC	1000
Breast Cancer	CTCTCTTCTTCCAGATCTTCAGGGGGCTAGAAATCTGTTGCT	1001
Met-1775-Arg	ATGGGCCCTTCACCAACATGCCCACAGGTAAGAGCCTGGGA
ATG to AGG	GAACCCCAGAGTTCCAGCACCAGCCTTTGTCTTACATA
	TATGTAAGACAAAGGCTGGTGCTGGAACTCTGGGGTTCTCCC	1002
	AGGCTCTTACCTGTGGGCATGTTGGTGAAGGGCCCATAGCA
	ACAGATTTCTAGCCCCCTGAAGATCTGGAAGAAGAGAG
	CACCAACATGCCCACAG	1003
	CTGTGGGCATGTTGGTG	1004
Breast Cancer	AGTATGCAGATTACTGCAGTGATTTTACATCTAAAATGTCCATT	1005
Trp-1782-Stop	TTAGATCAACTGGAATGGATGGTACAGCTGTGTGGTGCTTCT
TGG to TGA	GTGGTGAAGGAGCTTTCATCATTCACCCTTGGCACA
	TGTGCCAAGGGTGAATGATGAAAGCTCCTTCACCACAGAAGC	1006
	ACCACACAGCTGTACCATCCATTCCAGTTGATCTAAAATGGA
	CATTTAGATGTAAAATCACTGCAGTAATCTGCATACT
	CTGGAATGGATGGTACA	1007
	TGTACCATCCATTCCAG	1008
Breast Cancer	ATTACTGCAGTGATTTTACATCTAAATGTCCATTTTAGATCAAC	1009
Gln-1785-His	TGGAATGGATGGTACAGCTGTGTGGTGCTTCTGTGGTGAAG
CAG to CAT	GAGCTTTCATCATTCACCCTTGGCACAGTAAGTATT
	AATACTTACTGTGCCAAGGGTGAATGATGAAAGCTCCTTCAC	1010
	CACAGAAGCACCACACAGCTGTACCATCCATTCCAGTTGATC
	TAAAATGGACATTTAGATGTAAAATCACTGCAGTAAT
	ATGGTACAGCTGTGTGG	1011
	CCACACAGCTGTACCAT	1012
Breast Cancer	GTCCATTTTAGATCAACTGGAATGGATGGTACAGCTGTGTGG	1013
Glu-1794-Asp	TGCTTCTGTGGTGAAGGAGCTTTCATCATTCACCCTTGGCAC
GAG to GAT	AGTAAGTATTGGGTGCCCTGTCAGAGAGGGAGGACAC
	GTGTCCTCCCTCTCTGACAGGGCACCCAATACTTACTGTGCC	1014
	AAGGGTGAATGATGAAAGCTCCTTCACCACAGAAGCACCACA
	CAGCTGTACCATCCATTCCAGTTGATCTAAAATGGAC
	GTGAAGGAGCTTTCATC	1015
	GATGAAAGCTCCTTCAC	1016
Breast Cancer	CTCTGCTTGTGTTCTCTGTCTCCAGCAATTGGGCAGATGTGT	1017
Arg-1835-Stop	GAGGCACCTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGT
CGA to TGA	AGCACTCTACCAGTGCCAGGAGCTGGACACCTACCTGA
	TCAGGTAGGTGTCCAGCTCCTGGCACTGGTAGAGTGCTACA	1018
	CTGTCCAACACCCACTCTCGGGTCACCACAGGTGCCTCACA
	CATCTGCCCAATTGCTGGAGACAGAGAACACAAGCAGAG
	TGGTGACCCGAGAGTGG	1019
	CCACTCTCGGGTCACCA	1020
Breast Cancer	TTGTGTTCTCTGTCTCCAGCAATTGGGCAGATGTGTGAGGCA	1021
Trp-1837-Arg	CCTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGTAGCACT
TGG to CGG	CTACCAGTGCCAGGAGCTGGACACCTACCTGATACCCC
	GGGGTATCAGGTAGGTGTCCAGCTCCTGGCACTGGTAGAGT	1022
	GCTACACTGTCCAACACCCACTCTCGGGTCACCACAGGTGC
	CTCACACATCTGCCCAATTGCTGGAGACAGAGAACACAA
	CCCGAGAGTGGGTGTTG	1023
	CAACACCCACTCTCGGG	1024
Breast Cancer	TGTGTTCTCTGTCTCCAGCAATTGGGCAGATGTGTGAGGCAC	1025
Trp-1837-Stop	CTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGTAGCACTC
TGG to TAG	TACCAGTGCCAGGAGCTGGACACCTACCTGATACCCCA
	TGGGGTATCAGGTAGGTGTCCAGCTCCTGGCACTGGTAGAG	1026
	TGCTACACTGTCCAACACCCACTCTCGGGTCACCACAGGTG
	CCTCACACATCTGCCCAATTGCTGGAGACAGAGAACACA
	CCGAGAGTGGGTGTTGG	1027
	CCAACACCCACTCTCGG	1028

[0126]

TABLE 15
BRCA2 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Breast cancer	GTTAAAACTAAGGTGGGATTTTTTTTTTAAATAGATTTAGGAC	1029
PHE32LEU	CAATAAGTCTTAATTGGTTTGAAGAACTTTCTTCAGAAGCTCC
TTT to CTT	ACCCTATAATTCTGAACCTGCAGAAGAATCTGAAC
	GTTCAGATTCTTCTGCAGGTTCAGAATTATAGGGTGGAGCTT	1030
	CTGAAGAAAGTTCTTCAAACCAATTAAGACTTATTGGTCCTAA
	ATCTATTTAAAAAAAAAATCCCACCTTAGTTTTAAC
	TTAATTGGTTTGAAGAA	1031
	TTCTTCAAACCAATTAA	1032
Breast cancer	TAGATTTAGGACCAATAAGTCTTAATTGGTTTGAAGAACTTTC	1033
TYR42CYS	TTCAGAAGCTCCACCCTATAATTCTGAACCTGCAGAAGAATC
TAT to TGT	TGAACATAAAAACAACAATTACGAACCAAACCTATT
	AATAGGTTTGGTTCGTAATTGTTGTTTTTATGTTCAGATTCTTC	1034
	TGCAGGTTCAGAATTATAGGGTGGAGCTTCTGAAGAAGTTC
	TTCAAACCAATTAAGACTTATTGGTCCTAAATCTA
	TCCACCCTATAATTCTG	1035
	CAGAATTATAGGGTGGA	1036
Breast cancer	AAGAACTTTCTTCAGAAGCTCCACCCTATAATTCTGAACCTGC	1037
LYS53ARG	AGAAGAATCTGAACATAAAAACAACAATTACGAACCAAACCTA
AAA to AGA	TTTAAAACTCCACAAAGGAAACCATCTTATAATCA
	TGATTATAAGATGGTTTCCTTTGTGGAGTTTTAAATAGGTTTG	1038
	GTTCGTAATTGTTGTTTTTATGTTCAGATTCTTCTGCAGGTTC
	AGAATTATAGGGTGGAGCTTCTGAAGAAAGTTCTT
	TGAACATAAAAACAACA	1039
	TGTTGTTTTTATGTTCA	1040
Breast cancer	CTATTTAAAACTCCACAAAGGAAACCATCTTATAATCAGCTGG	1041
Phe81Leu	CTTCAACTCCAATAATATTCAAAGAGCAAGGGCTGACTCTGC
TTC to CTC	CGCTGTACCAATCTCCTGTAAAAGAATTAGATAAAT
	ATTTATCTAATTCTTTTACAGGAGATTGGTACAGCGGCAGAGT	1042
	CAGCCCTTGCTCTTTGAATATTATTGGAGTTGAAGCCAGCTG
	ATTATAAGATGGTTTCCTTTGTGGAGTTTTAAATAG
	CAATAATATTCAAAGAG	1043
	CTCTTTGAATATTATTG	1044
Breast cancer	GTCAGACACCAAAACATATTTCTGAAAGTCTAGGAGCTGAGG	1045
TRP194TERM	TGGATCCTGATATGTCTTGGTCAAGTTCTTTAGCTACACCACC
TGG to TAG	CACCCTTAGTTCTACTGTGCTCATAGGTAATAATAG
	CTATTATTACCTATGAGCACAGTAGAACTAAGGGTGGGTGGT	1046
	GTAGCTAAAGAACTTGACCAAGACATATCAGGATCCACCTCA
	GCTCCTAGACTTTCAGAAATATGTTTTGGTGTCTGAC
	TATGTCTTGGTCAAGTT	1047
	AACTTGACCAAGACATA	1048
Breast cancer	CTGAAAGTCTAGGAGCTGAGGTGGATCCTGATATGTCTTGGT	1049
PRO201ARG	CAAGTTCTTTAGCTACACCACCCACCCTTAGTTCTACTGTGCT
CCA to CGA	CATAGGTAATAATAGCAAATGTGTATTTACAAGAAA
	TTTCTTGTAAATACACATTTGCTATTATTACCTATGAGCACAGT	1050
	AGAACTAAGGGTGGGTGGTGTAGCTAAAGAACTTGACCAAGA
	CATATCAGGATCCACCTCAGCTCCTAGACTTTCAC
	AGCTACACCACCCACCC	1051
	GGGTGGGTGGTGTAGCT	1052
Breast cancer	ACAATACACATAAATTTTTATCTTACAGTCAGAAATGAAGAAG	1053
Pro222Ser	CATCTGAAACTGTATTTCCTCATGATACTACTGCTGTAAGTAA
CCT to TCT	ATATGACATTGATTAGACTGTTGAAATTGCTAACA
	TGTTAGCAATTTCAACAGTCTAATCAATGTCATATTTACTTACA	1054
	GCAGTAGTATCATGAGGAAATACAGTTTCAGATGCTTCTTCAT
	TTCTGACTGTAAGATAAAAATTTATGTGTATTGT
	CTGTATTTCCTCATGAT	1055
	ATCATGAGGAAATACAG	1056
Breast cancer	AATGGTCTCAACTAACCCTTTCAGGTCTAAATGGAGCCCAGA	1057
Leu-414-Term	TGGAGAAAATACCCCTATTGCATATTTCTTCATGTGACCAAAA
TTG to TAG	TATTTCAGAAAAAGACCTATTAGACACAGAGAACAA
	TTGTTCTCTGTGTCTAATAGGTCTTTTTCTGAAATATTTTGGTC	1058
	ACATGAAGAAATATGCAATAGGGGTATTTTCTCCATCTGGGC
	TCCATTTAGACCTGAAAGGGTTAGTTGAGACCATT
	ACCCCTATTGCATATTT	1059
	AAATATGCAATAGGGGT	1060
Breast cancer, male	AGCCTCTGAAAGTGGACTGGAAATACATACTGTTTGCTCACA	1061
Cys554Trp	GAAGGAGGACTCCTTATGTCCAAATTTAATTGATAATGGAAG
TGT to TGG	CTGGCCAGCCACCACCACACAGAATTCTGTAGCTTTG
	CAAAGCTACAGAATTCTGTGTGGTGGTGGCTGGCCAGCTTC	1062
	CATTATCAATTAAATTTGGACATAAGGAGTCCTCCTTCTGTGA
	GCAAACAGTATGTATTTCCAGTCCACTTTCAGAGGCT
	TCCTTATGTCCAAATTT	1063
	AAATTTGGACATAAGGA	1064
Breast cancer	AACTCTACCATGGTTTTATATGGAGACACAGGTGATAAACAA	1065
Lys944Term	GCMCCCAAGTGTCAATTAAAAAAGATTTGGTTTATGTTCTTG
AAA to TAA	CAGAGGAGAACAAAAATAGTGTAAAGCAGCATATAA
	TTATATGCTGCTTTACACTATTTTTGTTCTCCTCTGCAAGAAC	1066
	ATAAACCAAATCTTTTTTAATTGACACTTGGGTTGCTTGTTTAT
	CACCTGTGTCTCCATATAAAACCATGGTAGAGTT
	TGTCAATTAAAAAAGAT	1067
	ATCTTTTTTAATTGACA	1068
Breast cancer, male	ATGACTACTGGCACTTTTGTTGAAGAAATTACTGAAAATTACA	1069
Glu1320Term	AGAGAAATACTGAAAATGAAGATAACAAATATACTGCTGCCAG
GAA to TAA	TAGAAATTCTCATAACTTAGAATTTGATGGCAGTG
	CACTGCCATCAAATTCTAAGTTATGAGAATTTCTACTGGCAGC	1070
	AGTATATTTGTTATCTTCATTTCAGTATTTCTCTTGTAATTTTC
	AGTAATTTCTTCAACAAAAGTGCCAGTAGTCAT
	CTGAAAATGAAGATAAC	1071
	GTTATCTTCATTTTCAG	1072
Breast cancer	CATGAAACAATTAAAAAAGTGAAAGACATATTTACAGACAGTT	1073
Glu1876Term	TCAGTAAAGTAATTAAGGAAAACAACGAGAATAAATCAAAAAT
GAA to TAA	TTGCCAAACGAAAATTATGGCAGGTTGTTACGAGG
	CCTCGTAACAACCTGCCATAATTTTCGTTTGGCAAATTTTTGA	1074
	TTTATTCTCGTTGTTTTCCTTAATTACTTTACTGAAACTGTCTG
	TAAATATGTCTTTCACTTTTTTAATTGTTTCATG
	TAATTAAGGAAAACAAC	1075
	GTTGTTTTCCTTAATTA	1076
Breast cancer	TGAAAGACATATTTACAGACAGTTTCAGTAAAGTAATTAAGGA	1077
Ser1882Term	AAACAACGAGAATAAATCAAAAATTTGCCAAACGAAAATTATG
TCA to TAA	GCAGGTTGTTACGAGGCATTGGATGATTCAGAGGA
	TCCTCTGAATCATCCAATGCCTCGTAACAACCTGCCATAATTT	1078
	TCGTTTGGCAAATTTTTGATTTATTCTCGTTGTTTTCCTTAATT
	ACTTTACTGAAACTGTCTGTAAATATGTCTTTCA
	GAATAAATCAAAAATTT	1079
	AAATTTTTGATTTATTC	1080
Breast cancer	AACCAAAATATGTCTGGATTGGAGAAAGTTTCTAAAATATCAC	1081
Glu1953Term	CTTGTGATGTTAGTTTGGAAACTTCAGATATATGTAAATGTAG
GAA to TAA	TATAGGGAAGCTTCATAAGTCAGTCTCATCTGCAA
	TTGCAGATGAGACTGACTTATGAAGCTTCCCTATACTACATTT	1082
	ACATATATCTGAAGTTTCCAAACTAACATCACAAGGTGATATT
	TTAGAAACTTTCTCCAATCCAGACATATTTTGGTT
	TTAGTTTGGAAACTTCA	1083
	TGAAGTTTCCAAACTAA	1084
Breast cancer	TTAGTTTGGAAACTTCAGATATATGTAAATGTAGTATAGGGAA	1085
Ser1970Term	GCTTCATAAGTCAGTCTCATCTGCAAATACTTGTGGGATTTTT
TCA to TAA	AGCACAGCAAGTGGAAAATCTGTCCAGGTATCAGA
	TCTGATACCTGGACAGATTTTCCACTTGCTGTGCTAAAAATCC	1086
	CACAAGTATTTGCAGATGAGACTGACTTATGAAGCTTCCCTAT
	ACTACATTTACATATATCTGAAGTTTCCAAACTAA
	GTCAGTCTCATCTGCAA	1087
	TTGCAGATGAGACTGAC	1088
Breast cancer	AAGTCAGTCTCATCTGCAAATACTTGTGGGATTTTTAGCACAG	1089
Gln1987Term	CAAGTGGAAAATCTGTCCAGGTATCAGATGCTTCATTACAAAA
GAG to TAG	CGCAAGACAAGTGTTTTCTGAAATAGAAGATAGTA
	TACTATCTTCTATTTCAGAAAACACTTGTCTTGCGTTTTGTAAT	1090
	GAAGCATCTGATACCTGGACAGATTTTCCACTTGCTGTGCTA
	AAAATCCCACAAGTATTTGCAGATGAGACTGACTT
	AATCTGTCCAGGTATCA	1091
	TGATACCTGGACAGATT	1092
Breast cancer	AAAATAAGATTAATGACAATGAGATTCATCAGTTTAACAAAAA	1093
Ala2466Val	CAACTCCAATCAAGCAGCAGCTGTAACTTTCACAAAGTGTGA
GCA to GTA	AGAAGAACCTTTAGGTATTGTATGACAATTTGTGTG
	CACACAAATTGTCATACAATACCTAAAGGTTCTTCTTCACACT	1094
	TTGTGAAAGTTACAGCTGCTGCTTGATTGGAGTTGTTTTTGTT
	AAACTGATGAATCTCATTGTCATTAATCTTATTTT
	TCAAGCAGCAGCTGTAA	1095
	TTACAGCTGCTGCTTGA	1096
Breast cancer	AGGCAACGCGTCTTTCCACAGCCAGGCAGTCTGTATCTTGCA	1097
Arg2520Term	AAAACATCCACTCTGCCTCGAATCTCTCTGAAAGCAGCAGTA
CGA to TGA	GGAGGCCAAGTCCCCTCTGCGTGTCCTCATAAACAGG
	CCTGTTTATGAGGACACGCAGAGGGGACTTGGCCTCCTACT	1098
	GCTGCTTTCAGAGAGATTCGAGGCAGAGTGGATGTTTTTGCA
	AGATACAGACTGCCTGGCTGTGGAAAGACGCGTTGCCT
	CTCTGCCTCGAATCTCT	1099
	AGAGATTCGAGGCAGAG	1100
Breast cancer	ATTTCATTGAGCGCAAATATATCTGAAACTTCTAGCAATAAAA	1101
Gln2714Term	CTAGTAGTGCAGATACCCAAAAAGTGGCCATTATTGAACTTA
CAA to TAA	CAGATGGGTGGTATGCTGTTAAGGCCCCAGTTAGATC
	GATCTAACTGGGCCTTAACAGCATACCACCCATCTGTAAGTT	1102
	CAATAATGGCCACTTTTTGGGTATCTGCACTACTAGTTTTATT
	GCTAGAAGTTTCAGATATATTTGCGCTCAATGAAAT
	CAGATACCCAAAAAGTG	1103
	CACTTTTTGGGTATCTG	1104
Breast cancer	CAGAACTGGTGGGCTCTCCTGATGCCTGTACACCTCTTGAAG	1105
Leu2776Term	CCCCAGAATCTCTTATGTTAAAGGTAAATTAATTTGCACTCTT
TTA to TGA	GGTAAAAATCAGTCATTGATTCAGTTAAATTCTAGA
	TCTAGAATTTAACTGAATCAATGACTGATTTTTACCAAGAGTG	1106
	CAAATTAATTTACCTTTAACATAAGAGATTCTGGGGCTTCAAG
	AGGTGTACAGGCATCAGGAGAGCCCACCAGTTCTG
	TCTTATGTTAAAGATTT	1107
	AAATCTTTAACATAAGA	1108
Breast cancer	CCTTTTGTTTTCTTAGAAAACACAACAAAACCATATTTACCATC	1109
Gln2893Term	ACGTGCACTAACAAGACAGCAAGTTCGTGCTTTGCAAGATGG
CAG to TAG	TGCAGAGCTTTATGAAGCAGTGAAGAATGCAGCAG
	CTGCTGCATTCTTCACTGCTTCATAAAGCTCTGCACCATCTTG	1110
	CAAAGCACGAACTTGCTGTCTTGTTAGTGCACGTGATGGTAA
	ATATGGTETTGTTGTGTTTTCTAAGAAAACAAAAGG
	TAACAAGACAGCAAGTT	1111
	AACTTGCTGTCTTGTTA	1112
Breast cancer	AATCACAGGCAAATGTTGAATGATAAGAAACAAGCTCAGATC	1113
Ala2951Thr	CAGTTGGAAATTAGGAAGGCCATGGAATCTGCTGAACAAAAG
GCC to ACC	GAACAAGGTTTATCAAGGGATGTCACAACCGTGTGGA
	TCCACACGGTTGTGACATCCCTTGATAAACCTTGTTCCTTTTG	1114
	TTCAGCAGATTCCATGGCCTTCCTAATTTCCAACTGGATCTGA
	GCTTGTTTCTTATCATTCAACATTVGCCTGTGATT
	TTAGGAAGGCCATGGAA	1115
	TTCCATGGCCTTCCTAA	1116
Breast cancer	ACAATTTACTGGCAATAAAGTTTTGGATAGACCTTAATGAGGA	1117
Met3118Thr	CATTATTAAGCCTCATATGTTAATTGCTGCAAGCAACCTCCAG
ATG to ACG	TGGCGACCAGAATCCAAATCAGGCCTTCTTACTTT
	AAAGTAAGAAGGCCTGATTTGGATTCTGGTCGCCACTGGAG	1118
	GTTGCTTGCAGCAATTAACATATGAGGCTTAATAATGTCCTCA
	TTAAGGTCTATCCAAAACTTTATTGCCAGTAAATTGT
	GCCTCATATGTTAATTG	1119
	CAATTAACATATGAGGC	1120
Breast cancer	GACTGAAACGACGTTGTACTACATCTCTGATCAAAGAACAGG	1121
Thr3401Met	AGAGTTCCCAGGCCAGTACGGAAGAATGTGAGAAAAATAAGC
ACG to ATG	AGGACACAATTACAACTAAAAAATATATCTAAGCATT
	AATGCTTAGATATATTTTTTAGTTGTAATTGTGTCCTGCTTATT	1122
	TTTCTCACATTCTTCCGTACTGGCCTGGGAACTCTCCTGTTCT
	TTGATCAGAGATGTAGTACAACGTCGTTTCAGTC
	GGCCAGTACGGAAGAAT	1123
	ATTCTTCCGTACTGGCC	1124
Breast cancer	AAAGAACAGGAGAGTTCCCAGGCCAGTACGGAAGAATGTGA	1125
lle3412Val	GAAAAATAAGCAGGACACAATTACAACTAAAAAATATATCTAA
ATT to GTT	GCATTTGCAAAGGCGACAATAAATTATTGACGCTTAA
	TTAAGCGTCAATAATTTATTGTCGCCTTTTGCAAATGCTTAGAT	1126
	ATATTTTTTAGTTGTAATTGTGTCCTGCTTATTTTTCTCACATT
	CTTCCGTACTGGCCTGGGAACTCTCCTGTTCTTT
	AGGACACAATTACAACT	1127
	AGTTGTAATTGTGTCCT	1128

EXAMPLE 9

Cystic Fibrosis—CFTR

[0127] Cystic fibrosis is a lethal disease affecting approximately one in 2,500 live Caucasian births and is the most common autosomal recessive disease in Caucasians. Patents with this disease have reduced chloride ion permeability in the secretory and absorptive cells of organs with epithelial cell linings, including the airways, pancreas, intestine, sweat glands and male genital tract. This, in turn, reduces the transport of water across the epithelia. The lungs and the GI tract are the predominant organ systems affected in this disease and the pathology is characterized by blocking of the respiratory and GI tracts with viscous mucus. The chloride impermeability in affected tissues is due to mutations in a specific chloride channel, the cystic fibrosis transmembrane conductance regulator protein (CFTR), which prevents normal passage of chloride ions through the cell membrane (Welsh et al., Neuron, 8:821-829 (1992)). Damage to the lungs due to mucus blockage, frequent bacterial infections and inflammation is the primary cause of morbidity and mortality in CF patients and, although maintenance therapy has improved the quality of patients' lives, the median age at death is still only around 30 years. There is no effective treatment for the disease, and therapeutic research is focused on gene therapy using exogenous transgenes in viral vectors and/or activating the defective or other chloride channels in the cell membrane to normalize chloride permeability (Tizzano et al., J. Pediat., 120:337-349 (1992)). However, the death of a teenage patient treated with an adenovirus vector carrying an exogenous CFTR gene in clinical trials in the late 1990's has impacted this area of research.

[0128] The oligonucleotides of the invention for correction of the CFTR gene are attached as a table.

TABLE 16
CFTR Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Cystic fibrosis	AAGGATACAGACAGCGCCTGGAATTGTCAGACATATACCAAA	1129
Ala46Asp	TCCCTTCTGTTGATTCTGCTGACAATCTATCTGAAAAATTGGA
GCT to GAT	AAGGTATGTTCATGTACATTGTTTAGTTGAAGAGAG
	CTCTCTTCAACTAAACAATGTACATGAACATACCTTTCCAATTT	1130
	TTCAGATAGATTGTCAGCAGAATCAACAGAAGGGATTTGGTA
	TATGTCTGACAATTCCAGGCGCTGTCTGTATCCTT
	TGATTCTGCTGACAATC	1131
	GATTGTCAGCAGAATCA	1132
Cystic fibrosis	AGCGCCTGGAATTGTCAGACATATACCAAATCCCTTCTGTTG	1133
Ser50Tyr	ATTCTGCTGACAATCTATCTGAAAAATTGGAAAGGTATGTTCA
TCT to TAT	TGTACATTGTTTAGTTGAAGAGAGAAATTCATATTA
	TAATATGAATTTCTCTCTTCAACTAAACAATGTACATGAACATA	1134
	CCTTTCCAATTTTTCAGATAGATTGTCAGCAGAATCAACAGAA
	GGGATTTGGTATATGTCTGACAATTCCAGGCGCT
	CAATCTATCTGAAAAAT	1135
	ATTTTTCAGATAGATTG	1136
Congenital absence of	AGGACAACTAAAATATTTGCACATGCAACTTATTGGTCCCACT	1137
vas deferens	TTTTATTCTTTTGCAGAGAATGGGATAGAGAGCTGGCTTCAAA
Glu56Lys	GAAAAATCCTAAACTCATTAATGCCCTTCGGCGAT
GAA-AAA
	ATCGCCGAAGGGCATTAATGAGTTTAGGATTTTTTCTTGAAGC	1138
	CAGCTCTCTATCCCATTCTCTGCAAAAGAATAAAAAGTGGGA
	CCAATAAGTVGCATGTGCAAATATTTAGTTGTCCT
	TTTGCAGAGAATGGGAT	1139
	ATCCCATTCTCTGCAAA	1140
Cystic fibrosis	AGGACAACTAAAATATTTGCACATGCAACTTATTGGTCCCACT	1141
Trp57Gly	TTTTTATTCTTTTGCAGAGAATGGGATAGAGAGCTGGCTTCAAA
TGG to GGG	GAAAAATCCTAAACTCATTAATGCCCTTCGGCGAT
	ATCGCCGAAGGGCATTAATGAGTTTTAGGATTTTTTCTTTGAAGC	1142
	CAGCTCTCTATCCCATTCTCTGCAAAAGAATAAAAAGTGGGA
	CCAATAAGTTGCATGTGCAAATATTTTTAGTTGTCCT
	TTTGCAGAGAATGGGAT	1143
	ATCCCATTCTCTGCAAA	1144
Cystic fibrosis	AACTAAAATATTTTGCACATGCAACTTATTGGTCCCACTTTTTAT	1145
Trp57Term	TCTTTTGCAGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAA
TGG to TGA	ATCCTAAACTCATTAATGCCCTTCGGCGATGTTTT
	AAAACATCGCCGAAGGGCATTAATGAGTTTAGGATTTTTCTTT	1146
	GAAGCCAGCTCTCTATCCCATTCTCTGCAAAAGAATAAAAAGT
	GGGACCAATAAGTTGCATGTGCAAATATTTTAGTT
	AGAGAATGGGATAGAGA	1147
	TCTCTATCCCATTCTCT	1148
Congenital absence of	ACTAAAATATTTGCACATGCAACTTATTGGTCCCACTTTTTATT	1149
vas deferens	CTTTTGCAGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAA
Asp58Asn	TCCTAAACTCATTAATGCCCTTCGGCGATGTTTTT
GAT to AAT
	AAAAACATCGCCGAAGGGCATTAATGAGTTTAGGATTTTTCTT	1150
	TGAAGCCAGCTCTCTATCCCATTCTCTGCAAAAGAATAAAAAG
	TGGGACCAATAAGTTGCATGTGCAAATATTTTAGT
	GAGAATGGGATAGAGAG	1151
	CTCTCTATCCCATTCTC	1152
Cystic fibrosis	ATATTTGCACATGCAACTTATTGGTCCCACTTTTTATTCTTTTG	1153
Gtu60Term	CAGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAA
GAG to TAG	ACTCATTAATGCCCTTCGGCGATGTTTTTTCTGGA
	TCCAGAAAAAACATCGCCGAAGGGCATTAATGAGTTTAGGAT	1154
	TTTTCTTTGAAGCCAGCTCTCTATCCCATTCTCTGCAAAAGAA
	TAAAAAGTGGGACCAATAAGTTGCATGTGCAAATAT
	GGGATAGAGAGCTGGCT	1155
	AGCCAGCTCTCTATCCC	1156
Cystic fibrosis	GGTCCCACTTTTTATTCTTTTGCAGAGAATGGGATAGAGAGC	1157
Pro67Leu	TGGCTTCAAAGAAAAATCCTAAACTCATTAATGCCCTTCGGC
CCT to CTT	GATGTTTTTTCTGGAGATTTATGTTCTATGGAATCTT
	AAGATTCCATAGAACATAAATCTCCAGAAAAAACATCGCCGAA	1158
	GGGCATTAATGAGTTTAGGATTTTTCTTTGAAGCCAGCTCTCT
	ATCCCATTCTCTGCAAAAGAATAAAAAGTGGGACC
	GAAAAATCCTAAACTCA	1159
	TGAGTTTAGGAATTTTC	1160
Cystic fibrosis	TGCAGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCT	1161
Arg74Trp	AAACTCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTA
CGG to TGG	TGTTCTATGGAATCTTTTTATATTTAGGGGTAAGGA
	TCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAAATCT	1162
	CCAGAAAAAACATCGCCGAAGGGCATTAATGAGTTTAGGATT
	TTTCTTTGAAGCCAGCTCTCTATCCCATTCTCTGCA
	ATGCCCTTCGGCGATGT	1163
	ACATCGCCGAAGGGCAT	1164
Congenital absence of	GAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAAC	1165
vas deferens	TCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTTATGTT
ARG75GLN	CTATGGAATCTTTTTATATTTAGGGGTAAGGATCTC
CGA to CAA
	GAGATCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAA	1166
	ATCTCCAGAAAAAACATCGCCGAAGGGCATTAATGAGTTTAG
	GATTTTTTCTTTGAAGCCAGCTCTCTATCCCATTCTC
	CCTTCGGCGATGTTTTT	1167
	AAAAACATCGCCGAAGG	TT68
Cystic fibrosis	GAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAAC	1169
Arg75Leu	TCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTTATGTT
CGA to CTA	CTATGGAATCTTTTTATATTAGGGGTAAGGATCTC
	GAGATCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAA	1170
	ATCTCCAGAAAAAACATCGCCGAAGGGCATTAATGAGTTTAG
	GATTTTTCTTTGAAGCCAGCTCTCTATCCCATTCTC
	CCTTCGGCGATGTTTTT	1171
	AAAAACATCGCCGAAGG	1172
Cystic fibrosis	AGAGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAA	1173
Arg75Term	CTCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTATGT
CGA to TGA	TCTATGGAATCTTTTTATATTTAGGGGTAAGGATCT
	AGATCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAAA	1174
	TCTCCAGAAAAAACATCGCCGAAGGGCATTAATGAGTTTTAGG
	ATTTTTTCTTTGAAGCCAGCTCTCTATCCCATTCTCT
	CCCTTCGGCGATGTTTT	1175
	AAAACATCGCCGAAGGG	1176
Cystic fibrosis	ATTAAATCCTAAACTCATTAATGCCCTTCGGCGATGTTTTTTCTG	1177
Gly85Glu	GAGATTTATGTTCTATGGAATCTTTTTATATTTAGGGGTAAGG
GGA to GAA	ATCTCATTTGTACATTCATATGTATCACATAACT
	AGTTATGTGATACATAATGAATGTACAAATGAGATCCTTACCC	1178
	CTAAATATAAAAAGATTCCATAGAACATAAATCTCCAGAAAAA
	ACATCGCCGAAGGGCATTAATGAGTTTAGGATTTT
	GTTCTATGGAATCTTTT	1179
	AAAAGATTCCATAGAAC	1180
Cystic fibrosis	AAAATCCTAAACTCATTAATGCCCTTCGGCGATGTTTTTTCTG	1181
Gly85Val	GAGATTTATGTTCTATGGAATCTTTTTATATTTAGGGGTAAGG
GGA to GTA	ATCTCATTTGTACATTCATTATGTATCACATAACT
	AGTTATGTGATACATAATGAATGTACAAATGAGATCCTTTACCC	1182
	CTAAATATAAAAAGATTCCATAGAACATAAATCTCCAGAAAAA
	ACATCGCCGAAGGGCATTAATGAGTTTAGGATTTT
	GTTCTATGGAATCTTTT	1183
	AAAAGATTCCATAGAAC	1184
Cystic fibrosis	AACTCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTAT	1185
Leu88Ser	GTTCTATGGAATCTTTTTTATATTTAGGGGTAAGGATCTCATTT
TTA to TCA	GTACATTCATTATGTATCACATAACTATATGCATT
	AATGCATATAGTTATGTGATACATAATGAATGTACAAATGAGA	1186
	TCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAAATCT
	CCAGAAAAAACATCGCCGAAGGGCATTAATGAGTT
	AATCTTTTTATATTTAG	1187
	CTAAATATAAAAAGATT	1188
Cystic fibrosis	CCTAAACTCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGAT	1189
Phe87Leu	TTATGTTCTATGGAATCTTTTTATATTTAGGGGTAAGGATCTC
TTT to CTT	ATTTGTACATTCATTATGTATCACATAACTATATG
	CATATAGTTATGTGATACATAATGAATGTACAAATGAGATCCT	1190
	TACCCCTAAATATAAAAAGATTCCATAGAACATAAATCTCCAG
	AAAAAACATCGCCGAAGGGCATTAATGAGTTTAGG
	ATGGAATCTTTTTATAT	1191
	ATATAAAAAGATTCCAT	1192
Cystic fibrosis	AACTCATTAATGCCCHCGGCGATGTTTTTTCTGGAGATTTAT	1193
Leu88Term	GTTCTATGGAATCTTTTTATATTTAGGGGTAAGGATCTCATTT
TTA to TGA	GTACATTCATTATGTATCACATAACTATATGCATT
	AATGCATATAGTTATGTGATACATAATGAATGTACAAATGAGA	1194
	TCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAAATCT
	CCAGAAAAAACATCGCCGAAGGGCATTAATGAGTT
	AATCTTTTTATATTTAG	1195
	CTAAATATAAAAAGATT	1196
Cystic fibrosis	AACTCATTAATGCCCTTCGGCGATGTTTTTTCTGGAGATTTAT	1197
Leu88Term	GTTCTATGGAATCTTTTTATATTTAGGGGTAAGGATCTCATTT
TTA to TAA	GTACATTCATTATGTATCACATAACTATATGCATT
	AATGCATATAGTTATGTGATACATAATGAATGTACAAATGAGA	1198
	TCCTTACCCCTAAATATAAAAAGATTCCATAGAACATAGAATCT
	CCAGAAAAAACATCGCCGAAGGGCATTAATGAGTT
	AATCTTTTTATATTTAG	1199
	CTAAATATAAAAAGATT	1200
Cystic fibrosis	AATGCCCTTCGGCGATGTTTTTTCTGGAGATTTATGTTCTATG	1201
Gly91Arg	GAATCTTTTTATATTTAGGGGTAAGGATCTCATTTGTACATTC
GGG to AGG	ATTATGTATCACATAACTATATGCATTTTTGTGAT
	ATCACAAAAATGCATATAGTTATGTGATACATAATGAATGTAC	1202
	AAATGAGATCCTTACCCCTAAATATAAAAAGATTCCATAGAAC
	ATAAATCTCCAGAAAAAACATCGCCGAAGGGCATT
	TATATTTAGGGGTAAGG	1203
	CCTTACCCCTAAATATA	1204
Cystic fibrosis	AATAAATGAAATTTAATTTCTCTGGTTTTCCCCTTGTGTAGGAA	1205
Gln98Arg	GTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCATA
CAG to CGG	GCTTCCTATGACCCGGATAACAAGGAGGAACGCTC
	GAGCGTTCCTCCTTGTTATCCGGGTCATAGGAAGCTATGATT	1206
	CTTCCCAGTAAGAGAGGCTGTACTGCTTTGGTGACTTCCTAC
	AAAAGGGGAAAAACAGAGAAATTAAATTTCATTTATT
	AGCAGTACAGCCTCTCT	1207
	AGAGAGGCTGTACTGCT	1208
Cystic fibrosis	AAATAAATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGA	1209
Gln98Term	AGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCAT
CAG-TAG	AGCTTCCTATGACCCGGATAACAAGGAGGAACGCT
	AGCGTTCCTCCTTGTTATCCGGGTCATAGGAAGCTATGATTC	1210
	TTCCCAGTAAGAGAGGCTGTACTGCTTTGGTGACTTCCTACA
	AAAGGGGAAAAACAGAGAAATTAAATTTCATTTATTT
	AAGCAGTACAGCCTCTC	1211
	GAGAGGCTGTACTGCTT	1212
Cystic fibrosis	CCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCTTAC	1213
Ser108Phe	TGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGG
TCC to TTC	AACGCTCTATCGCGATTTATCTAGGCATAGGCTTATG
	CATAAGCCTATGCCTAGATAAATCGCGATAGAGCGTTCCTCC	1214
	TTGTTATCCGGGTCATAGGAAGCTATGATTCTTCCCAGTAAG
	AGAGGCTGTACTGCTTTGGTGACTTCCTACAAAAGGG
	CATAGCTTCCTATGACC	1215
	GGTCATAGGAAGCTATG	1216
Cystic fibrosis	TTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCTTACTGG	1217
Tyr109Cys	GAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAAC
TAT to TGT	GCTCTATCGCGATTATCTAGGCATAGGCTTATGCCT
	AGGCATAAGCCTATGCCTAGATAAATCGCGATAGAGCGTTCC	1218
	TCCTTGTTATCCGGGTCATAGGAAGCTATGATTCTTCCCAGT
	AAGAGAGGCTGTACTGCTTTGGTGACTTCCTACAAAA
	AGCTTCCTATGACCCGG	1219
	CCGGGTCATAGGAAGCT	1220
Cystic fibrosis	TTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGA	1221
Asp110His	AGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACGC
GAC to CAC	TCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTC
	GAAGGCATAAGCCTATGCCTAGATAAATCGCGATAGAGCGTT	1222
	CCTCCYTGTTATCCGGGTCATAGGAAGCTATGATTCTTCCCA
	GTAAGAGAGGCTGTACTGCTTTGGTGACTTCCTACAA
	CTTCCTATGACCCGGAT	1223
	ATCCGGGTCATAGGAAG	1224
Congenital absence of	AGGAAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAA	1225
vas deferens	TCATAGCTTCCTATGACCCGGATAACAAGGAGGAACGCTCTA
Pro111Leu	TCGCGATTTATCTAGGCATAGGCTTATGCCTTCTTCT
CCG to CTG
	AAGAGAAGGCATAAGCCTATGCCTAGATAAATCGCGATAGAG	1226
	CGTTCCTCCTTGTTATCCGGGTCATAGGAAGCTATGATTCTT
	CCCAGTAAGAGAGGCTGTACTGCTTTGGTGACTTCCT
	CTATGACCCGGATAACA	1227
	TGTTATCCGGGTCATAG	1228
Cystic fibrosis	GTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGAC	1229
Arg117Cys	CCGGATAACAAGGAGGAACGCTCTATCGCGATTTATCTAGGC
CGC to TGC	ATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGC
	GCAGTGTCCTCACAATAAAGAGAAGGCATAAGCCTATGCCTA	1230
	GATAAATCGCGATAGAGCGTTCCTCCTTGTTATCCGGGTCAT
	AGGAAGCTATGATTCTTCCCAGTAAGAGAGGCTGTAC
	AGGAGGAACGCTCTATC	1231
	GATAGAGCGTTCCTCCT	1232
Cystic fibrosis	TACAGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACC	1233
Arg117His	CGGATAACAAGGAGGAACGCTCTATCGCGATTTATCTAGGCA
CGC to CAC	TAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCT
	AGCAGTGTCCTCACAATAAAGAGAAGGCATAAGCCTATGCCT	1234
	AGATAAATCGCGATAGAGCGTTCCTCCTTGTTATCCGGGTCA
	TAGGAAGCTATGATTCTTCCCAGTAAGAGAGGCTGTA
	GGAGGAACGCTCTATCG	1235
	CGATAGAGCGTTCCTCC	1236
Cystic fibrosis	TACAGCCTCTCGTACTGGGAAGAATCATAGCTTCCTATGACC	1237
Arg117Leu	CGGATAACAAGGAGGAACGCTCTATCGCGATTTATCTAGGCA
CGC to CTC	TAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCT
	AGCAGTGTCCTCACAATAAAGAGAAGGCATAAGCCTATGCCT	1238
	AGATAAATCGCGATAGAGCGTTCCTCCTTGTTATCCGGGTCA
	TAGGAAGCTATGATTCTTCCCAGTAAGAGAGGCTGTA
	GGAGGAACGCTCTATCG	1239
	CGATAGAGCGTTCCTCC	1240
Cystic fibrosis	TACAGCCTCTCTTTACTGGGAAGAATCATAGCTTCCTATGACC	1241
Arg117Pro	CGGATAACAAGGAGGAACGCTCTATCGCGATTTATCTAGGCA
CGC to CCC	TAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCT
	AGCAGTGTCCTCACAATAAAGAGAAGGCATAAGCCTATGCCT	1242
	AGATAAATCGCGATAGAGCGTTCCTCCTTGTTATCCGGGTCA
	TAGGAAGCTATGATTCTTCCCAGTAAGAGAGGCTGTA
	GGAGGAACGCTCTATCG	1243
	CGATAGAGCGTTCCTCC	1244
Cystic fibrosis	CTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAAC	1245
Ala120Thr	AAGGAGGAACGCTCTATCGCGATTTATCTAGGCATAGGCTTA
GCG-ACG	TGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACC
	GGTGTAGGAGCAGTGTCCTCACAATAAAGAGAAGGCATAAG	1246
	CCTATGCCTAGATAAATCGCGATAGAGCGTTCCTCCTTGTTA
	TCCGGGTCATAGGAAGCTATGATTCTTCCCAGTAAGAG
	GCTCTATCGCGATTTAT	1247
	ATAAATCGCGATAGAGC	1248
Cystic fibrosis	GGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGA	1249
Tyr122Term	ACGCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCT
TAT to TAA	CTTTATTGTGAGGACACTGCTCCTACACCCAGCCATT
	AATGGCTGGGTGTAGGAGCAGTGTCCTCACAATAAAGAGAA	1250
	GGCATAAGCCTATGCCTAGATAAATCGCGATAGAGCGTTTCCT
	CCTTGTTATCCGGGTCATAGGAAGCTATGATTCTTCCC
	GCGATTTATCTAGGCAT	1251
	ATGCCTAGATAAATCGC	1252
Cystic fibrosis	TAGCTTCCTATGACCCGGATAACAAGGAGGAACGCTCTATCG	1253
Gly126Asp	CGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAG
GGC-GAC	GACACTGCTCCTACACCCAGCCATTTTTGGCCTTCA
	TGAAGGCCAAAAATGGCTGGGTGTAGGAGCAGTGTCCTCAC	1254
	AATAAAGAGAAGGCATAAGCCTATGCCTAGATAAATCGCGAT
	AGAGCGTTCCTCCTTGTTATCCGGGTCATAGGAAGCTA
	AGGCA	1255
	GGCATAAGCCTATGCCT	1256
Cystic fibrosis	TCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGT	1257
Hist139Arg	GAGGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCA
CAC to CGC	CATTGGAATGCAGATGAGAATAGCTATGTTTAGTTT
	AAACTAAACATAGCTATTCTCATCTGCATTCCAATGTGATGAA	1258
	GGCCAAAAATGGCTGGGTGTAGGAGCAGTGTCCTCACAATA
	AAGAGAAGGCATAAGCCTATGCCTAGATAAATCGCGA
	GCTCCTACACCCAGCCA	1259
	TGGCTGGGTGTAGGAGC	1260
Cystic fibrosis	TTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGAC	1261
Ala141Asp	ACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGG
GCC to GAC	AATGCAGATGAGAATAGCTATGTTTAGTTTGATTTA
	TAAATCAAACTAAACATAGCTATTCTCATCTGCATTCCAATGT	1262
	GATGAAGGCCAAAAATGGCTGGGTGTAGGAGCAGTGTCCTC
	ACAATAAAGAGAAGGCATAAGCCTATGCCTAGATAAA
	ACACCCAGCCATTTTTG	1263
	CAAAAATGGCTGGGTGT	1264
Cystic fibrosis	GCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCA	1265
lle148Thr	TTTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTAT
ATT to ACT	GTTAGTTTGATTTATAAGAAGGTAATACTTCCTTG
	CAAGGAAGTATTACCTTCTTATAAATCAAACTAAACATAGCTA	1266
	TTCTCATCTGCATTCCAATGTGATGAAGGCCAAAAATGGCTG
	GGTGTAGGAGCAGTGTCCTCACAATAAAGAGAAGGC
	TCATCACATTGGAATGC	1267
	GCATTCCAATGTGATGA	1268
Cystic fibrosis	CTTCTCGTTATTGTGAGGACACTGCTCCTACACCCAGCCATTT	1269
Gly149Arg	TTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTT
GGA to AGA	TAGTTTGATTATAAGAAGGTAATACTTCCTTGCA
	TGCAAGGAAGTATTACCTTCTTATAAATCAAACTAAACATAGC	1270
	TATTCTCATCTGCATTCCAATGTGATGAAGGCCAAAAATGGCT
	GGGTGTAGGAGCAGTGTCCTCACAATAAAGAGAAG
	ATCACATTGGAATGCAG	1271
	CTGCATTCCAATGTGAT	1272
Cystic fibrosis	TTTATTGTGAGGACACTGCTCCTACACCCAGCCATTTTTGGC	1273
Gln1511Term	CTTCATCACATTGGAATGCAGATGAGAATAGCTATGGTTAGTT
CAG to TAG	TGATTTATAAGAAGGTAATACTTCCTTGCACAGGCC
	GGCCTGTGCAAGGAAGTATTACCTTCTTATAAATCAAACTAAA	1274
	CATAGCTATTCTCATCTGCATTCCAATGTGATGAAGGCCAAAA
	ATGGCTGGGTGTAGGAGCAGTGTCCTCACAATAAA
	TTGGAATGCAGATGAGA	1275
	TCTCATCTGCATTCCAA	1276
Cystic fibrosis	AATATATTTGTATTTTGTTTGTTGAAATTATCTAACTTTCCATTT	1277
Lys166Glu	TTCTTTTAGACTTTAAAGCTGTCAAGCCGTGTTCTAGATAAAA
AAG-GAG	TAAGTATTGGACAACTTGTTAGTCTCCTTTCCA
	TGGAAAGGAGACTAACAAGTTGTCCAATACTTATTTTATCTAG	1278
	AACACGGCTTGACAGCTTTAAAGTCTAAAAGAAAAATGGAAA
	GTTAGATAATTTCAACAAACAAAATACAAATATATT
	AGACTTTAAAGCTGTCA	1279
	TGACAGCTTTAAAGTCT	1280
Cystic fibrosis	TTATCTAACTTTCCATTTTTCTTTTAGACTTTAAAGCTGTCAAG	1281
lle175Val	CCGTGTTCTAGATAAAATAAGTATTGGACAACTTGTTAGTCTC
ATA-GTA	CTTTCCAACAACCTGAACAAATTTGATGAAGTAT
	ATACTTCATCAAATTTGTTCAGGTTGTTGGAAAGGAGACTAAC	1282
	AAGTTGTCCAATACTTATTTTATCTAGAACACGGCTTGACAGC
	TTTAAAGTCTAAAAGAAAAATGGAAAGTTAGATAA
	TAGATAAAATAAGTATT	1283
	AATACTTATTTTATCTA	1284
Cystic fibrosis	TTTCCATTTTTCTTTTAGACTTTAAAGCTGTCAAGCCGTGTTCT	1285
Gly178Arg	AGATAAAATAAGTATTGGACAACTTGTTAGTCTCCTTTCCAAC
GGA to AGA	AACCTGAACAAATTTGATGAAGTATGTACCTATT
	AATAGGTACATACTTCATCAAATTTGTTCAGGTTGTTGGAAAG	1286
	GAGACTAACAAGTTGTCCAATACTTATTTTATCTAGAACACGG
	CTTGACAGCTTTAAAGTCTAAAAGAAAAATGGAAA
	TAAGTATTGGACAACTT	1287
	AAGTTGTCCAATACTTA	1288
Cystic fibrosis	AAGATACAATGACACCTGTTTTTGCTGTGCTTTTATTTTCCAG	1289
His199Gln	GGACTTGCATTGGCACATTTCGTGTGGATCGCTCCTTTGCAA
CAT to CAG	GTGGCACTCCTCATGGGGCTAATCTGGGAGTTGTTA
	TAACAACTCCCAGATTAGCCCCATGAGGAGTGCCACTTGCAA	1290
	AGGAGCGATCCACACGAAATGTGCCAATGCAAGTCCCTGGA
	AAATAAAAGCACAGCAAAAACAGGTGTCATTGTATCTT
	TTGGCACATTTCGTGTG	1291
	CACACGAAATGTGCCAA	1292
Cystic fibrosis	GGAAGATACAATGACACCTGTTTTTGCTGTGCTTTTATTTTCC	1293
His199Tyr	AGGGACTTGCATTGGCACATTTCGTGTGGATCGCTCCTTTGC
CAT to TAT	AAGTGGCACTCCTCATGGGGCTAATCTGGGAGTTGT
	ACAACTCCCAGATTAGCCCCATGAGGAGTGCCACTTGCAAAG	1294
	GAGCGATCCACACGAAATGTGCCAATGCAAGTCCCTGGAAA
	ATAAAAGCACAGCAAAAACAGGTGTCATTGTATCTTCC
	CATTGGCACATTTCGTG	1295
	CACGAAATGTGCCAATG	1296
Cystic fibrosis	TGTTTTTGCTGTGCTTTATTTTCCAGGGACTTGCATTGGCAC	1297
Pro205Ser	ATTTCGTGTGGATCGCTCCTTTGCAAGTGGCACTCCTCATGG
CCT to TCT	GGCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCT
	AGAAGGCAGACGCCTGTAACAACTCCCAGATTAGCCCCATG	1298
	AGGAGTGCCACTTGCAAAGGAGCGATCCACACGAAATGTGC
	CAATGCAAGTCCCTGGAAAATAAAAGCACAGCAAAAACA
	GGATCGCTCCTTTGCAA	1299
	TTGCAAAGGAGCGATCC	1300
Cystic fibrosis	TTTGCTGTGCTTTATTTTCCAGGGACTTGCATTGGCACATTT	1301
Leu206Trp	CGTGTGGATCGCTCCTTTGCAAGTGGCACTCCTCATGGGGC
TTG to TGG	TAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGTGG
	CCACAGAAGGCAGACGCCTGTAACAACTCCCAGATTAGCCC	1302
	CATGAGGAGTGCCACTTGCAAAGGAGCGATCCACACGAAAT
	GTGCCAATGCAAGTCCCTGGAAAATAAAAGCACAGCAAA
	CGCTCCTTTGCAAGTGG	1303
	CCACTTGCAAAGGAGCG	1304
Cystic fibrosis	TTCGTGTGGATCGCTCCTTTGCAAGTGGCACTCCTCATGGG	1305
Gln220Term	GCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGTGGACT
CAG to TAG	TGGTTTCCTGATAGTCCTTGCCCTTTTTCAGGCTGGGC
	GCCCAGCCTGAAAAAGGGCAAGGACTATCAGGAAACCAAGT	1306
	CCACAGAAGGCAGACGCCTGTAACAACTCCCAGATTAGCCC
	CATGAGGAGTGCCACTTGCAAAGGAGCGATCCACACGAA
	AGTTGTTACAGGCGTCT	1307
	AGACGCCTGTAACAACT	1308
Cystic fibrosis	CCTTTGCAAGTGGCACTCCTCATGGGGCTAATCTGGGAGTT	1309
Cys225Arg	GTTACAGGCGTCTGCCTTCTGTGGACTTGGTTTCCTGATAGT
TGT-CGT	CCTTGCCCTTTTTCAGGCTGGGCTAGGGAGAATGATGA
	TCATCATTCTCCCTAGCCCAGCCTGAAAAAGGGCAAGGACTA	1310
	TCAGGAAACCAAGTCCACAGAAGGCAGACGCCTGTAACAAC
	TCCCAGATTAGCCCCATGAGGAGTGCCACTTGCAAAGG
	CTGCCTTCTGTGGACTT	1311
	AAGTCCACAGAAGGCAG	1312
Cystic fibrosis	TGGGGCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGT	1313
Val232Asp	GGACTTGGTTTCCTGATAGTCCTTGCCCTTTTTCAGGCTGGG
GTC to GAC	CTAGGGAGAATGATGATGAAGTACAGGTAGCAACCTAT
	ATAGGTTGCTACCTGTACTTCATCATCATTCTCCCTAGCCCA 1314
	GCCTGAAAAAGGGCAAGGACTATCAGGAAACCAAGTCCACA
	GAAGGCAGACGCCTGTAACAACTCCCAGATTAGCCCCA
	CCTGATAGTCCTTGCCC	1315
	GGGCAAGGACTATCAGG	1316
Cystic fibrosis	GTTACAGGCGTCTGCCTTCTGTGGACTTGGTTTCCTGATAGT	1317
Gly239Arg	CCTTGCCCTTTTTCAGGCTGGGCTAGGGAGAATGATGATGAA
GGG to AGG	GTACAGGTAGCAACCTATTTTCATAACTTGAAAGTTT
	AAACTTTCAAGTTATGAAAATAGGTTGCTACCTGTACTTCATC	1318
	ATCATTCTCCCTAGCCCAGCCTGAAAATTAGGGCAAGGACTATC
	AGGAAACCAAGTCCACAGAAGGCAGACGCCTGTAAC
	TTTCAGGCTGGGCTAGG	1319
	CCTAGCCCAGCCTGAAA	1320

EXAMPLE 10

Cyclin-Dependent Kinase Inhibitor 2A—CDKN2A

[0129] The human CDKN2A gene was also designated MTS-1 for multiple tumor suppressor-1 and has been implicated in multiple cancers including, for example, malignant melanoma. Malignant melanoma is a cutaneous neoplasm of melanocytes. Melanomas generally have features of asymmetry, irregular border, variegated color, and diameter greater than 6 mm. The precise cause of melanoma is unknown, but sunlight and heredity are risk factors. Melanoma has been increasing during the past few decades.

[0130] The CDKN2A gene has been found to be homozygously deleted at high frequency in cell lines derived from tumors of lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphocyte. Melanoma cell lines carried at least one copy of CDKN2A in combination with a deleted allele. Melanoma cell lines that carried at least 1 copy of CDKN2A frequently showed nonsense, missense, or frameshift mutations in the gene. Thus, CDKN2A may rival p53 (see Example 5) in the universality of its involvement in tumorigenesis. The attached table discloses the correcting oligonucleotide base sequences for the CDKN2A oligonucleotides of the invention.

TABLE 17
CDKN2A Mutations and Genome-Correcting Oligos
		SEQ ID
Clinical Phenotype &	Correcting Oligos	NO:
Melanoma	GGGCGGCGGGGAGCAGCATGGAGCCGGCGGCGGGGAGCAG	1321
Trp15Term
TGG-TAG	CATGGAGCCTTCGGCTGACTGCTGGCCACGGCCGCGGCCC
	GGGGTCGGGTAGAGGAGGTGCGGGCGCTGCTGGAGGCGGG
	CCCGCCTCCAGCAGCGCCCGCACCTCCTCTACCCGACCCCG	1322
	GGCCGCGGCCGTGGCCAGCCAGTCAGCCGAAGGCTCCATGC
	TGCTCCCCGCCGCCGGCTCCATGCTGCTCCCCGCCGCCC
	GGCTGACTGGCTGGCCA	1323
	TGGCCAGCCAGTCAGCC	1324
Melanoma	CGGCGGGGAGCAGCATGGAGCCGGCGGCGGGGAGCAGCAT	1325
Leu16Pro
CTG-CCG	GGAGCCTTCGGCTGACTGGCTGGCCACGGCCGCGGCCCGG
	GGTCGGGTAGAGGAGGTGCGGGCGCTGCTGGAGGCGGGGG
	C
	GCCCCCGCCTCCAGCAGCGCCCGCACCTCCTCTACCGACC	1326
	CCGGGCCGCGGCCGTGGCCAGCCAGTCAGCCGAAGGCTCC
	ATGCTGCTCCCCGCCGCCGGCTCCATGCTGCTCCCCGCCG
	TGACTGGCTGGCCACGG	1327
	CCGTGGCCAGCCAGTCA	1328
Melanoma	CGGCGGCGGGGAGCAGCATGGAGCCTTCGGCTGACTGGCTG	1329
Gly23Asp
CTG-CCG	GCCACGGCCGCGGCCCGGGGTCGGGTAGAGGAGGTGCGGG
	CGCTGCTGGAGGCGGGGGCGCTGCCCAACGCACCGAATAG
	CTATTCGGTGCGTTGGGCAGCGCCCCCGCCTCCAGCAGCGC	1330
	CCGCACCTCCTCTACCCGACCCCGGGCCGCGGCCGTGGCCA
	GCCAGTCAGCCGAAGGCTCCATGCTGCTCCCCGCCGCCG
	GGCCCGGGGTCGGGTAG	1331
	CTACCCGACCCCGGGCC	1332
Melanoma	CGGCGGGGAGCAGCATGGAGCCTTCGGCTGACTGGCTGGCC	1333
Arg24Pro
CGG-CCG	ACGGCCGCGGCCCGGGGTCGGGTAGAGGAGGTGCGGGCGC
	TGCTGGAGGCGGGGGCGCTGCCCAACGCACCGAATAGTTA
	TAACTATTCGGTGCGTTGGGCAGCGCCCCCGCCTCCAGCAGC	1334
	GCCCGCACCTCCTCTACCCGACCCCGGGCCGCGGCCGTGGC
	CAGCCAGTCAGCCGAAGGCTCCATGCTGCTCCCCGCCG
	CCGGGGTCGGGTAGAGG	1335
	CCTCTACCCGACCCCGG	1336
Melanoma	CGGCTGACTGGCTGGCCACGGCCGCGGCCCGGGGTCGGGT	1337
Leu32Pro
CTG-CCG	AGAGGAGGTGCGGGCGCTGCTGGAGGCGGGGGCGCTGCCC
	AACGCACCGAATAGTTACGGTCGGAGGCCGATCCAGGTGGG
	CCCACCTGGATCGGCCTCCGACCGTAACTATTCGGTGCGTTG	1338
	GGCAGCGCCCCCGCCTCCAGCAGCGCCCGCACCTCCTCTAC
	CCGACCCCGGGCCGCGGCCGTGGCCAGCCAGTCAGCCG
	GGCGCTGCTGGAGGCGG	1339
	CCGCCTCCAGCAGCGCC	1340
Melanoma	GGCTGGCCACGGCCGCGGCCCGGGGTCGGGTAGAGGAGGT	1341
Gly35Ala
GGG-GCG	GCGGGCGCTGCTGGAGGCGGGGGCGCTGCCCAACGCACCG
	AATAGTTACGGTCGGAGGCCGATCCAGGTGGGTAGAGGGTC
	GACCCTCTACCCACCTGGATCGGCCTCCGACCGTAACTATTC	1342
	GGTGCGTTGGGCAGCGCCCCCGCCTCCAGCAGCGCCCGCAC
	CTCCTCTACCCGACCCCGGGCCGCGGCCGTGGCCAGCC
	GGAGGCGGGGGCGCTGC	1343
	GCAGCGCCCCCGCCTCC	1344
Melanoma	GGTAGAGGAGGTGCGGGCGCTGCTGGAGGCGGGGGCGCTG	1345
Tyr44Term
TACg-TAA	CCCAACGCACCGAATAGTTACGGTCGGAGGCCGATCCAGGTG
	GGTAGAGGGTCTGCAGCGGGAGCAGGGGATGGCGGGCGA
	TCGCCCGCCATCCCCTGCTCCCGCTGCAGACCCTCTACCCAC	1346
	CTGGATCGGCCTCCGACCGTAACTATTCGGTGCGTTGGGCAG
	CGCCCCCGCCTCCAGCAGCGCCCGCACCTCCTCTACC
	AATAGTTACGGTCGGAG	1346
	CTCCGACCGTAACTATT	1348
Melanoma	TCTCCCATACCTGCCCCCACCCTGGCTCTGACCACTCTGCTC	1349
Met53IIe
ATGa-ATC	TCTCTGGCAGGTCATGATGATGGGCAGCGCCCGCGTGGCGG
	AGCTGCTGCTGCTCCACGGCGCGGAGCCCAACTGCGCA
	TGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCAGCAGCTCCG	1350
	CCACGCGGGCGCTGCCCATCATCATGACCTGCCAGAGAGAG
	CAGAGTGGTCAGAGCCAGGGTGGGGGCAGGTATGGGAGA
	GTCATGATGATGGGCAG	1351
	CTGCCCATCATCATGAC	1352
Melanoma	CCCATACCTGCCCCCACCCTGGCTCTGACACTCTGCTCTCT	1353
Met54IIe
ATGg-ATV	CTGGCAGGTCATGATGATGGGCAGCGCCCGCGTGGCGGAGC
	TGCTGCTGCTCCACGGCGCGGAGCCCAACTGCGCAGAC
	GTCTGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCAGCAGCT	1354
	CCGCCACGCGGGCGCTGCCCATCATCATGACCTGCCAGAGA
	GAGCAGAGTGGTCAGAGCCAGGGTGGGGGCAGGTATGGG
	ATGATGATGGGCAGCGC	1355
	GCGCTGCCCATCATCAT	1356
Melanoma	GCCGGCCCCACCCTGGCTCTGACCATTCTGTTCTCTCTGGC	1357
Ser56IIe
AGC-ATC	AGGTCATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTG
	CTGCTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGC
	GCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCA	1358
	GCAGCTCCGCCACTCGGGCGCTGCCCATCATCATGACCTGCC
	AGAGAGAACAGAATGGTCAGAGCCAGGGTGGGGGCCGGC
	GATGGGCAGCGCCCGAG	1359
	CTCGGGCGCTGCCCATC	1360
Melanoma	GGCCCCCACCCTGGCTCTGACCATTCTGTTCTCTCTGGCAGG	1361
Ala57Val
GCC-GTC	TCATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCTG
	CTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCAC
	GTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAGCA	1362
	GCAGCAGCTCCGCCACTCGGGCGCTGCCCATCATCATGACCT
	GCCAGAGAGAACAGAATGGTCAGAGCCAGGGTGGGGGCC
	GGGCAGCGCCCGAGTGG	1363
	CCACTCGGGCGCTGCCC	1364
Melanoma	CCCCCACCCTGGCTCTGACCATTCTGTTCTCTCTGGCAGGTC	1365
Arg58Term
cCGA-TGA	ATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCTGCT
	CCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTC
	GAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAG	1366
	CAGCAGCAGCTCCGCCACTCGGGCGCTGCCCATCATCATGAC
	CTGCCAGAGAGAACAGAATGGTCAGAGCCAGGGTGGGGG
	GCAGCGCCCGAGTGGCG	1367
	CGCCACTCGGGCGCTGC	1368
Melanoma	CACCCTGGCTCTGACCATTCTGTTCTCTCTGGCAGGTCATGAT	1369
Val59Gly
GTG-GGG	GATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCTGCTCCACG
	GCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCAC
	GTGAGAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTG	1370
	GAGCAGCAGCAGCTCCGCCACTCGGGCGCTGCCCATCATCA
	TGACCTGCCAGAGAGAACAGAATGGTCAGAGCCAGGGTG
	CGCCCGAGTGGCGGAGC	1371
	GCTCCGCCACTCGGGCG	1372
Melanoma	TCTGACCACTCTGCTCTCTCTGGCAGGTCATGATGATGGGCA	1373
Leu62Pro
CTG-CCG	GCGCCCGCGTGGCGGAGCTGCTGCTGCTCCACGGCGCGGA
	GCCCAACTGCGCAGACCCTGCCACTCTCACCCGACCGGT
	ACCGGTCGGGTGAGAGTGGCAGGGTCTGCGCAGTTGGGCTC	1374
	CGCGCCGTGGAGCAGCAGCAGCTCCGCCACGCGGGCGCTG
	CCCATCATCATGACCTGCCAGAGAGAGCAGAGTGGTCAGA
	GGCGGAGCTGCTGCTGC	1375
	GCAGCAGCAGCTCCGCC	1376
Melanoma	TCTGGCAGGTCATGATGATGGGCAGCGCCCGCGTGGCGGAG	1377
Ala68Val
GCG-GTG	CTGCTGCTGCTCCACGGCGCGGAGCCCAACTGCGCAGACCC
	TGCCACTCTCACCCGACCGGTGCATGATGCTGCCCGGGA
	TCCCGGGCAGCATCATGCACCGGTCGGGTGAGAGTGGCAGG	1378
	GTCTGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCAGCAGCT
	CCGCCACGCGGGCGCTGCCCATCATCATGACCTGCCAGA
	CCACGGCGCGGAGCCCA	1379
	TGGGCTCCGCGCCGTGG	1380
Melanoma	CATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCTGC	1381
Asn71Lys
AACt-AAA	TCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTC
	ACCCGACCCGTGCACGACGCTGCCCGGGAGGGCTTCCTG
	CAGGAAGCCCTCCCGGGCAGCGTCGTGCACGGGTCGGGTGA	1382
	GAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAG
	CAGCAGCAGCTCCGCCACTCGGGCGCTGCCCATCATCATG
	GAGCCCAACTGCGCCGA	1383
	TCGGCGCAGTTGGGCTC	1384
Melanoma	TCATGATGATGGGCAGCGCCCGAGTGGCGGAGCTGCTGCTG	1385
Asn71Ser
AAC-AGC	CTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCT
	CACCCGACCCGTGCACGACGCTGCCCGGGAGGGCTTCCT
	AGGAAGCCCTCCCGGGCAGCGTCGTGCACGGGTCGGGTGAG	1386
	AGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAGCA
	GCAGCAGCTCCGCCACTCGGGCGCTGCCCATCATCATGA
	GGAGCCCAACTGCGCCG	1387
	CGGCGCAGTTGGGCTCC	1388
Melanoma	AGCTGCTGCTGCTCCACGGCGCGGAGCCCAACTGCGCCGAC	1389
Pro81Leu
CCC-CTC	CCCGCCACTCTCACCCGACCCGTGCACGACGCTGCCCGGGA
	GGGCTTCCTGGACACGCTGGTGGTGCTGCACCGGGCCGG
	CCGGCCCGGTGCAGCACCACCAGCGTGTCCAGGAAGCCCTC	1390
	CCGGGCAGCGTCGTGCACGGGTCGGGTGAGAGTGGCGGGG
	TCGGCGCAGTTGGGCTCCGCGCCGTGGAGCAGCAGCAGCT
	CACCCGACCCGTGCACG	1391
	CGTGCACGGGTCGGGTG	1392
Melanoma	CTGCTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCAC	1393
Asp84Tyr
cGAC-TAC	TCTCACCCGACCCGTGCACGACGCTGCCCGGGAGGGCTTCC
	TGGACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGC
	GCCGCGCCCCGGCCCGGTGCAGCACCACCAGCGTGTCCAGG	1394
	AAGCCCTCCCGGGCAGCGTCGTGCACGGGTCGGGTGAGAGT
	GGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAGCAG
	CCGTGCACGACGCTGCC	1395
	GGCAGCGTCGTGCACGG	1396
Melanoma	CTCCACGGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCT	1397
Ala85Thr
cGCT-ACT	CACCCGACCCGTGCACGACGCTGCCCGGGAGGGCTTCCTGG
	ACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGG
	CCAGCCGCGCCCCGGCCCGGTGCAGCACCACCAGCGTGTCC	1398
	AGGAAGCCCTCCCGGGCAGCGTCGTGCACGGGTCGGGTGAG
	AGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCCGTGGAG
	TGCACGACGCTGCCCGG	1399
	CCGGGCAGCGTCGTGCA	1400
Melanoma	GCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCACCCGA	1401
Arg87Pro
CGG-CCG	CCCGTGCACGACGCTGCCCGGGAGGGCTTCCTGGACACGCT
	GGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGCG
	CGCACGTCCAGCCGCGCCCCGGCCCGGTGCAGCACCACCAG	1402
	CGTGTCCAGGAAGCCCTCCCGGGCAGCGTCGTGCACGGGTC
	GGGTGAGAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGC
	CGCTGCCCGGGAGGGCT	1403
	AGCCCTCCCGGGCAGCG	1404
Melanoma	GGCGCGGAGCCCAACTGCGCCGACCCCGCCACTCTCACCCG	1405
Arg87Trp
cCGG-TGG	ACCCGTGCACGACGCTGCCCGGGAGGGCTTCCTGGACACGC
	TGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGC
	GCACGTCCAGCCGCGCCCCGGCCCGGTGCAGCACCACCAGC	1406
	GTGTCCAGGAAGCCCTCCCGGGCAGCGTCGTGCACGGGTCG
	GGTGAGAGTGGCGGGGTCGGCGCAGTTGGGCTCCGCGCC
	ACGCTGCCCGGGAGGGC	1407
	GCCCTCCCGGGCAGCGT	1408
Melanoma	CTCTCACCCGACCGGTGCATGATGCTGCCCGGGAGGGCTTC	1409
Leu97Arg
CTG-CGG	CTGGACACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCT
	GGACGTGCGCGATGCCTGGGGTCGTCTGCCCGTGGACTT
	AAGTCCACGGGCAGACGACCCCAGGCATCGCGCACGTCCAG	1410
	CCGCGCCCCGGGCCGGTGCAGCACCACCAGCGTGTCCAGGA
	AGCCCTCCCGGGCAGCATCATGCACCGGTCGGGTGAGAG
	GGTGGTGCTGCACCGGG	1411
	CCCGGTGCAGCACCACC	1412
Melanoma	CCCGACCGGTGCATGATGCTGCCCGGGAGGGCTTCCTGGAC	1413
Arg99Pro
CGG-CCG	ACGCTGGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACG
	TGCGCGATGCCTGGGGTCGTCTGCCCGTGGACTTGGCCGA
	TCGGCCAAGTCCACGGGCAGACGACCCCAGGCATCGCGCAC	1414
	GTCCAGCCGCGCCCCGGCCCGGTGCAGCACCACCAGCGTGT
	CCAGGAAGCCCTCCCGGGCAGCATCATGCACCGGTCGGG
	GCTGCACCGGGCCGGGG	1415
	CCCCGGCCCGGTGCAGC	1416
Melanoma	CCGGTGCATGATGCTGCCCGGGAGGGCTTCCTGGACACGCT	1417
Gly101Trp
cGGG-TGG	GGTGGTGCTGCACCGGGCCGGGGCGCGGCTGGACGTGCGC
	GATGCCTGGGGTCGTCTGCCCGTGGACTTGGCCGAGGAGC
	GCTCCTCGGCCAAGTCCACGGGCAGACGACCCCAGGCATCG	1418
	CGCACGTCCAGCCGCGCCCCGGCCCGGTGCAGCACCACCAG
	CGTGTCCAGGAAGCCCTCCCGGGCAGCATCATGCACCGG
	ACCGGGCCGGGGCGCGG	1419
	CCGCGCCCCGGCCCGGT	1420
Melanoma	CGGGAGGGCTTCCTGGACACGCTGGTGGTGCTGCACCGGGC	1421
Arg107Cys
gCGC-TGC	CGGGGCGCGGCTGGACGTGCGCGATGCCTGGGGTCGTCTGC
	CCGTGGACTTGGCCGAGGAGCGGGGCCACCGCGACGTTG
	CAACGTCGCGGTGGCCCCGCTCCTCGGCCAAGTCCACGGGC	1422
	AGACGACCCCAGGCATCGCGCACGTCCAGCCGCGCCCCGGC
	CCGGTGCAGCACCACCAGCGTGTCCAGGAAGCCCTCCCG
	TGGACGTGCGCGATGCC	1423
	GGCATCGCGCACGTCCA	1424
Melanoma	CACCGGGCCGGGGCGCGGCTGGACGTGCGCGATGCCTGGG	1425
Ala118Thr
gGCT-ACT	GCCGTCTGCCCGTGGACCTGGCTGAGGAGCTGGGCCATCGC
	GATGTCGCACGGTACCTGCGCGCGGCTGCGGGGGGCACCA
	TGGTGCCCCCCGCAGCCGCGCGCAGGTACCGTGCGACATCG	1426
	CGATGGCCCAGCTCCTCAGCCAGGTCCACGGGCAGACGGCC
	CCAGGCATCGCGCACGTCCAGCCGCGCCCCGGCCCGGTG
	TGGACCTGGCTGAGGAG	1427
	CTCCTCAGCCAGGTCCA	1428
Melanoma	TGCGCGATGCCTGGGGCCGTCTGCCCGTGGACCTGGCTGAG	1429
Val126Asp
GTC-GAC	GAGCTGGGCCATCGCGATGTCGCACGGTACCTGCGCGCGGC
	TGCGGGGGGCACCAGAGGCAGTAACCATGCCCGCATAGA
	TCTATGCGGGCATGGTTACTGCCTCTGGTGCCCCCCGCAGCC	1430
	GCGCGCAGGTACCGTGCGACATCGCGATGGCCCAGCTCCTC
	AGCCAGGTCCACGGGCAGACGGCCCCAGGCATCGCGCA
	TCGCGATGTCGCACGGT	1431
	ACCGTGCGACATCGCGA	1432

EXAMPLE 11

Adenomatous Polyposis of the Colon—APC

[0131] Adenomatous polyposis of the colon is characterized by adenomatous polyps of the colon and rectum; in extreme cases the bowel is carpeted with a myriad of polyps. This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.

[0132] Mutations in the APC gene are an initiating event for both familial and sporadic colorectal tumorigenesis and many alleles of the APC gene have been identified. Carcinoma may arise at any age from late childhood through the seventh decade with presenting features including, for example, weight loss and inanition, bowel obstruction, or bloody diarrhea. Cases of new mutation still present in these ways but in areas with well organized registers most other gene carriers are detected. The attached table discloses the correcting oligonucleotide base sequences for the APC oligonucleotides of the invention.

TABLE 18
APC Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting oligos	NO:
Adenomatous polyposis	GGATCTGTATCAAGCCGTTCTGGAGAGTGCAGTCCTGTTCCT	1433
coli	ATGGGTTCATTTCCAAGAAGAGGGTTTGTAAATGGAAGCAGA
Arg121Term	GAAAGTACTGGATATTTAGAAGAACTTGAGAAAGAGA
AGA-TGA
	TCTCTTTCTCAAGTTCTTCTAAATATCCAGTACTTTCTCTGCTT	1434
	CCATTTACAAACCCTCTTCTTGGAAATGAACCCATAGGAACAG
	GACTGCACTCTCCAGAACGGCTTGATACAGATCC
	TTCCAAGAAGAGGGTTT	1435
	AAACCCTCTTCTTGGAA	1436
Adenomatous polyposis	AAAAAAAAAATAGGTCATTGCTTCTTGCTGATCTTGACAAAGAA	1437
coil	GAAAAGGAAAAAGACTGGTATTACGCTCAACTTCAGAATCTCA
Trp157Term	CTAAAAGAATAGATAGTCTTCCTTTAACTGAAAA
TGG-TAG
	TTTTCAGTTAAAGGAAGACTATCTATTCTTTTAGTGAGATTCTG	1438
	AAGTTGAGCGTAATACCAGTCTTTTTCCTTTTCTTCTTTGTCAA
	GATCAGCAAGAAGCAATGACCTATTTTTTTTTT
	AAAAGACTGGTATTACG	1439
	CGTAATACCAGTCTTTT	1440
Adenomatous polyposis	AAATAGGTCATTGCTTCTTGCTGATCTTGACAAAGAAGAAAAG	1441
coli	GAAAAAGACTGGTATTACGCTCAACTTCAGAATCTCACTAAAA
Tyr159Term	GAATAGATAGTCTTCCTTTAACTGAAAATGTAAGT
TAG-TAG
	ACTTACATTTTCAGTTAAAGGAAGACTATCTATTCTTTTAGTGA	1442
	GATTCTGAAGTTGAGCGTAATACCAGTCTTTTTCCTTTTCTTCT
	TTGTCAAGATCAGCAAGAAGCAATGACCTATTT
	TGGTATTACGCTCAACT	1443
	AGTTGAGCGTAATACCA	1444
Adenomatous polyposis	TTGCTTCTTGCTGATCTTGACAAAGAAGAAAAGGAAAAAGACT	1445
coli	GGTATTACGCTCAACTTCAGAATCTCACTAAAAGAATAGATAG
Gln163Term	TCTTCCTTTAACTGAAAATGTAAGTAACTGGCAGT
CAG-TAG
	ACTGCCAGTTACTTACATTTTCAGTTAAAGGAAGACTATCTATT	1446
	CTTTTAGTGAGATTCTGAAGTTGAGCGTAATACCAGTCTTTTTC
	CTTTTCTTCTTTGTCAAGATCAGCAAGAAGCAA
	CTCAACTTCAGAATCTC	1447
	GAGATTCTGAAGTTGAG 1448
Adenomatous polyposis	CTTGACAAAGAAGAAAAGGAAAAAGACTGGTATTACGCTCAAC	1449
coli	TTCAGAATCTCACTAAAAGAATAGATAGTCTTCCTTTAACTGAA
Arg168Term	AATGTAAGTAACTGGCAGTACAACTTATTTGAAA
AGA-TGA
	TTTCAAATAAGTTGTACTGCCAGTTACTTACATTTTCAGTTAAA	1450
	GGAAGACTATCTATTCTTTTAGTGAGATTCTGAAGTTGAGCGT
	AATACCAGTCTTTTTCCTTTTCTTCTTTGTCAAG
	TCACTAAAAGAATAGAT	1451
	ATCTATTCTTTTAGTGA	1452
Adenomatous polyposis	AAGAAAAGGAAAAAGACTGGTATTACGCTCAACTTCAGAATCT	1453
coli	CACTAAAAGAATAGATAGTCTTCCTTTAACTGAAAATGTAAGTA
Ser171Ile	ACTGGCAGTACAACTTATTTGAAACTTTAATAAC
AGT-ATT
	GTTATTAAAGTTTCAAATAAGTTGTACTGCCAGTTACTTACATT	1454
	TTCAGTTAAAGGAAGACTATCTATTCTTTTAGTGAGATTCTGAA
	GTTGAGCGTAATACCAGTCTTTTTCCTTTTCTT
	AATAGATAGTCTTCCTT	1455
	AAGGAAGACTATCTATT	1456
Adenomatous polyposis	GATTAACGTAAATACAAGATATTGATACTTTTTTATTATTTGTGG	1457
coli	TTTTAGTTTTCCTTACAAACAGATATGACCAGAAGGCAATTGG
Gln181Term	AATATGAAGCAAGGCAAATCAGAGTTGCGATGG
CAA-TAA
	CCATCGCAACTCTGATTTGCCTTGCTTCATATTCCAATTGCCT	1458
	TCTGGTCATATCTGTTTGTAAGGAAAACTAAAACCACAAATAAT
	AAAAAAGTATCAATATCTTGTATTTACGTTAATC
	TTTCCTTACAAACAGAT	1459
	ATCTGTTTGTAAGGAAA	1460
Adenomatous polyposis	CTTTTTTATTATTTGTGGTTTTAGTTTTCCTTACAAACAGATATG	1461
coli	ACCAGAAGGCAATTGGAATATGAAGCAAGGCAAATCAGAGTT
Glu190Term	GCGATGGAAGAACAACTAGGTACCTGCCAGGATA
GAA-TAA
	TATCCTGGCAGGTACCTAGTTGTTCTTCCATCGCAACTCTGAT	1462
	TTGCCTTGCTTCATATTCCAATTGCCTTCTGGTCATATCTGTTT
	GTAAGGAAAACTAAAACCACAAATAATAAAAAAG
	GGCAATTGGAATATGAA	1463
	TTCATATTCCAATTGCC	1464
Adenomatous polyposis	CAATTGGAATATGAAGCAAGGCAAATCAGAGTTGCGATGGAA
coli	GAACAACTAGGTACCTGCCAGGATATGGAAAAACGAGCACAG
Gln208Term	GTAAGTTACTTGTTTCTAAGTGATAAAACAGCGAAGA
CAG-TAG
	TCTTCGCTGTTTTATCACTTAGAAACAAGTAACTTACCTGTGCT	1466
	CGTTTTTCCATATCCTGGCAGGTACCTAGTTGTTCTTCCATCG
	CAACTCTGATTTGCCTTGCTTCATATTCCAATTG
	GTACCTGCCGCAGGTAC	1467
	CATATCCTGGCAGGTAC	1468
Adenomatous polyposis	GCAAGGCAAATCAGAGTTGCGATGGAAGAACAACTAGGTACC	1469
coli	TGCCAGGATATGGAAAAACGAGCACAGGTAAGTTACTTGTTTC
Arg213Term	TAAGTGATAAAACAGCGAAGAGCTATTAGGAATAAA
CGA-TGA
	TTTATTCCTAATAGCTCTTCGCTGTTTTATCACTTAGAAACAAG	1470
	TAACTTACCTGTGCTCGTTTTTCCATATCCTGGCAGGTACCTA
	GTTGTTCTTCCATCGCAACTCTGATTTGCCTTGC
	TGGAAAAACGAGCACAG	1471
	CTGTGCTCGTTTTTCCA	1472
Adenomatous polyposis	GTTTTATTTTAGCGAAGAATAGCCAGAATTCAGCAAATCGAAA	1473
coli	AGGACATACTTCGTATACGACAGCTTTTACAGTCCCAAGCAAC
Arg232Term	AGAAGCAGAGGTTAGTAAATTGCCTTTCTTGTTTG
CGA-TGA
	CAAACAAGAAAGGCAATTTACTAACCTCTGCTTCTGTTGCTTG	1474
	GGACTGTAAAAGCTGTCGTATACGAAGTATGTCCTTTTCGATT
	TGCTGAATTCTGGCTATTCTTCGCTAAAATAAAAC
	TTCGTATACGACAGCTT	1475
	AAGCTGTCGTATACGAA	1476
Adenomatous polyposis	TTATTTTAGCGAAGAATAGCCAGAATTCAGCAAATCGAAAAGG	1477
coli	ACATACTTCGTATACGACAGCTTTTACAGTCCCAAGCAACAGA
Gln233Term	AGCAGAGGTTAGTAAATTGCCTTTCTTGTTTGTGG
CAG-TAG
	CCACAAACAAGAAAGGCAATTTACTAACCTCTGCTTCTGTTGC	1478
	TTGGGACTGTAAAAGCTGTCGTATACGAAGTATGTCCTTTTCG
	ATTTGCTGAATTCTGGCTATTCTTCGCTAAAATAA
	GTATACGACAGCTTTTA	1479
	TAAAAGCTGTCGTATAC	1480
Adenomatous polyposis	AGAAAGCCTACACCATTTTTGCATGTACTGATGTTAACTCCAT	1481
coli	CTTAACAGAGGTCATCTCCTCAC	AGAACAAGCATGAAACCGGCTCAC
Gln247Term	ATGATGCTGAGCGGCAGAATGAAGGTCAAGGAGTGG
CAG-TAG
	CCACTCCTTGACCTTCATTCTGCCGCTCAGCATCATGTGAGC	1482
	CGGTTTCATGCTTGTTCTGAGATGACCTCTGTTAAGATGGAGT
	TAACATCAGTACATGCAAAAATGGTGTAGGCTTTCT
	GGTCATCTCAGAACAAG	1483
	CTTGTTCTGAGATGACC	1484
Adenomatous polyposis	CAGAACAAGCATGAAACCGGCTCACATGATGCTGAGCGGCAG	1485
coli	AATGAAGGTCAAGGAGTGGGAGAAATCAACATGGCAACTTCT
Gly267Term	GGTAATGGTCAGGTAAATAAATTATTTTATCATATTT
GGA-TGA
	AAATATGATAAAATAATTTATTTACCTGACCATTACCAGAAGTT	1486
	GCCATGTTGATTTCTCCCACTCCTTGACCTTCATTCTGCCGCT
	CAGCATCATGTGAGCCGGTTTCATGCTTGTTCTG
	AAGGAGTGGGAGAAATC	1487
	GATTTCTCCCACTCCTT	1488
Adenomatous polyposis	CTTCAAATAACAAAGCATTATGGTTTATGTTGATTTTATTTTTCA	1489
coli	GTGCCAGCTCCTGTTGAACATCAGATCTGTCCTGCTGTGTGT
Glu443Term	GTTCTAATGAAACTTTCATTTGATGAAGAGCATA
GAA-TAA
	TATGCTCTTCATCAAATGAAAGTTTCATTAGAACACACACAGCA	1490
	GGACAGATCTGATGTTCAACAGGAGCTGGCACTGAAAAATAA
	AATCAACATAAACCATAATGCTTTGTTATTTGAAG
	CTCCTGTTGAACATCAG	1491
	CTGATGTTCAACAGGAG	1492
Adenomatous polyposis	CAGTGCCAGCTCCTGTTGAACATCAGATCTGTCCTGCTGTGT	1493
coli	GTGTTCTAATGAAACTTTCATTTGATGAAGAGCATAGACATGC
SER457TER	AATGAATGAACTAGGTAAGACAAAAATGTTTTTTAA
TCA-TAA
	TTAAAAACATTTTTGTCTTACCTAGTTCATTCATTGCATGTCTA	1494
	TGCTCTTCATCAAATGAAAGTTTCATTAGAACACACACAGCAG
	GACAGATCTGATGTTCAACAGGAGCTGGCACTG
	GAAACTTTCATTTGATG	1495
	CATCAAATGAAAGTTTC	1496
Adenomatous polyposis	AGTTGTTTTATTTTAGATGATTGTCTTTTTCCTCTTGCCCTTTTT	1497
coli	AAATTAGGGGGACTACAGGCCATTGCAGAATTATTGCAAGTG
Gln473Term	GACTGTGAAATGTACGGGCTTACTAATGACCACT
CAG-TAG
	AGTGGTCATTAGTAAGCCCGTACATTTCACAGTCCACTTGCAA	1498
	TAATTCTGCAATGGCCTGTAGTCCCCCTAATTTAAAAAGGGCA
	AGAGGAAAAAGACAATCATCTAAAATAAAACAACT
	GGGGACTACAGGCCATT	1499
	AATGGCCTGTAGTCCCC	1500
Adenomatous polyposis	TTTTAAATTAGGGGGACTACAGGCCATTGCAGAATTATTGCAA	1501
coli	GTGGACTGTGAAATGTACGGGCTTACTAATGACCACTACAGTA
Tyr486Term	TTACACTAAGACGATATGCTGGAATGGCTTTGACA
TAC-TAG
	TGTCAAAGCCATTCCAGCATATCGTCTTAGTGTAATACTGTAG	1502
	TGGTCATTAGTAAGCCCGTACATTTCACAGTCCACTTGCAATA
	ATTCTGCAATGGCCTGTAGTCCCCCTAATTTAAAA
	GAAATGTACGGGCTTAC	1503
	GTAAGCCCGTACATTTC	1504
Adenomatous polyposis	TTGCAAGTGGACTGTGAAATGTATGGGCTTACTAATGACCACT	1505
coli	ACAGTATTACACTAAGACGATATGCTGGAATGGCTTTGACAAA
Arg499Term	CTTGACTTTTGGAGATGTAGCCAACAAGGTATGTT
CGA-TGA
	AACATACCTTGTTGGCTACATCTCCAAAAGTCAAGTTTGTCAA	1506
	AGCCATTCCAGCATATCGTCTTAGTGTAATACTGTAGTGGTCA
	TTAGTAAGCCCATACATTTCACAGTCCACTTGCAA
	CACTAAGACGATATGCT	1507
	AGCATATCGTCTTAGTG	1508
Adenomatous polyposis	AGTGGACTGTGAAATGTATGGGCTTACTAATGACCACTACAGT	1509
coli	ATTACACTAAGACGATATGCTGGAATGGCTTTGACAAACTTGA
Tyr500Term	CTTTTGGAGATGTAGCCAACAAGGTATGTTTTTAT
TAT-TAG
	ATAAAAACATACCTTGTTGGCTACATCTCCAAAAGTCAAGTTTG	1510
	TCAAAGCCATTCCAGCATATCGTCTTAGTGTAATACTGTAGTG
	GTCATTAGTAAGCCCATACATTTCACAGTCCACT
	AGACGATATGCTGGAAT	1511
	ATTCCAGCATATCGTCT	1512
Adenomatous polyposis	GACAAATTCCAACTCTAATTAGATGACCCATATTCTGTTTCTTA	1513
coli	CTAGGAATCAACCCTCAAAAGCGTATTGAGTGCCTTATGGAAT
Lys586Term	TTGTCAGCACATTGCACTGAGAATAAAGCTGATA
AAA-TAA
	TATCAGCTTTATTCTCAGTGCAATGTGCTGACAAATTCCATAA	1514
	GGCACTCAATACGCTTTTGAGGGTTGATTCCTAGTAAGAAACA
	GAATATGGGTCATCTAATTAGAGTTGGAATTTGTC
	CAACCCTCAAAAGCGTA	1515
	TACGCTTTTGAGGGTTG	1516
Adenomatous polyposis	TAGATGACCCATATTCTGTTTCTTACTAGGAATCAACCCTCAAA	1517
coli	AGCGTATTGAGTGCCTTATGGAATTTGTCAGCACATTGCACTG
Leu592Term	AGAATAAAGCTGATATATGTGCTGTAGATGGTGC
TTA-TGA
	GCACCATCTACAGCACATATATCAGCTTTATTCTCAGTGCAAT	1518
	GTGCTGACAAATTCCATAAGGCACTCAATACGCTTTTGAGGGT
	TGATTCCTAGTAAGAAACAGAATATGGGTCATCTA
	GAGTGCCTTATGGAATT	1519
	AATTCCATAAGGCACTC	1520
Adenomatous polyposis	ATGACCCATATTCTGTTTCTTACTAGGAATCAACCCTCAAAAG	1521
coli	CGTATTGAGTGCCTTATGGAATTTGTCAGCACATTGCACTGAG
Trp593Term	AATAAAGCTGATATATGTGCTGTAGATGGTGCACT
TGG-TAG
	AGTGCACCATCTACAGCACATATATCAGCTTTATTCTCAGTGC	1522
	AATGTGCTGACAAATTCCATAAGGCACTCAATACGCTTTTGAG
	GGTTGATTCCTAGTAAGAAACAGAATATGGGTCAT
	TGCCTTATGGAATTTGT	1523
	ACAAATTCCATAAGGCA	1524
Adenomatous polyposis	TGACCCATATTCTGTTTCTTACTAGGAATCAACCCTCAAAAGC	1525
coli	GTATTGAGTGCCTTATGGAATTTGTCAGCACATTGCACTGAGA
Trp593Term	ATAAAGCTGATATATGTGCTGTAGATGGTGCACTT
TGG-TGA
	AAGTGCACCATCTACAGCACATATATCAGCTTTATTCTCAGTG	1526
	CAATGTGCTGACAAATTCCATAAGGCACTCAATACGCTTTTGA
	GGGTTGATTCCTAGTAAGAAACAGAATATGGGTCA
	GCCTTATGGAATTTGTC	1527
	GACAAATTCCATAAGGC	1528
Adenomatous polyposis	TAAAGCTGATATATGTGCTGTAGATGGTGCACTTGCATTTTTG	1529
coli	GTTGGCACTCTTACTTAICCGGAGCCAGACAAACACTTTAGCC
Tyr622Term	ATTATTGAAAGTGGAGGTGGGATATTACGGAATGTG
TAC-TAA
	CACATTCCGTAATATCCCACCTCCACTTTCAATAATGGCTAAA	1530
	GTGTTTGTCTGGCTCCGGTAAGTAAGAGTGCCAACCAAAAAT
	GCAAGTGCACCATCTACAGCACATATATCAGCTTTA
	CTTACTTACCGGAGCCA	1531
	TGGCTCCGGTAAGTAAG	1532
Adenomatous polyposis	GATATATGTGCTGTAGATGGTGCACTTGCATTTTTGGTTGGCA	1533
coli	CTCTTACTTACCGGAGCCAGACAAACACTTTAGCCATTATTGA
Gln625Term	AAGTGGAGGTGGGATATTACGGAATGTGTCCAGCT
CAG-TAG
	AGCTGGACACATTCCGTAATATCCCACCTCCACTTTCAATAAT	1534
	GGCTAAAGTGTTTGTCTGGCTCCGGTAAGTAAGAGTGCCAAC
	CAAAAATGCAAGTGCACCATCTACAGCACATATATC
	ACCGGAGCCAGACAAAC	1535
	GTTTGTCTGGCTCCGGT	1536
Adenomatous polyposis	TAGATGGTGCACTTGCATTTTTGGTTGGCACTCTTACTTACCG	1537
coli	GAGCCAGACAAACACTTTAGCCATTATTGAAAGTGGAGGTGG
Leu629Term	GATATTACGGAATGTGTCCAGCTTGATAGCTACAAA
TTA-TAA
	TTTGTAGCTATCAAGCTGGACACATTCCGTAATATCCCACCTC	1538
	CACTTTCAATAATGGCTAAAGTGTTTGTCTGGCTCCGGTAAGT
	AAGAGTGCCAACCAAAAATGCAAGTGCACCATCTA
	AAACACTTTAGCCATTA	1539
	TAATGGCTAAAGTGTTT	1540
Adenomatous polyposis	GCCATTATTGAAAGTGGAGGTGGGATATTACGGAATGTGTCC	1541
coli	AGCTTGATAGCTACAAATGAGGACCACAGGTATATATAGAGTT
Glu650Term	TTATATTACTTTTAAAGTACAGAATTCATACTCTCA
GAG-TAG
	TGAGAGTATGAATTCTGTACTTTAAAAGTAATATAAAACTCTAT	1542
	ATATACCTGTGGTCCTCATTTGTAGCTATCAAGCTGGACACAT
	TCCGTAATATCCCACCTCCACTTTCAATAATGGC
	CTACAAATGAGGACCAC	1543
	GTGGTCCTCATTTGTAG	1544
Adenomatous polyposis	TGCATGTGGAACTTTGTGGAATCTCTCAGCAAGAAATCCTAAA	1545
coli	GACCAGGAAGCATTATGGGACATGGGGGCAGTTAGCATGCTC
Trp699Term	AAGAACCTCATTCATTCAAAGCACAAAATGATTGCT
TGG-TGA
	AGCAATCATTTTGTGCTTTGAATGAATGAGGTTCTTGAGCATG	1546
	CTAACTGCCCCCATGTCCCATAATGCTTCCTGGTCTTTAGGAT
	TTCTTGCTGAGAGATTCCACAAAGTTCCACATGCA
	GCATTATGGGACATGGG	1547
	CCCATGTCCCATAATGC	1548
Adenomatous polyposis	AAGACCAGGAAGCATTATGGGACATGGGGGCAGTTAGCATGC	1549
coli	TCAAGAACCTCATTCATTCAAAGCACAAAATGATTGCTATGGG
Ser713Term	AAGTGCTGCAGCTTTAAGGAATCTCATGGCAAATAG
TCA-TGA
	CTATTTGCCATGAGATTCCTTAAAGCTGCAGCACTTCCCATAG	1550
	CAATCATTTTGTGCTTTGAATGAATGAGGTTCTTGAGCATGCT
	AACTGCCCCCCATGTCCCATAATGCTTCCTGGTCTT
	CATTCATTCAAAGCACA	1551
	TGTGCTTTGAATGAATG	1552
Adenomatous polyposis	GGGGCAGTTAGCATGCTCAAGAACCTCATTCATTCAAAGCAC	1553
coli	AAAATGATTGCTATGGGAAGTGCTGCAGCTTTAAGGAATCTCA
Ser722Gly	TGGCAAATAGGCCTGCGAAGTACAAGGATGCCAATA
AGT-GGT
	TATTGGCATCCTTGTACTTCGCAGGCCTATTTGCCATGAGATT	1554
	CCTTAAAGCTGCAGCACTTCCCATAGCAATCATTTTGTGCTTT
	GAATGAATGAGGTTCTTGAGCATGCTAACTGCCCC
	CTATGGGAAGTGCTGCA	1555
	TGCAGCACTTCCCATAG	1556
Adenomatous polyposis	TCTCCTGGCTCAGCTTGCCATCTCTTCATGTTAGGAAACAAAA	1557
coli	AGCCCTAGAAGCAGAATTAGATGCTCAGCACTTATCAGAAACT
Leu764Term	TTTGACAATATAGACAATTTAAGTCCCAAGGCATC
TTA-TAA
	GATGCCTTGGGACTTAAATTGTCTATATTGTCAAAAGTTTCTGA	1558
	TAAGTGCTGAGCATCTAATTCTGCTTCTAGGGCTTTTTGTTTC
	CTAACATGAAGAGATGGCAAGCTGAGCCAGGAGA
	AGCAGAATTAGATGCTC	1559
	GAGCATCTAATTCTGCT	1560
Adenomatous polyposis	TTAGATGCTCAGCACTTATCAGAAACTTTTGACAATATAGACAA	1561
coli	TTTAAGTCCCAAGGCATCTCATCGTAGTAAGCAGAGACACAG
Ser784Thr	CAAGTCTCTATGGTGATTATGTTTTTGACACCATC
TCT-ACT
	GATGGTGTCAAAAACATAATCACCATAGAGACTTGCTGTGTCT	1562
	CTGCTTACTACGATGAGATGCCTTGGGACTTAAATTGTCTATA
	TTGTCAAAAGTTTCTGATAAGTGCTGAGCATCTAA
	CCAAGGCATCTCATCGT	1563
	ACGATGAGATGCCTTGG	1564
Adenomatous potyposis	CTCATCGTAGTAAGCAGAGACACAGCAAGTCTCTATGGTGATT	1565
coli	ATGTTTTTGACACCAATCGACATGATGATAATAGGTCAGACAT
Arg805Term	TTTAATACTGGCACATGACTGTCCTTTCACCATAT
CGA-TGA
	ATATGGTGAAAGGACAGTCATGTGCCAGTATTAAAATGTCTGA	1566
	CCTATTATCATCATGTCGATTGGTGTCAAAAACATAATCACCAT
	AGAGACTTGCTGTGTCTCTGCTTACTACGATGAG
	ACACCAATCGACATGAT	1567
	ATCATGTCGATTGGTGT	1568
Adenomatous polyposis	GGTCTAGGCAACTACCATCCAGCAACAGAAAATCCAGGAACT	1569
coli	TCTTCAAAGCGAGGTTTGCAGATCTCCACCACTGCAGCCCAG
Gln879Term	ATTGCCAAAGTCATGGAAGAAGTGTCAGCCATTCATA
CAG-TAG
	TATGAATGGCTGACACTTCTTCCATGACTTTGGCAATCTGGGC	1570
	TGCAGTGGTGGAGATCTGCAAACCTCGCTTTGAAGAAGTTCC
	TGGATTTTCTGTTGCTGGATGGTAGTTGCCTAGACC
	GAGGTTTGCAGATCTCC	1571
	GGAGATCTGCAAACCTC	1572
Adenomatous polyposis	TACATTGTGTGACAGATGAGAGAAATGCACTTAGAAGAAGCTC	1573
coli	TGCTGCCCATACACATTCAAACACTTACAATTTCACTAAGTCG
Ser932Term	GAAAATTCAAATAGGACATGTTCTATGCCTTATGC
TCA-TAA
	GCATAAGGCATAGAACATGTCCTATTTGAATTTTCCGACTTAG	1514
	TGAAATTGTAAGTGTTTGAATGTGTATGGGCAGCAGAGCTTCT
	TCTAAGTGCATTTCTCTCATCTGTCACACAATGTA
	TACACATTCAAACACTT	1575
	AAGTGTTTGAATGTGTA	1576
Adenomatous potyposis	TACATTGTGTGACAGATGAGAGAAATGCACTTAGAAGAAGCTC	1577
coli	TGCTGCCCATACACATTCAAACACTTACAATTTCACTAAGTCG
Ser932Term	GAAAATTCAAATAGGACATGTTCTATGCCTTATGC
TCA-TGA
	GCATAAGGCATAGAACATGTCCTATTTGAATTTTCCGACTTAG	1578
	TGAAATTGTAAGTGTTTGAATGTGTATGGGCAGCAGAGCTTCT
	TCTAAGTGCATTTCTCTCATCTGTCACACAATGTA
	TACACATTCAAACACTT	1579
	AAGTGTTTGAATGTGTA	1580
Adenomatous polyposis	GACAGATGAGAGAAATGCACTTAGAAGAAGCTCTGCTGCCCA	1581
coli	TACACATTCAAACACTTACAATTTCACTAAGTCGGAAAATTCAA
Tyr935Term	ATAGGACATGTTCTATGCCTTATGCCAAATTAGAA
TAC-TAG
	TTCTAATTTGGCATAAGGCATAGAACATGTCCTATTTGAATTTT	1582
	CCGACTTAGTGAAATTGTAAGTGTTTGAATGTGTATGGGCAGC
	AGAGCTTCTTCTAAGTGCATTTCTCTCATCTGTC
	AACACTTACAATTTCAC	1583
	GTGAAATTGTAAGTGTT	1584
Adenomatous polyposis	GACAGATGAGAGAAATGCACTTAGAAGAAGCTCTGCTGCCCA	1585
coli	TACACATTCAAACACTTACAATTTCACTAAGTCGGAAAATTCAA
Tyr935Term	ATAGGACATGTTCTATGCCTTATGCCAAATTAGAA
TAC-TAA
	TTCTAATTTGGCATAAGGCATAGAACATGTCCTATTTGAATTTT	1586
	CCGACTTAGTGAAATTGTAAGTGTTTGAATGTGTATGGGCAGC
	AGAGCTTCTTCTAAGTGCATTTCTCTCATCTGTC
	AACACTTACAATTTCAC	1587
	GTGAAATTGTAAGTGTT	1588
Adenomatous polyposis	ACCCTCGATTGAATCCTATTCTGAAGATGATGAAAGTAAGTTTT	1589
coli	GCAGTTATGGTCAATACCCAGCCGACCTAGCCCATAAAATACA
Tyr1000Term	TAGTGCAAATCATATGGATGATAATGATGGAGAA
TAC-TAA
	TTCTCCATCATTATCATCCATATGATTTGCACTATGTATTTTAT	1590
	GGGCTAGGTCGGCTGGGTATTGACCATAACTGCAAAACTTAC
	TTTCATCATCTTCAGAATAGGATTCAATCGAGGGT
	GGTCAATACCCAGCCGA	1591
	TCGGCTGGGTATTGACC	1592
Adenomatous polyposis	TACCCAGCCGACCTAGCCCATAAAATACATAGTGCAAATCATA	1593
coli	TGGATGATAATGATGGAGAACTAGATACACCAATAAATTATAG
Glu1020Term	TCTTAAATATTCAGATGAGCAGTTGAACTCTGGAA
GAA-TAA
	TTCCAGAGTTCAACTGCTCATCTGAATATTTAAGACTATAATTT	1594
	ATTGGTGTATCTAGTTCTCCATCATTATCATCCATATGATTTGC-
	ACTATGTATTTTATGGGCTAGGTCGGCTGGGTA
	ATGATGGAGAACTAGAT	1595
	ATCTAGTTCTCCATCAT	1596
Adenomatous polyposis	ATGAAACCCTCGATTGAATCCTATTCTGAAGATGATGAAAGTA	1597
coli	AGTTTTGCAGTTATGGTCAATACCCAGCCGACCTAGCCCATAA
Ser1032Term	AATACATAGTGCAAATCATATGGATGATAATGATG
TCA-TAA
	CATCATTATCATCCATATGATTTGCACTATGTATTTTATGGGCT	1598
	AGGTCGGCTGGGTATTGACCATAACTGCAAAACTTACTTTCAT
	CATCTTCAGAATAGGATTCAATCGAGGGTTTCAT
	GTTATGGTCAATACCCA	1599
	TGGGTATTGACCATAAC	1600
Adenomatous polyposis	TGAAGATGATGAAAGTAAGTTTTGCAGTTATGGTCAATACCCA	1601
coli	GCCGACCTAGCCCATAAAATACATAGTGCAAATCATATGGATG
Gln1041Term	ATAATGATGGAGAACTAGATACACCAATAAATTAT
CAA-TAA
	ATAATTTATTGGTGTATCTAGTTCTCCATCATTATCATCCATAT	1602
	GATTTGCACTATGTATTTTATGGGCTAGGTCGGCTGGGTATTG
	ACCATAACTGCAAAACTTACTTTCATCATCTTCA
	GCCCATAAAATACATAG	1603
	CTATGTATTTTATGGGC	1604
Adenomatous polyposis	ATAAATTATAGTCTTAAATATTCAGATGAGCAGTTGAACTCTGG	1605
coli	AAGGCAAAGTCCTTCACAGAATGAAAGATGGGCAAGACCCAA
Gln1045Term	ACACATAATAGAAGATGAAATAAAACAAAGTGAGC
CAG-TAG
	GCTCACTTTGTTTTATTTCATCTTCTATTATGTGTTTGGGTCTT	1606
	GCCCATCTTTCATTCTGTGAAGGACTTTGCCTTCCAGAGTTCA
	ACTGCTCATCTGAATATTTAAGACTATAATTTAT
	GTCCTTCACAGAATGAA	1607
	TTCATTCTGTGAAGGAC	1608
Adenomatous polyposis	GAAAGATGGGCAAGACCCAAACACATAATAGAAGATGAAATAA	1609
coli	AACAAAGTGAGCAAAGACAATCAAGGAATCAAAGTACAACTTA
Gln1067Term	TCCTGTTTATACTGAGAGCACTGATGATAAACACC
CAA-TAA
	GGTGTTTATCATCAGTGCTCTCAGTATAAACAGGATAAGTTGT	1610
	ACTTTGATTCCTTGATTGTCTTTGCTCACTTTGTTTTATTTCATC
	TTCTATTATGTGTTTGGGTCTTGCCCATCTTTC
	AGCAAAGACAATCAAGG	1611
	CCTTGATTGTCTTTGCT	1612
Adenomatous polyposis	AATAGAAGATGAAATAAAACAAAGTGAGCAAAGACAATCAAGG	1613
coli	AATCAAAGTACAACTTATCCTGTTTATACTGAGAGCACTGATG
Tyr1075Term	ATAAACACCTCAAGTTCCAACCACATTTTGGACAG
TAT-TAG
	CTGTCCAAAATGTGGTTGGAACTTGAGGTGTTTATCATCAGTG	1614
	CTCTCAGTATAAACAGGATAAGTTGTACTTTGATTCCTTGATTG
	TCTTTGCTCACTTTGTTTTATTTCATCTTCTATT
	ACAACTTATCCTGTTTA	1615
	TAAACAGGATAAGTTGT	1616
Adenomatous polyposis	TGATGATAAACACCTCAAGTTCCAACCACATTTTGGACAGCAG	1617
coli	GAATGTGTTTCTCCATACAGGTCACGGGGAGCCAATGGTTCA
Tyr1102Term	GAAACAAATCGAGTGGGTTCTAATCATGGAATTAAT
TAC-TAG
	ATTAATTCCATGATTAGAACCCACTCGATTTGTTTCTGAACCAT	1618
	TGGCTCCCCGTGACCTGTATGGAGAAACACATTCCTGCTGTC
	CAAAATGTGGTTGGAACTTGAGGTGTTTATCATCA
	TCTCCATACAGGTCACG	1619
	CGTGACCTGTATGGAGA	1620
Adenomatous polyposis	AACCACATTTTGGACAGCAGGAATGTGTTTCTCCATACAGGTC	1621
coli	ACGGGGAGCCAATGGTTCAGAAACAAATCGAGTGGGTTCTAA
Ser1101Term	TCATGGAATTAATCAAAATGTAAGCCAGTCTTTGTG
TCA-TGA
	CACAAAGACTGGCTTACATTTTGATTAATTCCATGATTAGAACC	1622
	CACTCGATTTGTTTCTGAACCATTGGCTCCCCGTGACCTGTAT
	GGAGAAACACATTCCTGCTGTCCAAAATGTGGTT
	CAATGGTTCAGAAACAA	1623
	TTGTTTCTGAACCATTG	1624
Adenomatous polyposis	GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGGGGAGCC	1625
coli	AATGGTTCAGAAACAAATCGAGTGGGTTCTAATCATGGAATTA
Arg1114Term	ATCAAAATGTAAGCCAGTCTTTGTGTCAAGAAGATG
CGA-TGA
	CATCTTCTTGACACAAAGACTGGCTTACATTTTGATTAATTCCA	1626
	TGATTAGAACCCACTCGATTTGTTTCTGAACCATTGGCTCCCC
	GTGACCTGTATGGAGAAACACATTCCTGCTGTCC
	AAACAAATCGAGTGGGT	1627
	ACCCACTCGATTTGTTT	1628
Adenomatous polyposis	GGGTTCTAATCATGGAATTAATCAAAATGTAAGCCAGTCTTTG	1629
coli	TGTCAAGAAGATGACTATGAAGATGATAAGCCTACCAATTATA
Tyr1135Term	GTGAACGTTACTCTGAAGAAGAACAGCATGAAGAA
TAT-TAG
	TTCTTCATGCTGTTCTTCTTCAGAGTAACGTTCACTATAATTGG	1630
	TAGGCTTATCATCTTCATAGTCATCTTCTTGACACAAAGACTG
	GCTTACATTTTGATTAATTCCATGATTAGAACCC
	GATGACTATGAAGATGA	1631
	TCATCTTCATAGTCATC	1632
Adenomatous polyposis	GAAGATGACTATGAAGATGATAAGCCTACCAATTATAGTGAAC	1633
coli	GTTACTCTGAAGAAGAACAGCATGAAGAAGAAGAGAGACCAA
Gln1152Term	CAAATTATAGCATAAAATATAATGAAGAGAAACGTC
CAG-TAG
	GACGTTTCTCTTCATTATATTTTATGCTATAATTTGTTGGTCTCT	1634
	CTTCTTCTTCATGCTGTTCTTCTTCAGAGTAACGTTCACTATAA
	TTGGTAGGCTTATCATCTTCATAGTCATCTTC
	AAGAAGAACAGCATGAA	1635
	TTCATGCTGTTCTTCTT	1636
Adenomatous polyposis	GAAGAAGAGAGACCAACAAATTATAGCATAAAATATAATGAAG	1637
coli	AGAAACGTCATGTGGATCAGCCTATTGATTATAGTTTAAAATAT
Gln1175Term	GCCACAGATATTCCTTCATCACAGAAACAGTCAT
CAG-TAG
	ATGACTGTTTCTGTGATGAAGGAATATCTGTGGCATATTTTAAA	1638
	CTATAATCAATAGGCTGATCCACATGACGTTTCTCTTCATTATA
	TTTTATGCTATAATTTGTTGGTCTCTCTTCTTC
	ATGTGGATCAGCCTATT	1639
	AATAGGCTGATCCACAT	1640
Adenomatous polyposis	AAGAGAGACCAACAAATTATAGCATAAAATATAATGAAGAGAA	1641
coli	ACGTCATGTGGATCAGCCTATTGATTATAGTTTAAAATATGCCA
Pro1176Leu	CAGATATTCCTTCATCACAGAAACAGTCATTTTC
CCT-CTT
	GAAAATGACTGTTTCTGTGATGAAGGAATATCTGTGGCATATT	1642
	TTAAACTATAATCAATAGGCTGATCCACATGACGTTTCTCTTCA
	TTATATTTTATGCTATAATTTGTTGGTCTCTCTT
	GGATCAGCCTATTGATT	1643
	AATCAATAGGCTGATCC	1644
Adenomatous polyposis	ATAAAATATAATGAAGAGAAACGTCATGTGGATCAGCCTATTG	1645
coli	ATTATAGTTTAAAATATGCCACAGATATTCCTTCATCACAGAAA
Ala1184Pro	CAGTCATTTTCATTCTCAAAGAGTTCATCTGGAC
GCC-CCC
	GTCCAGATGAACTCTTTGAGAATGAAAATGACTGTTTCTGTGA	1646
	TGAAGGAATATCTGTGGCATATTTTAAACTATAATCAATAGGCT
	GATCCACATGACGTTTCTCTTCATTATATTTTAT
	TAAAATATGCCACAGAT	1647
	ATCTGTGGCATATTTTA	1648
Adenomatous polyposis	ATCAGCCTATTGATTATAGTTTAAAATATGCCACAGATATTCCT	1649
coli	TCATCACAGAAACAGTCATTTTCATTCTCAAAGAGTTCATCTG
Ser1194Term	GACAAAGCAGTAAAACCGAACATATGTCTTCAAG
TCA-TGA
	CTTGAAGACATATGTTCGGTTTTACTGCTTTGTCCAGATGAAC	1650
	TCTTTGAGAATGAAAATGACTGTTTCTGTGATGAAGGAATATCT
	GTGGCATATTTTAAACTATAATCAATAGGCTGAT
	GAAACAGTCATTTTCAT	1651
	ATGAAAATGACTGTTTC	1652
Adenomatous polyposis	ATTATAGTTTAAAATATGCCACAGATATTCCTTCATCACAGAAA	1653
coli	CAGTCATTTTCATTCTCAAAGAGTTCATCTGGACAAAGCAGTA
Ser1198Term	AAACCGAACATATGTCTTCAAGCAGTGAGAATAC
TCA-TGA
	GTATTCTCACTGCTTGAAGACATATGTTCGGTTTTACTGCTTTG	1654
	TCCAGATGAACTCTTTGAGAATGAAAATGACTGTTTCTGTGAT
	GAAGGAATATCTGTGGCATATTTTAAACTATAAT
	TTCATTCTCAAAGAGTT	1655
	AACTCTTTGAGAATGAA	1656
Adenomatous polyposis	ACCGAACATATGTCTTCAAGCAGTGAGAATACGTCCACACCTT	1657
coli	CATCTAATGCCAAGAGGCAGAATCAGCTCCATCCAGTTCTGC
Gln1228Term	ACAGAGTAGAAGTGGTCAGCCTCAAAGGCTGCCACT
CAG-TAG
	AGTGGCAGCCTTTGAGGCTGACCACTTCTACTCTGTGCAGAA	1658
	CTGGATGGAGCTGATTCTGCCTCTTGGCATTAGATGAAGGTG
	TGGACGTATTCTCACTGCTTGAAGACATATGTTCGGT
	CCAAGAGGCAGAATCAG	1659
	CTGATTCTGCCTCTTGG	1660
Adenomatous polyposis	CATATGTCTTCAAGCAGTGAGAATACGTCCACACCTTCATCTA	1661
coli	ATGCCAAGAGGCAGAATCAGCTCCATCCAGTTCTGCACAGAG
Gln1230Term	TAGAAGTGGTCAGCCTCAAAGGCTGCCACTTGCAAG
CAG-TAG
	CTTGCAAGTGGCAGCCTTTGAGGCTGACCACTTCTACTCTGT	1662
	GCAGAACTGGATGGAGCTGATTCTGCCTCTTGGCATTAGATG
	AAGGTGTGGACGTATTCTCACTGCTTGAAGACATATG
	GGCAGAATCAGCTCCAT	1663
	ATGGAGCTGATTCTGCC	1664
Adenomatous polyposis	TCAGCTCCATCCAAGTTCTGCACAGAGTAGAAGTGGTCAGCC	1665
coli	TCAAAAGGCTGCCACTTGCAAAGTTTCTTCTATTAACCAAGAA
Cys1249Term	ACAATACAGACTTATTGTGTAGAAGATACTCCAATA
TGC-TGA
	TATTGGAGTATCTTCTACACAATAAGTCTGTATTGTTTCTTGGT	1666
	TAATAGAAGAAACTTTGCAAGTGGCAGCCTTTTGAGGCTGACC
	ACTTCTACTCTGTGCAGAACTTGGATGGAGCTGA
	GCCACTTGCAAAGTTTC	1667
	GAAACTTTGCAAGTGGC	1668
Adenomatous polyposis	AGTTTCTTCTATTAACCAAGAAACAATACAGACTTATTGTGTAG	1669
coli	AAGATACTCCAATATGTTTTTCAAGATGTAGTTCATTATCATCT
Cys1270Term	TTGTCATCAGCTGAAGATGAAATAGGATGTAAT
TGT-TGA
	ATTACATCCTATTTCATCTTCAGCTGATGACAAAGATGATAATG	1670
	AACTACATCTTGAAAAACATATTGGAGTATCTTCTACACAATAA
	GTCTGTATTGTTTCTTGGTTAATAGAAGAAACT
	CCAATATGTTTTTCAAG	1671
	CTTGAAAAACATATTGG	1672
Adenomatous polyposis	AAGAAACAATACAGACTTATTGTGTAGAAGATACTCCAATATGT	1673
coli	TTTTCAAGATGTAGTTCATTATCATCTTTGTCATCAGCTGAAGA
Ser1276Term	TGAAATAGGATGTAATCAGACGACACAGGAAGC
TCA-TGA
	GCTTCCTGTGTCGTCTGATTACATCCTATTTCATCTTCAGCTG	1674
	ATGACAAAGATGATAATGAACTACATCTTGAAAAACATATTGGA
	GTATCTTCTACACAATAAGTCTGTATTGTTTCTT
	ATGTAGTTCATTATCAT	1675
	ATGATAATGAACTACAT	1676
Adenomatous polyposis	GATACTCCAATATGTTTTTCAAGATGTAGTTCATTATCATCTTT	1677
coli	GTCATCAGCTGAAGATGAAATAGGATGTAATCAGACGACACA
Glu1286Term	GGAAGCAGATTCTGCTAATACCCTGCAAATAGCAG
GAA-TAA
	CTGCTATTTGCAGGGTATTAGCAGAATCTGCTTCCTGTGTCGT	1678
	CTGATTACATCCTATTTCATCTTCAGCTGATGACAAAGATGATA
	ATGAACTACATCTTGAAAAACATATTGGAGTATC
	CTGAAGATGAAATAGGA	1679
	TCCTATTTCATCTTCAG	1680
Adenomatous polyposis	TGTAGTTCATTATCATCTTTGTCATCAGCTGAAGATGAAATAGG	1681
coli	ATGTAATCAGACGACACAGGAAGCAGATTCTGCTAATACCCTG
Gln1294Term	CAAATAGCAGAAATAAAAGAAAAGATTGGAACTA
CAG-TAG
	TAGTTCCAATCTTTTCTTTTATTTCTGCTATTTGCAGGGTATTA	1682
	GCAGAATCTGCTTCCTGTGTCGTCTGATTACATCCTATTTCAT
	CTTCAGCTGATGACAAAGATGATAATGAACTACA
	AGACGACACAGGAAGCA	1683
	TGCTTCCTGTGTCGTCT	1684
Predisposition to,	TAGGATGTAATCAGACGACACAGGAAGCAGATTCTGCTAATAC	1685
association with,	CCTGCAAATAGCAGAAATAAAAGAAAAGATTGGAACTAGGTCA
colorectal cancer	GCTGAAGATCCTGTGAGCGAAGTTCCAGCAGTGTC
Ile1307Lys
ATA-AAA
	GACACTGCTGGAACTTCGCTCACAGGATCTTCAGCTGACCTA	1686
	GTTCCAATCTTTTCTTTTATTTCTGCTATTTGCAGGGTATTAGC
	AGAATCTGCTTCCTGTGTCGTCTGATTACATCCTA
	AGCAGAAATAAAAGAAA	1687
	TTTCTTTTATTTCTGCT	1688
Adenomatous polyposis	CCAAGAAACAATACAGACTTATTGTGTAGAAGATACTCCAATA 1689
coil	TGTTTTTCAAGATGTAGTTCATTATCATCTTTGTCATCAGCTGA
Glu1309Term	AGATGAAATAGGATGTAATCAGACGACACAGGAA
GAA-TAA
	TTCCTGTGTCGTCTGATTACATCCTATTTCATCTTCAGCTGATG	1690
	ACAAAGATGATAATGAACTACATCTTGAAAAACATATTGGAGTA
	TCTTCTACACAATAAGTCTGTATTGTTTCTTGG
	AGATGTAGTTCATTATC	1691
	GATAATGAACTACATCT	1692
Predisposition to	GATTCTGCTAATACCCTGCAAATAGCAGAAATAAAAGAAAAGA	1693
Colorectal Cancer	TTGGAACTAGGTCAGCTGAAGATCCTGTGAGCGAAGTTCCAG
Glu1317Gln	CAGTGTCACAGCACCCTAGAACCAAATCCAGCAGAC
GAA-CAA
	GTCTGCTGGATTTGGTTCTAGGGTGCTGTGACACTGCTGGAA	1694
	CTTCGCTCACAGGATCTTCAGCTGACCTAGTTCCAATCTTTTC
	TTTTATTTCTGCTATTTGCAGGGTATTAGCAGAATC
	GGTCAGCTGAAGATCCT	1695
	AGGATCTTCAGCTGACC	1696
Adenomatous polyposis	AAAGAAAAGATTGGAACTAGGTCAGCTGAAGATCCTGTGAGC	1697
coli	GAAGTTCCAGCAGTGTCACAGCACCCTAGAACCAAATCCAGC
Gln1328Term	AGACTGCAGGGTTCTAGTTTATCTTCAGAATCAGCCA
CAG-TAG
	TGGCTGATTCTGAAGATAAACTAGAACCCTGCAGTCTGCTGG 1698
	ATTTGGTTCTAGGGTGCTGTGACACTGCTGGAACTTCGCTCA
	CAGGATCTTCAGCTGACCTAGTTCCAATCTTTTCTTT
	CAGTGTCACAGCACCCT	1699
	AGGGTGCTGTGACACTG	1700
Adenomatous polyposis	GATCCTGTGAGCGAAGTTCCAGCAGTGTCACAGCACCCTAGA	1701
coli	ACCAAATCCAGCAGACTGCAGGGTTCTAGTTTATCTTCAGAAT
Gln1338Term	CAGCCAGGCACAAAGCTGTTGAATTTTCTTCAGGAG
CAG-TAG
	CTCCTGAAGAAAATTCAACAGCTTTGTGCCTGGCTGATTCTGA	1702
	AGATAAACTAGAACCCTGCAGTCTGCTGGATTTGGTTCTAGG
	GTGCTGTGACACTGCTGGAACTTCGCTCACAGGATC
	GCAGACTGCAGGGTTCT	1703
	AGAACCCTGCAGTCTGC	1704
Adenomatous polyposis	AAGTTCCAGCAGTGTCACAGCACCCTAGAACCAAATCCAGCA	1705
coli	GACTGCAGGGTTCTAGTTTATCTTCAGAATCAGCCAGGCACAA
Leu1342Term	AGCTGTTGAATTTTCTTCAGGAGCGAAATCTCCCTC
TTA-TAA
	GAGGGAGATTTCGCTCCTGAAGAAAATTCAACAGCTTTGTGC	1706
	CTGGCTGATTCTGAAGATAAACTAGAACCCTGCAGTCTGCTG
	GATTTGGTTCTAGGGTGCTGTGACACTGCTGGAACTT
	TTCTAGTTTATCTTCAG	1707
	CTGAAGATAAACTAGAA	1708
Adenomatous polyposis	CAGCACCCTAGAACCAAATCCAGCAGACTGCAGGGTTCTAGT	1709
coli	TTATCTTCAGAATCAGCCAGGCACAAAGCTGTTGAATTTTCTT
Arg1348Trp	CAGGAGCGAAATCTCCCTCCCGAAAGTGGTGCTCAG
AGG-TGG
	CTGAGCACCACTTTCGGGAGGGAGATTTCGCTCCTGAAGAAA	1710
	ATTCAACAGCTTTGTGCCTGGCTGATTCTGAAGATAAACTAGA
	ACCCTGCAGTCTGCTGGATTTGGTTCTAGGGTGCTG
	AATCAGCCAGGCACAAA	1711
	TTTGTGCCTGGCTGATT	1712
Adenomatous polyposis	CTGCAGGGTTCTAGTTTATCTTCAGAATCAGCCAGGCACAAAG	1713
coli	CTGTTGAATTTTCTTCAGGAGCGAAATCTCCCTCCCGAAAGTG
Gly1357Term	GTGCTCAGACACCCCAAAGTCCACCTGAACACTAT
GGA-TGA
	ATAGTGTTCAGGTGGACTTTGGGGTGTCTGAGCACCACTTTC	1714
	GGGAGGGAGATTTCGCTCCTGAAGAAAATTCAACAGCTTTGT
	GCCTGGCTGATTCTGAAGATAAACTAGAACCCTGCAG
	TTTCTTCAGGAGCGAAA	1715
	TTTCGCTCCTGAAGAAA	1716
Adenomatous polyposis	CCAGGCACAAAGCTGTTGAATTTTCTTCAGGAGCGAAATCTCC	1717
coli	CTCCCGAAAGTGGTGCTCAGACACCCCAAAGTCCACCTGAAC
Gln1367Term	ACTATGTTCAGGAGACCCCACTCATGTTTAGCAGAT
CAG-TAG
	ATCTGCTAAACATGAGTGGGGTCTCCTGAACATAGTGTTCAG	1718
	GTGGACTTTGGGGTGTCTGAGCACCACTTTCGGGAGGGAGAT
	TTCGCTCCTGAAGAAAATTCAACAGCTTTGTGCCTGG
	GTGGTGCTCAGACACCC	1719
	GGGTGTCTGAGCACCAC	1720
Adenomatous polyposis	AAAGCTGTTGAATTTTCTTCAGGAGCGAAATCTCCCTCCAAAA	1721
coli	GTGGTGCTCAGACACCCAAAAGTCCACCTGAACACTATGTTC
Lys1370Term	AGGAGACCCCACTCATGTTTAGCAGATGTACTTCTG
AAA-TAA
	CAGAAGTACATCTGCTAAACATGAGTGGGGTCTCCTGAACATA	1722
	GTGTTCAGGTGGACTTTTGGGTGTCTGAGCACCACTTTTGGA
	GGGAGATTTCGCTCCTGAAGAAAATTCAACAGCTTT
	AGACACCCAAAAGTCCA	1723
	TGGACTTTTGGGTGTCT	1724
Adenomatous polyposis	CACCTGAACACTATGTTCAGGAGACCCCACTCATGTTTAGCA	1725
coli	GATGTACTTCTGTCAGTTCACTTGATAGTTTTGAGAGTCGTTC
Ser1392Term	GATTGCCAGCTCCGTTCAGAGTGAACCATGCAGTGG
TCA-TAA
	CCACTGCATGGTTCACTCTGAACGGAGCTGGCAATCGAACGA	1726
	CTCTCAAAACTATCAAGTGAACTGACAGAAGTACATCTGCTAA
	ACATGAGTGGGGTCTCCTGAACATAGTGTTCAGGTG
	TGTCAGTTCACTTGATA	1727
	TATCAAGTGAACTGACA	1728
Adenomatous polyposis	CACCTGAACACTATGTTCAGGAGACCCCACTCATGTTTAGCA	1729
coli	GATGTACTTCTGTCAGTTCACTTGATAGTTTTGAGAGTCGTTC
Ser1392Term	GATTGCCAGCTCCGTTCAGAGTGAACCATGCAGTGG
TCA-TGA
	CCACTGCATGGTTCACTCTGAACGGAGCTGGCAATCGAACGA	1730
	CTCTCAAAACTATCAAGTGAACTGACAGAAGTACATCTGCTAA
	ACATGAGTGGGGTCTCCTGAACATAGTGTTCAGGTG
	TGTCAGTTCACTTGATA	1731
	TATCAAGTGAACTGACA	1732
Adenomatous polyposis	GTTCAGGAGACCCCACTCATGTTTAGCAGATGTACTTCTGTCA	1733
coli	GTTCACTTGATAGTTTTGAGAGTCGTTCGATTGCCAGCTCCGT
Glu1397Term	TCAGAGTGAACCATGCAGTGGAATGGTAGGTGGCA
GAG-TAG
	TGCCACCTACCATTCCACTGCATGGTTCACTCTGAACGGAGC	1734
	TGGAATCGAACGACTCTCAAAACTATCAAGTGAACTGACAGA
	AGTACATCTGCTAAACATGAGTGGGGTCTCCTGAAC
	ATAGTTTTGAGAGTCGT	1735
	ACGACTCTCAAAACTAT	1736
Adenomatous polyposis	CAAACCATGCCACCAAGCAGAAGTAAAACACCTCCACCACCT	1737
coli	CCTCAAACAGCTCAAACCAAGCGAGAAGTACCTAAAAATAAAG
Lys1449Term	CACCTACTGCTGAAAAGAGAGAGAGTGGACCTAAGC
AAG-TAG
	GCTTAGGTCCACTCTCTCTCTTTTCAGCAGTAGGTGCTTTATT	1738
	TTTAGGTACTTCTCGCTTGGTTTGAGCTGTTTGAGGAGGTGGT
	GGAGGTGTTTTACTTCTGCTTGGTGGCATGGTTTG
	CTCAAACCAAGCGAGAA	1739
	TTCTCGCTTGGTTTGAG	1740
Adenomatous polyposis	ACCATGCCACCAAGCAGAAGTAAAACACCTCCACCACCTCCT	1741
coli	CAAACAGCTCAAACCAAGCGAGAAGTACCTAAAAATAAAGCAC
Arg1450Term	CTACTGCTGAAAAGAGAGAGAGTGGACCTAAGCAAG
CGA-TGA
	CTTGCTTAGGTCCACTCTCTCTCTTTTCAGCAGTAGGTGCTTT	1742
	ATTTTTAGGTACTTCTCGCTTGGTTTGAGCTGTTTGAGGAGGT
	GGTGGAGGTGTTTTACTTCTGCTTGGTGGCATGGT
	AAACCAAGCGAGAAGTA	1743
	TACTTCTCGCTTGGTTT	1744
Adenomatous polyposis	CAGATGCTGATACTTTATTACATTTTGCCACGGAAAGTACTCC	1145
coli	AGATGGATTTTCTTGTTCATCCAGCCTGAGTGCTCTGAGCCTC
SeR1503Term	GATGAGCCATTTATACAGAAAGATGTGGAATTAAG
TCA-TAA
	CTTAATTCCACATCTTTCTGTATAAATGGCTCATCGAGGCTCA	1746
	GAGCACTCAGGCTGGATGAACAAGAAAATCCATCTGGAGTAC
	TTTCCGTGGCAAAATGTAATAAAGTATCAGCATCTG
	TTCTTGTTCATCCAGCC	1747
	GGCTGGATGAACAAGAA	1748
Adenomatous polyposis	CTGAGCCTCGATGAGCCATTTATACAGAAAGATGTGGAATTAA	1749
coli	GAATAATGCCTCCAGTTCAGGAAAATGACAATGGGAATGAAAC	I
Gln1529Term	AGAATCAGAGCAGCCTAAAGAATCAAATGAAAACC
CAG-TAG
	GGTTTTCATTTGATTCTTTAGGCTGCTCTGATTCTGTTTCATTC	1750
	CCATTGTCATTTTCCTGAACTGGAGGCATTATTCTTAATTCCAC
	ATCTTTCTGTATAAATGGCTCATCGAGGCTCAG
	CTCCAGTTCAGGAAAAT	1751
	ATTTTCCTGAACTGGAG	1752
Adenomatous polyposis	ATGTGGAATTAAGAATAATGCCTCCAGTTCAGGAAAATGACAA	1753
coli	TGGGAATGAAACAGAATCAGAGCAGCCTAAAGAATCAAATGAA
Ser1539Term	AACCAAGAGAAAGAGGCAGAAAAAACTATTGATTC
TCA-TAA
	GAATCAATAGTTTTTTCTGCCTCTTTCTCTTGGTTTTCATTTGA	1754
	TTCTTTAGGCTGCTCTGATTCTGTTTCATTCCCATTGTCATTTT
	CCTGAACTGGAGGCATTATTCTTAATTCCACAT
	AACAGAATCAGAGCAGC	1755
	GCTGCTCTGATTCTGTT	1756
Adenomatous polyposis	AAAACCAAGAGAAAGAGGCAGAAAAAACTATTGATTCTGAAAA	1757
coli	GGACCTATTAGATGATTCAGATGATGATGATATTGAAATACTA
Ser1567Term	GAAGAATGTATTATTTCTGCCATGCCAACAAAGTC
TCA-TGA
	GACTTTGTTGGCATGGCAGAAATAATACATTCTTCTAGTATTTC	1758
	AATATCATCATCATCTGAATCATCTAATAGGTCCTTTTCAGAAT
	CAATAGTTTTTTCTGCCTCTTTCTCTTGGTTTT
	AGATGATTCAGATGATG	1759
	CATCATCTGAATCATCT	1760
Adenomatous poiyposis	AGAGAGTTTTCTCAGACAACAAAGATTCAAAGAAACAGAATTT	1761
coli	GAAAAATAATTCCAAGGACTTCAATGATAAGCTCCCAAATAAT
Asp1822Val	GAAGATAGAGTCAGAGGAAGTTTTGCTTTTGATTC
GAC-GTC
	GAATCAAAAGCAAAACTTCCTCTGACTCTATCTTCATTATTTGG	1762
	GAGCTTATCATTGAAGTCCTTGGAATTATTTTTCAAATTCTGTT
	TCTTTGAATCTTTGTTGTCTGAGAAAACTCTCT
	TTCCAAGGACTTCAATG	1763
	CATTGAAGTCCTTGGAA 1764
Adenomatous polyposis	AAAACTGACAGCACAGAATCCAGTGGAACCCAAAGTCCTAAG	1765
coli	CGCCATTCTGGGTCTTACCTTGTGACATCTGTTTAAAAGAGAG
Leu2839Phe	GAAGAATGAAACTAAGAAAATTCTATGTTAATTACA
CTT-TTT
	TGTAATTAACATAGAATTTTCTTAGTTTCATTCTTCCTCTCTTTT	1766
	AAACAGATGTCACAAGGTAAGACCCAGAATGGCGCTTAGGAC
	TTTGGGTTCCACTGGATTCTGTGCTGTCAGTTTT
	GGTCTTACCTTGTGACA	1767
	TGTCACAAGGTAAGACC	1768

EXAMPLE 12

Parahemophilia—Factor V Deficiency

[0133] Deficiency in clotting Factor V is associated with a lifelong predisposition to thrombosis. The disease typically manifests itself with usually mild bleeding, although bleeding times and clotting times are consistently prolonged. Individuals that are heterozygous for a mutation in Factor V have lowered levels of factor V but probably never have abnormal bleeding. A large number of alleles with a range of presenting symptoms have been identified. The attached table discloses the correcting oligonucleotide base sequences for the Factor V oligonucleotides of the invention.

TABLE 19
Factor V Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Factor V deficiency	TTGACTGAATGCTTATTTTGGCCTGTGTCTCTCCCTCTTTCTCA	1768
Ala221Val	GATATAACAGTTTGTGCCCATGACCACATCAGCTGGCATCTGC
GCC-GTC	TGGGAATGAGCTCGGGGCCAGAATTATTCTCCAT
	ATGGAGAATAATTCTGGCCCCGAGCTCATTCCCAGCAGATGC	1769
	CAGCTGATGTGGTCATGGGCACAAACTGTTATATCTGAGAAAG
	AGGGAGAGACACAGGCCAAAATAAGCATTCAGTCAA
	AGTTTGTGCCCATGACC	1770
	GGTCATGGGCACAAACT	1771
Thrombosis	TGTCCTAACTCAGCTGGGATGCAGGCTTACATTGACATTAAAA	1712
Arg306Gly	ACTGCCCAAAGAAAACCAGGAATCTTAAGAAAATAACTCGTGA
AGG-GGG	GCAGAGGCGGCACATGAAGAGGTGGGAATACTTCA
	TGAAGTATTCCCACCTCTTCATGTGCCGCCTCTGCTCACGAGT	1773
	TATTTTCTTAAGATTCCTGGTTTTCTTTGGGCAGTTTTTAATGT
	CAATGTAAGCCTGCATCCCAGCTGAGTTAGGACA
	AGAAAACCAGGAATCTT	1774
	AAGATTCCTGGTTTTCT	1775
Thrombosis	GTCCTAACTCAGCTGGGATGCAGGCTTACATTGACATTAAAAA	1776
Arg306Thr	CTGCCCAAAGAAAACCAGGAATCTTAAGAAAATAACTCGTGAG
AGG-ACG	CAGAGGCGGCACATGAAGAGGTGGGAATACTTCAT
	ATGAAGTATTCCCACCTCTTCATGTGCCGCCTCTGCTCACGA	1777
	GTTATTTTCTTAAGATTCCTGGTTTTCTTTGGGCAGTTTTTAAT
	GTCAATGTAAGCCTGCATCCCAGCTGAGTTAGGAC
	GAAAACCAGGAATCTTA	1778
	TAAGATTCCTGGTTTTC	1779
Increased Risk	CCACAGAAAATGATGCCCAGTGCTTAACAAGACCATACTACAG	1780
Thrombosis	TGACGTGGACATCATGAGAGACATCGCCTCTGGGCTAATAGG
Arg485Lys	ACTACTTCTAATCTGTAAGAGCAGATCCCTGGACAG
AGA-AAA
	CTGTCCAGGGATCTGCTCTTACAGATTAGAAGTAGTCCTATTA	1781
	GCCCAGAGGCGATGTCTCTCATGATGTCCACGTCACTGTAGT
	ATGGTCTTGTTAAGCACTGGGCATCATTTTCTGTGG
	CATCATGAGAGACATCG	1782
	CGATGTCTCTCATGATG	1783
Increased Risk	ACATCGCCTCTGGGCTAATAGGACTACTTCTAATCTGTAAGAG	1784
Thrombosis	CAGATCCCTGGACAGGCGAGGAATACAGGTATTTTGTCCTTG
Arg506Gln	AAGTAACCTTTCAGAAATTCTGAGAATTTCTTCTGG
CGA-CAA
	CCAGAAGAAATTCTCAGAATTTCTGAAAGGTTACTTCAAGGAC	1785
	AAAATACCTGTATTCCTCGCCTGTCCAGGGATCTGCTCTTACA
	GATTAGAAGTAGTCCTATTAGCCCAGAGGCGATGT
	GGACAGGCGAGGAATAC	1786
	GTATTCCTCGCCTGTCC	1787
Factor V Deficiency	GACATCGCCTCTGGGCTAATAGGACTACTTCTAATCTGTAAGA	1788
Arg506Term	GCAGATCCCTGGACAGGCGAGGAATACAGGTATTTTGTCCTT
CGA-TGA	GAAGTAACCTTTCAGAAATTCTGAGAATTTCTTCTG
	CAGAAGAAATTCTCAGAATTTCTGAAAGGTTACTTCAAGGACA	1789
	AAATACCTGTATTCCTCGCCTGTCCAGGGATCTGCTCTTACAG
	ATTAGAAGTAGTCCTATTAGCCCAGAGGCGATGTC
	TGGACAGGCGAGGAATA	1790
	TATTCCTCGCCTGTCCA	1791
Thrombosis	AGTGATGCTGACTATGATTACCAGAACAGACTGGCTGCAGCA	1792
Arg712Term	TTAGGAATCAGGTCATTCCGAAACTCATCATTGAATCAGGAAG
CGA-TGA	AAGAAGAGTTCAATCTTACTGCCCTAGCTCTGGAGA
	TCTCCAGAGCTAGGGCAGTAAGATTGAACTCTTCTTCTTCCTG	1793
	ATTCAATGATGAGTTTCGGAATGACCTGATTCCTAATGCTGCA
	GCCAGTCTGTTCTGGTAATCATAGTCAGCATCACT
	GGTCATTCCGAAACTCA	1794
	TGAGTTTCGGAATGACC	1795
Thrombosis	TCAGTCAGACAAACCTTTCCCCAGCCCTCGGTCAGATGCCCA	1796
His1299Arg	TTTCTCCAGACCTCAGCCATACAACCCTTTCTCTAGACTTCAG
CAT-CGT	CCAGACAAACCTCTCTCCAGAACTCAGTCAAACAAA
	TTTGTTTGACTGAGTTCTGGAGAGAGGTTTGTCTGGCTGAAGT	1797
	CTAGAGAAAGGGTTGTATGGTCTGGAGAAATGGGCA
	TCTGACCGAGGGCTGGGGAAAGGTTTGTCTGACTGA
	CCTCAGCCATACAACCC	1798
	GGGTTGTATGGCTGAGG	1799

EXAMPLE 13

Hemophilia—Factor VIII Deficiency

[0134] The attached table discloses the correcting oligonucleotide base sequences for the Factor VIII oligonucleotides of the invention.

TABLE 20
Factor VIII Mutations and Genome-Correcting Oligos
ClinicaI Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Haemophilia A	AGCTCTCCACCTGCTTCTTTCTGTGCCTTTTGCGATTCTGCTT	1800
Tyr5Cys	TAGTGCCACCAGAAGATACTACCTGGGTGCAGTGGAACTGTC
TAC-TGC	ATGGGACTATATGCAAAGTGATCTCGGTGAGCTGCC
	GGCAGCTCACCGAGATCACTTTGCATATAGTCCCATGACAGT	1801
	TCCACTGCACCCAGGTAGTATCTTCTGGTGGCACTAAAGCAG
	AATCGCAAAAGGCACAGAAAGAAGCAGGTGGAGAGCT
	CAGAAGATACTACCTGG	1802
	CCAGGTAGTATCTTCTG	1803
Haemophilia A	CCACCTGCTTCTTTCTGTGCCTTTTGCGATTCTGCTTTAGTGC	1804
Leu7Arg	CACCAGAAGATACTACCTGGGTGCAGTGGAACTGTCATGGGA
CTG-CGG	CTATATGCAAAGTGATCTCGGTGAGCTGCCTGTGGA
	TCCACAGGCAGCTCACCGAGATCACTTTGCATATAGTCCCAT	1805
	GACAGTTCCACTGCACCCAGGTAGTATCTTCTGGTGGCACTA
	AAGCAGAATCGCAAAAGGCACAGAAAGAAGCAGGTGG
	ATACTACCTGGGTGCAG	1806
	CTGCACCCAGGTAGTAT	1807
Haemophilia A	AGTCATGCAAATAGAGCTCTCCACCTGCTTCTTTCTGTGCCTT	1808
Ser(−1)Arg	TTGCGATTCTGCTTTAGTGCCACCAGAAGATACTACCTGGGT
AGTg-AGG	GCAGTGGAACTGTCATGGGACTATATGCAAAGTGAT
	ATCACTTTGCATATAGTCCCATGACAGTTCCACTGCACCCAG	1809
	GTAGTATCTTCTGGTGGCACTAAAGCAGAATCGCAAAAGGCA
	CAGAAAGAAGCAGGTGGAGAGCTCTATTTGCATGACT
	TGCTTTAGTGCCACCAG	1810
	CTGGTGGCACTAAAGCA	1811
Haemophilia A	CATTTGTAGCAAATAAGTCATGCAAATAGAGCTCTCCACCTGCT	1812
Arg(−5)Term	TCTTTCTGTGCCTTTTGCGATTCTGCTTTAGTGCCACCAGAAG
gCGA-TGA	ATACTACCTGGGTGCAGTGGAACTGTCATGGGACT
	AGTCCCATGACAGTTCCACTGCACCCAGGTAGTATCTTCTGG	1813
	TGGCACTAAAGCAGAATCGCAAAAGGCACAGAAAGAAGCAGG
	TGGAGAGCTCTATTTGCATGACTTATTGCTACAAATG
	GCCTTTTGCGATTCTGC	1814
	GCAGAATCGCAAAAGGC	1815
Haemophilia A	TTCTGTGCCTTTTGCGATTCTGCTTTAGTGCCACCAGAAGATA	1816
Glu11Val	CTACCTGGGTGCAGTGGAACTGTCATGGGACTATATGCAAAG
GAA-GTA	TGATCTCGGTGAGCTGCCTGTGGACGCAAGGTAAAG
	CTTTACCTTGCGTCCACAGGCAGCTCACCGAGATCACTTTGC	1817
	ATATAGTCCCATGACAGTTCCACTGCACCCAGGTAGTATCTTC
	TGGTGGCACTAAAGCAGAATCGCAAAAGGCACAGAA
	TGCAGTGGAACTGTCAT	1818
	ATGACAGTTCCACTGCA	1819
Haemophilia A	CTTTTGCGATTCTGCTTTAGTGCCACCAGAAGATACTACCTGG	1820
Trp14Gly	GTGCAGTGGAACTGTCATGGGACTATATGCAAAGTGATCTCG
aTGG-GGG	GTGAGCTGCCTGTGGACGCAAGGTAAAGGCATGTCC
	GGACATGCCTTTACCTTGCGTCCACAGGCAGCTCACCGAGAT	1821
	CACTTTGCATATAGTCCCATGACAGTTCCACTGCACCCAGGT
	AGTATCTTCTGGTGGCACTAAAGCAGAATCGCAAAAG
	AACTGTCATGGGACTAT	1822
	ATAGTCCCATGACAGTT	1823
Haemophilia A	TTCACGCAGATTTCCTCCTAGAGTGCCAAAATCTTTTCCATTC	1824
Tyr46Term	AACACCTCAGTCGTGTACAAAAAGACTCTGTTTGTAGAATTCA
TACa-TAA	CGGATCACCTTTTCAACATCGCTAAGCCAAGGCCA
	TGGCCTTGGCTTAGCGATGTTGAAAAGGTGATCCGTGAATTC	1825
	TACAAACAGAGTCTTTTTGTACACGACTGAGGTGTTGAATGGA
	AAAGATTTTGGCACTCTAGGAGGAAATCTGCGTGAA
	GTCGTGTACAAAAAGAC	1826
	GTCTTTTTGTACACGAC	1827
Haemophilia A	ATCTTTTCCATTCAACACCTCAGTCGTGTACAAAAAGACTCTG	1828
Asp56Glu	TTTGTAGAATTCACGGATCACCTTTTCAACATCGCTAAGCCAA
GATc-GAA	GGCCACCCTGGATGGGTAATGAAAACAATGTTGAA
	TTCAACATTGTTTTCATTACCCATCCAGGGTGGCCTTGGCTTA	1829
	GCGATGTTGAAAAGGTGATCCGTGAATTCTACAAACAGAGTC
	TTTTTGTACACGACTGAGGTGTTGAATGGAAAAGAT
	TTCACGGATCACCTTTT	1830
	AAAAGGTGATCCGTGAA	1831
Haemophilia A	TTCTGGAGTACTATCCCCAAGTAACCTTTGGCGGACATCTCAT	1832
Gly73Val	TCTTACAGGTCTGCTAGGTCCTACCATCCAGGCTGAGGTTTA
GGT-GTT	TGATACAGTGGTCATTACACTTAAGAACATGGCTTC
	GAAGCCATGTTCTTAAGTGTAATGACCACTGTATCATAAACCT	1833
	CAGCCTGGATGGTAGGACCTAGCAGACCTGTAAGAATGAGAT
	GTCCGCCAAAGGTTACTTGGGGATAGTACTCCAGAA
	TCTGCTAGGTCCTACCA	1834
	TGGTAGGACCTAGCAGA	1835
Haemophilia A	CAAGTAACCTTTGGCGGACATCTCATTCTTACAGGTCTGCTAG	1836
Glu79Lys	GTCCTACCATCCAGGCTGAGGTTTATGATACAGTGGTCATTAC
tGAG-AAG	ACTTAAGAACATGGCTTCCCATCCTGTCAGTCTTC
	GAAGACTGACAGGATGGGAAGCCATGTTCTTAAGTGTAATGA	1837
	CCACTGTATCATAAACCTCAGCCTGGATGGTAGGACCTAGCA
	GACCTGTAAGAATGAGATGTCCGCCAAAGGTTACTTG
	TCCAGGCTGAGGTTTAT	1838
	ATAAACCTCAGCCTGGA	1839
Haemophilia A	TAACCTTTGGCGGACATCTCATTCTTACAGGTCTGCTAGGTCC	1840
Val80Asp	TACCATCCAGGCTGAGGTTTATGATACAGTGGTCATTACACTT
GTT-GAT	AAGAACATGGCTTCCCATCCTGTCAGTCTTCATGC
	GCATGAAGACTGACAGGATGGGAAGCCATGTTCTTAAGTGTA	1841
	ATGACCACTGTATCATAAACCTCAGCCTGGATGGTAGGACCT
	AGCAGACCTGTAAGAATGAGATGTCCGCCAAAGGTTA
	GGCTGAGGTTTATGATA	1842
	TATCATAAACCTCAGCC	1843
Haemophilia A	TTGGCGGACATCTCATTCTTACAGGTCTGCTAGGTCCTACCAT	1844
Asp82Val	CCAGGCTGAGGTTTATGATACAGTGGTCATTACACTTAAGAAC
GAT-GTT	ATGGCTTCCCATCCTGTCAGTCTTCATGCTGTTGG
	CCAACAGCATGAAGACTGACAGGATGGGAAGCCATGTTCTTA	1845
	AGTGTAATGACCACTGTATCATAAACCTCAGCCTGGATGGTA
	GGACCTAGCAGACCTGTAAGAATGAGATGTCCGCCAA
	GGTTTATGATACAGTGG	1846
	CCACTGTATCATAAACC	1847
Haemophilia A	TTGGCGGACATCTCATTCTTACAGGTCTGCTAGGTCCTACCAT	1848
Asp82Gly	CCAGGCTGAGGTTTATGATACAGTGGTCATTACACTTAAGAAC
GAT-GGT	ATGGCTTCCCATCCTGTCAGTCTTCATGCTGTTGG
	CCAACAGCATGAAGACTGACAGGATGGGAAGCCATGTTCTTA	1849
	AGTGTAATGACCACTGTATCATAAACCTCAGCCTGGATGGTA-
	GGACCTAGCAGACCTGTAAGAATGAGATGTCCGCCAA
	GGTTTATGATACAGTGG	1850
	CCACTGTATCATAAACC	1851
Haemophilia A	ATCTCATTCTTACAGGTCTGCTAGGTCCTACCATCCAGGCTGA	1852
Val85Asp	GGTTTATGATACAGTGGTCATTACACTTAAGAACATGGCTTCC
GTC-GAC	CATCCTGTCAGTCTTCATGCTGTTGGTGTATCCTA
	TAGGATACACCAACAGCATGAAGACTGACAGGATGGGAAGCC	1853
	ATGTTCTTAAGTGTAATGACCACTGTATCATAAACCTCAGCCT
	GGATGGTAGGACCTAGCAGACCTGTAAGAATGAGAT
	TACAGTGGTCATTACAC	1854
	GTGTAATGACCACTGTA	1855
Haemophilia A	CAGGTCTGCTAGGTCCTACCATCCAGGCTGAGGTTTATGATA	1856
Lys89Thr	CAGTGGTCATTACACTTAAGAACATGGCTTCCCATCCTGTCA
AAG-ACG	GTCTTCATGCTGTTGGTGTATCCTACTGGAAAGCTTC
	GAAGCTTTCCAGTAGGATACACCAACAGCATGAAGACTGACA	1857
	GGATGGGAAGCCATGTTCTTAAGTGTAATGACCACTGTATCAT
	AAACCTCAGCCTGGATGGTAGGACCTAGCAGACCTG
	TACACTTAAGAACATGG	1858
	CCATGTTCTTAAGTGTA	1859
Haemophilia A	CTGCTAGGTCCTACCATCCAGGCTGAGGTTTATGATACAGTG	1860
Met91Val	GTCATTACACTTAAGAACATGGCTTCCCATCCTGTCAGTCTTC
cATG-GTG	ATGCTGTTGGTGTATCCTACTGGAAAGCTTCTGAGG
	CCTCAGAAGCTTTCCAGTAGGATACACCAACAGCATGAAGAC	1861
	TGACAGGATGGGAAGCCATGTTCTTAAGTGTAATGACCACTG
	TATCATAAACCTCAGCCTGGATGGTAGGACCTAGCAG
	TTAAGAACATGGCTTCC	1862
	GGAAGCCATGTTCTTAA	1863
Haemophilia A	CTACCATCCAGGCTGAGGTTTATGATACAGTGGTCATTACACT	1864
His94Arg	TAAGAACATGGCTTCCCATCCTGTCAGTCTTCATGCTGTTGGT
CAT-CGT	GTATCCTACTGGAAAGCTTCTGAGGGTGAGTAAAA
	TTTTACTCACCCTCAGAAGCTTTCCAGTAGGATACACCAACAG	1865
	CATGAAGACTGACAGGATGGGAAGCCATGTTCTTAAGTGTAA
	TGACCACTGTATCATAAACCTCAGCCTGGATGGTAG
	GGCTTCCCATCCTGTCA	1866
	TGACAGGATGGGAAGCC	1867
Haemophilia A	CCTACCATCCAGGCTGAGGTTTATGATACAGTGGTCATTACAC	1868
His94Tyr	TTAAGAACATGGCTTCCCATCCTGTCAGTCTTCATGCTGTTGG
cCAT-TAT	TGTATCCTACTGGAAAGCTTCTGAGGGTGAGTAAA
	TTTACTCACCCTCAGAAGCTTTCCAGTAGGATACACCAACAGC	1869
	ATGAAGACTGACAGGATGGGAAGCCATGTTCTTAAGTGTAAT
	GACCACTGTATCATAAACCTCAGCCTGGATGGTAGG
	TGGCTTCCCATCCTGTC	1870
	GACAGGATGGGAAGCCA	1871
Haemophilia A	CTGAGGTTTATGATACAGTGGTCATTACACTTAAGAACATGGC	1872
Leu98Arg	TTCCCATCCTGTCAGTCTTCATGCTGTTGGTGTATCCTACTGG
CTT-CGT	AAAGCTTCTGAGGGTGAGTAAAATACCCTCCTATT
	AATAGGAGGGTATTTTACTCACCCTCAGAAGCTTTCCAGTAGG	1873
	ATACACCAACAGCATGAAGACTGACAGGATGGGAAGCCATGT
	TCTTAAGTGTAATGACCACTGTATCATAAACCTCAG
	TGTCAGTCTTCATGCTG	1874
	CAGCATGAAGACTGACA	1875
Haemophilia A	GATACAGTGGTCATTACACTTAAGAACATGGCTTCCCATCCTG	1876
Gly102Ser	TCAGTCTTCATGCTGTTGGTGTATCCTACTGGAAAGCTTCTGA
tGGT-AGT	GGGTGAGTAAAATACCCTCCTATTGTCCTGTCATT
	AATGACAGGACAATAGGAGGGTATTTTACTCACCCTCAGAAG	1877
	CTTTCCAGTAGGATACACCAACAGCATGAAGACTGACAGGAT
	GGGAAGCCATGTTCTTAAGTGTAATGACCACTGTATC
	ATGCTGTTGGTGTATCC	1878
	GGATACACCAACAGCAT	1879
Haemophilia A	CTTTGAGTGTACAGTGGATATAGAAAGGACAATTTTATTTCTTC	1880
Glu113Asp	CTGCTATAGGAGCTGAATATGATGATCAGACCAGTCAAAGGG
GAAt-GAC	AGAAAGAAGATGATAAAGTCTTCCCTGGTGGAAGC
	GCTTCCACCAGGGAAGACTTTATCATCTTCTTTCTCCCTTTGA	1881
	CTGGTCTGATCATCATATTCAGCTCCTATAGCAGGAAGAAATA
	AAATTGTCCTTTCTATATCCACTGTACACTCAAAG
	GGAGCTGAATATGATGA	1882
	TCATCATATTCAGCTCC	1883
Haemophilia A	TTGAGTGTACAGTGGATATAGAAAGGACAATTTTATTTCTTCCT	1884
Tyr114Cys	GCTATAGGAGCTGAATATGATGATCAGACCAGTCAAAGGGAG
TAT-TGT	AAAGAAGATGATAAAGTCTTCCCTGGTGGAAGCCA
	TGGCTTCCACCAGGGAAGACTTTATCATCTTCTTTCTCCCTTT	1885
	GACTGGTCTGATCATCATATTCAGCTCCTATAGCAGGAAGAAA
	TAAATTGTCCTTTCTATATCCACTGTACACTCAA
	AGCTGAATATGATGATC	1886
	GATCATCATATTCAGCT	1887
Haemophilia A	GTACAGTGGATATAGAAAGGACAATTTTATTTCTTCCTGCTATA	1888
Asp116Gly	GGAGCTGAATATGATGATCAGACCAGTCAAAGGGAGAAAGAA
GAT-GGT	GATGATAAAGTCTTCCCTGGTGGAAGCCATACATA
	TATGTATGGCTTCCACCAGGGAAGACTTTATCATCTTCTTTCT	1889
	CCCTTTGACTGGTCTGATCATCATATTCAGCTCCTATAGCAGG
	AAGAAATAAAATTGTCCTTTCTATATCCACTGTAC
	ATATGATGATCAGACCA	1890
	TGGTCTGATCATCATAT	1891
Haemophilia A	ACAGTGGATATAGAAAGGACAATTTTATTTCTTCCTGCTATAG	1892
Gln117Term	GAGCTGAATATGATGATCAGACCAGTCAAAGGGAGAAAGAAG
tCAG-TAG	ATGATAAAGTCTTCCCTGGTGGAAGCCATACATATG
	CATATGTATGGCTTCCACCAGGGAAGACTTTATCATCTTCTTT	1893
	CTCCCTTTGACTGGTCTGATCATCATATTCAGCTCCTATAGCA
	GGAAGAAATAAAATTGTCCTTTCTATATCCACTGT
	ATGATGATCAGACCAGT	1894
	ACTGGTCTGATCATCAT	1895
Haemophilia A	TGGATATAGAAAGGACAATTTTATTTCTTCCTGCTATAGGAGC	1896
Thr118Ile	TGAATATGATGATCAGACCAGTCAAAGGGAGAAAGAAGATGA
ACC-ATC	TAAAGTCTTCCCTGGTGGAAGCCATACATATGTCTG
	CAGACATATGTATGGCTTCCACCAGGGAAGACTTTATCATCTT	1897
	CTTTCTCCCTTTGACTGGTCTGATCATCATATTCAGCTCCTAT
	AGCAGGAAGAAATAAAATTGTCCTTTCTATATCCA
	TGATCAGACCAGTCAAA	1898
	TTTGACTGGTCTGATCA	1899
Haemophilia A	AGGACAATTTTATTTCTTCCTGCTATAGGAGCTGAATATGATG	1900
Glu122Term	ATCAGACCAGTCAAAGGGAGAAAGAAGATGATAAAGTCTTCC
gGAG-TAG	CTGGTGGAAGCCATACATATGTCTGGCAGGTCCTGA
	TCAGGACCTGCCAGACATATGTATGGCTTCCACCAGGGAAGA	1901
	CTTTATCATCTTCTTTCTCCCTTTGACTGGTCTGATCATCATAT
	TCAGCTCCTATAGCAGGAAGAAATAAAATTGTCCT
	GTCAAAGGGAGAAAGAA	1902
	TTCTTTCTCCCTTTGAC	1903
Haemophilia A	TTTCTTCCTGCTATAGGAGCTGAATATGATGATCAGACCAGTC	1904
Asp126His	AAAGGGAGAAAGAAGATGATAAAGTCTTCCCTGGTGGAAGCC
tGAT-CAT	ATACATATGTCTGGCAGGTCCTGAAAGAGAATGGTC
	GACCATTCTCTTTCAGGACCTGCCAGACATATGTATGGCTTCC	1905
	ACCAGGGAAGACTTTATCATCTTCTTTCTCCCTTTGACTGGTC
	TGATCATCATATTCAGCTCCTATAGCAGGAAGAAA
	AAGAAGATGATAAAGTC	1906
	GACTTTATCATCTTCTT	1907
Haemophilia A	AGTCAAAGGGAGAAAGAAGATGATAAAGTCTTCCCTGGTGGA	1908
Gln139Term	AGCCATACATATGTCTGGCAGGTCCTGAAAGAGAATGGTCCA
gCAG-TAG	ATGGCCTCTGACCCACTGTGCCTTACCTACTCATATC
	GATATGAGTAGGTAAGGCACAGTGGGTCAGAGGCCATTGGA	1909
	CCATTCTCTTTCAGGACCTGCCAGACATATGTATGGCTTCCAC
	CAGGGAAGACTTTATCATCTTCTTTCTCCCTTTGACT
	ATGTCTGGCAGGTCCTG	1910
	CAGGACCTGCCAGACAT	1911
Haemophilia A	AAAGGGAGAAAGAAGATGATAAAGTCTTCCCTGGTGGAAGCC	1912
Val140Ala	ATACATATGTCTGGCAGGTCCTGAAAGAGAATGGTCCAATGG
GTC-GCC	CCTCTGACCCACTGTGCCTTACCTACTCATATCTTTC
	GAAAGATATGAGTAGGTAAGGCACAGTGGGTCAGAGGCCATT	1913
	GGACCATTCTCTTTCAGGACCTGCCAGACATATGTATGGCTT
	CCACCAGGGAAGACTTTATCATCTTCTTTCTCCCTTT
	CTGGCAGGTCCTGAAAG	1914
	CTTTCAGGACCTGCCAG	1915
Haemophilia A	AGATGATAAAGTCTTCCCTGGTGGAAGCCATACATATGTCTG	1916
Asn144Lys	GCAGGTCCTGAAAGAGAATGGTCCAATGGCCTCTGACCCACT
AATg-AAA	GTGCCTTACCTACTCATATCTTTCTCATGTGGACCTG
	CAGGTCCACATGAGAAAGATATGAGTAGGTAAGGCACAGTGG	1917
	GTCAGAGGCCATTGGACCATTCTCTTTCAGGACCTGCCAGAC
	ATATGTATGGCTTCCACCAGGGAAGACTTTATCATCT
	AAAGAGAATGGTCCAAT	1918
	ATTGGACCATTCTCTTT	1919
Haemophilia AG	ATGATAAAGTCTTCCCTGGTGGAAGCCATACATATGTCTGGCA	1920
Gly145Asp	GGTCCTGAAAGAGAATGGTCCAATGGCCTCTGACCCACTGTG
GGT-GAT	CCTTACCTACTCATATCTTTCTCATGTGGACCTGGT
	ACCAGGTCCACATGAGAAAGATATGAGTAGGTAAGGCACAGT	1921
	GGGTCAGAGGCCATTGGACCATTCTCTTTCAGGACCTGCCAG
	ACATATGTATGGCTTCCACCAGGGAAGACTTTATCAT
	AGAGAATGGTCCAATGG	1922
	CCATTGGACCATTCTCT	1923
Haemophilia A	ATGATAAAGTCTTCCCTGGTGGAAGCCATACATATGTCTGGCA	1924
Gly145Val	GGTCCTGAAAGAGAATGGTCCAATGGCCTCTGACCCACTGTG
GGT-GTT	CCTTACCTACTCATATCTTTCTCATGTGGACCTGGT
	ACCAGGTCCACATGAGAAAGATATGAGTAGGTAAGGCACAGT	1925
	GGGTCAGAGGCCATTGGACCATTCTCTTTCAGGACCTGCCAG
	ACATATGTATGGCTTCCACCAGGGAAGACTTTATCAT
	AGAGAATGGTCCAATGG	1926
	CCATTGGACCATTCTCT	1927
Haemophilia A	GATAAAGTCTTCCCTGGTGGAAGCCATACATATGTCTGGCAG	1928
Pro146Ser	GTCCTGAAAGAGAATGGTCCAATGGCCTCTGACCCACTGTGC
tCCA-TCA	CTTACCTACTCATATCTTTCTCATGTGGACCTGGTAA
	TTACCAGGTCCACATGAGAAAGATATGAGTAGGTAAGGCACA	1929
	GTGGGTCAGAGGCCATTGGACCATTCTCTTTCAGGACCTGCC
	AGACATATGTATGGCTTCCACCAGGGAAGACTTTATC
	AGAATGGTCCAATGGCC	1930
	GGCCATTGGACCATTCT	1931
Haemophilia A	CCATACATATGTCTGGCAGGTCCTGAAAGAGAATGGTCCAAT	1932
Cys153Trp	GGCCTCTGACCCACTGTGCCTTACCTACTCATATCTTTCTCAT
TGCc-TGG	GTGGACCTGGTAAAAGACTTGAATTCAGGCCTCATT
	AATGAGGCCTGAATTCAAGTCTTTTACCAGGTCCACATGAGAA	1933
	AGATATGAGTAGGTAAGGCACAGTGGGTCAGAGGCCATTGGA
	CCATTCTCTTTCAGGACCTGCCAGACATATGTATGG
	CCACTGTGCCTTACCTA	1934
	TAGGTAAGGCACAGTGG	1935
Haemophilia A	TGTCTGGCAGGTCCTGAAAGAGAATGGTCCAATGGCCTCTGA	1936
Tyr156Term	CCCACTGTGCCTTACCTACTCATATCTTTCTCATGTGGACCTG
TACt-TAA	GTAAAAGACTTGAATTCAGGCCTCATTGGAGCCCTA
	TAGGGCTCCAATGAGGCCTGAATTCAAGTCTTTTACCAGGTC	1937
	CACATGAGAAAGATATGAGTAGGTAAGGCACAGTGGGTCAGA
	GGCCATTGGACCATTCTCTTTCAGGACCTGCCAGACA
	CTTACCTACTCATATCT	1938
	AGATATGAGTAGGTAAG	1939
Haemophilia A	GTCTGGCAGGTCCTGAAAGAGAATGGTCCAATGGCCTCTGAC	1940
Ser157Pro	CCACTGTGCCTTACCTACTCATATCTTTCTCATGTGGACCTGG
cTCA-CCA	TAAAAGACTTGAATTCAGGCCTCATTGGAGCCCTAC
	GTAGGGCTCCAATGAGGCCTGAATTCAAGTCTTTTACCAGGT	1941
	CCACATGAGAAAGATATGAGTAGGTAAGGCACAGTGGGTCAG
	AGGCCATTGGACCATTCTCTTTCAGGACCTGCCAGAC
	TTACCTACTCATATCTT	1942
	AAGATATGAGTAGGTAA	1943
Haemophilia A	GTCCTGAAAGAGAATGGTCCAATGGCCTCTGACCCACTGTGC	1944
Ser160Pro	CTTACCTACTCATATCTTTCTCATGTGGACCTGGTAAAAGACT
tTCT-CCT	TGAATTCAGGCCTCATTGGAGCCCTACTAGTATGTA
	TACATACTAGTAGGGCTCCAATGAGGCCTGAATTCAAGTCTTT	1945
	TACCAGGTCCACATGAGAAAGATATGAGTAGGTAAGGCACAG
	TGGGTCAGAGGCCATTGGACCATTCTCTTTCAGGAC
	CATATCTTTCTCATGTG	1946
	CACATGAGAAAGATATG	1947
Haemophilia A	AAAGAGAATGGTCCAATGGCCTCTGACCCACTGTGCCTTACC	1948
Val162Met	TACTCATATCTTTCTCATGTGGACCTGGTAAAAGACTTGAATT
tGTG-ATG	CAGGCCTCATTGGAGCCCTACTAGTATGTAGAGAAG
	CTTCTCTACATACTAGTAGGGCTCCAATGAGGCCTGAATTCAA	1949
	GTCTTTTACCAGGTCCACATGAGAAAGATATGAGTAGGTAAG
	GCACAGTGGGTCAGAGGCCATTGGACCATTCTCTTT
	TTTCTCATGTGGACCTG	1950
	CAGGTCCACATGAGAAA	1951
Haemophilia A	CAATGGCCTCTGACCCACTGTGCCTTACCTACTCATATCTTTC	1952
Lys166Thr	TCATGTGGACCTGGTAAAAGACTTGAATTCAGGCCTCATTGG
AAA-ACA	AGCCCTACTAGTATGTAGAGAAGGTAAGTGTATGAA
	TTCATACACTTACCTTCTCTACATACTAGTAGGGCTCCAATGA	1953
	GGCCTGAATTCAAGTCTTTTACCAGGTCCACATGAGAAAGATA
	TGAGTAGGTAAGGCACAGTGGGTCAGAGGCCATTG
	CCTGGTAAAAGACTTGA	1954
	TCAAGTCTTTTACCAGG	1955
Haemophilia A	ACCCACTGTGCCTTACCTACTCATATCTTTCTCATGTGGACCT	1956
Ser170Leu	GGTAAAAGACTTGAATTCAGGCCTCATTGGAGCCCTACTAGT
TCA-TTA	ATGTAGAGAAGGTAAGTGTATGAAAGCGTAGGATTG
	CAATCCTACGCTTTCATACACTTACCTTCTCTACATACTAGTAG	1957
	GGCTCCAATGAGGCCTGAATTCAAGTCTTTTACCAGGTCCAC
	ATGAGAAAGATATGAGTAGGTAAGGCACAGTGGGT
	CTTGAATTCAGGCCTCA	1958
	TGAGGCCTGAATTCAAG	1959
Haemophilia A	AATGTTCTCACTTCTTTTTCAGGGAGTCTGGCCAAGGAAAAGA	1960
Phe195Val	CACAGACCTTGCACAAATTTATACTACTTTTTGCTGTATTTGAT
aTTT-GTT	GAAGGTTAGTGAGTCTTAATCTGAATTTTGGATT
	AATCCAAAATTCAGATTAAGACTCACTAACCTTCATCAAATACA	1961
	GCAAAAAGTAGTATAAATTTGTGCAAGGTCTGTGTCTTTTCCT
	TGGCCAGACTCCCTGAAAAAGAAGTGAGAACATT
	TGCACAAATTTATACTA	1962
	TAGTATAAATTTGTGCA	1963
Haemophilia A	CTTCTTTTTCAGGGAGTCTGGCCAAGGAAAAGACACAGACCT	1964
Leu198His	TGCACAAATTTATACTACTTTTTGCTGTATTTGATGAAGGTTAG
CTT-CAT	TGAGTCTTAATCTGAATTTTGGATTCCTGAAAGAA
	TTCTTTCAGGAATCCAAAATTCAGATTAAGACTCACTAACCTTC	1965
	ATCAAATACAGCAAAAAGTAGTATAAATTTGTGCAAGGTCTGT
	GTCTTTTCCTTGGCCAGACTCCCTGAAAAAGAAG
	TATACTACTTTTTGCTG	1966
	CAGCAAAAAGTAGTATA	1967
Haemophilia A	TTTCAGGGAGTCTGGCCAAGGAAAAGACACAGACCTTGCACA	1968
Ala200Asp	AATTTATACTACTTTTTGCTGTATTTGATGAAGGTTAGTGAGTC
GCT-GAT	TTAATCTGAATTTTGGATTCCTGAAAGAAATCCTC
	GAGGATTTCTTTCAGGAATCCAAAATTCAGATTAAGACTCACT	1969
	AACCTTCATCAAATACAGCAAAAAGTAGTATAAATTTGTGCAA
	GGTCTGTGTCTTTTCCTTGGCCAGACTCCCTGAAA
	ACTTTTTGCTGTATTTG	1970
	CAAATACAGCAAAAAGT	1971
Haemophilia A	TTTTCAGGGAGTCTGGCCAAGGAAAAGACACAGACCTTGCAC	1972
Ala200Thr	AAATTTATACTACTTTTTGCTGTATTTGATGAAGGTTAGTGAGT
tGCT-ACT	CTTAATCTGAATTTTGGATTCCTGAAAGAAATCCT
	AGGATTTCTTTCAGGAATCCAAAATTCAGATTAAGACTCACTA	1973
	ACCTTCATCAAATACAGCAAAAAGTAGTATAAATTTGTGCAAG
	GTCTGTGTCTTTTCCTTGGCCAGACTCCCTGAAAA
	TACTTTTTGCTGTATTT	1974
	AAATACAGCAAAAAGTA	1975
Haemophilia A	AACTCCTTGATGCAGGATAGGGATGCTGCATCTGCTCGGGCC	1976
Val234Phe	TGGCCTAAAATGCACACAGTCAATGGTTATGTAAACAGGTCTC
aGTC-TTC	TGCCAGGTATGTACACACCTGCTCAACAATCCTCAG
	CTGAGGATTGTTGAGCAGGTGTGTACATACCTGGCAGAGACC	1977
	TGTTTACATAACCATTGACTGTGTGCATTTTAGGCCAGGCCCG
	AGCAGATGCAGCATCCCTATCCTGCATCAAGGAGTT
	TGCACACAGTCAATGGT	1978
	ACCATTGACTGTGTGCA	1979
Haemophilia A	ATTTCAGATTCTCTACTTCATAGCCATAGGTGTCTTATTCCTAC	1980
Gly247Glu	TTTACAGGTCTGATTGGATGCCACAGGAAATCAGTCTATTGGC
GGA-GAA	ATGTGATTGGAATGGGCACCACTCCTGAAGTGCA
	TGCACTTCAGGAGTGGTGCCCATTCCAATCACATGCCAATAG	1981
	ACTGATTTCCTGTGGCATCCAATCAGACCTGTAAAGTAGGAAT
	AAGACACCTATGGCTATGAAGTAGAGAATCTGAAAT
	TCTGATTGGATGCCACA	1982
	TGTGGCATCCAATCAGA	1983
Haemophilia A	ATAGGTGTCTTATTCCTACTTTACAGGTCTGATTGGATGCCAC	1984
Trp255Cys	AGGAAATCAGTCTATTGGCATGTGATTGGAATGGGCACCACT
TGGc-TGT	CCTGAAGTGCACTCAATATTCCTCGAAGGTCACACA
	TGTGTGACCTTCGAGGAATATTGAGTGCACTTCAGGAGTGGT	1985
	GCCCATTCCAATCACATGCCAATAGACTGATTTCCTGTGGCAT
	CCAATCAGACCTGTAAAGTAGGAATAAGACACCTAT
	GTCTATTGGCATGTGAT	1986
	ATCACATGCCAATAGAC	1987
Haemophilia A	ATAGGTGTCTTATTCCTACTTTACAGGTCTGATTGGATGCCAC	1988
Trp255Term	AGGAAATCAGTCTATTGGCATGTGATTGGAATGGGCACCACT
TGGc-TGA	CCTGAAGTGCACTCAATATTCCTCGAAGGTCACACA
	TGTGTGACCTTCGAGGAATATTGAGTGCACTTCAGGAGTGGT	1989
	GCCCATTCCAATCACATGCCAATAGACTGATTTCCTGTGGCAT
	CCAATCAGACCTGTAAAGTAGGAATAAGACACCTAT
	GTCTATTGGCATGTGAT	1990
	ATCACATGCCAATAGAC	1991
Haemophilia A	AGGTGTCTTATTCCTACTTTACAGGTCTGATTGGATGCCACAG	1992
His256Leu	GAAATCAGTCTATTGGCATGTGATTGGAATGGGCACCACTCC
CAT-CTT	TGAAGTGCACTCAATATTCCTCGAAGGTCACACATT
	AATGTGTGACCTTCGAGGAATATTGAGTGCACTTCAGGAGTG	1993
	GTGCCCATTCCAATCACATGCCAATAGACTGATTTCCTGTGG
	CATCCAATCAGACCTGTAAAGTAGGAATAAGACACCT
	CTATTGGCATGTGATTG	1994
	CAATCACATGCCAATAG	1995
Haemophilia A	TATTCCTACTTTACAGGTCTGATTGGATGCCACAGGAAATCAG	1996
Gly259Arg	TCTATTGGCATGTGATTGGAATGGGCACCACTCCTGAAGTGC
tGGA-AGA	ACTCAATATTCCTCGAAGGTCACACATTTCTTGTGA
	TCACAAGAAATGTGTGACCTTCGAGGAATATTGAGTGCACTTC	1997
	AGGAGTGGTGCCCATTCCAATCACATGCCAATAGACTGATTT
	CCTGTGGCATCCAATCAGACCTGTAAAGTAGGAATA
	ATGTGATTGGAATGGGC	1998
	GCCCATTCCAATCACAT	1999
Haemophilia A	TTGGATGCCACAGGAAATCAGTCTATTGGCATGTGATTGGAAT	2000
Val266Gly	GGGCACCACTCCTGAAGTGCACTCAATATTCCTCGAAGGTCA
GTG-GGG	CACATTTCTTGTGAGGAACCATCGCCAGGCGTCCTT
	AAGGACGCCTGGCGATGGTTCCTCACAAGAAATGTGTGACCT	2001
	TCGAGGAATATTGAGTGCACTTCAGGAGTGGTGCCCATTCCA
	ATCACATGCCAATAGACTGATTTCCTGTGGCATCCAA
	TCCTGAAGTGCACTCAA	2002
	TTGAGTGCACTTCAGGA	2003
Haemophilia A	CAGTCTATTGGCATGTGATTGGAATGGGCACCACTCCTGAAG	2004
Glu272Gly	TGCACTCAATATTCCTCGAAGGTCACACATTTCTTGTGAGGAA
GAA-GGA	CCATCGCCAGGCGTCCTTGGAAATCTCGCCAATAAC
	GTTATTGGCGAGATTTCCAAGGACGCCTGGCGATGGTTCCTC	2005
	ACAAGAAATGTGTGACCTTCGAGGAATATTGAGTGCACTTCAG
	GAGTGGTGCCCATTCCAATCACATGCCAATAGACTG
	ATTCCTCGAAGGTCACA	2006
	TGTGACCTTCGAGGAAT	2007
Haemophilia A	TCAGTCTATTGGCATGTGATTGGAATGGGCACCACTCCTGAA	2008
Glu272Lys	GTGCACTCAATATTCCTCGAAGGTCACACATTTCTTGTGAGGA
cGAA-AAA	ACCATCGCCAGGCGTCCTTGGAAATCTCGCCAATAA
	TTATTGGCGAGATTTCCAAGGACGCCTGGCGATGGTTCCTCA	2009
	CAAGAAATGTGTGACCTTCGAGGAATATTGAGTGCACTTCAG
	GAGTGGTGCCCATTCCAATCACATGCCAATAGACTGA
	TATTCCTCGAAGGTCAC	2010
	GTGACCTTCGAGGAATA	2011
Haemophilia A	GGCATGTGATTGGAATGGGCACCACTCCTGAAGTGCACTCAA	2012
Thr275Ile	TATTCCTCGAAGGTCACACATTTCTTGTGAGGAACCATCGCCA
ACA-ATA	GGCGTCCTTGGAAATCTCGCCAATAACTTTCCTTAC
	GTAAGGAAAGTTATTGGCGAGATTTCCAAGGACGCCTGGCGA	2013
	TGGTTCCTCACAAGAAATGTGTGACCTTCGAGGAATATTGAGT
	GCACTTCAGGAGTGGTGCCCATTCCAATCACATGCC
	AGGTCACACATTTCTTG	2014
	CAAGAAATGTGTGACCT	2015
Haemophilia A	TTGGAATGGGCACCACTCCTGAAGTGCACTCAATATTCCTCG	2016
Val278Ala	AAGGTCACACATTTCTTGTGAGGAACCATCGCCAGGCGTCCT
GTG-GCG	TGGAAATCTCGCCAATAACTTTCCTTACTGCTCAAAC
	GTTTGAGCAGTAAGGAAAGTTATTGGCGAGATTTCCAAGGAC	2017
	GCCTGGCGATGGTTCCTCACAAGAAATGTGTGACCTTCGAGG
	AATATTGAGTGCACTTCAGGAGTGGTGCCCATTCCAA
	ATTTCTTGTGAGGAACC	2018
	GGTTCCTCACAAGAAAT	2019
Haemophilia A	TGGGCACCACTCCTGAAGTGCACTCAATATTCCTCGAAGGTC	2020
Asn280Ile	ACACATTTCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAA
AAC-ATC	TCTCGCCAATAACTTTCCTTACTGCTCAAACACTCTT
	AAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGATTTCCA	2021
	AGGACGCCTGGCGATGGTTCCTCACAAGAAATGTGTGACCTT
	CGAGGAATATTGAGTGCACTTCAGGAGTGGTGCCCA
	TGTGAGGAACCATCGCC	2022
	GGCGATGGTTCCTCACA	2023
Haemophilia A	ACCACTCCTGAAGTGCACTCAATATTCCTCGAAGGTCACACAT	2024
Arg282Cys	TTCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGC
tCGC-TGC	CAATAACTTTCCTTACTGCTCAAACACTCTTGATGG
	CCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGA	2025
	TTTCCAAGGACGCCTGGCGATGGTTCCTCACAAGAAATGTGT
	GACCTTCGAGGAATATTGAGTGCACTTCAGGAGTGGT
	GGAACCATCGCCAGGCG	2026
	CGCCTGGCGATGGTTCC	2027
Haemophilia A	CCACTCCTGAAGTGCACTCAATATTCCTCGAAGGTCACACATT	2028
Arg282His	TCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGCC
CGC-CAC	AATAACTTTCCTTACTGCTCAAACACTCTTGATGGA
	TCCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAG	2029
	ATTTCCAAGGACGCCTGGCGATGGTTCCTCACAAGAAATGTG
	TGACCTTCGAGGAATATTGAGTGCACTTCAGGAGTGG
	GAACCATCGCCAGGCGT	2030
	ACGCCTGGCGATGGTTC	2031
Haemophilia A	CCACTCCTGAAGTGCACTCAATATTCCTCGAAGGTCACACATT	2032
Arg282Leu	TCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGCC
CGC-CTC	AATAACTTTCCTTACTGCTCAAACACTCTTGATGGA
	TCCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAG	2033
	ATTTCCAAGGACGCCTGGCGATGGTTCCTCACAAGAAATGTG
	TGACCTTCGAGGAATATTGAGTGCACTTCAGGAGTGG
	GAACCATCGCCAGGCGT	2034
	ACGCCTGGCGATGGTTC	2035
Haemophilia A	CTGAAGTGCACTCAATATTCCTCGAAGGTCACACATTTCTTGT	2036
Ala284Glu	GAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGCCAATAAC
GCG-GAG	TTTCCTTACTGCTCAAACACTCTTGATGGACCTTGG
	CCAAGGTCCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATT	2037
	GGCGAGATTTCCAAGGACGCCTGGCGATGGTTCCTCACAAG
	AAATGTGTGACCTTCGAGGAATATTGAGTGCACTTCAG
	TCGCCAGGCGTCCTTGG	2038
	CCAAGGACGCCTGGCGA	2039
Haemophilia A	CCTGAAGTGCACTCAATATTCCTCGAAGGTCACACATTTCTTG	2040
Ala284Pro	TGAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGCCAATAA
gGCG-CCG	CTTTCCTTACTGCTCAAACACTCTTGATGGACCTTG
	CAAGGTCCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTG	2041
	GCGAGATTTCCAAGGACGCCTGGCGATGGTTCCTCACAAGAA
	ATGTGTGACCTTCGAGGAATATTGAGTGCACTTCAGG
	ATCGCCAGGCGTCCTTG	2042
	CAAGGACGCCTGGCGAT	2043
Haemophilia A	TATTCCTCGAAGGTCACACATTTCTTGTGAGGAACCATCGCCA	2044
Ser289Leu	GGCGTCCTTGGAAATCTCGCCAATAACTTTCCTTACTGCTCAA
TCG-TTG	ACACTCTTGATGGACCTTGGACAGTTTCTACTGTT
	AACAGTAGAAACTGTCCAAGGTCCATCAAGAGTGTTTGAGCA	2045
	GTAAGGAAAGTTATTGGCGAGATTTCCAAGGACGCCTGGCGA
	TGGTTCCTCACAAGAAATGTGTGACCTTCGAGGAATA
	GGAAATCTCGCCAATAA	2046
	TTATTGGCGAGATTTCC	2047
Haemophilia A	GTCACACATTTCTTGTGAGGAACCATCGCCAGGCGTCCTTGG	2048
Phe293Ser	AAATCTCGCCAATAACTTTCCTTACTGCTCAAACACTCTTGAT
TTC-TCC	GGACCTTGGACAGTTTCTACTGTTTTGTCATATCTC
	GAGATATGACAAAACAGTAGAAACTGTCCAAGGTCCATCAAG	2049
	AGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGATTTCCAAG
	GACGCCTGGCGATGGTTCCTCACAAGAAATGTGTGAC
	AATAACTTTCCTTACTG	2050
	CAGTAAGGAAAGTTATT	2051
Haemophilia A	ACATTTCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATC	2052
Thr295Ala	TCGCCAATAACTTTCCTTACTGCTCAAACACTCTTGATGGACC
tACT-GCT	TTGGACAGTTTCTACTGTTTTGTCATATCTCTTCCC
	GGGAAGAGATATGACAAAACAGTAGAAACTGTCCAAGGTCCA	2053
	TCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGATTTC
	CAAGGACGCCTGGCGATGGTTCCTCACAAGAAATGT
	CTTTCCTTACTGCTCAA	2054
	TTGAGCAGTAAGGAAAG	2055
Haemophilia A	CATTTCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATCT	2056
Thr295Ile	CGCCAATAACTTTCCTTACTGCTCAAACACTCTTGATGGACCT
ACT-ATT	TGGACAGTTTCTACTGTTTTGTCATATCTCTTCCCA
	TGGGAAGAGATATGACAAAACAGTAGAAACTGTCCAAGGTCC	2057
	ATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGATTT
	CCAAGGACGCCTGGCGATGGTTCCTCACAAGAAATG
	TTTCCTTACTGCTCAAA	2058
	TTTGAGCAGTAAGGAAA	2059
Haemophilia A	TTCTTGTGAGGAACCATCGCCAGGCGTCCTTGGAAATCTCGC	2060
Ala296Val	CAATAACTTTCCTTACTGCTCAAACACTCTTGATGGACCTTGG
GCT-GTT	ACAGTTTCTACTGTTTTGTCATATCTCTTCCCACCA
	TGGTGGGAAGAGATATGACAAAACAGTAGAAACTGTCCAAGG	2061
	TCCATCAAGAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAG
	ATTTCCAAGGACGCCTGGCGATGGTTCCTCACAAGAA
	CCTTACTGCTCAAACAC	2062
	GTGTTTGAGCAGTAAGG	2063
Haemophilia A	TCTCGCCAATAACTTTCCTTACTGCTCAAACACTCTTGATGGA	2064
Leu308Pro	CCTTGGACAGTTTCTACTGTTTTGTCATATCTCTTCCCACCAA
CTG-CCG	CATGGTAATATCTTGGATCTTTAAAATGAATATTA
	TAATATTCATTTTAAAGATCCAAGATATTACCATGTTGGTGGGA	2065
	AGAGATATGACAAAACAGTAGAAACTGTCCAAGGTCCATCAA
	GAGTGTTTGAGCAGTAAGGAAAGTTATTGGCGAGA
	GTTTCTACTGTTTTGTC	2066
	GACAAAACAGTAGAAAC	2067
Haemophilia A	ACAGCCTAATATAGCAAGACACTCTGACATTGTTTGGTTTGTC	2068
Glu321Lys	TGACTCCAGATGGCATGGAAGCTTATGTCAAAGTAGACAGCT
gGAA-AAA	GTCCAGAGGAACCCCAACTACGAATGAAAAATAATG
	CATTATTTTTCATTCGTAGTTGGGGTTCCTCTGGACAGCTGTC	2069
	TACTTTGACATAAGCTTCCATGCCATCTGGAGTCAGACAAACC
	AAACAATGTCAGAGTGTCTTGCTATATTAGGCTGT
	ATGGCATGGAAGCTTAT	2070
	ATAAGCTTCCATGCCAT	2071
Haemophilia A	ATATAGCAAGACACTCTGACATTGTTTGGTTTGTCTGACTCCA	2072
Tyr323Term	GATGGCATGGAAGCTTATGTCAAAGTAGACAGCTGTCCAGAG
TATg-TAA	GAACCCCAACTACGAATGAAAAATAATGAAGAAGCG
	CGCTTCTTCATTATTTTTCATTCGTAGTTGGGGTTCCTCTGGA	2073
	CAGCTGTCTACTTTGACATAAGCTTCCATGCCATCTGGAGTCA
	GACAAACCAAACAATGTCAGAGTGTCTTGCTATAT
	GAAGCTTATGTCAAAGT	2074
	ACTTTGACATAAGCTTC	2075
Haemophilia A	AAGACACTCTGACATTGTTTGGTTTGTCTGACTCCAGATGGCA	2076
Val326Leu	TGGAAGCTTATGTCAAAGTAGACAGCTGTCCAGAGGAACCCC
aGTA-CTA	AACTACGAATGAAAAATAATGAAGAAGCGGAAGACT
	AGTCTTCCGCTTCTTCATTATTTTTCATTCGTAGTTGGGGTTC	2077
	CTCTGGACAGCTGTCTACTTTGACATAAGCTTCCATGCCATCT
	GGAGTCAGACAAACCAAACAATGTCAGAGTGTCTT
	ATGTCAAAGTAGACAGC	2078
	GCTGTCTACTTTGACAT	2079
Haemophilia A	TGACATTGTTTGGTTTGTCTGACTCCAGATGGCATGGAAGCTT	2080
Cys329Arg	ATGTCAAAGTAGACAGCTGTCCAGAGGAACCCCAACTACGAA
cTGT-CGT	TGAAAAATAATGAAGAAGCGGAAGACTATGATGATG
	CATCATCATAGTCTTCCGCTTCTTCATTATTTTTCATTCGTAGT	2081
	TGGGGTTCCTCTGGACAGCTGTCTACTTTGACATAAGCTTCC
	ATGCCATCTGGAGTCAGACAAACCAAACAATGTCA
	TAGACAGCTGTCCAGAG	2082
	CTCTGGACAGCTGTCTA	2083
Haemophilia A	GACATTGTTTGGTTTGTCTGACTCCAGATGGCATGGAAGCTTA	2084
Cys329Tyr	TGTCAAAGTAGACAGCTGTCCAGAGGAACCCCAACTACGAAT
TGT-TAT	GAAAAATAATGAAGAAGCGGAAGACTATGATGATGA
	TCATCATCATAGTCTTCCGCTTCTTCATTATTTTTCATTCGTAG	2085
	TTGGGGTTCCTCTGGACAGCTGTCTACTTTGACATAAGCTTCC
	ATGCCATCTGGAGTCAGACAAACCAAACAATGTC
	AGACAGCTGTCCAGAGG	2086
	CCTCTGGACAGCTGTCT	2087
Haemophilia A	ACTCCAGATGGCATGGAAGCTTATGTCAAAGTAGACAGCTGT	2088
Arg336Term	CCAGAGGAACCCCAACTACGAATGAAAAATAATGAAGAAGCG
aCGA-TGA	GAAGACTATGATGATGATCTTACTGATTCTGAAATGG
	CCATTTCAGAATCAGTAAGATCATCATCATAGTCTTCCGCTTC	2089
	TTCATTATTTTTCATTCGTAGTTGGGGTTCCTCTGGACAGCTG
	TCTACTTTGACATAAGCTTCCATGCCATCTGGAGT
	CCCAACTACGAATGAAA	2090
	TTTCATTCGTAGTTGGG	2091
Haemophilia A	GATTCTGAAATGGATGTGGTCAGGTTTGATGATGACAACTCTC	2092
Arg372Cys	CTTCCTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAA
tCGC-TGC	AACTTGGGTACATTACATTGCTGCTGAAGAGGAGG
	CCTCCTCTTCAGCAGCAATGTCAATGTACCCAAGTTTTAGGATG	2093
	CTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGGAGAGTT
	GTCATCATCAAACCTGACCACATCCATTTCAGAATC
	TCCAAATTCGCTCAGTT	2094
	AACTGAGCGAATTTGGA	2095
Haemophilia A	ATTCTGAAATGGATGTGGTCAGGTTTGATGATGACAACTCTCC	2096
Arg372His	TTCCTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAAA
CGC-CAC	ACTTGGGTACATTACATTGCTGCTGAAGAGGAGGA
	TCCTCCTCTTCAGCAGCAATGTAATGTACCCAAGTTTTAGGAT	2097
	GCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGGAGAGT
	TGTCATCATCAAACCTGACCACATCCATTTCAGAAT
	CCAAATTCGCTCAGTTG	2098
	CAACTGAGCGAATTTGG	2099
Haemophilia A	CTGAAATGGATGTGGTCAGGTTTGATGATGACAACTCTCCTTC	2100
Ser373Leu	CTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAAAACT
TCA-TTA	TGGGTACATTACATTGCTGCTGAAGAGGAGGACTG
	CAGTCCTCCTCTTCAGCAGCAATGTAATGTACCCAAGTTTTAG	2101
	GATGCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGGAG
	AGTTGTCATCATCAAACCTGACCACATCCATTTCAG
	AATTCGCTCAGTTGCCA	2102
	TGGCAACTGAGCGAATT	2103
Haemophilia A	TCTGAAATGGATGTGGTCAGGTTTGATGATGACAACTCTCCTT	2104
Ser373Pro	CCTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAAAAC
cTCA-CCA	TTGGGTACATTACATTGCTGCTGAAGAGGAGGACT
	AGTCCTCCTCTTCAGCAGCAATGTAATGTACCCAAGTTTTAGG	2105
	ATGCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGGAGA
	GTTGTCATCATCAAACCTGACCACATCCATTTCAGA
	AAATTCGCTCAGTTGCC	2106
	GGCAACTGAGCGAATTT	2107
Haemophilia A	CTGAAATGGATGTGGTCAGGTTTGATGATGACAACTCTCCTTC	2108
Ser373Term	CTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAAAACT
TCA-TAA	TGGGTACATTACATTGCTGCTGAAGAGGAGGACTG
	CAGTCCTCCTCTTCAGCAGCAATGTAATGTACCCAAGTTTTAG	2109
	GATGCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGGAG
	AGTTGTCATCATCAAACCTGACCACATCCATTTCAG
	ATTCGCTCAGTTGCCA	2110
	TGGCAACTGAGCGAATT	2111
Haemophilia A	CCTTCCTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTA	2112
Ile386Phe	AAACTTGGGTACATTACATTGCTGCTGAAGAGGAGGACTGGG
cATT-TTT	ACTATGCTCCCTTAGTCCTCGCCCCCGATGACAGGT
	ACCTGTCATCGGGGGCGAGGACTAAGGGAGCATAGTCCCAG	2113
	TCCTCCTCTTCAGCAGCAATGTAATGTACCCAAGTTTTAGGAT
	GCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAGG
	TACATTACATTGCTGCT	2114
	AGCAGCAATGTAATGTA	2115
Haemophilia A	CTTCCTTTATCCAAATTCGCTCAGTTGCCAAGAAGCATCCTAA	2116
Ile386Ser	AACTTGGGTACATTACATTGCTGCTGAAGAGGAGGACTGGGA
ATT-AGT	CTATGCTCCCTTAGTCCTCGCCCCCGATGACAGGTA
	TACCTGTCATCGGGGGCGAGGACTAAGGGAGCATAGTCCCA	2117
	GTCCTCCTCTTCAGCAGCAIATGTAATGTACCCAAGTTTTAGGA
	TGCTTCTTGGCAACTGAGCGAATTTGGATAAAGGAAG
	ACATTACATTGCTGCTG	2118
	CAGCAGCAATGTAATGT	2119
Haemophilia A	AAATTCGCTCAGTTGCCAAGAAGCATCCTAAAACTTGGGTACA	2120
Glu390Gly	TTACATTGCTGCTGAAGAGGAGGACTGGGACTATGCTCCCTT
GAG-GGG	AGTCCTCGCCCCCGATGACAGGTAAGCACTTTTTGA
	TCAAAAAGTGCTTACCTGTCATCGGGGGCGAGGACTAAGGGA	2121
	GCATAGTCCCAGTCCTCCTCTTCAGCAGCAATGTAATGTACC
	CAAGTTTTAGGATGCTTCTTGGCAACTGAGCGAATTT
	TGCTGAAGAGGAGGACT	2122
	AGTCCTCCTCTTCAGCA	2123
Haemophilia A	TCAGTTGCCAAGAAGCATCCTAAAACTTGGGTACATTACATTG	2124
Trp393Gly	CTGCTGAAGAGGAGGACTGGGACTATGCTCCCTTAGTCCTCG
cTGG-GGG	CCCCCGATGACAGGTAAGCACTTTTTGACTATTGGT
	ACCAATAGTCAAAAAGTGCTTACCTGTCATCGGGGGCGAGGA	2125
	CTAAGGGAGCATAGTCCCAGTCCTCCTCTTCAGCAGCAATGT
	AATGTACCCAAGTTTTAGGATGCTTCTTGGCAACTGA
	AGGAGGACTGGGACTAT	2126
	ATAGTCCCAGTCCTCCT	2127
Haemophilia A	GCCTACCTAGAATTTTTCTTCCCAACCTCTCATCTTTTTTTCTC	2128
Lys408Ile	TTATACAGAAGTTATAAAAGTCAATATTTGAACAATGGCCCTC
AAA-ATA	AGCGGATTGGTAGGAAGTACAAAAAAGTCCGATT
	AATCGGACTTTTTTGTACTTCCTACCAATCCGCTGAGGGCCAT	2129
	TGTTCAAATATTGACTTTTATAACTTCTGTATAAGAGAAAAAAA
	GATGAGAGGTTGGGAAGAAAAATTCTAGGTAGGC
	AAGTTATAAAAGTCAAT	2130
	ATTGACTTTTATAACTT	2131
Haemophilia A	TTTTCTTCCCAACCTCTCATCTTTTTTTCTCTTATACAGAAGTT	2132
Leu412Phe	ATAAAAGTCAATATTTGAACAATGGCCCTCAGCGGATTGGTAG
TTGa-TTT	GAAGTACAAAAAAGTCCGATTTATGGCATACACA
	TGTGTATGCCATAAATCGGACTTTTTTGTACTTCCTACCAATC	2133
	CGCTGAGGGCCATTGTTCAAATATTGACTTTTATAACTTCTGT
	ATAAGAGAAAAAAAGATGAGAGGTTGGGAAGAAAA
	CAATATTTGAACAATGG	2134
	CCATTGTTCAAATATTG	2135
Haemophilia A	TCATCTTTTTTTCTCTTATACAGAAGTTATAAAAGTCAATATTTG	2136
Arg418Trp	AACAATGGCCCTCAGCGGATTGGTAGGAAGTACAAAAAAGTC
gCGG-TGG	CGATTTATGGCATACACAGATGAAACCTTTAAGA
	TCTTAAAGGTTTCATCTGTGTATGCCATAAATCGGACTTTTTTG	2137
	TACTTCCTACCAATCCGCTGAGGGCCATTGTTCAAATATTGAC
	TTTATAACTTCTGTATAAGAGAAAAAAAGATGA
	GCCCTCAGCGGATTGGT	2138
	ACCAATCCGCTGAGGGC	2139
Haemophilia A	TTTTTCTCTTATACAGAAGTTATAAAAGTCAATATTTGAACAAT	2140
Gly420Val	GGCCCTCAGCGGATTGGTAGGAAGTACAAAAAAGTCCGATTT
GGT-GTT	ATGGCATACACAGATGAAACCTTTAAGACTCGTGA
	TCACGAGTCTTAAAGGTTTCATCTGTGTATGCCATAAATCGGA	2141
	CTTTTTTGTACTTCCTACCAATCCGCTGAGGGCCATTGTTCAA
	ATATTGGACTTTTATAACTTCTGTATAAGAGAAAAA
	GCGGATTGGTAGGAAGT	2142
	ACTTCCTACCAATCCGC	2143
Haemophilia A	GAAGTTATAAAAGTCAATATTTGAACAATGGCCCTCAGCGGAT	2144
Lys425Arg	TGGTAGGAAGTACAAAAAAGTCCGATTTATGGCATACACAGAT
AAA-AGA	GAAACCTTTAAGACTCGTGAAGCTATTCAGCATGA
	TCATGCTGAATAGCTTCACGAGTCTTAAAGGTTTCATCTGTGT	2145
	ATGCCATAAATCGGACTTTTTTGTACTTCCTACCAATCCGCTG
	AGGGCCATTGTTCAAATATTGACTTTTATAACTTC
	GTACAAAAAAGTCCGAT	2146
	ATCGGACTTTTTTGTAC	2147
Haemophilia A	TATAAAAGTCAATATTTGAACAATGGCCCTCAGCGGATTGGTA	2148
Arg427Term	GGAAGTACAAAAAAGTCCGATTTATGGCATACACAGATGAAAC
cCGA-TGA	CTTTAAGACTCGTGAAGCTATTCAGCATGAATCAG
	CTGATTCATGCTGAATAGCTTCACGAGTCTTAAAGGTTTCATC	2149
	TGTGTATGCCATAAATCGGACTTTTTTGTACTTCCTACCAATC
	CGCTGAGGGCCATTGTTCAAATATTGACTTTTATA
	AAAAAGTCCGATTTATG	2150
	CATAAATCGGACTTTTT	2151
Haemophilia A	TATTTGAACAATGGCCCTCAGCGGATTGGTAGGAAGTACAAA	2152
Tyr431Asn	AAAGTCCGATTTATGGCATACACAGATGAAACCTTTAAGACTC
aTAC-AAC	GTGAAGCTATTCAGCATGAATCAGGAATCTTGGGAC
	GTCCCAAGATTCCTGATTCATGCTGAATAGCTTCACGAGTCTT	2153
	AAAGGTTTCATCTGTGTATGCCATAAATCGGACTTTTTTGTAC
	TTCCTACCAATCCGCTGAGGGCCATTGTTCAAATA
	TTATGGCATACACAGAT	2154
	ATCTGTGTATGCCATAA	2155
Haemophilia A	GCCCTCAGCGGATTGGTAGGAAGTACAAAAAAGTCCGATTTA	2156
Thr435Ile	TGGCATACACAGATGAAACCTTTAAGACTCGTGAAGCTATTCA
ACC-ATC	GCATGAATCAGGAATCTTGGGACCTTTACTTTATGG
	CCATAAAGTAAAGGTCCCAAGATTCCTGATTCATGCTGAATAG	2157
	CTTCACGAGTCTTAAAGGTTTCATCTGTGTATGCCATAAATCG
	GACTTTTTTGTACTTCCTACCAATCCGCTGAGGGC
	AGATGAAACCTTTAAGA	2158
	TCTTAAAGGTTTCATCT	2159
Haemophilia A	ACACAGATGAAACCTTTAAGACTCGTGAAGCTATTCAGCATGA	2160
Pro451Leu	ATCAGGAATCTTGGGACCTTTACTTTATGGGGAAGTTGGAGA
CCT-CTT	CACACTGTTGGTAAGTTGAAGAAAAGATTTAAGGTC
	GACCTTAAATCTTTTCTTCAACTTACCAACAGTGTGTCTCCAA	2161
	CTTCCCCATCAAAGTAAAGGTCCCAAGATTCCTGATTCATGCTG
	AATAGCTTCACGAGTCTTAAAGGTTTCATCTGTGT
	CTTGGGACCTTTACTTT	2162
	AAAGTAAAGGTCCCAAG	2163
Haemophilia A	TACACAGATGAAACCTTTAAGACTCGTGAAGCTATTCAGCATG	2164
Pro451Thr	AATCAGGAATCTTGGGACCTTTACTTTATGGGGAAGTTGGAGA
aCCT-ACT	CACACTGTTGGTAAGTTGAAGAAAAGATTTAAGGT
	ACCTTAAATCTTTTCTTCAACTTACCAACAGTGTGTCTCCAACT	2165
	TCCCCATAAAGTAAAGGTCCCAAGATTCCTGATTCATGCTGAA
	TAGCTTCACGAGTCTTAAAGGTTTCATCTGTGTA
	TCTTGGGACCTTTACTT	2166
	AAGTAAAGGTCCCAAGA	2167
Haemophilia A	ACCTTTAAGACTCGTGAAGCTATTCAGCATGAATCAGGAATCT	2168
Gly455Arg	TGGGACCTTTACTTTATGGGGAAGTTGGAGACACACTGTTGG
tGGG-AGG	TAAGTTGAAGAAAAGATTTAAGGTCAGGTAAGAAGA
	TCTTCTTACCTGACCTTAAATCTTTTCTTCAACTTACCAACAGT	2169
	GTGTCTCCAACTTCCCCATAAAGTAAAGGTCCCAAGATTCCTG
	ATTCATGCTGAATAGCTTCACGAGTCTTAAAGGT
	TACTTTATGGGGAAGTT	2170
	AACTTCCCCATAAAGTA	2171
Haemophilia A	CCTTTAAGACTCGTGAAGCTATTCAGCATGAATCAGGAATCTT	2172
Gly455Glu	GGGACCTTTACTTTATGGGGAAGTTGGAGACACACTGTTGGT
GGG-GAG	AAGTTGAAGAAAAGATTTAAGGTCAGGTAAGAAGAA
	TTCTTCTTACCTGACCTTAAATCTTTTCTTCAACTTACCAACAG	2173
	TGTGTCTCCAACTTCCCATAAAGTAAAGGTCCCAAGATTCCT
	GATTCATGCTGAATAGCTTCACGAGTCTTAAAGG
	ACTTTATGGGGAAGTTG	2174
	CAACTTCCCCATAAAGT	2175
Haemophilia A	CGTGAAGCTATTCAGCATGAATCAGGAATCTTGGGACCTTTAC	2176
Asp459Asn	TTTATGGGGAAGTTGGAGACACACTGTTGGTAAGTTGAAGAA
aGAC-AAC	AAGATTTAAGGTCAGGTAAGAAGAAAAAGTCTGGAG
	CTCCAGACTTTTTCTTCTTACCTGACCTTAAATCTTTTCTTCAA	2177
	CTTACCAACAGTGTGTCTCCAACTTCCCCATAAAGTAAAGGTC
	CCAAGATTCCTGATTCATGCTGAATAGCTTCACG
	AAGTTGGAGACACACTG	2178
	CAGTGTGTCTCCAACTT	2179
Haemophilia A	TGTTGATCCTAGTCGTTTTAGGATTTGATCTTAGATCTCGCTTA	2180
Phe465Cys	TACTTTCAGATTATATTTAAGAATCAAGCAAGCAGACCATATAA
TTT-TGT	CATCTACCCTCACGGAATCACTGATGTCCGTCC
	GGACGGACATCAGTGATTCCGTGAGGGTAGATGTTATATGGT	2181
	CTGCTTGCTTGATTCTTAAATATAATCTGAAAGTATAAGCGAG
	ATCTAAGATCAAATCCTAAAACGACTAGGATCAACA
	GATTATATTTAAGAATC	2182
	GATTCTTAAATATAATC	2183
Haemophilia A	TCGTTTTAGGATTTGATCTTAGATCTCGCTTATACTTTCAGATT	2184
Ala469Gly	ATATTTAAGAATCAAGCAAGCAGACCATATAACATCTACCCTC
GCA-GGA	ACGGAATCACTGATGTCCGTCCTTTGTATTCAAG
	CTTGAATACAAAGGACGGACATCAGTGATTCCGTGAGGGTAG	2185
	ATGTTATATGGTCTGCTTGCTTGATTCTTAAATATAATCTGAAA
	GTATAAGCGAGATCTAAGATCAAATCCTAAAACGA
	GAATCAAGCAAGCAGAC	2186
	GTCTGCTTGCTTGATTC	2187
Haemophilia A	TTAGGATTTGATCTTAGATCTCGCTTATACTTTCAGATTATATT	2188
Arg471Gly	TAAGAATCAAGCAAGCAGACCATATAACATCTACCCTCACGG
cAGA-GGA	AATCACTGATGTCCGTCCTTTGTATTCAAGGAGAT
	ATCTCCTTGAATACAAAGGACGGACATCAGTGATTCCGTGAG	2189
	GGTAGATGTTATATGGTCTGCTTGCTTGATTCTTAAATATAATC
	TGAAAGTATAAGCGAGATCTAAGATCAAATCCTAA
	AAGCAAGCAGACCATAT	2190
	ATATGGTCTGCTTGCTT	2191
Haemophilia A	TTGATCTTAGATCTCGCTTATACTTTCAGATTATATTTAAGAAT	2192
Tyr473Cys	CAAGCAAGCAGACCATATAACATCTACCCTCACGGAATCACT
TAT-TGT	GATGTCCGTCCTTTGTATTCAAGGAGATTACCAAA
	TTTGGTAATCTCCTTGAATACAAAGGACGGACATCAGTGATTC	2193
	CGTGAGGGTAGATGTTATATGGTCTGCTTGCTTGATTCTTAAA
	TATAATCTGAAAGTATAAGCGAGATCTAAGATCAA
	CAGACCATATAACATCT	2194
	AGATGTTATATGGTCTG	2195
Haemophilia A	TTTGATCTTAGATCTCGCTTATACTTTCAGATTATATTTAAGAA	2196
Tyr473His	TCAAGCAAGCAGACCATATAACATCTACCCTCACGGAATCACT
aTAT-CAT	GATGTCCGTCCTTTGTATTCAAGGAGATTACCAA
	TTGGTAATCTCCTTGAATACAAAGGACGGACATCAGTGATTCC	2197
	GTGAGGGTAGATGTTATATGGTCTGCTTGCTTGATTCTTAAAT
	ATAATCTGAAAGTATAAGCGAGATCTAAGATCAAA
	GCAGACCATATAACATC	2198
	GATGTTATATGGTCTGC	2199
Haemophilia A	TTAGATCTCGCTTATACTTTCAGATTATATTTAAGAATCAAGCA	2200
Ile475Thr	AGCAGACCATATAACATCTACCCTCACGGAATCACTGATGTCC
ATC-ACC	GTCCTTTGTATTCAAGGAGATTACCAAAAGGTAA
	TTACCTTTTGGTAATCTCCTTGAATACAAAGGACGGACATCAG	2201
	TGATTCCGTGAGGGTAGATGTTATATGGTCTGCTTGCTTGATT
	CTTAAATATAATCTGAAAGTATAAGCGAGATCTAA
	ATATAACATCTACCCTC	2202
	GAGGGTAGATGTTATAT	2203
Haemophilia A	TTATACTTTCAGATTATATTTAAGAATCAAGCAAGCAGACCATA	2204
Gly419Arg	TAACATCTACCCTCACGGAATCACTGATGTCCGTCCTTTGTAT
cGGA-AGA	TCAAGGAGATTACCAAAAGGTAAATATTCCCTCG
	CGAGGGAATATTTACCTTTTGGTAATCTCCTTGAATACAAAGG	2205
	ACGGACATCAGTGATTCCGTGAGGGTAGATGTTATATGGTCT
	GCTTGCTTGATTCTTAAATATAATCTGAAAGTATAA
	ACCCTCACGGAATCACT	2206
	AGTGATTCCGTGAGGGT	2207
Haemophilia A	CCAATTCTGCCAGGAGAAATATTCAAATATAAATGGACAGTGA	2208
Thr522Ser	CTGTAGAAGATGGGCCAACTAAATCAGATCCTCGGTGCCTGA
aACT-TCT	CCCGCTATTACTCTAGTTTCGTTAATATGGAGAGAG
	CTCTCTCCATATTAACGAAACTAGAGTAATAGCGGGTCAGGC	2209
	ACCGAGGATCTGATTTAGTTGGCCCATCTTCTACAGTCACTGT
	CCATTTATATTTGAATATTTCTCCTGGCAGAATTGG
	ATGGGCCAACTAAATCA	2210
	TGATTTAGTTGGCCCAT	2211
Haemophilia A	CCAGGAGAAATATTCAAATATAAATGGACAGTGACTGTAGAAG	2212
Asp525Asn	ATGGGCCAACTAAATCAGATCCTCGGTGCCTGACCCGCTATT
aGAT-AAT	ACTCTAGTTTCGTTAATATGGAGAGAGATCTAGCTT
	AAGCTAGATCTCTCTCCATATTAACGAAACTAGAGTAATAGCG	2213
	GGTCAGGCACCGAGGATCTGATTTAGTTGGCCCATCTTCTAC
	AGTCACTGTCCATTTATATTTGAATATTTCTCCTGG
	CTAAATCAGATCCTCGG	2214
	CCGAGGATCTGATTTAG	2215
Haemophilia A	GAAATATTCAAATATAAATGGACAGTGACTGTAGAAGATGGGC	2216
Arg527Trp	CAACTAAATCAGATCCTCGGTGCCTGACCCGCTATTACTCTA
tCGG-TGG	GTTTCGTTAATATGGAGAGAGATCTAGCTTCAGGAC
	GTCCTGAAGCTAGATCTCTCTCCATATTAACGAAACTAGAGTA	2217
	ATAGCGGGTCAGGCACCGAGGATCTGATTTAGTTGGCCCATC
	TTCTACAGTCACTGTCCATTTATATTTGAATATTTC
	CAGATCCTCGGTGCCTG	2218
	CAGGCACCGAGGATCTG	2219
Haemophilia A	TATAAATGGACAGTGACTGTAGAAGATGGGCCAACTAAATCA	2220
Arg531Cys	GATCCTCGGTGCCTGACCCGCTATTACTCTAGTTTCGTTAATA
cCGC-TGC	TGGAGAGAGATCTAGCTTCAGGACTCATTGGCCCTC
	GAGGGCCAATGAGTCCTGAAGCTAGATCTCTCTCCATATTAA	2221
	CGAAACTAGAGTAATAGCGGGTCAGGCACCGAGGATCTGATT
	TAGTTGGCCCATCTTCTACAGTCACTGTCCATTTATA
	GCCTGACCCGCTATTAC	2222
	GTAATAGCGGGTCAGGC	2223
Haemophilia A	TATAAATGGACAGTGACTGTAGAAGATGGGCCAACTAAATCA	2224
Arg531Gly	GATCCTCGGTGCCTGACCCGCTATTACTCTAGTTTCGTTAATA
cCGC-GGC	TGGAGAGAGATCTAGCTTCAGGACTCATTGGCCCTC
	GAGGGCCAATGAGTCCTGAAGCTAGATCTCTCTCCATATTAA	2225
	CGAAACTAGAGTAATAGCGGGTCAGGCACCGAGGATCTGATT
	TAGTTGGCCCATCTTCTACAGTCACTGTCCATTTATA
	GCCTGACCCGCTATTAC	2226
	GTAATAGCGGGTCAGGC	2227
Haemophilia A	ATAAATGGACAGTGACTGTAGAAGATGGGCCAACTAAATCAG	2228
Arg531His	ATCCTCGGTGCCTGACCCGCTATTACTCTAGTTTCGTTAATAT
CGC-CAC	GGAGAGAGATCTAGCTTCAGGACTCATTGGCCCTCT
	AGAGGGCCAATGAGTCCTGAAGCTAGATCTCTCTCCATATTAA	2229
	CGAAACTAGAGTAATAGCGGGTCAGGCACCGAGGATCTGATT
	TAGTTGGCCCATCTTCTACAGTCACTGTCCATTTAT
	CCTGACCCGCTATTACT	2230
	AGTAATAGCGGGTCAGG	2231
Haemophilia A	ACAGTGACTGTAGAAGATGGGCCAACTAAATCAGATCCTCGG	2232
Ser534Pro	TGCCTGACCCGCTATTACTCTAGTTTCGTTAATATGGAGAGAG
cTCT-CCT	ATCTAGCTTCAGGACTCATTGGCCCTCTCCTCATCT
	AGATGAGGAGAGGGCCAATGAGTCCTGAAGCTAGATCTCTCT	2233
	CCATATTAACGAAACTAGAGTAATAGCGGGTCAGGCACCGAG
	GATCTGATTTAGTTGGCCCATCTTCTACAGTCACTGT
	GCTATTACTCTAGTTTC	2234
	GAAACTAGAGTAATAGC	2235
Haemophilia A	GTGACTGTAGAAGATGGGCCAACTAAATCAGATCCTCGGTGC	2236
Ser535Gly	CTGACCCGCTATTACTCTAGTTTCGTTAATATGGAGAGAGATC
tAGT-GGT	TAGCTTCAGGACTCATTGGCCCTCTCCTCATCTGCT
	AGCAGATGAGGAGAGGGCCAATGAGTCCTGAAGCTAGATCTC	2237
	TCTCCATATTAACGAAACTAGAGTAATAGCGGGTCAGGCACC
	GAGGATCTGATTTAGTTGGCCCATCTTCTACAGTCAC
	ATTACTCTAGTTTCGTT	2238
	AACGAAACTAGAGTAAT	2239
Haemophilia A	TAGAAGATGGGCCAACTAAATCAGATCCTCGGTGCCTGACCC	2240
Val537Asp	GCTATTACTCTAGTTTCGTTAATATGGAGAGAGATCTAGCTTC
GTT-GAT	AGGACTCATTGGCCCTCTCCTCATCTGCTACAAAGA
	TCTTTGTAGCAGATGAGGAGAGGGCCAATGAGTCCTGAAGCT	2241
	AGATCTCTCTCCATATTAACGAAACTAGAGTAATAGCGGGTCA
	GGCACCGAGGATCTGATTTAGTTGGCCCATCTTCTA
	TAGTTTCGTTAATATGG	2242
	CCATATTAACGAAACTA	2243
Haemophilia A	CAACTAAATCAGATCCTCGGTGCCTGACCCGCTATTACTCTA	2244
Arg541Thr	GTTTCGTTAATATGGAGAGAGATCTAGCTTCAGGACTCATTGG
AGA-ACA	CCCTCTCCTCATCTGCTACAAAGAATCTGTAGATCA
	TGATCTACAGATTCTTTGTAGCAGATGAGGAGAGGGCCAATG	2245
	AGTCCTGAAGCTAGATCTCTCTCCATATTAACGAAACTAGAGT
	AATAGCGGGTCAGGCACCGAGGATCTGATTTAGTTG
	TATGGAGAGAGATCTAG	2246
	CTAGATCTCTCTCCATA	2247
Haemophilia A	CTAAATCAGATCCTCGGTGCCTGACCCGCTATTACTCTAGTTT	2248
Asp542Gly	CGTTAATATGGAGAGAGATCTAGCTTCAGGACTCATTGGCCC
GAT-GGT	TCTCCTCATCTGCTACAAAGAATCTGTAGATCAAAG
	CTTTGATCTACAGATTCTTTGTAGCAGATGAGGAGAGGGCCA	2249
	ATGAGTCCTGAAGCTAGATCTCTCTCCATATTAACGAAACTAG
	AGTAATAGCGGGTCAGGCACCGAGGATCTGATTTAG
	GGAGAGAGATCTAGCTT	2250
	AAGCTAGATCTCTCTCC	2251
Haemophilia A	ACTAAATCAGATCCTCGGTGCCTGACCCGCTATTACTCTAGTT	2252
AspS42His	TCGTTAATATGGAGAGAGATCTAGCTTCAGGACTCATTGGCC
aGAT-CAT	CTCTCCTCATCTGCTACAAAGAATCTGTAGATCAAA
	TTTGATCTACAGATTCTTTGTAGCAGATGAGGAGAGGGCCAAT	2253
	GAGTCCTGAAGCTAGATCTCTCTCCATATTAACGAAACTAGAG
	TAATAGCGGGTCAGGCACCGAGGATCTGATTTAGT
	TGGAGAGAGATCTAGCT	2254
	AGCTAGATCTCTCTCCA	2255
Haemophilia A	ACTAAATCAGATCCTCGGTGCCTGACCCGCTATTACTCTAGTT	2256
Asp542Tyr	TCGTTAATATGGAGAGAGATCTAGCTTCAGGACTCATTGGCC
aGAT-TAT	CTCTCCTCATCTGCTACAAAGAATCTGTAGATCAAA
	TTTGATCTACAGATTCTTTGTAGCAGATGAGGAGAGGGCCAAT	2257
	GAGTCCTGAAGCTAGATCTCTCTCCATATTAACGAAACTAGAG
	TAATAGCGGGTCAGGCACCGAGGATCTGATTTAGT
	TGGAGAGAGATCTAGCT	2258
	AGCTAGATCTCTCTCCA	2259
Haemophilia A	GTTAATATGGAGAGAGATCTAGCTTCAGGACTCATTGGCCCT	2260
Glu557Term	CTCCTCATCTGCTACAAAGAATCTGTAGATCAAAGAGGAAACC
aGAA-TAA	AGGTGAGTTCTTGCCTTTCCAAGTGCTGGGTTTCAT
	ATGAAACCCAGCACTTGGAAAGGCAAGAACTCACCTGGTTTC	2261
	CTCTTTGATCTACAGATTCTTTGTAGCAGATGAGGAGAGGGC
	CAATGAGTCCTGAAGCTAGATCTCTCTCCATATTAAC
	GCTACAAAGAATCTGTA	2262
	TACAGATTCTTTGTAGC	2263
Haemophilia A	ATATGGAGAGAGATCTAGCTTCAGGACTCATTGGCCCTCTCC	2264
Ser558Phe	TCATCTGCTACAAAGAATCTGTAGATCAAAGAGGAAACCAGGT
TCT-TTT	CAGTTCTTGCCTTTCCAAGTGCTGGGTTTCATTCTC
	GAGAATGAAACCCAGCACTTGGAAAGGCAAGAACTCACCTGG	2265
	TTTCCTCTTTGATCTACAGATTCTTTGTAGCAGATGAGGAGAG
	GGCCAATGAGTCCTGAAGCTAGATCTCTCTCCATAT
	CAAAGAATCTGTAGATC	2266
	GATCTACAGATTCTTTG	2267
Haemophilia A	TGGAGAGAGATCTAGCTTCAGGACTCATTGGCCCTCTCCTCA	2268
Val559Ala	TCTGCTACAAAGAATCTGTAGATCAAAGAGGAAACCAGGTGA
GTA-GCA	GTTCTTGCCTTTCCAAGTGCTGGGTTTCATTCTCAGT
	ACTGAGAATGAAACCCAGCACTTGGAAAGGCAAGAACTCACC	2269
	TGGTTTCCTCTTTGATCTACAGATTCTTTGTAGCAGATGAGGA
	GAGGGCCAATGAGTCCTGAAGCTAGATCTCTCTCCA
	AGAATCTGTAGATCAAA	2270
	TTTGATCTACAGATTCT	2271

EXAMPLE 14

Hemophilia—Factor IX Deficiency

[0135] The attached table discloses the correcting oligonucleotide base sequences for the Factor IX oligonucleotides of the invention.

TABLE 21
Factor IX Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Haemophilia B	ATTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAA	2272
Asn2Asp	TCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTT
tAAT-GAT	CAAGGGAACCTTGAGAGAGAATGTATGGAAGAAA
	TTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTCT	2273
	TCCAATTTACCTGAATTATACCTCTTTGGCCGATTCAGAATTTT
	GTTGGCGTTTTCATGATCAAGAAAAACTGAAAT
	AGAGGTATAATTCAGGT	2274
	ACCTGAATTATACCTCT	2275
Haemophilia B	TTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAAT	2276
Asn2lle	CGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTT
AAT-ATT	CAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAA
	TTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTC	2277
	TTCCAATTTACCTGAATTATACCTCTTTGGCCGATTCAGAATTT
	TGTTGGCGTTTTCATGATCAAGAAAAACTGAAA
	GAGGTATAATTCAGGTA	2278
	TACCTGAATTATACCTC	2279
Haemophilia B	ATTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAA	2280
Asn2Tyr	TCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTT
tAAT-TAT	CAAGGGAACCTTGAGAGAGAATGTATGGAAGAAA
	TTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTCT	2281
	TCCAATTTACCTGAATTATACCTCTTTGGCCGATTCAGAATTTT
	GTTGGCGTTTTCATGATCAAGAAAAACTGAAAT
	AGAGGTATAATTCAGGT	2282
	ACCTGAATTATACCTCT	2283
Haemophilia B	TCAGTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAATC	2284
Ser3Pro	GGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCA
tTCA-CCA	AGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGT
	ACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAAC	2285
	TCTTCCAATTTACCTGAATTATACCTCTTTGGCCGATTCAGAA
	TTTTGTTGGCGTTTTCATGATCAAGAAAAACTGA
	GGTATAATTCAGGTAAA	2286
	TTTACCTGAATTATACC	2287
Haemophilia B	TTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAATCGGCC	2288
Gly4Asp	AAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGG
GGT-GAT	AACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAG
	CTACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAAC	2289
	AAACTCTTCCAATTTACCTGAATTATACCTCTTTGGCCGATTCA
	GAATTTTGTTGGCGTTTTCATGATCAAGAAAAA
	TAATTCAGGTAAATTGG	2290
	CCAATTTACCTGAATTA	2291
Haemophilia B	GTTTTTCTTGATCATGAAAACGCCAACAAAATTCTGAATCGGC	2292
Gly4Ser	CAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGG
aGGT-AGT	GAACCTTGAGAGAGAATGTATGGAAGAAAAGTGTA
	TACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACA	2293
	AACTCTTCCAATTTACCTGAATTATACCTCTTTGGCCGATTCA
	GAATTTTGTTGGCGTTTTCATGATCAAGAAAAAC
	ATAATTCAGGTAAATTG	2294
	CAATTTACCTGAATTAT	2295
Haemophilia B	TTTCTTGATCATGAAAACGCCAACAAAATTCTGAATCGGCCAA	2296
Lys5Glu	AGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAA
tAAA-GAA	CCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTT
	AACTACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGA	2297
	ACAAACTCTTCCAATTTACCTGAATTATACCTCTTTGGCCGATT
	CAGAATTTTGTTGGCGTTTTCATGATCAAGAAA
	ATTCAGGTAAATTGGAA	2298
	TTCCAATTTACCTGAAT	2299
Haemophilia B	ATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTA	2300
Glu7Ala	TAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAG
GAA-GCA	AGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGA
	TCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAGGTT	2301
	CCCTTGAACAAACTCTTCCAATTTACCTGAATTATACCTCTTTG
	GCCGATTCAGAATTTTGTTGGCGTTTTCATGAT
	TAAATTGGAAGAGTTTG	2302
	CAAACTCTTCCAATTTA	2303
Haemophilia B	GATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGG	2304
Glu7Lys	TATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTG
gGAA-AAA	AGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAG
	CTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAGGTTC	2305
	CCTTGAACAAACTCTTCCAATTTACCTGAATTATACCTCTTTGG
	CCGATTCAGAATTTTGTTGGCGTTTTCATGATC
	GTAAATTGGAAGAGTTT	2306
	AAACTCTTCCAATTTAC	2307
Haemophilia B	ATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTA	2308
Glu7Val	TAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAG
GAA-GTA	AGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGA
	TCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAGGTT	2309
	CCCTTGAACAAACTCTTCCAATTTACCTGAATTATACCTCTTTG
	GCCGATTCAGAATTTTGTTGGCGTTTTCATGAT
	TAAATTGGAAGAGTTTG	2310
	CAAACTCTTCCAATTTA	2311
Haemophilia B	ATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTATAA	2312
Glu8Ala	TTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAG
GAG-GCG	AGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGC
	GCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAG	2313
	GTTCCCTTGAACAAACTCTTCCAATTTACCTGAATTATACCTCT
	TTGGCCGATTCAGAATTTTGTTGGCGTTTTCAT
	ATTGGAAGAGTTTGTTC	2314
	GAACAAACTCTTCCAAT	2315
Haemophilia B	ATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTATAA	2316
Glu8Gly	TTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAG
GAG-GGG	AGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGC
	GCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAG	2317
	GTTCCCTTGAACAAACTCTTCCAATTTACCTGAATTATACCTCT
	TTGGCCGATTCAGAATTTTGTTGGCGTTTTCAT
	ATTGGAAGAGTTTGTTC	2318
	GAACAAACTCTTCCAAT	2319
Haemophilia B	AAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTATAATTC	2320
Phe9Cys	AGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGA
TTT-TGT	ATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCACG
	CGTGCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTC	2321
	AAGGTTCCCTTGAACAAACTCTTCCAATTTACCTGAATTATAC
	CTCTTTGGCCGATTCAGAATTTTGTTGGCGTTTT
	GGAAGAGTTTGTTCAAG	2322
	CTTGAACAAACTCTTCC	2323
Haemophilia B	GAAAACGCCAACAAAATTCTGAATCGGCCAAAGAGGTATAATT	2324
Phe9lle	CAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAG
gTTT-ATT	AATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCAC
	GTGCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCA	2325
	AGGTTCCCTTGAACAAACTCTTCCAATTTACCTGAATTATACC
	TCTTTGGCCGATTCAGAATTTTGTTGGCGTTTTC
	TGGAAGAGTTTGTTCAA	2326
	TTGAACAAACTCTTCCA	2327
Haemophilia B	TTACATTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAATTC	2328
Arg(-1)Ser	TGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTT
AGGt-AGC	TGTTCAAGGGAACCTTGAGAGAGAATGTATGGAA
	TTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTCTTCC	2329
	AATTTACCTGAATTATACCTCTTTGGCCGATTCAGAATTTTGTT
	GGCGTTTTCATGATCAAGAAAAACTGAAATGTAA
	CCAAAGAGGTATAATTC	2330
	GAATTATACCTCTTTGG	2331
Haemophilia B	TTTACATTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAATT	2332
Arg(-1)Thr	CTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAG
AGG-ACG	TTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGA
	TCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCA	2333
	ATTTACCTGAATTATACCTCTTTGGCCGATTCAGAATTTTGTTG
	GCGTTTTCATGATCAAGAAAAACTGAAATGTAAA
	GCCAAAGAGGTATAATT	2334
	AATTATACCTCTTTGGC	2335
Haemophilia B	CTTTTACATTTCAGTTTTTCTTGATCATGAAAACGCCAACAAAA	2336
Lys(-2)Asn	TTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGA
AAGa-AAT	GTTTGTTCAAGGGAACCTTGAGAGAGAATGTATG
	CATACATTCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAAT	2337
	TTACCTGAATTATACCTCTTTGGCCGATTCAGAATTTTGTTGG
	CGTTTTCATGATCAAGAAAAACTGAAATGTAAAAG
	CGGCCAAAGAGGTATAA	2338
	TTATACCTCTTTGGCCG	2339
Haemophilia B	AATTATTCTTTTACATTTCAGTTTTTCTTGATCATGAAAACGCC	2340
Arg(-4)Gln	AACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAAT
CGG-CAG	TGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGA
	TCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCTG	2341
	AATTATACCTCTTTGGCCGATTCAGAATTTTGTTGGCGTTTTCA
	TGATCAAGAAAAACTGAAATGTAAAAGAATAATT
	TCTGAATCGGCCAAAGA	2342
	TCTTTGGCCGATTCAGA	2343
Haemophilia B	AATTATTCTTTTACATTTCAGTTTTTCTTGATCATGAAAACGCC	2344
Arg (-4) Leu	AACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAAT
CGG-CTG	TGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGA
	TCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCTG	2345
	AATTATACCTCTTTGGCCGATTCAGAATTTTGTTGGCGTTTTCA
	TGATCAAGAAAAACTGAAATGTAAAAGAATAATT
	TCTGAATCGGCCAAAGA	2346
	TCTTTGGCCGATTCAGA	2347
Haemophilia B	GAATTATTCTTTTACATTTCAGTTTTTCTTGATCATGAAAACGC	2348
Arg(-4)Trp	CAACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAA
tCGG-TGG	TTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAG
	CTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCTGA	2349
	ATTATACCTCTTTGGCCGATTCAGAATTTTGTTGGCGTTTTCAT
	GATCAAGAAAAACTGAAATGTAAAAGAATAATTC
	TTCTGAATCGGCCAAAG	2350
	CTTTGGCCGATTCAGAA	2351
Haemophilia B	GCCAACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTA	2352
Gln11Term	AATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTAT
tCAA-TAA	GGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAG
	CTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACATTCT	2353
	CTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCTGAAT
	TATACCTCTTTGGCCGATTCAGAATTTTGTTGGC
	AGTTTGTTCAAGGGAAC	2354
	GTTCCCTTGAACAAACT	2355
Haemophilia B	ACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATT	2356
Gly12Ala	GGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGA
GGG-GCG	AGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTT
	AAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACA	2357
	TTCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCT
	GAATTATACCTCTTTGGCCGATTCAGAATTTTGT
	TGTTCAAGGGAACCTTG	2358
	CAAGGTTCCCTTGAACA	2359
Haemophilia B	AACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAAT	2360
Gly12Arg	TGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGG
aGGG-AGG	AAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTT
	AAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACAT	2361
	TCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCTG
	AATTATACCTCTTTGGCCGATTCAGAATTTTGTT
	TTGTTCAAGGGAACCTT	2362
	AAGGTTCCCTTGAACAA	2363
Haemophilia B	ACAAAATTCTGAATCGGCCAAAGAGGTATAATTCAGGTAAATT	2364
Gly12Glu	GGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGA
GGG-GAG	AGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTT
	AAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACA	2365
	TTCTCTCTCAAGGTTCCCTTGAACAAACTCTTCCAATTTACCT
	GAATTATACCTCTTTGGCCGATTCAGAATTTTGT
	TGTTCAAGGGAACCTTG	2366
	CAAGGTTCCCTTGAACA	2367
Haemophilia B	CGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTC	2368
Glu17Gln	AAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTT
aGAA-CAA	TTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAA
	TTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACAC	2369
	TTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTC
	TTCCAATTTACCTGAATTATACCTCTTTGGCCG
	TTGAGAGAGAATGTATG	2370
	CATACATTCTCTCTCAA	2371
Haemophilia B	CGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTC	2372
Glu17Lys	AAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTT
aGAA-AAA	TTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAA
	TTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACAC	2373
	TTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAAACTC
	TTCCAATTTACCTGAATTATACCTCTTTGGCCG
	TTGAGAGAGAATGTATG	2374
	CATACATTCTCTCTCAA	2375
Haemophilia B	CCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAG	2376
Cys18Arg	GGAACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTG
aTGT-CGT	AAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAA
	TTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTA	2377
	CACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAA
	ACTCTTCCAATTTACCTGAATTATACCTCTTTGG
	AGAGAGAATGTATGGAA	2378
	TTCCATACATTCTCTCT	2379
Haemophilia B	CAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGG	2380
Cys18Tyr	GAACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAA
TGT-TAT	GAAGCACGAGAAGTTTTTGAAAACACTGAAAGAAC
	GTTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACT	2381
	ACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTTGAACAA
	ACTCTTCCAATTTACCTGAATTATACCTCTTTG
	GAGAGAATGTATGGAAG	2382
	CTTCCATACATTCTCTC	2383
Haemophilia B	GGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCT	2384
Glu20Val	TGAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGC
GAA-GTA	ACGAGAAGTTTTTGAAAACACTGAAAGAACAGTGAG
	CTCACTGTTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTC	2385
	AAAACTACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCCTT
	GAACAAACTCTTCCAATTTACCTGAATTATACC
	ATGTATGGAAGAAAAGT	2386
	ACTTTTCTTCCATACAT	2387
Haemophilia B	TATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTG	2388
Glu21Lys	AGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCAC
aGAA-AAA	GAGAAGTTTTTGAAAACACTGAAAGAACAGTGAGTA
	TACTCACTGTTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCT	2389
	TCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAGGTTCCC
	TTGAACAAACTCTTCCAATTTACCTGAATTATA
	GTATGGAAGAAAAGTGT	2390
	ACACTTTTCTTCCATAC	2391
Haemophilia B	TCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGA	2392
Cys23Arg	GAATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAA
gTGT-CGT	GTTTTTGAAAACACTGAAAGAACAGTGAGTATTTCCA
	TGGAAATACTCACTGTTCTTTCAGTGTTTTCAAAAACTTCTCGT	2393
	GCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCAAG
	GTTCCCTTGAACAAACTCTTCCAATTTACCTGA
	AAGAAAAGTGTAGTTTT	2394
	AAAACTACACTTTTCTT	2395
Haemophilia B	CAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAG	2396
Cys23Tyr	AATGTATGGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGT
TGT-TAT	TTTTGAAAACACTGAAAGAACAGTGAGTATTTCCAC
	GTGGAAATACTCACTGTTCTTTCAGTGTTTTCAAAAACTTCTC	2397
	GTGCTTCTTCAAAACTACACTTTTCTTCCATACATTCTCTCTCA
	AGGTTCCCTTGAACAAACTCTTCCAATTTACCTG
	AGAAAAGTGTAGTTTTG	2398
	CAAAACTACACTTTTCT	2399
Haemophilia B	AATTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTAT	2400
Phe25Ser	GGAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAA
TTT-TCT	AACACTGAAAGAACAGTGAGTATTTCCACATAATA
	TATTATGTGGAAATACTCACTGTTCTTTCAGTGTTTTCAAAAAC	2401
	TTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACATTCTC
	TCTCAAGGTTCCCTTGAACAAACTCTTCCAATT
	GTGTAGTTTTGAAGAAG	2402
	CTTCTTCAAAACTACAC	2403
Haemophilia B	TTGGAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATG	2404
Glu26Gln	GAAGAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAA
tGAA-CAA	ACACTGAAAGAACAGTGAGTATTTCCACATAATACC
	GGTATTATGTGGAAATACTCACTGTTCTTTCAGTGTTTTCAAAA	2405
	ACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATACATTC
	TCTCTCAAGGTTCCCTTGAACAAACTCTTCCAA
	GTAGTTTTGAAGAAGCA	2406
	TGCTTCTTCAAAACTAC	2407
Haemophilia B	AAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAAG	2408
Glu27Ala	AAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACAC
GAA-GCA	TGAAAGAACAGTGAGTATTTCCACATAATACCCTTC
	GAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAGTGTTTT	2409
	CAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATA
	CATTCTCTCTCAAGGTTCCCTTGAACAAACTCTT
	TTTTGAAGAAGCACGAG	2410
	CTCGTGCTTCTTCAAAA	2411
Haemophilia B	AGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGA	2412
Glu27Asp	AAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACT
GAAg-GAC	GAAAGAACAGTGAGTATTTCCACATAATACCCTTCA
	TGAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAGTGTTT	2413
	TCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCAT
	ACATTCTCTCTCAAGGTTCCCTTGAACAAACTCT
	TTTGAAGAAGCACGAGA	2414
	TCTCGTGCTTCTTCAAA	2415
Haemophilia B	GAAGAGTTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAA	2416
Glu27Lys	GAAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACA
aGAA-AAA	CTGAAAGAACAGTGAGTATTTCCACATAATACCCTT
	AAGGGTATTATGTGGAAATACTCACTGTTCTTTCAGTGTTTTC	2417
	AAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATAC
	ATTCTCTCTCAAGGTTCCCTTGAACAAACTCTTC
	GTTTTGAAGAAGCACGA	2418
	TCGTGCTTCTTCAAAAC	2419
Haemophilia B	AAGAGTTTGTTCAAGGGAACTTGAGAGAGAATGTATGGAAG	2420
Glu27Val	AAAAGTGTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACAC
GAA-GTA	TGAAAGAACAGTGAGTATTTCCACATAATACCCTTC
	GAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAGTGTTTT	2421
	CAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTTCCATA
	CATTCTCTCTCAAGGTTCCCTTGAACAAACTCTT
	TTTTGAAGAAGCACGAG	2422
	CTCGTGCTTCTTCAAAA	J 2423
Haemophilia B	TTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGT	2424
Arg29Gln	GTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAG
CGA-CAA	AACAGTGAGTATTTCCACATAATACCCTTCAGATGC
	GCATCTGAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAG	2425
	TGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCT
	TCCATACATTCTCTCTCAAGGTTCCCTTGAACAA
	AGAAGCACGAGAAGTTT	2426
	AAACTTCTCGTGCTTCT	2427
Haemophilia B	TTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGT	2428
Arg29Pro	GTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAG
CGA-CCA	AACAGTGAGTATTTCCACATAATACCCTTCAGATGC
	GCATCTGAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAG	2429
	TGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCT
	TCCATACATTCTCTCTCAAGGTTCCCTTGAACAA
	AGAAGCACGAGAAGTTT	2430
	AAACTTCTCGTGCTTCT	2431
Haemophilia B	TTTGTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGT	2432
Arg29Term	GTAGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAG
aCGA-TGA	AACAGTGAGTATTTCCACATAATACCCTTCAGATG
	CATCTGAAGGGTATTATGTGGAAATACTCACTGTTCTTTCAGT	2433
	GTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTTCTT
	CCATACATTCTCTCTCAAGGTTCCCTTGAACAAA
	AAGAAGCACGAGAAGTT	2434
	AACTTCTCGTGCTTCTT	2435
Haemophilia B	GTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGTGT	2436
Glu30Lys	AGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAA
aGAA-AAA	CAGTGAGTATTTCCACATAATACCCTTCAGATGCAG
	CTGCATCTGAAGGGTATTATGTGGAAATACTCACTGTTCTTTC	2437
	AGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTT
	CTTCCATACATTCTCTCTCAAGGTTCCCTTGAAC
	AAGCACGAGAAGTTTTT	2438
	AAAAACTTCTCGTGCTT	2439
Haemophilia B	GTTCAAGGGAACCTTGAGAGAGAATGTATGGAAGAAAAGTGT	2440
Glu30Term	AGTTTTGAAGAAGCACGAGAAGTTTTTGAAAACACTGAAAGAA
aGAA-TAA	CAGTGAGTATTTCCACATAATACCCTTCAGATGCAG
	CTGCATCTGAAGGGTATTATGTGGAAATACTCACTGTTCTTTC	2441
	AGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAACTACACTTTT
	CTTCCATACATTCTCTCTCAAGGTTCCCTTGAAC
	AAGCACGAGAAGTTTTT	2442
	AAAAACTTCTCGTGCTT	2443
Haemophilia B	CCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAA	2444
Glu33Asp	GCACGAGAAGTTTTTGAAAACACTGAAAGAACAGTGAGTATTT
GAAa-GAC	CCACATAATACCCTTCAGATGCAGAGCATAGAATA
	TATTCTATGCTCTGCATCTGAAGGGTATTATGTGGAAATACTC	2445
	ACTGTTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAA
	ACTACACTTTTCTTCCATACATTCTCTCTCAAGG
	GTTTTTGAAAACACTGA	2446
	TCAGTGTTTTCAAAAAC	2447
Haemophilia B	AACCTTGAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAG	2448
Glu33Term	AAGCACGAGAAGTTTTTGAAAACACTGAAAGAACAGTGAGTAT
tGAA-TAA	TTCCACATAATACCCTTCAGATGCAGAGCATAGAA
	TTCTATGCTCTGCATCTGAAGGGTATTATGTGGAAATACTCAC	2449
	TGTTCTTTCAGTGTTTTCAAAAACTTCTCGTGCTTCTTCAAAAC
	TACACTTTTCTTCCATACATTCTCTCTCAAGGTT
	AAGTTTTTGAAAACACT	2450
	AGTGTTTTCAAAAACTT	2451
Haemophilia B	CAAAACACTTTAGATATTACCGTTAATTTGTCTTCTTTTATTCTT	2452
Trp42Term	TATAGACTGAATTTTGGAAGCAGTATGTTGGTAAGCAATTCAT
TGG-TAG	TTTATCCTCTAGCTAATATATGAAACATATGAG
	CTCATATGTTTCATATATTAGCTAGAGGATAAAATGAATTGCTT	2453
	ACCAACATACTGCTTCCAAAATTCAGTCTATAAAGAATAAAAG
	AAGACAAATTAACGGTAATATCTAAAGTGTTTTG
	TGAATTTTGGAAGCAGT	2454
	ACTGCTTCCAAAATTCA	2455
Haemophilia B	AAACACTTTAGATATTACCGTTAATTTGTCTTCTTTTATTCTTTA	2456
Lys43Glu	TAGACTGAATTTTGGAAGCAGTATGTTGGTAAGCAATTCATTT
gAAG-GAG	TATCCTCTAGCTAATATATGAAACATATGAGAA
	TTCTCATATGTTTCATATATTAGCTAGAGGATAAAATGAATTGC	2457
	TTACCAACATACTGCTTCCAAAATTCAGTCTATAAAGAATAAAA
	GAAGACAAATTAACGGTAATATCTAAAGTGTTT
	AATTTTGGAAGCAGTAT	2458
	ATACTGCTTCCAAAATT	2459
Haemophilia B	CACTTTAGATATTACCGTTAATTTGTCTTCTTTTATTCTTTATAG	2460
Gln44Term	ACTGAATTTTGGAAGCAGTATGTTGGTAAGCAATTCATTTTATC
gCAG-TAG	CTCTAGCTAATATATGAAACATATGAGAATTA
	TAATTCTCATATGTTTCATATATTAGCTAGAGGATAAAATGAAT	2461
	TGCTTACCAACATACTGCTTCCAAAATTCAGTCTATAAAGAATA
	AAAGAAGACAAATTAACGGTAATATCTAAAGTG
	TTTGGAAGCAGTATGTT	2462
	AACATACTGCTTCCAAA	2463
Haemophilia B	CCGGGCATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAAC	2464
Asp49Gly	CTATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTA
GAT-GGT	AATGGCGGCAGTTGCAAGGATGACATTAATTCCTA
	TAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAACATG	2465
	GATTGGACTCACACTGATCTCCATCTTTGAGATAGGTTAAGAA
	ATTGAATTGGCACGTAAACTGCTTAGAATGCCCGG
	AGATGGAGATCAGTGTG	2466
	CACACTGATCTCCATCT	2467
Haemophilia B	GCATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTATC	2468
Gln50His	TCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGG
CAGt-CAC	CGGCAGTTGCAAGGATGACATTAATTCCTATGAA
	TTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAA	2469
	CATGGATTGGACTCACACTGATCTCCATCTTTGAGATAGGTTA
	AGAAATTGAATTGGCACGTAAACTGCTTAGAATGC
	GGAGATCAGTGTGAGTC	2470
	GACTCACACTGATCTCC	2471
Haemophilia B	GGCATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTA	2472
Gln50Pro	TCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAAT
CAG-CCG	GGCGGCAGTTGCAAGGATGACATTAATTCCTATGA
	TCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAAC	2473
	ATGGATTGGACTCACACTGATCTCCATCTTTGAGATAGGTTAA
	GAAATTGAATTGGCACGTAAACTGCTTAGAATGCC
	TGGAGATCAGTGTGAGT	2474
	ACTCACACTGATCTCCA	2475
Haemophilia B	GGGCATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCT	2476
Gln50Term	ATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAA
tCAG-TAG	TGGCGGCAGTTGCAAGGATGACATTAATTCCTATG
	CATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAACA	2477
	TGGATTGGACTCACACTGATCTCCATCTTTGAGATAGGTTAAG
	AAATTGAATTGGCACGTAAACTGCTTAGAATGCCC
	ATGGAGATCAGTGTGAG	2478
	CTCACACTGATCTCCAT	2479
Haemophilia B	CATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTATCT	2480
Cys51Arg	CAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGG
gTGT-CGT	CGGCAGTTGCAAGGATGACATTAATTCCTATGAAT
	ATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAA	2481
	ACATGGATTGGACTCACACTGATCTCCATCTTTGAGATAGGTT
	AAGAAATTGAATTGGCACGTAAACTGCTTAGAATG
	GAGATCAGTGTGAGTCC	2482
	GGACTCACACTGATCTC	2483
Haemophilia B	CATTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTATCT	2484
Cys51Ser	CAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGG
gTGT-AGT	CGGCAGTTGCAAGGATGACATTAATTCCTATGAAT
	ATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAA	2485
	ACATGGATTGGACTCACACTGATCTCCATCTTTGAGATAGGTT
	AAGAAATTGAATTGGCACGTAAACTGCTTAGAATG
	GAGATCAGTGTGAGTCC	2486
	GGACTCACACTGATCTC	2487
Haemophilia B	TTCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTATCTCA	2488
Cys51Trp	AAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCG
TGTg-TGG	GCAGTTGCAAGGATGACATTAATTCCTATGAATGT
	ACATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTT	2489
	AAACATGGATTGGACTCACACTGATCTCCATCTTTGAGATAGG
	TTAAGAAATTGAATTGGCACGTAAACTGCTTAGAA
	GATCAGTGTGAGTCCAA	2490
	TTGGACTCACACTGATC	2491
Haemophilia B	TCTAAGCAGTTTACGTGCCAATTCAATTTCTTAACCTATCTCAA	2492
Glu52Term	AGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGG
tGAG-TAG	CAGTTGCAAGGATGACATTAATTCCTATGAATGTT
	AACATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATT	2493
	TAAACATGGATTGGACTCACACTGATCTCCATCTTTGAGATAG
	GTTAAGAAATTGAATTGGCACGTAAACTGCTTAGA
	ATCAGTGTGAGTCCAAT	2494
	ATTGGACTCACACTGAT	2495
Haemophilia B	TTTACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAG	2496
Pro55Ala	ATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCA
tCCA-GCA	AGGATGACATTAATTCCTATGAATGTTGGTGTCCCT
	AGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAACT	2497
	GCCGCCATTTAAACATGGATTGGACTCACACTGATCTCCATCT
	TTGAGATAGGTTAAGAAATTGAATTGGCACGTAAA
	AGTCCAATCCATGTTTA	2498
	TAAACATGGATTGGACT	2499
Haemophilia B	TTACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGA	2500
Pro55Arg	TCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAA
CCA-CGA	GGATGACATTAATTCCTATGAATGTTGGTGTCCCTT
	AAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAAC	2501
	TGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCCATC
	TTTGAGATAGGTTAAGAAATTGAATTGGCACGTAA
	GTCCAATCCATGTTTAA	2502
	TTAAACATGGATTGGAC	2503
Haemophilia B	TTACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGA	2504
Pro55Gln	TCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAA
CCA-CAA	GGATGACATTAATTCCTATGAATGTTGGTGTCCCTT
	AAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAAC	2505
	TGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCCATC
	TTTGAGATAGGTTAAGAAATTGAATTGGCACGTAA
	GTCCAATCCATGTTTAA	2506
	TTAAACATGGATTGGAC	2507
Haemophilia B	TTACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGA	2508
Pro55Leu	TCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAA
CCA-CTA	GGATGACATTAATTCCTATGAATGTTGGTGTCCCTT
	AAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAAC	2509
	TGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCCATC
	TTTGAGATAGGTTAAGAAATTGAATTGGCACGTAA
	GTCCAATCCATGTTTAA	2510
	TTAAACATGGATTGGAC	2511
Haemophilia B	TTTACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAG	2512
Pro55Ser	ATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCA
tCCA-TCA	AGGATGACATTAATTCCTATGAATGTTGGTGTCCCT
	AGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAACT	2513
	GCCGCCATTTAAACATGGATTGGACTCACACTGATCTCCATCT
	TTGAGATAGGTTAAGAAATTGAATTGGCACGTAAA
	AGTCCAATCCATGTTTA	2514
	TAAACATGGATTGGACT	2515
Haemophilia B	ACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGATC	2516
Cys56Arg	AGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGG
aTGT-CGT	ATGACATTAATTCCTATGAATGTTGGTGTCCCTTTG
	CAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCA	2517
	ACTGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCC
	ATCTTTGAGATAGGTTAAGAAATTGAATTGGCACGT
	CCAATCCATGTTTAAAT	2518
	ATTTAAACATGGATTGG	2519
Haemophilia B	ACGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGATC	2520
Cys56Ser	AGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGG
aTGT-AGT	ATGACATTAATTCCTATGAATGTTGGTGTCCCTTTG
	CAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGCA	2521
	ACTGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCC
	ATCTTTGAGATAGGTTAAGAAATTGAATTGGCACGT
	CCAATCCATGTTTAAAT	2522
	ATTTAAACATGGATTGG	2523
Haemophilia B	CGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGATCA	2524
Cys56Ser	GTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGA
TGT-TCT	TGACATTAATTCCTATGAATGTTGGTGTCCCTTTGG
	CCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGC	2525
	AACTGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCC
	ATCTTTGAGATAGGTTAAGAAATTGAATTGGCACG
	CAATCCATGTTTAAATG	2526
	CATTTAAACATGGATTG	2527
Haemophilia B	CGTGCCAATTCAATTTCTTAACCTATCTCAAAGATGGAGATCA	2528
Cys56Tyr	GTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGA
TGT-TAT	TGACATTAATTCCTATGAATGTTGGTGTCCCTTTGG
	CCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGC	2529
	AACTGCCGCCATTTAAACATGGATTGGACTCACACTGATCTCC
	ATCTTTGAGATAGGTTAAGAAATTGAATTGGCACG
	CAATCCATGTTTAAATG	2530
	CATTTAAACATGGATTG	2531
Haemophilia B	ATTCAATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAG	2532
Asn58Lys	TCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTA
AATg-AAG	ATTCCTATGAATGTTGGTGTCCCTTGGATTTGAA
	TTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTCA	2533
	TCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCACACT
	GATCTCCATCTTTGAGATAGGTTAAGAAATTGAAT
	TGTTTAAATGGCGGCAG	2534
	CTGCCGCCATTTAAACA	2535
Haemophilia B	TCAATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTC	2536
Gly59Asp	CAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAAT
GGC-GAC	TCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGG
	CCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGT	2537
	CATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCACA
	CTGATCTCCATCTTTGAGATAGGTTAAGAAATTGA
	TTTAAATGGCGGCAGTT	2538
	AACTGCCGCCATTTAAA	2539
Haemophilia B	TCAATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTC	2540
Gly59Val	CAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAAT
GGC-GTC	TCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGG
	CCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGT	2541
	CATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCACA
	CTGATCTCCATCTTTGAGATAGGTTAAGAAATTGA
	TTTAAATGGCGGCAGTT	2542
	AACTGCCGCCATTTAAA	2543
Haemophilia B	TTCAATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGT	2544
Gly59Ser	CCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAA
tGGC-AGC	TTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAG
	CTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTC	2545
	ATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCACAC
	TGATCTCCATCTTTGAGATAGGTTAAGAAATTGAA
	GTTTAAATGGCGGCAGT	2546
	ACTGCCGCCATTTAAAC	2547
Haemophilia B	AATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCA	2548
Gly60Ser	ATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTC
cGGC-AGC	CTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAA
	TTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAAT	2549
	GTCATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCA
	CACTGATCTCCATCTTTGAGATAGGTTAAGAAATT
	TAAATGGCGGCAGTTGC	2550
	GCAACTGCCGCCATTTA	2551
Haemophilia B	AATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCA	2552
Gly60Cys	ATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTC
cGGC-TGC	CTATGAATGTTGGTGTCCCTTTGGATTGAAGGAA
	TTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAAT	2553
	GTCATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCA
	CACTGATCTCCATCTTTGAGATAGGTTAAGAAATT
	TAAATGGCGGCAGTTGC	2554
	GCAACTGCCGCCATTTA	2555
Haemophilia B	ATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCAA	2556
Gly60Asp	TCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCC
GGC-GAC	TATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAA
	TTTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAA	2557
	TGTCATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTC
	ACACTGATCTCCATCTTTGAGATAGGTTAAGAAAT
	AAATGGCGGCAGTTGCA	2558
	TGCAACTGCCGCCATTT	2559
Haemophilia B	AATTTCTTAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCA	2560
Gly60Arg	ATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTC
cGGC-CGC	CTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAA
	TTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAAT	2561
	GTCATCCTTGCAACTGCCGCCATTTAAACATGGATTGGACTCA
	CACTGATCTCCATCTTTGAGATAGGTTAAGAAATT
	TAAATGGCGGCAGTTGC	2562
	GCAACTGCCGCCATTTA	2563
Haemophilia B	TAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATG	2564
Cys62Tyr	TTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAA
TGC-TAC	TGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTG
	CAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAGG	2565
	AATTAATGTCATCCTTGCAACTGCCGCCATTTAAACATGGATT
	GGACTCACACTGATCTCCATCTTTGAGATAGGTTA
	CGGCAGTTGCAAGGATG	2566
	CATCCTTGCAACTGCCG	2567
Haemophilia B	TAACCTATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATG	2568
Cys62Ser	TTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAA
TGC-TCC	TGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTG
	CAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAGG	2569
	AATTAATGTCATCCTTGCAACTGCCGCCATTTAAACATGGATT
	GGACTCACACTGATCTCCATCTTTGAGATAGGTTA
	CGGCAGTTGCAAGGATG	2570
	CATCCTTGCAACTGCCG	2571
Haemophilia B	AACCTATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGT	2572
Cys62Term	TTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAAT
TGCa-TGA	GTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGT
	ACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAG	2573
	GAATTAATGTCATCCTTGCAACTGCCGCCATTTAAACATGGAT
	TGGACTCACACTGATCTCCATCTTTGAGATAGGTT
	GGCAGTTGCAAGGATGA	2574
	TCATCCTTGCAACTGCC	2575
Haemophilia B	TCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAAT	2576
Asp64Glu	GGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGG
GATg-GAG	TGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTA
	TAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACAT	2577
	TCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAAC
	ATGGATTGGACTCACACTGATCTCCATCTTTGAGA
	TGCAAGGATGACATTAA	2578
	TTAATGTCATCCTTGCA	2579
Haemophilia B	ATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAA	2580
Asp64Gly	TGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTG
GAT-GGT	GTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT
	AATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATT	2581
	CATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAACA
	TGGATTGGACTCACACTGATCTCCATCTTTGAGAT
	TTGCAAGGATGACATTA	2582
	TAATGTCATCCTTGCAA	2583
Haemophilia B	TATCTCAAAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAA	2584
Asp64Asn	ATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTG
gGAT-AAT	GTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAAT
	ATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTC	2585
	ATAGGAATTAATGTCATCCTTGCAACTGCCGCCATTTAAACAT
	GGATTGGACTCACACTGATCTCCATCTTTGAGATA
	GTTGCAAGGATGACATT	2586
	AATGTCATCCTTGCAAC	2587
Haemophilia B	AAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCG	2588
lle66Ser	GCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCC
ATT-AGT	CTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAA
	TTACCTAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACC	2589
	AACATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATT
	TAAACATGGATTGGACTCACACTGATCTCCATCTT
	GGATGACATTAATTCCT	2590
	AGGAATTAATGTCATCC	2591
Haemophilia B	AAGATGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCG	2592
lle66Thr	GCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCC
ATT-ACT	CTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAA
	TTACCTAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACC	2593
	AACATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCCATT
	TAAACATGGATTGGACTCACACTGATCTCCATCTT
	GGATGACATTAATTCCT	2594
	AGGAATTAATGTCATCC	2595
Haemophilia B	TGGAGATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAG	2596
Asn67Lys	TTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCCCTTT
AATt-AAA	GGATTTGAAGGAAAGAACTGTGAATTAGGTAAGTAA
	TTACTTACCTAATTCACAGTTCTTTCCTTCAAATCCAAAGGGAC	2597
	ACCAACATTCATAGGAATTAATGTCATCCTTGCAACTGCCGCC
	ATTTAAACATGGATTGGACTCACACTGATCTCCA
	GACATTAATTCCTATGA	2598
	TCATAGGAATTAATGTC	2599
Haemophilia B	ATCAGTGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCA	2600
Tyr69Cys	AGGATGACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATT
TAT-TGT	TGAAGGAAAGAACTGTGAATTAGGTAAGTAACTATT
	AATAGTTACTTACCTAATTCACAGTTCTTTCCTTCAAATCCAAA	2601
	GGGACACCAACATTCATAGGAATTAATGTCATCCTTGCAACTG
	CCGCCATTTAAACATGGATTGGACTCACACTGAT
	TAATTCCTATGAATGTT	2602
	AACATTCATAGGAATTA	2603
Haemophilia B	TGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGA	2604
Cys71Term	CATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGA
TGTt-TGA	AAGAACTGTGAATTAGGTAAGTAACTATTTTTTGAA
	TTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTTCAA	2605
	ATCCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTT
	GCAACTGCCGCCATTTAAACATGGATTGGACTCA
	TATGAATGTTGGTGTCC	2606
	GGACACCAACATTCATA	2607
Haemophilia B	GTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATG	2608
Cys71Ser	ACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGG
TGT-TCT	AAAGAACTGTGAATTAGGTAAGTAACTATTTTTTGA
	TCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTTCAAA	2609
	TCCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTG
	CAACTGCCGCCATTTAAACATGGATTGGACTCAC
	CTATGAATGTTGGTGTC	2610
	GACACCAACATTCATAG	2611
Haemophilia B	GTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATG	2612
Cys71Tyr	ACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGG
TGT-TAT	AAAGAACTGTGAATTAGGTAAGTAACTATTTTTTGA
	TCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTTCAAA	2613
	TCCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTG
	CAACTGCCGCCATTTAAACATGGATTGGACTCAC
	CTATGAATGTTGGTGTC	2614
	GACACCAACATTCATAG	2615
Haemophilia B	TGTGAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGAT	2616
Cys71Ser	GACATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAG
aTGT-AGT	GAAAGAACTGTGAATTAGGTAAGTAACTATTTTTTG
	CAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTTCAAAT	2617
	CCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCTTGC
	AACTGCCGCCATTTAAACATGGATTGGACTCACA
	CCTATGAATGTTGGTGT	2618
	ACACCAACATTCATAGG	2619
Haemophilia B	GAGTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGAC	2620
Trp72Arg	ATTAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAA
tTGG-AGG	AGAACTGTGAATTAGGTAAGTAACTATTTTTTGAAT
	ATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTTCA	2621
	AATCCAAAGGGACACCAACATTCATAGGAATTAATGTCATCCT
	TGCAACTGCCGCCATTTAAACATGGATTGGACTC
	ATGAATGTTGGTGTCCC	2622
	GGGACACCAACATTCAT	2623
Haemophilia B	GTCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACAT	2624
Trp72Term	TAATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAG
TGGt-TGA	AACTGTGAATTAGGTAAGTAACTATTTTTTGAATAC
	GTATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCTT	2625
	CAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTCATC
	CTTGCAACTGCCGCCATTTAAACATGGATTGGAC
	GAATGTTGGTGTCCCTT	2626
	AAGGGACACCAACATTC	2627
Haemophilia B	CCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAA	2628
Cys73Tyr	TTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAAC
TGT-TAT	TGTGAATTAGGTAAGTAACTATTTTTTGAATACTC
	GAGTATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCC	2629
	TTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTCA
	TCCTTGCAACTGCCGCCATTTAAACATGGATTGG
	ATGTTGGTGTCCCTTTG	2630
	CAAAGGGACACCAACAT	2631
Haemophilia B	TCCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTA	2632
Cys73Arg	ATTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAA
gTGT-CGT	CTGTGAATTAGGTAAGTAACTATTTTTTGAATACT
	AGTATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCCT	2633
	TCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTCAT
	CCTTGCAACTGCCGCCATTTAAACATGGATTGGA
	AATGTTGGTGTCCCTTT	2634
	AAAGGGACACCAACATT	2635
Haemophilia B	CCAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAA	2636
Cys73Phe	TTCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAAC
TGT-TTT	TGTGAATTAGGTAAGTAACTATTTTTTGAATACTC
	GAGTATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTCC	2637
	TTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTCA
	TCCTTGCAACTGCCGCCATTTAAACATGGATTGG
	ATGTTGGTGTCCCTTTG	2638
	CAAAGGGACACCAACAT	2639
Haemophilia B	CAATCCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAAT	2640
Cys73Term	TCCTATGAATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACT
TGTc-TGA	GTGAATTAGGTAAGTAACTATTTTTTGAATACTCA
	TGAGTATTCAAAAAATAGTTACTTACCTAATTCACAGTTCTTTC	2641
	CTTCAAATCCAAAGGGACACCAACATTCATAGGAATTAATGTC
	ATCCTTGCAACTGCCGCCATTTAAACATGGATTG
	TGTTGGTGTCCCTTTGG	2642
	CCAAAGGGACACCAACA	2643
Haemophilia B	GTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGA	2644
Gly76Val	ATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTA
GGA-GTA	GGTAAGTAACTATTTTTTGAATACTCATGGTTCAA
	TTGAACCATGAGTATTCAAAAAATAGTTACTTACCTAATTCACA	2645
	GTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAA
	TTAATGTCATCCTTGCAACTGCCGCCATTTAAAC
	TCCCTTTGGATTTGAAG	2646
	CTTCAAATCCAAAGGGA	2647
Haemophilia B	TGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATG	2648
Gly76Arg	AATGTTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATT
tGGA-AGA	AGGTAAGTAACTATTTTTTGAATACTCATGGTTCA
	TGAACCATGAGTATTCAAAAAATAGTTACTTACCTAATTCACAG	2649
	TTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAGGAAT
	TAATGTCATCCTTGCAACTGCCGCCATTTAAACA
	GTCCCTTTGGATTTGAA	2650
	TTCAAATCCAAAGGGAC	2651
Haemophilia B	TAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATG	2652
Phe77Cys	TTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGT
TTT-TGT	AAGTAACTATTTTTTGAATACTCATGGTTCAAAGT
	ACTTTGAACCATGAGTATTCAAAAAATAGTTACTTACCTAATTC	2653
	ACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAG
	GAATTAATGTCATCCTTGCAACTGCCGCCATTTA
	CTTTGGATTTGAAGGAA	2654
	TTCCTTCAAATCCAAAG	2655
Haemophilia B	TAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATG	2656
Phe77Ser	TTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGT
TTT-TCT	AAGTAACTATTTTTTGAATACTCATGGTTCAAAGT
	ACTTTGAACCATGAGTATTCAAAAAATAGTTACTTACCTAATTC	2657
	ACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAG
	GAATTAATGTCATCCTTGCAACTGCCGCCATTTA
	CTTTGGATTTGAAGGAA	2658
	TTCCTTCAAATCCAAAG	2659
Haemophilia B	TAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATG	2660
Phe77Tyr	TTGGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGT
TTT-TAT	AAGTAACTATTTTTTGAATACTCATGGTTCAAAGT
	ACTTTGAACCATGAGTATTCAAAAAATAGTTACTTACCTAATTC	2661
	ACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCATAG
	GAATTAATGTCATCCTTGCAACTGCCGCCATTTA
	CTTTGGATTTGAAGGAA	2662
	TTCCTTCAAATCCAAAG	2663
Haemophiiia B	AATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTT	2664
Glu78Lys	GGTGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAA
tGAA-AAA	GTAACTATTTTTTGAATACTCATGGTTCAAAGTTT
	AAACTTTGAACCATGAGTATTCAAAAAATAGTTACTTACCTAAT	2665
	TCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACATTCAT
	AGGAATTAATGTCATCCTTGCAACTGCCGCCATT
	TTGGATTTGAAGGAAAG	2666
	CTTTCCTTCAAATCCAA	2667
Haemophilia B	GCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGT	2668
Gly79Val	GTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAAGTA
GGA-GTA	ACTATTTTTTGAATACTCATGGTTCAAAGTTTCCCT
	AGGGAAACTTTGAACCATGAGTATTCAAAAAATAGTTACTTAC	2669
	CTAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACA
	TTCATAGGAATTAATGTCATCCTTGCAACTGCCGC
	ATTTGAAGGAAAGAACT	2670
	AGTTCTTTCCTTCAAAT	2671
Haemophilia B	GGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGG	2672
Gly79Arg	TGTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAAGT
aGGA-AGA	AACTATTTTTTGAATACTCATGGTTCAAAGTTTCCC
	GGGAAACTTTGAACCATGAGTATTCAAAAAATAGTTACTTACC	2673
	TAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACAT
	TCATAGGAATTAATGTCATCCTTGCAACTGCCGCC
	GATTTGAAGGAAAGAAC	2674
	GTTCTTTCCTTCAAATC	2675
Haemophilia B	GCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGT	2676
Gly79Glu	GTCCCTTTGGATTTGAAGGAAAGAACTGTGAATTAGGTAAGTA
GGA-GAA	ACTATTTTTTGAATACTCATGGTTCAAAGTTTCCCT
	AGGGAAACTTTGAACCATGAGTATTCAAAAAATAGTTACTTAC	2677
	CTAATTCACAGTTCTTTCCTTCAAATCCAAAGGGACACCAACA
	TTCATAGGAATTAATGTCATCCTTGCAACTGCCGC
	ATTTGAAGGAAAGAACT	2678
	AGTTCTTTCCTTCAAAT	2679
Haemophilia B	TTAGAAATGCATGTTAAATGATGCTGTTACTGTCTATTTTGCTT	2680
Cys88Ser	CTTTTAGATGTAACATGTAACATTAAGAATGGCAGATGCGAGC
TGT-TCT	AGTTTTGTAAAAATAGTGCTGATAACAAGGTGGT
	ACCACCTTGTTATCAGCACTATTTTTACAAAACTGCTCGCATC	2681
	TGCCATTCTTAATGTTACATGTTACATCTAAAAGAAGCAAAATA
	GACAGTAACAGCATCATTTAACATGCATTTCTAA
	TGTAACATGTAACATTA	2682
	TAATGTTACATGTTACA	2683
Haemophilia B	TTAGAAATGCATGTTAAATGATGCTGTTACTGTCTATTTTGCTT	2684
Cys88Phe	CTTTTAGATGTAACATGTAACATTAAGAATGGCAGATGCGAGC
TGT-TTT	AGTTTTGTAAAAATAGTGCTGATAACAAGGTGGT
	ACCACCTTGTTATCAGCACTATTTTTACAAAACTGCTCGCATC	2685
	TGCCATTCTTAATGTTACATGTTACATCTAAAAGAAGCAAAATA
	GACAGTAACAGCATCATTTAACATGCATTTCTAA
	TGTAACATGTAACATTA	2686
	TAATGTTACATGTTACA	2687
Haemophilia B	TTTAGAAATGCATGTTAAATGATGCTGTTACTGTCTATTTTGCT	2688
Cys88Arg	TCTTTTAGATGTAACATGTAACATTAAGAATGGCAGATGCGAG
aTGT-CGT	CAGTTTTGTAAAAATAGTGCTGATAACAAGGTGG
	CCACCTTGTTATCAGCACTATTTTTACAAAACTGCTCGCATCT	2689
	GCCATTCTTAATGTTACATGTTACATCTAAAAGAAGCAAAATA
	GACAGTAACAGCATCATTTAACATGCATTTCTAAA
	ATGTAACATGTAACATT	2690
	AATGTTACATGTTACAT	2691
Haemophilia B	TTAGAAATGCATGTTAAATGATGCTGTTACTGTCTATTTTGCTT	2692
Cys88Tyr	CTTTTAGATGTAACATGTAACATTAAGAATGGCAGATGCGAGC
TGT-TAT	AGTTTTGTAAAAATAGTGCTGATAACAAGGTGGT
	ACCACCTTGTTATCAGCACTATTTTTACAAAACTGCTCGCATC	2693
	TGCCATTCTTAATGTTACATGTTACATCTAAAAGAAGCAAAATA
	GACAGTAACAGCATCATTTAACATGCATTTCTAA
	TGTAACATGTAACATTA	2694
	TAATGTTACATGTTACA	2695
Haemophilia B	ATGCATGTTAAATGATGCTGTTACTGTCTATTTTGCTTCTTTTA	2696
lle90Thr	GATGTAACATGTAACATTAAGAATGGCAGATGCGAGCAGTTTT
ATT-ACT	GTAAAAATAGTGCTGATAACAAGGTGGTTTGCTC
	GAGCAAACCACCTTGTTATCAGCACTATTTTTACAAAACTGCT	2697
	CGCATCTGCCATTCTTAATGTTACATGTTACATCTAAAAGAAG
	CAAAATAGACAGTAACAGCATCATTTAACATGCAT
	ATGTAACATTAAGAATG	2698
	CATTCTTAATGTTACAT	2699
Haemophilia B	TGTTAAATGATGCTGTTACTGTCTATTTTGCTTCTTTTAGATGT	2700
Asn92His	AACATGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAA
gAAT-CAT	AATAGTGCTGATAACAAGGTGGTTTGCTCCTGTA
	TACAGGAGCAAACCACCTTGTTATCAGCACTATTTTTACAAAA	2701
	CTGCTCGCATCTGCCATTCTTAATGTTACATGTTACATCTAAAA
	GAAGCAAAATAGACAGTAACAGCATCATTTAACA
	ACATTAAGAATGGCAGA	2702
	TCTGCCATTCTTAATGT	2703
Haemophilia B	TTAAATGATGCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAA	2704
Asn92Lys	CATGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAA
AATg-AAA	TAGTGCTGATAACAAGGTGGTTTGCTCCTGTACT
	AGTACAGGAGCAAACCACCTTGTTATCAGCACTATTTTTACAA	2705
	AACTGCTCGCATCTGCCATTCTTAATGTTACATGTTACATCTA
	AAAGAAGCAAAATAGACAGTAACAGCATCATTTAA
	ATTAAGAATGGCAGATG	2706
	CATCTGCCATTCTTAAT	2707
Haemophilia B	AAATGATGCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAACA	2708
Gly93Asp	TGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATA
GGC-GAC	GTGCTGATAACAAGGTGGTTTGCTCCTGTACTGA
	TCAGTACAGGAGCAAACCACCTTGTTATCAGCACTATTTTTAC	2709
	AAAACTGCTCGCATCTGCCATTCTTAATGTTACATGTTACATCT
	AAAAGAAGCAAAATAGACAGTAACAGCATCATTT
	TAAGAATGGCAGATGCG	2710
	CGCATCTGCCATTCTTA	2711
Haemophilia B	TAAATGATGCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAAC	2712
Gly93Ser	ATGTAACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAAT
tGGC-AGC	AGTGCTGATAACAAGGTGGTTTGCTCCTGTACTG
	CAGTACAGGAGCAAACCACCTTGTTATCAGCACTATTTTTACA	2713
	AAACTGCTCGCATCTGCCATTCTTAATGTTACATGTTACATCTA
	AAAGAAGCAAAATAGACAGTAACAGCATCATTTA
	TTAAGAATGGCAGATGC	2714
	GCATCTGCCATTCTTAA	2715
Haemophilia B	GATGCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAACATGTA	2716
Arg94Ser	ACATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGC
AGAt-AGT	TGATAACAAGGTGGTTTGCTCCTGTACTGAGGGA
	TCCCTCAGTACAGGAGCAAACCACCTTGTTATCAGCACTATTT	2717
	TTACAAAACTGCTCGCATCTGCCATTCTTAATGTTACATGTTAC
	ATCTAAAAGAAGCAAAATAGACAGTAACAGCATC
	AATGGCAGATGCGAGCA	2718
	TGCTCGCATCTGCCATT	2719
Haemophilia B	TGCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAACATGTAAC	2720
Cys95Tyr	ATTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTG
TGC-TAC	ATAACAAGGTGGTTTGCTCCTGTACTGAGGGATA
	TATCCCTCAGTACAGGAGCAAACCACCTTGTTATCAGCACTAT	2721
	TTTTACAAAACTGCTCGCATCTGCCATTCTTAATGTTACATGTT
	ACATCTAAAAGAAGCAAAATAGACAGTAACAGCA
	TGGCAGATGCGAGCAGT	2722
	ACTGCTCGCATCTGCCA	2723
Haemophilia B	GCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAACATGTAACA	2724
Cys95Trp	TTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGA
TGCg-TGG	TAACAAGGTGGTTTGCTCCTGTACTGAGGGATAT
	ATATCCCTCAGTACAGGAGCAAACCACCTTGTTATCAGCACTA	2725
	TTTTTACAAAACTGCTCGCATCTGCCATTCTTAATGTTACATGT
	TACATCTAAAAGAAGCAAAATAGACAGTAACAGC
	GGCAGATGCGAGCAGTT	2726
	AACTGCTCGCATCTGCC	2727
Haemophilia B	GCTGTTACTGTCTATTTTGCTTCTTTTAGATGTAACATGTAACA	2728
Cys95Term	TTAAGAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGA
TGCg-TGA	TAACAAGGTGGTTTGCTCCTGTACTGAGGGATAT
	ATATCCCTCAGTACAGGAGCAAACCACCTTGTTATCAGCACTA	2729
	TTTTTACAAAACTGCTCGCATCTGCCATTCTTAATGTTACATGT
	TACATCTAAAAGAAGCAAAATAGACAGTAACAGC
	GGCAGATGCGAGCAGTT	2730
	AACTGCTCGCATCTGCC	2731
Haemophilia B	TACTGTCTATTTTGCTTCTTTTAGATGTAACATGTAACATTAAG	2732
Gln97Pro	AATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAACA
CAG-CCG	AGGTGGTTTGCTCCTGTACTGAGGGATATCGACT
	AGTCGATATCCCTCAGTACAGGAGCAAACCACCTTGTTATCA	2733
	GCACTATTTTTACAAAACTGCTCGCATCTGCCATTCTTAATGTT
	ACATGTTACATCTAAAAGAAGCAAAATAGACAGTA
	ATGCGAGCAGTTTTGTA	2734
	TACAAAACTGCTCGCAT	2735
Haemophilia B	TTACTGTCTATTTTGCTTCTTTTAGATGTAACATGTAACATTAA	2736
Gln97Glu	GAATGGCAGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAAC
gCAG-GAG	AAGGTGGTTTGCTCCTGTACTGAGGGATATCGAC
	GTCGATATCCCTCAGTACAGGAGCAAACCACCTTGTTATCAG	2737
	CACTATTTTTACAAAACTGCTCGCATCTGCCATTCTTAATGTTA
	CATGTTACATCTAAAAGAAGCAAAATAGACAGTAA
	GATGCGAGCAGTTTTGT	2738
	ACAAAACTGCTCGCATC	2739
Haemophilia B	TCTATTTTGCTTCTTTTAGATGTAACATGTAACATTAAGAATGG	2740
Cys99Arg	CAGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAAGGTG
tTGT-CGT	GTTTGCTCCTGTACTGAGGGATATCGACTTGCAG
	CTGCAAGTCGATATCCCTCAGTACAGGAGCAAACCACCTTGT	2741
	TATCAGCACTATTTTTACAAAACTGCTCGCATCTGCCATTCTT
	AATGTTACATGTTACATCTAAAAGAAGCAAAATAGA
	AGCAGTTTTGTAAAAAT	2742
	ATTTTTACAAAACTGCT	2743
Haemophilia B	CTATTTTGCTTCTTTTAGATGTAACATGTAACATTAAGAATGGC	2744
Cys99Tyr	AGATGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAAGGTG
TGT-TAT	GTTTGCTCCTGTACTGAGGGATATCGACTTGCAGA
	TCTGCAAGTCGATATCCCTCAGTACAGGAGCAAACCACCTTG	2745
	TTATCAGCACTATTTTTACAAAACTGCTCGCATCTGCCATTCTT
	AATGTTACATGTTACATCTAAAAGAAGCAAAATAG
	GCAGTTTTGTAAAAATA	2746
	TATTTTTACAAAACTGC	2747
Warfarin sensitivity	TTTTTTGCTAAAACTAAAGAATTATTCTTTTACATTTCAGTTTTT	2748
Ala(-10)Thr	CTTGATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGA
cGCC-ACC	GGTATAATTCAGGTAAATTGGAAGAGTTTGTTC
	GAACAAACTCTTCCAATTTACCTGAATTATACCTCTTTGGCCG	2749
	ATTCAGAATTTTGTTGGCGTTTTCATGATCAAGAAAAACTGAAA
	TGTAAAAGAATAATTCTTTAGTTTTAGCAAAAAA
	ATGAAAACGCCAACAAA	2750
	TTTGTTGGCGTTTTCAT	2751
Warfarin sensitivity	TTTTTGCTAAAACTAAAGAATTATTCTTTTACATTTCAGTTTTTC	2752
Ala(-10)Val	TTGATCATGAAAACGCCAACAAAATTCTGAATCGGCCAAAGAG
GCC-GTC	GTATAATTCAGGTAAATTGGAAGAGTTTGTTCA
	TGAACAAACTCTTCCAATTTACCTGAATTATACCTCTTTGGCC	2753
	GATTCAGAATTTTGTTGGCGTTTTCATGATCAAGAAAAACTGA
	AATGTAAAAGAATAATTCTTTAGTTTTAGCAAAAA
	TGAAAACGCCAACAAAA	2754
	TTTTGTTGGCGTTTTCA	2755
Haemophilia B	TGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCA	2756
Gly(-26)Val	TCACCATCTGCCTTTTAGGATATCTACTCAGTGCTGAATGTAC
GGA-GTA	AGGTTTGTTTCCTTTTTTAAAATACATTGAGTATGC
	GCATACTCAATGTATTTTAAAAAAGGAAACAAACCTGTACATTC	2757
	AGCACTGAGTAGATATCCTAAAAGGCAGATGGTGATGAGGCC
	TGGTGATTCTGCCATGATCATGTTCACGCGCTGCA
	CCTTTTAGGATATCTAC	2758
	GTAGATATCCTAAAAGG	2759
Haemophilia B	TTATGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCC	2760
Leu(-27)Term	TCATCACCATCTGCCTTTTAGGATATCTACTCAGTGCTGAATG
TTA-TAA	TACAGGTTTGTTTCCTTTTTTAAAATACATTGAGTA
	TACTCAATGTATTTTAAAAAAGGAAACAAACCTGTACATTCAGC	2761
	ACTGAGTAGATATCCTAAAAGGCAGATGGTGATGAGGCCTGG
	TGATTCTGCCATGATCATGTTCACGCGCTGCATAA
	CTGCCTTTTAGGATATC	2762
	GATATCCTAAAAGGCAG	2763
Haemophilia B	TAGCAAAGGTTATGCAGCGCGTGAACATGATCATGGCAGAAT	2764
lle(-30)Asn	CACCAGGCCTCATCACCATCTGCCTTTTAGGATATCTACTCAG
ATC-AAC	TGCTGAATGTACAGGTTTGTTTCCTTTTTTAAAATA
	TATTTTAAAAAAGGAAACAAACCTGTACATTCAGCACTGAGTA	2765
	GATATCCTAAAAGGCAGATGGTGATGAGGCCTGGTGATTCTG
	CCATGATCATGTTCACGCGCTGCATAACCTTTGCTA
	CATCACCATCTGCCTTT	2766
	AAAGGCAGATGGTGATG	2767
Haemophilia B	ACTAATCGACCTTACCACTTTCACAATCTGCTAGCAAAGGTTTA	2768
lle(-40)Phe	TGCAGCGCGTGAACATGATCATGGCAGAATCACCAGGCCTCA
gATC-TTC	TCACCATCTGCCTTTTAGGATATCTACTCAGTGCTG
	CAGCACTGAGTAGATATCCTAAAAGGCAGATGGTGATGAGGC	2769
	CTGGTGATTCTGCCATGATCATGTTCACGCGCTGCATAACCTT
	TGCTAGCAGATTGTGAAAGTGGTAAGGTCGATTAGT
	TGAACATGATCATGGCA	2770
	TGCCATGATCATGTTCA	2771
Haemophilia B	ACTTTGGTACAACTAATCGACCTTACCACTTTCACAATCTGCT	2772
Arg(-44)His	AGCAAAGGTTATGCAGCGCGTGAACATGATCATGGCAGAATC
CGC-CAC	ACCAGGCCTCATCACCATCTGCCTTTTAGGATATCT
	AGATATCCTAAAAGGCAGATGGTGATGAGGCCTGGTGATTCT	2773
	GCCATGATCATGTTCACGCGCTGCATAACCTTTGCTAGCAGA
	TTGTGAAAGTGGTAAGGTCGATTAGTTGTACCAAAGT
	TATGCAGCGCGTGAACA	2774
	TGTTCACGCGCTGCATA	2775

EXAMPLE 15

Alpha Thalassemia—Hemoglobin Alpha Locus 1

[0136] The thalassemia syndromes are a heterogeneous group of inherited anemias characterized by defects in the synthesis of one or more globin chain subunits. For example, beta-thalassemia discussed in Example 6, is caused by a decrease in beta-chain production relative to alpha-chain production; the converse is the case for alpha-thalassemia. The attached table discloses the correcting oligonucleotide base sequences for the hemoglobin alpha locus 1 oligonucleotides of the invention.

TABLE 22
HBA1 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Thalassaemia alpha	CCCTGGCGCGCTCGCGGCCCGGCACTCTTCIGGTCCCCACA	2776
Met(−1)Val	GACTCAGAGAGAACCCACCATGGTGCTGICTCCTGCCGACA
cATG-GTG	AGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGC
	GCGCGCCGACCTTACCCCAGGCGGCCTTGACGTTGGTCTTG	2777
	TCGGCAGGAGACAGCACCATGGTGGGTTCTCTCTGAGTCTGT
	GGGGACCAGAAGAGTGCCGGGCCGCGAGCGCGCCAGGG
	AACCCACCATGGTGCTG	2778
	CAGCACCATGGTGGGTT	2779
Haemoglobin variant	CACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCC	2780
Ala12Asp	GACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGC
GCC-GAC	GCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGTG
	CACCTCTCCAGGGCCTCCGCACCATACTCGCCAGCGTGCGC	2781
	GCCGACCTTACCCCAGGCGGCCTTGACGTTGGTCTTGTCGG
	CAGGAGACAGCACCATGGTGGGTTCTCTCTGAGTCTGTG
	CGTCAAGGCCGCCTGGG	2782
	CCCAGGCGGCCTTGACG	2783
Haemoglobin variant	AGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCA	2784
Gly15Asp	ACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGG
GGT-GAT	CGAGTATGGTGCGGAGGCCCTGGAGAGGTGAGGCTCCCT
	AGGGAGCCTCACCTCTCCAGGGCCTCCGCACCATACTCGCC	2785
	AGCGTGCGCGCCGACCTTACCCCAGGCGGCCTTGACGTTGG
	TCTTGTCGGCAGGAGACAGCACCATGGTGGGTTCTCTCT
	CGCCTGGGGTAAGGTCG	2786
	CGACCTTACCCCAGGCG	2787
Haemoglobin variant	CTGCCGACAAGACCMCGTCAAGGCCGCCTGGGGTAAGGTC	2788
Tyr24Cys	GGCGCGCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGA
TAT-TGT	GGTGAGGCTCCCTCCCCTGCTCCGACCCGGGCTCCTCGCC
	GGCGAGGAGCCCGGGTCGGAGCAGGGGAGGGAGCCTCACC	2789
	TCTCCAGGGCCTCCGCACCATACTCGCCAGCGTGCGCGCCG
	ACCTTACCCCAGGCGGCCTTGACGTTGGTCTTGTCGGCAG
	TGGCGAGTATGGTGCGG	2790
	CCGCACCATACTCGCCA	2791
Haemoglobin variant	GACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCAC	2792
Glu27Asp	GCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGTGAGGCT
GAGg-GAT	CCCTCCCCTGCTCCGACCCGGGCTCCTCGCCCGCCCGGAC
	C
	GGTCCGGGCGGGCGAGGAGCCCGGGTCGGAGCAGGGGAG	2793
	GGAGCCTCACCTCTCCAGGGCCTCCGCACCATACTCGCCAG
	CGTGCGCGCCGACCTTACCCCAGGCGGCCTTGACGTTGGTC
	GGTGCGGAGGCCCTGGA	2794
	TCCAGGGCCTCCGCACC	27955
Haemoglobin variant	GAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGG	2796
Asn68Lys	TGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGA
AACg-AAG	CATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCG
	CGCGTGCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATG	2797
	TCGTCCACGTGCGCCACGGCGTTGGTCAGCGCGTCGGCCAC
	CTTCTTGCCGTGGCCCTTAACCTGGGCAGAGCCGTGGCTC
	CTGACCAACGCCGTGGC	2798
	GCCACGGCGTTGGTCAG	2799
Haemoglobin variant	AGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACC	2800
Asp74Gly	AACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGTC
GAC-GGC	CGCCCTGAGCGACCTGCACGCGCACAAGCHCGGGTGGA
	TCCACCCGAAGCTTGTGCGCGTGCAGGTCGCTCAGGGCGGA	2801
	CAGCGCGTTGGGCATGTCGTCCACGTGCGCCACGGCGTTGG
	TCAGCGCGTCGGCCACCTTCTTGCCGTGGCCCTTAACCT
	GCACGTGGACGACATGC	2802
	GCATGTCGTCCACGTGC	2803
Haemoglobin variant	CAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGAC	2804
Asp74His	CAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCTGT
gGAC-CAC	CCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGG
	CCACCCGAAGCTTGTGCGCGTGCAGGTCGCTCAGGGCGGAC	2805
	AGCGCGTTGGGCATGTCGTCCACGTGCGCCACGGCGTTGGT
	CAGCGCGTCGGCCACCTTCTTGCCGTGGCCCTTAACCTG
	CGCACGTGGACGACATG	2806
	CATGTCGTCCACGTGCG	2807
Haemoglobin variant	CACGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGG	2808
Asn78His	CGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGC
cAAC-CAC	GACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACT
	AGTTGACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGTCG	2809
	CTCAGGGCGGACAGCGCGTTGGGCATGTCGTCCACGTGCGC
	CACGGCGTTGGTCAGCGCGTCGGCCACCTTCTTGCCGTG
	ACATGCCCAACGCGCTG	2810
	CAGCGCGTTGGGCATGT	2811
Haemoglobin variant	ACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCGCT	2812
His87Tyr	GTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGG
gCAC-TAC	ACCCGGTCAACTTCAAGGTGAGCGGCGGGCCGGGAGCGA
	TCGCTCCCGGCCCGCCGCTCACCTTGAAGTTGACCGGGTCC	2813
	ACCCGAAGCTTGTGCGCGTGCAGGTCGCTCAGGGCGGACAG
	CGCGTTGGGCATGTCGTCCACGTGCGCCACGGCGHGGT
	GCGACCTGCACGCGCAC	2814
	GTGCGCGTGCAGGTCGC	2815
Haemogiobin variant	GGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGA	2816
Lys90Asn	GCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAAC
AAGc-AAC	TTCAAGGTGAGCGGCGGGCCGGGAGCGATCTGGGTCGAG
	CTCGACCCAGATCGCTCCCGGCCCGCCGCTCACCTTGAAGT	2817
	TGACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGTCGCTC
	AGGGCGGACAGCGCGTTGGGCATGTCGTCCACGTGCGCC
	GCGCACAAGCTTCGGGT	2818
	ACCCGAAGCTTGTGCGC	2819
Haemoglobin variant	TGGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTG	2820
Lys90Thr	AGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAA
AAG-ACG	CTTCAAGGTGAGCGGCGGGCCGGGAGCGATCTGGGTCGA
	TCGACCCAGATCGCTCCCGGCCCGCCGCTCACCTTGAAGTT	2821
	GACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGTCGCTCA
	GGGCGGACAGCGCGTTGGGCATGTCGTCCACGTGCGCCA
	CGCGCACAAGCTTCGGG	2822
	CCCGAAGCTTGTGCGCG	2823
Haemoglobin variant	ACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGAC	2824
Arg92Gln	CTGCACGCGCACAAGAAGCTTCGGGTGGACCCGGTCAACTTCAA
CGG-CAG	GGTGAGCGGCGGGCCGGGAGCGATCTGGGTCGAGGGGCG
	CGCCCCTCGACCCAGATCGCTCCCGGCCCGCCGCTCACCTT	2825
	GAAGTTGACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGT
	CGCTCAGGGCGGACAGCGCGTTGGGCATGTCGTCCACGT
	CAAGCTTCGGGTGGACC	2826
	GGTCCACCCGAAGCTTG	2827
Haemoglobin variant	ACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCAC	2828
Asp94Gly	GCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGGTGAG
GAC-GGC	CGGCGGGCCGGGAGCGATCTGGGTCGAGGGGCGAGATGG
	CCATCTCGCCCCTCGACCCAGATCGCTCCCGGCCCGCCGCT	2829
	CACCTTGAAGTTGACCGGGTCCACCCGAAGCTTGTGCGCGT
	GCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATGTCGT
	TCGGGTGGACCCGGTCA	2830
	TGACCGGGTCCACCCGA	2831
Haemoglobin variant	ACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCG	2832
Pro95Arg	CACAAGCTTCGGGTGGACCCGGTCAACTTCAAGGTGAGCGG
CCG-CGG	CGGGCCGGGAGCGATCTGGGTCGAGGGGCGAGATGGCGC
	GCGCCATCTCGCCCCTCGACCCAGATCGCTCCCGGCCCGCC 2833
	GCTCACCTTGAAGTTGACCGGGTCCACCCGAAGCTTGTGCG
	CGTGCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATGT
	GGTGGACCCGGTCAACT	2834
	AGTTGACCGGGTCCACC	2835
Haemoglobin variant	CGGCGGCTGCGGGCCTGGGCCCTCGGCCCCACTGACCCTC	2836
Ser102Arg	TCTCTGCACAGCTCCTAAGCCACTGCCTGCTGGTGACCCTG
AGCc-AGA	GCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCAC
	GTGCACCGCAGGGGTGAACTCGGCGGGGAGGTGGGCGGCC	2837
	AGGGTCACCAGCAGGCAGTGGCTTAGGAGCTGTGCAGAGAA
	GAGGGTCAGTGGGGCCGAGGGCCCAGGCCCGCAGCCGCCG
	CTCCTAAGCCACTGCCT	2838
	AGGCAGTGGCTTAGGAG	2839
Haemoglobin variant	TTCTCTGCACAGCTCCTAAGCCACTGCCTGCTGGTGACCCTG	2840
Glu116Lys	GCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGC
cGAG-AAG	CTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGC
	GCACGGTGCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCG	2841
	TGCACCGCAGGGGTGAACTCGGCGGGGAGGTGGGCGGCCA
	GGGTCACCAGCAGGCAGTGGCTTAGGAGCTGTGCAGAGAA
	TCCCCGCCGAGTTCACC	2842
	GGTGAACTCGGCGGGGA	2843
Haemoglobin variant	TCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTC	2844
Ala120Glu	CCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAA
GCG-GAG	GTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATA
	TATTTGGAGGTCAGCACGGTGCTCACAGAAGCCAGGAACTTG	2845
	TCCAGGGAGGCGTGCACCGCAGGGGTGAACTCGGCGGGGA
	GGTGGGCGGCCAGGGTCACCAGCAGGCAGTGGCTTAGGA
	CACCCCTGCGGTGCACG	2846
	CGTGCACCGCAGGGGTG	2847
Thalassaemia alpha	TGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCAC	2848
Leu129Pro	GCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTG
CTG-CCG	ACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCAT
	ATGGCCACCGAGGCTCCAGCHAACGGTATTTGGAGGTCAGC	2849
	ACGGTGCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCGTG
	CACCGCAGGGGTGAACTCGGCGGGGAGGTGGGCGGCCA
	CAAGTTCCTGGCTTCTG	2850
	CAGAAGCCAGGAACTTG	2851
Haemoglobin variant	TGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCG	2852
Arg141Leu	TGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTGGCCA
CGT-CTT	TGCTTCTTGCCCCTTGGGCCTCCCCCCAGCCCCTCCT
	AGGAGGGGCTGGGGGGAGGCCCAAGGGGCMGMGCATGG	2853
	CCACCGAGGCTCCAGCTTAACGGTATTTGGAGGTCAGCACG
	GTGCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCGTGCA
	CMATACCGTTAAGCTG	2854
	CAGCTTAACGGTATTTG	2855

EXAMPLE 16

Alpha-Thalassemia—Hemoglobin Alpha Locus 2

[0137] The attached table discloses the correcting oligonucleotide base sequences for the hemoglobin alpha locus 2 oligonucleotides of the invention.

TABLE 23
HBA2 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO
Thalassaemia alpha	CCTGGCGCGCTCGCGGGCCGGCACTCTTCTGGTCCCCACAG	2856
Met(-1)Thr	ACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAG
ATG-ACG	ACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCA
	TGCGCGCCGACCTTACCCCAGGCGGCCTTGACGTTGGTCTT	2857
	GTCGGCAGGAGACAGCACCATGGTGGGTTCTCTCTGAGTCT
	GTGGGGACCAGAAGAGTGCCGGCCCGCGAGCGCGCCAGG
	ACCCACCATGGTGCTGT	2858
	ACAGCACCATGGTGGGT	2859
Haemoglobin variant	CACAGACTCAGAGAGAACCCACCATGGTGCTGTCTCCTGCC	2860
Ala12Asp	GACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGC
GCC-GAC	GCACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGTG
	CACCTCTCCAGGGCCTCCGCACCATACTCGCCAGCGTGCGC 2861
	GCCGACCTTACCCCAGGCGGCCTTGACGTTGGTCTTGTCGG
	CAGGAGACAGCACCATGGTGGGTTCTCTCTGAGTCTGTG
	CGTCAAGGCCGCCTGGG	2862
	CCCAGGCGGCCTTGACG	2863
Haemoglobin variant	AGAGAACCCACCATGGTGCTGTCTCCTGCCGACAAGACCAAC	2864
Lys16Glu	GTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGGCG
tAAG-GAG	AGTATGGTGCGGAGGCCCTGGAGAGGTGAGGCTCCCTCC
	GGAGGGAGCCTCACCTCTCCAGGGCCTCCGCACCATACTCG 2865
	CCAGCGTGCGCGCCGACCTTACCCCAGGCGGCCTTGACGTT
	GGTCTTGTCGGCAGGAGACAGCACCATGGTGGGTTCTCT
	CCTGGGGTAAGGTCGGC	2866
	GCCGACCTTACCCCAGG	2867
Haemoglobin variant	GGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCT	2868
His20Gln	GGGGTAAGGTCGGCGCGCACGCTGGCGAGTATGGTGCGGA
CACg-CAA	GGCCCTGGAGAGGTGAGGCTCCCTCCCCTGCTCCGACCCG
	CGGGTCGGAGCAGGGGAGGGAGCCTCACCTCTCCAGGGCC	2869
	TCCGCACCATACTCGCCAGCGTGCGCGCCGACCTTACCCCA
	GGCGGCCTTGACGTTGGTCTTGTCGGCAGGAGACAGCACC
	GGCGCGCACGCTGGCGA	2870
	TCGCCAGCGTGCGCGCC	2871
Haemoglobin variant	GACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCAC	2872
Glu27Asp	GCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGTGAGGCT
GAGg-GAC	CCCTCCCCTGCTCCGACCCGGGCTCCTCGCCCGCCCGGAC
	C
	GGTCCGGGCGGGCGAGGAGCCCGGGTCGGAGCAGGGGAG	2873
	GGAGCCTCACCTCTCCAGGGCCTCCGCACCATACTCGCCAG
	CGTGCGCGCCGACCTTACCCCAGGCGGCCHGACGHGGTC
	GGTGCGGAGGCCCTGGA	2874
	TCCAGGGCCTCCGCACC	2875
Thalassaemia alpha	ACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCGCACGCTGG	2876
Leu29Pro	CGAGTATGGTGCGGAGGCCCTGGAGAGGTGAGGCTCCCTCC
CTG-CCG	CCTGCTCCGACCCGGGCTCCTCGCCCGCCCGGACCCACAG
	CTGTGGGTCCGGGCGGGCGAGGAGCCCGGGTCGGAGCAGG 2877
	GGAGGGAGCCTCACCTCTCCAGGGCCTCCGCACCATACTCG
	CCAGCGTGCGCGCCGACCTTACCCCAGGCGGCCTTGACGT
	GGAGGCCCTGGAGAGGT	2878
	ACCTCTCCAGGGCCTCC	2879
Haemoglobin variant	GCTTCTCCCCGCAGGATGTTCCTGTCCTTCCCCACCACCAAG	2880
Asp47His	ACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCA
cGAC-CAC	GGHAAGGGCCACGGCAAGAAGGTGGCCGACGCGCTGA
	TCAGCGCGTCGGCCACCTTCTTGCCGTGGCCCTTAACCTGG	2881
	GCAGAGCCGTGGCTCAGGTCGAAGTGCGGGAAGTAGGTCTT
	GGTGGTGGGGAAGGACAGGAACATCCTGCGGGGAGAAGC
	CGCACTTCGACCTGAGC	2882
	GCTCAGGTCGAAGTGCG	2883
Haemoglobin variant	CTCCCCGCAGGATGTTCCTGTCCTTCCCCACCACCAAGACCT	2884
Leu48Arg	ACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTA
CTG-CGG	AGGGCCACGGCAAGAAGGTGGCCGACGCGCTGACCAA
	TTGGTCAGCGCGTCGGCCACCTTCTTGCCGTGGCCCTTAAC	2885
	CTGGGCAGAGCCGTGGCTCAGGTCGAAGTGCGGGAAGTAG
	GTCTTGGTGGTGGGGAAGGACAGGAACATCCTGCGGGGAG
	CTTCGACCTGAGCCACG	2886
	CGTGGCTCAGGTCGAAG	2887
Haemoglobin variant	CTGTCCTTCCCCACCACCAAGACCTACTTCCCGCACTTCGAC	2888
Gln54Glu	CTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAA
cCAG-GAG	GGTGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGG
	CCACGTGCGCCACGGCGTTGGTCAGCGCGTCGGCCACCHC 2889
	TTGCCGTGGCCCTTAACCTGGGCAGAGCCGTGGCTCAGGTC
	GAAGTGCGGGAAGTAGGTCTTGGTGGTGGGGAAGGACAG
	GCTCTGCCCAGGTTAAG	2890
	CTTAACCTGGGCAGAGC	2891
Haemoglobin variant	CCAAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTG 2892
Gly59Asp	CCCAGGTTAAGGGCCACGGCAAGAAGGTGGCCGACGCGCT
GGC-GAC	GACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGC
	GCGTTGGGCATGTCGTCCACGTGCGCCACGGCGTTGGTCAG 2893
	CGCGTCGGCCACCTTCTTGCCGTGGCCCTTAACCTGGGCAG
	AGCCGTGGCTCAGGTCGAAGTGCGGGAAGTAGGTCTTGG
	GGGCCACGGCAAGAAGG	2894
	CCTTCTTGCCGTGGCCC	2895
Haemoglobin variant	GAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGCAAGAAGG	2896
Asn68Lys	TGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGA
AACg-AAG	T CATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCG
	CGCGTGCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATG 2897
	TCGTCCACGTGCGCCACGGCGTTGGTCAGCGCGTCGGCCAC
	CTTCTTGCCGTGGCCCTTAACCTGGGCAGAGCCGTGGCTC
	CTGACCAACGCCGTGGC	2898
	GCCACGGCGTTGGTCAG	2899
Haemoglobin variant	GAGCCACGGCTCTGCCCAGGTAAAGGGCCACGGCAAGAAGG	2900
Asn68Lys	TGGCCGACGCGCTGACCAACGCCGTGGCGCACGTGGACGA
AACg-AAA	CATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCG
	CGCGTGCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATG	2901
	TCGTCCACGTGCGCCACGGCGTTGGTCAGCGCGTCGGCCAC
	CTTCTTGCCGTGGCCCTTAACCTGGGCAGAGCCGTGGCTC
	CTGACCAACGCCGTGGC	2902
	GCCACGGCGTTGGTCAG	2903
Haemoglobin variant	CGGCAAGAAGGTGGCCGACGCGCTGACCAACGCCGTGGCG	2904
Asn78Lys	CACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGAGCGA
AACg-AAA	CCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTC
	GAAGTTGACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGT	2905
	CGCTCAGGGCGGACAGCGCGTTGGGCATGTCGTCCACGTGC
	GCCACGGCGTTGGTCAGCGCGTCGGCCACCTTCTTGCCG
	ATGCCCAACGCGCTGTC	2906
	GACAGCGCGTTGGGCAT	2907
Haemoglobin variant	CGCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAAC	2908
Asp85Val	GCGCTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCG
GAC-GTC	GGTGGACCCGGTCAACTTCAAGGTGAGCGGCGGGCCGGG
	CCCGGCCCGCCGCTCACCTTGAAGTTGACCGGGTCCACCCG	2909
	AAGCTTGTGCGCGTGCAGGTCGCTCAGGGCGGACAGCGCGT
	TGGGCATGTCGTCCACGTGCGCCACGGCGTTGGTCAGCG
	CCTGAGCGACCTGCACG	2910
	CGTGCAGGTCGCTCAGG	2911
Haemoglobin variant	GGCGCACGTGGACGACATGCCCAACGCGCTGTCCGCCCTGA	2912
Lys90Asn	GCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAAC
AAGc-AAT	TTCAAGGTGAGCGGCGGGCCGGGAGCGATCTGGGTCGAG
	CTCGACCCAGATCGCTCCCGGCCCGCCGCTCACCTTGAAGT	2913
	TGACCGGGTCCACCCGAAGCTTGTGCGCGTGCAGGTCGCTC
	AGGGCGGACAGCGCGTTGGGCATGTCGTCCACGTGCGCC
	GCGCACAAGCTTCGGGT	2914
	ACCCGAAGCTTGTGCGC	2915
Haemoglobin variant	GACGACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCA	2916
Asp94His	CGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAGGTGA
gGAC-CAC	GCGGCGGGCCGGGAGCGATCTGGGTCGAGGGGCGAGATG
	CATCTCGCCCCTCGACCCAGATCGCTCCCGGCCCGCCGCTC	2917
	ACCTTGAAGTTGACCGGGTCCACCCGAAGCTTGTGCGCGTG
	CAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATGTCGTC	.
	TTCGGGTGGACCCGGTC	2918
	GACCGGGTCCACCCGAA	2919
Haemoglobin variant	ACATGCCCAACGCGCTGTCCGCCCTGAGCGACCTGCACGCG	2920
Pro95Leu	CACAAGCTTCGGGTGGACCCGGTCAACTTCAAGGTGAGCGG
CCG-CTG	CGGGCCGGGAGCGATCTGGGTCGAGGGGCGAGATGGCGC
	GCGCCATCTCGCCCCTCGACCCAGATCGCTCCCGGCCCGCC	2921
	GCTCACCTTGAAGTTGACCGGGTCCACCCGAAGCTTGTGCG
	CGTGCAGGTCGCTCAGGGCGGACAGCGCGTTGGGCATGT
	GGTGGACCCGGTCAACT	2922
	AGTTGACCGGGTCCACC	2923
Haemoglobin variant	TAGCGCAGGCGGCGGCTGCGGGCCTGGGCCGCACTGACCC	2924
Ser102Arg	TCTTCTCTGCACAGCTCCTAAGCCACTGCCTGCTGGTGACCC
aAGC-CGC	TGGCCGCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGC
	GCACCGCAGGGGTGAACTCGGCGGGGAGGTGGGCGGCCAG	2925
	GGTCACCAGCAGGCAGTGGCTTAGGAGCTGTGCAGAGAAGA
	GGGTCAGTGCGGCCCAGGCCCGCAGCCGCCGCCTGCGCTA
	AGCTCCTAAGCCACTGC	2926
	GCAGTGGCTTAGGAGCT	2927
Haemoglobin H disease	GGCGGCGGCTGCGGGCCTGGGCCGCACTGACCCTCTTCTCT	2928
Cys104Tyr	GCACAGCTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGC
TGC-TAC	CCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTC
	GAGGCGTGCACCGCAGGGGTGAACTCGGCGGGGAGGTGGG	2929
	CGGCCAGGGTCACCAGCAGGCAGTGGCTTAGGAGCTGTGCA
	GAGAAGAGGGTCAGTGCGGCCCAGGCCCGCAGCCGCCGCC
	AAGCCACTGCCTGCTGG	2930
	CCAGCAGGCAGTGGCTT	2931
Haemoglobin variant	CCGCACTGACCCTCTTCTCTGCACAGCTCCTAAGCCACTGCC	2932
Ala111Val	TGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACC
GCC-GTC	CCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTC
	GAAGCCAGGAACTTGTCCAGGGAGGCGTGCACCGCAGGGGT	2933
	GAACTCGGCGGGGAGGTGGGCGGCCAGGGTCACCAGCAGG
	CAGTGGCTTAGGAGCTGTGCAGAGAAGAGGGTCAGTGCGG
	CCTGGCCGCCCACCTCC	2934
	GGAGGTGGGCGGCCAGG	2935
Haemoglobin variant	TCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTC	2936
Ala210Glu	CCCGCCGAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAA
GCG-GAG	GTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAATA
	TATTTGGAGGTCAGCACGGTGCTCACAGAAGCCAGGAACTTG	2937
	TCCAGGGAGGCGTGCACCGCAGGGGTGAACTCGGCGGGGA
	GGTGGGCGGCCAGGGTCACCAGCAGGCAGTGGCTTAGGA
	CACCCCTGCGGTGCACG	2938
	CGTGCACCGCAGGGGTG	2939
Haemoglobin variant	CCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCG	2940
His122Gln	AGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTG
CACq-CAG	GCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAA
	TTAACGGTATTTGGAGGTCAGCACGGTGCTCACAGAAGCCAG	2941
	GAACTTGTCCAGGGAGGCGTGCACCGCAGGGGTGAACTCGG
	CGGGGAGGTGGGCGGCCAGGGTCACCAGCAGGCAGTGG
	GCGGTGCACGCCTCCCT	2942
	AGGGAGGCGTGCACCGC	2943
Haemoglobin variant	CACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGA	2944
Ala123Ser	GTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGG
cGCC-TCC	CTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAG
	CTTAACGGTATTTGGAGGTCAGCACGGTGCTCACAGAAGCCA	2945
	GGAACTTGTCCAGGGAGGCGTGCACCGCAGGGGTGAACTCG
	GCGGGGAGGTGGGCGGCCAGGGTCACCAGCAGGCAGTG
	CGGTGCACGCCTCCCTG	2946
	CAGGGAGGCGTGCACCG	2947
Thalassaemia alpha	TGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACC	2948
Leu125Pro	CCTGCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGT
CTG-CCG	GAGCACCGTGCTGACCTCCAAATACCGTTAAGCTGGAGC
	GQTCCAGCTTAACGGTATTTGGAGGTCAGCACGGTGCTCACA	2949
	GAAGCCAGGAACHGTCCAGGGAGGCGTGCACCGCAGGGG
	TGAACTCGGCGGGGAGGTGGGCGGCCAGGGTCACCAGCA
	CGCCTCCCTGGACAAGT	2950
	ACTTGTCCAGGGAGGCG	2951
Haemoglobin variant	GCCCACCTCCCCGCCGAGTTCACCCCTGCGGTGCACGCCTC	2952
Ser131Pro	CCTGGACAAGTfCCTGGCTTCTGTGAGCACCGTGCTGACCTC
tTCT-CCT	CAAATACCGTTAAGCTGGAGCCTCGGTAGCCGTTCCTC
	GAGGAACGGCTACCGAGGCTCCAGCTTAACGGTATTTGGAG	2953
	GTCAGCACGGTGCTCACAGAAGCCAGGAACTTGTCCAGGGA
	GGCGTGCACCGCAGGGGTGAACTCGGCGGGGAGGTGGGC
	TCCTGGCTTCTGTGAGC	2954
	GCTCACAGAAGCCAGGA	2955
Haemoglobin variant	GAGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCT	2956
Leu136Met	GGCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGC
gCTG-ATG	TGGAGCCTCGGTAGCCGTTCCTCCTGCCCGCTGGGCCT
	AGGCCCAGCGGGCAGGAGGAACGGCTACCGAGGCTCCAGC	2957
	TTAACGGTATTTGGAGGTCAGCACGGTGCTCACAGAAGCCAG
	GAACTTGTCCAGGGAGGCGTGCACCGCAGGGGTGAACTC
	GCACCGTGCTGACCTCC	2958
	GGAGGTCAGCACGGTGC	2959
Haemoglobin variant	AGTTCACCCCTGCGGTGCACGCCTCCCTGGACAAGTTCCTG	2960
Leu136Pro	GCTTCTGTGAGCACCGTGCTGACCTCCAAATACCGTTAAGCT
CTG-CCG	GGAGCCTCGGTAGCCGTTCCTCCTGCCCGCTGGGCCTC
	GAGGCCCAGCGGGCAGGAGGAACGGCTACCGAGGCTCCAG	2961
	CTTAACGGTATTTGGAGGTCAGCACGGTGCTCACAGAAGCCA
	GGAACTTGTCCAGGGAGGCGTGCACCGCAGGGGTGAACT
	CACCGTGCTGACCTCCA	2962
	TGGAGGTCAGCACGGTG	2963
Haemoglobin variant	GTGCACGCCTCGCTGGACAAGTTCCTGGCTTCTGTGAGCACC	2964
Arg141Cys	GTGCTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTAGCC
cCGT-TGT	GTTCCTCCTGCCCGCTGGGCCTCCCAACGGGCCCTCC
	GGAGGGCCCGTTGGGAGGCCCAGCGGGGAGGAGGAACGGC	2965
	TACCGAGGCTCCAGCTTAACGGTATTTGGAGGTCAGCACGGT
	GCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCGTGCAC
	CCAAATACCGTTAAGCT	2966
	AGCTTAACGGTATTTGG	2967
Haemoglobin variant	CACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTG	2968
Term142Gln	CTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTAGCCGTT
tTAA-CAA	CCTCCTGCCCGCTGGGCCTCCCAACGGGCCCTCCTCC
	GGAGGAGGGCCCGTTGGGAGGCCCAGCGGGCAGGAGGAAC	2969
	GGCTACCGAGGCTCCAGCTTAACGGTATTTGGAGGTCAGCA
	CGGTGCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCGTG
	AATACCGTTAAGCTGGA	2970
	TCCAGCTTAACGGTATT	2971
Haemoglobin variant	CACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTG	2972
Term142Lys	CTGACCTCCAAATACCGTTAAGCTGGAGCCTCGGTAGCCGTT
tTAA-AAA	CCTCCTGCCCGCTGGGCCTCCCAACGGGCCCTCCTCC
	GGAGGAGGGCCCGTTGGGAGGCCCAGCGGGCAGGAGGAAC	2973
	GGCTACCGAGGCTCCAGCTTAACGGTATTTGGAGGTCAGCA
	CGGTGCTCACAGAAGCCAGGAACTTGTCCAGGGAGGCGTG
	AATACCGTTAAGCTGGA	2974
	TCCAGCTTAACGGTATT	2975
Haemoglobin variant	CGCCTCCGTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCT	2976
Term142Tyr	GACCTCCAAATACCGTTAAGCTGGAGCCTCGGTAGCCGTTCC
TAAg-TAT	TCCTGCCCGCTGGGCCTCCCAACGGGCCCTCCTCCCC
	GGGGAGGAGGGCCCGTTGGGAGGCCCAGCGGGCAGGAGG	2977
	AACGGCTACCGAGGCTCCAGCTTAACGGTATTTGGAGGTCAG
	CACGGTGCTCACAGAAGCCAGGAACHGTCCAGGGAGGCG
	TACCGTTAAGCTGGAGC	2978
	GCTCCAGCTTAACGGTA	2979

EXAMPLE 17

Human Mismatch Repair—MLH1

[0138] The human MLH1 gene is homologous to the bacterial mutL gene, which is involved in mismatch repair. Mutations in the MLH1 gene have been identified in many individuals with hereditary nonpolyposis colorectal cancer (HNPCC). Mutations in the MLH1 gene are also implicated in predisposition to a variety of cancers associated with, for example, Muir-Torre syndrome and Turcot syndrome. The attached table discloses the correcting oligonucleotide base sequences for the MLH1 oligonucleotides of the invention.

TABLE 24
MLH1 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Non-polyposis	TTGGCTGAAGGCACTTCCGTTGAGCATCTAGACGTTTCCTTG	2980
colorectal cancer	GCTCTTCTGGCGCCAAAATGTCGTTCGTGGCAGGGGTTATTC
Met1Arg	GGCGGCTGGACGAGACAGTGGTGAACCGCATCGCGGC
ATG-AGG	GCCGCGATGCGGTTCACCACTGTCTCGTCCAGCCGCCGAAT	2981
	AACCCCTGCCACGAACGACATTTTGGCGCCAGAAGAGCCAA
	GGAAACGTCTAGATGCTCAACGGAAGTGCCTTCAGCCAA
	CGCCAAAATGTCGTTCG	2982
	CGAACGACATTTTGGCG	2983
Non-polyposis	TTGGCTGAAGGCACTTCCGTTGAGCATCTAGACGTTTCCTTG	2984
colorectal cancer	GCTCTTCTGGCGCCAAAATGTCGTTCGTGGCAGGGGTTATTC
Met1Lys	GGCGGCTGGACGAGACAGTGGTGAACCGCATCGCGGC
ATG-AAG	GCCGCGATGCGGTTCACCACTGTCTCGTCCAGCCGCCGAAT	2985
	AACCCCTGCCACGAACGACATTTTGGCGCCAGAAGAGCCAA
	GGAAACGTCTAGATGCTCAACGGAAGTGCCTTCAGCCAA
	CGCCAAAATGTCGTTCG	2986
	CGAACGACATTTTGGCG	2987
Non-polyposis	TGGTGAACCGCATCGCGGCGGGGGAAGTTATCCAGCGGCCA	2988
colorectal cancer	GCTAATGCTATCAAAGAGATGATTGAGAACTGGTACGGAGGG
Met35Arg	AGTCGAGCCGGGCTCACTTAAGGGCTACGACTTAACGG
ATG-AGG	CCGTTAAGTCGTAGCCCTTAAGTGAGCCCGGCTCGACTCCCT	2989
	CCGTACCAGTTCTCAATCATCTCTTTGATAGCATTAGCTGGCC
	GCTGGATAACTTCCCCCGCCGCGATGCGGTTCACCA
	CAAAGAGATGATTGAGA	2990
	TCTCAATCATCTCTTTG	2991
Non-polyposis	TAGAGTAGTTGCAGACTGATAAATTATTTTCTGTTTGATTTGCC	2992
colorectal cancer	AGTTTAGATGCTAAAATCCACAAGTATTCAAGTGATTGTTAAAG
Ser44Phe	AGGGAGGCCTGAAGTTGATTCAGATCCAAGACAA
TCC-TTC	TTGTCTTGGATCTGAATCAACTTGAGGCCTCCCTCTTTAACAA	2993
	TCACTTGAATACTTGTGGATTTTGCATCTTAAACTGGCAAATCA
	AACAGAAAATAATTTATCAGTCTGCAACTACTCTA
	TGCAAAATCCACAAGTA	2994
	TACTTGTGGATTTTGCA	2995
Non-polyposis	GCAAAATCCACAAGTATTCAAGTGATTGTTAAAGAGGGAGGC	2996
colorectal cancer	CTGAAGTTGATTCAGATCCAAGACAATGGCACCGGGATCAGG
Gln62Lys	GTAAGTAAAACCTCAAAGTAGCAGGATGTTTGTGCGC
CAA-AAA	GCGCACTAAACATCCTGCTACTTTGAGGTTTTACTTACCCTGAT	2997
	CCCGGTGCCATTGTCTTGGATCTGAATCAACTTCAGGCCTCC
	CTCTTTAACAATCACTTGAATACTTGTGGATTTTGC
	TTCAGATCCAAGACAAT	2998
	ATTGTCTTGGATCTGAA	2999
Non-polyposis	GCAAAATCCACAAGTATTCAAGTGATTGTTAAAGAGGGAGGC	3000
colorectal cancer	CTGAAGTTGATTCAGATCCAAGACAATGGCACCGGGATCAGG
Gln62Term	GTAAGTAAAACCTCAAAGTAGCAGGATGTTTGTGCGC
CAA-TAA	GCGCACAAACATCCTGCTACTTTGAGGTTTTACTTACCCTGAT	3001
	CCCGGTGCCATTGTCTTGGATCTGAATCAACTTCAGGCCTCC
	CTCTTTAACAATCACTTGAATACTTGTGGATTTTGC
	TTCAGATCCAAGACAAT	3002
	ATTGTCTTGGATCTGAA	3003
Non-polyposis	CCACAAGTATTCAAGTGATTGTTAAAGAGGGAGGCCTGAAGT	3004
colorectal cancer	TGATTCAGATCCAAGACAATGGCACCGGGATCAGGGTAAGTA
Asn64Ser	AAACCTCAAAGTAGCAGGATGTTTGTGCGCTTCATGG
AAT-AGT	CCATGAAGCGCACAAACATCCTGCTACTTTGAGGTTTTACTTA	3005
	CCCTGATCCCGGTGCCATTCTCTTGGATCTGAATCAACTTCA
	GGCCTCCCTCTTTAACAATCACTTGAATACTTGTGG
	CCAAGACAATGGCACCG	3006
	CGGTGCCATTGTCTTGG	3007
Non-polyposis	ATTCAAGTGATTGTTAAAGAGGGAGGCCTGAAGTTGATTCAGA	3008
colorectal cancer	TCCAAGACAATGGCACCGGGATCAGGGTAAGTAAAAACCTCAA
Gly67Arg	AGTAGCAGGATGTTTGTGCGCTTCATGGAAGAGTCA
GGG-AGG	TGACTCTTCCATGAAGCGCACAAACATCCTGCTACTTTGAGGT	3009
	TTTACTTACCCTGATCCCGGTGCCATTGTCTTGGATCTGAATC
	AACTTCAGGCCTCCGTCTTTAACAATCACTTGAAT
	ATGGCACCGGGATCAGG	3010
	CCTGATCCCGGTGCCAT	3011
Non-polyposis	ATTCAAGTGATTGTTAAAGAGGGAGGCCTGAAGTTGATTCAGA	3012
colorectal cancer	TCCAAGACAATGGCACCGGGATCAGGGTAAGTAAAACCTCAA
Gly67Arg	AGTAGCAGGATGTTTGTGCGCTTCATGGAAGAGTCA
GGG-CGG	TGACTCTTCCATGAAGCGCACAAACATCCTGCTACTTTGAGGT	3013
	TTTACTTACCCTGATCCCGGTGCCATTGTCTTGGATCTGAATC
	AACTTCAGGCCTCCCTCTTTAACAATCACTTGAAT
	ATGGCACCGGGATCAGG	3014
	CCTGATCCCGGTGCCAT	3015
Non-polyposis	ATTCAAGTGATTGTTAAAGAGGGAGGCCTGAAGTTGATTTCAGA	3016
colorectal cancer	TCCAAGACAATGGCACCGGGATCAGGGTAAGTAAAACCTCAA
Gly67Trp	AGTAGCAGGATGTTTGTGCGCTTCATGGAAGAGTCA
GGG-TGG	TGACTCTTCCATGAAGCGCACAAACATCCTGCTACTTTGAGGT	3017
	TTTACTTACCCTGATCCCGGTGCCATTGTCTTGGATCTGAATC
	AACTTCAGGCCTCCCTCTTTAACAATCACTTGAAT
	ATGGCACCGGGATCAGG	3018
	CCTGATCCCGGTGCCAT	3019
Non-polyposis	GTAACATGATTATTTACTCATCTTTTGGTATCTAACAGAPAGA	3020
colorectal cancer	AGATCTGGATATTGTATGTGAAAGGTTCACTACTAGTAAACTG
Cys77Arg	CAGTCCTTTGAGGATTTAGCCAGTATTTCTACCT
TGT-CGT	AGGTAGAAATACTGGCTAAATCCTCAAAGGACTGCAGTTTACT	3021
	AGTAGTGAACCTTTCACATACAATATCCAGATCTTTCTTTGTT
	AGATACCAAAAAGATGAGTAAATAATCATGTTAC
	ATATTGTATGTGAAAGG	3022
	CCTTTCACATACAATAT	3023
Non-polyposis	TAACATGATTATTTACTCATCTTTTTGGTATCTAACAGAAGAA	3024
colorectal cancer	GATCTGGATATTGTATGTGAAAGGTTCACTACTAGTAAACTGC
Cys77Tyr	AGTCCTTTGAGGATTTAGCCAGTATTTCTACCTA
TGT-TAT	TAGGTAGAAATACTGGCTAAATCCTCAAAGGACTGCAGTTTAC	3025
	TAGTAGTGAACCTTTCACATACAATATCCAGATCTTCTTTCTGT
	TAGATACCAAAAAGATGAGTAAATAATCATGTTA
	TATTGTATGTGAAAGGT	3026
	ACCTTTCACATACAATA	3027
Non-polyposis	CTGGATATTGTATGTGAAAGGTTCACTACTAGTAAACTGCAGT	3028
colorectal cancer	CCTTTGAGGATTTAGCCAGTATTTCTACCTATGGCTTTCGAGG
Ser93Gly	TGAGGTAAGCTAAAGATTCAAGAAATGTGTAAAAT
AGT-GGT	ATTTTACACATTTCTTGAATCTTTAGCTTACCTCACCTCGAAAG	3029
	CCATAGGTAGAAATACTGGCTAAATCCTCAAAGGACTGCAGTT
	TACTAGTAGTGAACCTTTCACATACAATATCCAG
	ATTTAGCCAGTATTTCT	3030
	AGAAATACTGGCTAAAT	3031
Non-polyposis	TTCACTACTAGTAAACTGCAGTCCTTTGAGGATTTAGCCAGTA	3032
colorectal cancer	TTTCTACCTATGGCTTTCGAGGTGAGGTAAGCTAAAGATTCAA
Arg100Term	GAAATGTGTAAAATATCCTCCTGTGATGACATTGT
CGA-TGA	ACAATGTCATCACAGGAGGATATTTTACACATTTCTTGAATCTT 3033
	TAGCTTACCTCACCTCGAAAGCCATAGGTAGAAATACTGGCTA
	AATCCTCAAAGGACTGCAGTTTACTAGTAGTGAA
	ATGGCTTTCGAGGTGAG	3034
	CTCACCTCGAAAGCCAT	3035
Non-polyposis	ACCCAGCAGTGAGTTTTTCTTTCAGTCTATTTTCTTTTCTTCCT	3036
colorectal cancer	TAGGCTTTGGCCAGCATAAGCCATGTGGCTCATGTTACTATTA
Ile107Arg	CAACGAAAACAGCTGATGGAAAGTGTGCATACAG
ATA-AGA	CTGTATGCACACTTTCCATCAGCTGTTTTCGTTGTAATAGTAA	3037
	CATGAGCCACATGGCTTATGCTGGCCAAAGCCTTAGGAAGAA
	AAGAAAATAGACTGAAAGAAAAACTCACTGCTGGGT
	GGCCAGCATAAGCCATG	3038
	CATGGCTTATGCTGGCC	3039
Non-polyposis	TTTCTTTTCTTCCTTAGGCTTTGGCCAGCATAAGCCATGTGGC	3040
colorectal cancer	TCATGTTACTATTACAACGAAAACAGCTGATGGAAAGTGTGCA
Thr117Arg	TACAGGTATAGTGCTGACTTCTTTTACTCATATAT
ACG-AGG	ATATATGAGTAAAAGAAGTCAGCACTATACCTGTATGCACACT	3041
	TTCCATCAGCTGTTTTCGTTGTAATAGTAACATGAGCCACATG
	GCTTATGCTGGCCAAAGCCTAAGGAAGAAAAGAAA
	TATTACAACGATAAACAG	3042
	CTGTTTTCGTTGTAATA	3043
Non-polyposis	TTTCTTTTCTTCCTTAGGCTTTGGCCAGCATAAGCCATGTGGC	3044
colorectal cancer	TCATGTTACTATTACAACGAAAACAGCTGATGGAAAGTGTGCA
Thr117Met	TACAGGTATAGTGCTGACTTCTTTTACTCATATAT
ACG-ATG	ATATATGAGTTAAAAGAAGTCAGCACTATACCTGTATGCACACT	3045
	TTCCATCAGCTGTTTTCGTTGTAATAGTAACATGAGCCACATG
	GCTTATGCTGGCCAAAGCGTAAGGAAGAAAAGAAA
	TATTACAACGAAAACAG	3046
	CTGTTTTCGTTGTAATA	3047
Non-polyposis	TCTATCTCTCTACTGGATATTAATTTGTTATATTTTCTCATTAGA	3048
colorectal cancer	GCAAGTTACTCAGATGGAAAACTGAAAGCCCCTCCTAAACCA
Gly133Term	TGTGCTGGCAATCAAGGGACCCAGATCACGGTAA
GGA-TGA	TTACCGTGATCTGGGTCCCTTGATTGCCAGCACATGGTTTAG	3049
	GAGGGGCTTTCAGTTTTCCATCTGAGTAACTTGCTCTAATGAG
	ATAAATATAACAAATTAATATCCAGTAGAGAGATAGA
	ACTCAGATGGAAAACTG	3050
	CAGTTTTCCATCTGAGT	3051
Non-polyposis	TAGTGTGTGTTTTTGGCAACTCTTTTCTTACTCTTTTGTTTTTC	3052
colorectal cancer	TTTTCCAGGTATTCAGTACACAATGCAGGCATTAGTTTTCTCAG
Val185Gly	TTAAAAAAGTAAGTTCTTGGTTTATGGGGGATGG
GTA-GGA	CCATCCCCCATAAACCAAGAAGTTACTTTTTTAACTGAGAAAC	3053
	TAATGCCTGCATTGTGTACTGAATACCTGGAAAAGAATAAACAA
	AAGAGTAAGTAAAAGAGTTGCCAAAAACACACACTA
	GTATTCAGTACACAATG	3054
	CATTGTGTACTGAATAC	3055
Non-polyposis	TTTCTTACTCTTTTGTTTTTCTTTTCCAGGTATTCAGTACACAAT	3056
colorectal cancer	GCAGGCATTAGTTTCTCAGTTAAAAAAGTAAGTTCTTGGTTTAT
Ser193Pro	GGGGGATGGTTTTGTTTTATGTAAAAGAAAAAA
TCA-CCA	TTTTTTCTTTTCATAAAACAAAACCATCCCCCATAAACCAAGAA	3057
	CTTACTTTTTTAACTGAGAAACTAATGCCTGCATTGTGTACTG
	AATACCTGGAAAAGAAAAACAAAAGAGTAAGAAA
	TTAGTTTCTCAGTTAAA	3058
	TTTAACTGAGAAACTAA	3059
Non-polyposis	TTTGTTTATCAGCTAGGAGAGACAGTAGCTGATGTTAGGACA	3060
colorectal cancer	CTACCCAATGCCTCAACCGTGGACAATATTCGCTCCATCTTTG
	GAAATGCTGTTAGTCGGTATGTCGATAACCTATATA
	TATATAGGTTATCGACATACCGACTAACAGCATTTCCAAAGAT	3061
	GGAGCGAATATTGTCCACGGTTGAGGCATTGGGTAGTGTCCT
	AACATCAGCTACTGTCTCTCCTTGCTGATAAACAAA
	CCTCAACCGTGGACAAT	3062
	ATTGTCCACGGTTGAGG	3063
Non-polyposis	CAAGGAGAGACAGTAGCTGATGTTAGGACACTACCCAATGCC	3064
colorectal cancer	TCAACCGTGGACAATATTCGCTCCATCTTTGGAAATGCTGTTA
Arg217Cys	GTCGGTATGTCGATAACCTATATAAAAAAAATCTTTT
CGC-TGC	AAAAGATTTTTTTATATAGGTTATCGACATACCGACTAACAGCA	3065
	TTTCCAAAGATGGAGCGAATATTGTCCACGGTTGAGGCATTG
	GGTAGTGTCCTAACATCAGCTACTGTCTCTCCTTG
	ACAATATTCGCTCCATC	3066
	GATGGAGCGAATATTGT	3067
Non-polyposis	GAGACAGTAGCTGATGTTAGGACACTACCCAATGCCTCAACC	3068
colorectal cancer	GTGGACAATATTCGCTCCATCTTTGGAAATGCTGTTAGTCGGT
Ile219Val	ATGTCGATAACCTATATAAAAAAATCTTTTACATTT
ATC-GTC	AAATGTAAAAGATTTTTTTATATAGGTTATCGACATACCGACTA	3069
	ACAGCATTTCCAAAGATGGAGCGAATATTGTCCACGGTTGAG
	GCATTGGGTAGTGTCCTAACATCAGCTACTGTCTC
	TTCGCTCCATCTTTGGA	3070
	TCCAAAGATGGAGCGAA	3071
Non-polyposis	CTAATAGAGAACTGATAGTAAATTGGATGTGAGGATAAAACCCT	3072
colorectal cancer	AGCCTTCAAAATGAATGGTTACATATCCAATGCAAACTACTCA
Gly244Asp	GTGAAGAAGTGCATCTTCTTACTCTTCATCAACCG
GGT-GAT	CGGTTGATGAAGAGTAAGAAGATGCACTTCTTCACTGAGTAG	3073
	TTTGCATTGGATATGTAACCATTCATTTTGAAGGCTAGGGTT
	TATCCTCACATCCAATTTCTATCAGTTCTCTATTAG
	AATGAATGGTTACATAT	3074
	ATATGTAACCATTCATT	3075
Non-polyposis	GATGTGAGGATAAAACCCTAGCCTTCAAPATGAATGGTTACAT	3076
colorectal cancer	ATCCAATGCAAACTACTCAGTGAAGAAGTGCATCTCTTACTC
Ser252Term	TTCATCAACCGTAAGTTAAAAAGAACCACATGGGA
TCA-TAA	TCCCATGTGGTTCTTTTTAACTTACGGTTGATGAAGAGTAAGA	3077
	AGATGCACTTCTTCACTGAGTAGTTTGCATTGGATATGTAACC
	ATTCATTTTGAAGGCTAGGGTTTTATCCTCACATC
	AAACTACTCAGTGAAGA	3078
	TCTTCACTGAGTAGTTT	3079
Non-polyposis	CACCCCTCAGGACAGTTTTGAACTGGTTGCTTTCTTTTTATTG	3080
colorectal cancer	TTTAGATCGTCTGGTAGAATCAACTTCCTTGAGAAAAGCCATA
Glu268Gly	GAAACAGTGTATGCAGCCTATTTGCCCAAAAACAC
GAA-GGA	GTGTTTTTGGGCAAATAGGCTGCATACACTGTTTCTATGGCTT	3081
	TTCTCAAGGAAGTTGATTCTACCAGACGATCTAAACAATAAAA
	AGAAAGCAACCAGTTCAAAACTGTCCTGAGGGGTG
	TCTGGTAGAATCAACTT	3082
	AAGTTGATTCTACCAGA	3083
Non-polyposis	CCCTCAGGACAGTTTTGAACTGGTTGCTTTCTTTTTATTGTTTA	3084
colorectal cancer	GATCGTCTGGTAGAATCAACTTCCTTGAGTAAAGCCATAGAAA
Ser269Term	CAGTGTATGCAGCCTATTTGCCCAAAAACACACA
TCA-TGA	TGTGTGTTTTTGGGCAAATAGGCTGCATACACTGTTTCTATGG	3085
	CTTTTCTCAAGGAAGTTGATTCTACCAGACGATCTAAACAATA
	AAAAGAAAGCAACCAGTTCAAAACTGTCCTGAGGG
	GGTAGAATCAACTTCCT	3086
	AGGAAGTTGATTCTACC	3087
Non-polyposis	CTTTTTCTCCCCCTCCCACTATCTAAGGTAATTGTTCTCTCTTA	3088
colorectal cancer	TTTTCCTGACAGTTTAGAAATCAGTCCCCAGAATGTGGATGTT
Glu297Term	AATGTGCACCCCACTAAAGCATGAAGTTCACTTCC
GAA-TAA	GGAAGTGAACTTCATGCTTTGTGGGGTGCACATTAACATCCA	3089
	CATTCTGGGGACTGATTTCTAAACTGTCAGGAAAATAAGAGAG
	AACAATTACCTTAGATAGTGGGAGGGGGAGAAAAAG
	ACAGTTTAGAAATCAGT	3090
	ACTGATTTCTAAACTGT	3091
Non-polyposis	CTCCCACTATCTAAGGTAATTGTTCTCTCTTATTTTCCTGACAG	3092
colorectal cancer	TTTAGAAATCAGTCCCCAGAATGTGGATGTTAATGTGCACCCC
Gln301Term	ACAAAGCATGAAGTTCACTTCCTGCACGAGGAGA
CAG-TAG	TCTCCTCGTGCAGGAAGTGAACTTCATGCTTTGTGGGGTGCA	3093
	CATTAACATCCACATTCTGGGGACTGATTTCTAAACTGTCAGG
	AAAATAAGAGAGAACAATTACCTTAGATAGTGGGAG
	TCAGTCCCCAGAATGTG	3094
	CACATTCTGGGGACTGA	3095
Non-polyposis	ATGTGCACCCCACAAAGCATGAAGTTCACTTCGTGCACGAGG	3096
colorectal cancer	AGAGCATCCTGGAGCGGGTGCAGCAGCACATCGAGAGCAAG
Val326Ala	CTCCTGGGCTCCAATTCCTCCAGGATGTACTTCACCCA
GTG-GCG	TGGGTGAAGTACATCCTGGAGGAATTGGAGCCCAGGAGCTT	3097
	GCTCTCGATGTGCTGCTGCACCCGCTCCAGGATGCTCTCCT
	CGTGCAGGAAGTGAACTTCATGCTTTGTGGGGTGCACAT
	GGAGCGGGTGCAGCAGC	3098
	GCTGCTGCACCCGCTCC	3099
Non-polyposis	CCACAAAGCATGAAGTTCACTTCCTGCACGAGGAGAGCATCC	3100
colorectal cancer	TGGAGCGGGTGCAGCAGCACATCGAGAGCAAGCTCCTGGGC
His329Pro	TCCAATTCCTCCAGGATGTACTTCACCCAGGTCAGGGC
CAC-CCC	GCCCTGACCTGGGTGAAGTACATCCTGGAGGAATTGGAGCC	3101
	CAGGAGCTTGCTCTCGATGTGCTGCTGCACCCGCTCCAGGA
	TGCTCTCCTCGTGCAGGAAGTGAACTTCATGCTTTGTGG
	GCAGCAGCACATCGAGA	3102
	TCTCGATGTGCTGCTGC	3103
Non-polyposis	CAAGTCTGACCTCGTCTTCTACTTCTGGAAGTAGTGATAAGGT	3104
colorectal cancer	CTATGCCCACCAGATGGTTCGTACAGATTCCCGGGAACAGAA
Val384Asp	GCTTGATGCATTTCTGCAGCCTCTGAGCAAACCCCT
GTT-GAT	AGGGGTTTGCTCAGAGGCTGCAGAAATGCATCAAGCTTCTGT	3105
	TCCCGGGAATCTGTACGAACCATCTGGTGGGCATAGACCTTA
	TCACTACTTCCAGAAGTAGAAGACGAGGTCAGACTTG
	CCAGATGGTTCGTACAG	3106
	CTGTACGAACCATCTGG	3107
Non-polyposis	AGTGGCAGGGCTAGGCAGCAAGATGAGGAGATGCTTGAACT	3108
colorectal cancer	CCCAGCCCCTGCTGAAGTGGCTGCCAAAAATCAGAGCTTGGA
Ala441Thr	GGGGGATACAACAAAGGGGACTTCAGAAATGTCAGAGA
GCT-ACT	TCTCTGACATTTCTGAAGTCCCCTTTGTTGTATCCCCCTCCAA 3109
	GCTCTGATTTTTGGCAGCCACTTCAGCAGGGGCTGGGAGTTC
	AAGCATCTCCTCATCTTGCTGCCTAGCCCTGCCACT
	CTGAAGTGGCTGCCAAA	3110
	TTTGGCAGCCACTTCAG	3111
Non-polyposis	CTTCATTGCAGAAAGAGACATCGGGAAGATTCTGATGTGGAA	3112
colorectal cancer	ATGGTGGAAGATGATTCCCGAAAGGAAATGACTGCAGCTTGT
Arg487Term	ACCCCCCGGAGAAGGATCATTAACCTCACTAGTGTTT
CGA-TGA	AAACACTAGTGAGGTTAATGATCCTTCTCCGGGGGGTACAAG	3113
	CTGCAGTCATTTCCTTTCGGGAATCATCTTCCACCATTTCCAC
	ATCAGAATCTTCCCGATGTCTCTTTCTGCAATGAAG
	ATGATTCCCGTAAAGGAA	3114
	TTCCTTTCGGGAATCAT	3115
Non-polyposis	AGACATCGGGAAGATTCTGATGTGGAAATGGTGGAAGATGAT	3116
colorectal cancer	TCCCGAAAGGAAATGACTGCAGCTTGTACCCCCCGGAGAAG
Ala492Thr	GATCATTAACCTCACTAGTGTTTTGAGTCTCCAGGAAG
GCA-ACA	CTTCCTGGAGACTCAAAACACTAGTGAGGTTAATGATCCTTCT	3117
	CCGGGGGGTACAAGCTGCAGTCATTTCCTTTCGGGAATCATC
	TTCCACCATTTCCACATCAGAATCTTCCCGATGTCT
	AAATGACTGCAGCTTGT	3118
	ACAAGCTGCAGTCATTT	3119
Non-polyposis	CCCGAAAGGAAATGACTGCAGCTTGTACCCCCCGGAGAAGG	3120
colorectal cancer	ATCATTAACCTCACTAGTGTTTTGAGTCTCCAGGAAGAAATTA
Val506Ala	ATGAGCAGGGACATGAGGGTACGTAAACGCTGTGGCC
GTT-GCT	GGCCACAGCGTTTACGTACCCTCATGTCCCTGCTCATTAATTT	3121
	CTTCCTGGAGACTCAAAACACTAGTGAGGTTAATGATCCTTCT
	CCGGGGGGTACAAGCTGCAGTCATTTCCTTTCGGG
	CACTAGTGTTTTGAGTC	3122
	GACTCAAAACACTAGTG	3123
Non-polyposis	GGGAGATGTTGCATAACCACTCCTTCGTGGGCTGTGTGTGAATC	3124
colorectal cancer	CTCAGTGGGCCTTGGCACAGCATCAAACCAAGTTATACCTTCT
Gln542Leu	TTCAACACCACCAAGCTTAGGTAAATCAGCTGAGTGTG
CAG-CTG	CACACTCAGCTGATTTACCTAAGCTTGGTGGTGTTGAGAAGG	3125
	TATAACTTGGTTTGATGCTGTGCCAAGGCCCACTGAGGATTC
	ACACAGCCCACGTAGGAGTGGTTATGCTACATCTCCC
	CTTGGCACAGCATCAAA	3126
	TTTGATGCTGTGCCAAG	3127
Non-polyposis	CCTTCGTGGGCTGTGTGAATCCTCAGTGGGCCTTGGCACAG	3128
colorectal cancer	CATCAAACCAAGTTATACCTTCTCAACACCACCAAGCTTAGGT
Leu549Pro	AAATCAGCTGAGTGTGTGAACAAGCAGAGCTACTACA
CTT-CCT	TGTAGTAGCTCTGCTTGTTCACACACTCAGCTGATTTACCTAA	3129
	GCTTGGTGGTGTTGAGAAGGTATAACTTGGTTTGATGCTGTG
	CCAAGGCCCACTGAGGATTCACACAGCCCACGAAGG
	GTTATACCTTCTCAACA	3130
	TGTTGAGAAGGTATAAC	3131
Non-polyposis	TGGGCTGTGTGAATCCTCAGTGGGCCTTGGCACAGCATCAAA	3132
colorectal cancer	CCAAGTTATACCTTCTCAACACCACCAAGCTTAGGTAAATCAG
Asn551Thr	CTGAGTGTGTGAACAAGCAGAGCTACTACAACAATG
AAC-ACC	CATTGTTGTAGTAGCTCTGCTTGTTCACACACTCAGCTGATTT	3133
	ACCTAAGCTTGGTGGTGTTGAGAAGGTATAACTTGGTTTGATG
	CTGTGCCAAGGCCCACTGAGGATTCACACAGCCCA
	CCTTCTCAACACCACCA	3134
	TGGTGGTGTTGAGAAGG	3135
Non-polyposis	ATGAATTCAGCTTTTCCTTAAAGTCACTTCATTTTTATTTTCAG	3136
colorectal cancer	TGAAGAACTGTTCTACCAGATACTCATTTATGATTTTGCCAATT
Gln562Term	TTGGTGTTCTCAGGTTATCGGTAAGTTTAGATC
CAG-TAG	GATCTAAACTTACCGATAACCTGAGAACACCAAAATTGGCAAA	3137
	ATCATAAATGAGTATCTGGTAGAACAGTTCTTCACTGAAAATA
	AAAATGAAGTGACTTTAAGGAAAAGCTGAATTCAT
	TGTTCTACCAGATACTC	3138
	GAGTATCTGGTAGAACA	3139
Non-polyposis	GCTTTTCCTTAAAGTCACTTCATTTTTATTTTCAGTGAAGAACT	3140
colorectal cancer	GTTCTACCAGATACTCATTTATGATTTTGCCAATTTTGGTGTTC
Ile565Phe	TCAGGTTATCGGTAAGTTTAGATCCTTTTCACT
ATT-TTT	AGTGAAAAGGATCTAAACTTACCGATAACCTGAGAACACCAAA	3141
	ATTGGCAAAATCATAAATGAGTATCTGGTAGAACAGTTCTTCA
	CTGAAAATAAAAATGAAGTGACTTTAAGGAAAAGC
	AGATACTCATTTATGAT	3142
	ATCATAAATGAGTATCT	3143
Non-polyposis	TTTTCAGTGAAGAACTGTTCTACCAGATACTCATTTATGATTTT	3144
colorectal cancer	GCCAATTTTGGTGTTCTCAGGTTATCGGTAAGTTTAGATCCTT
Leu574Pro	TTCACTTCTGAAATTTCAACTGATCGTTTCTGAA
CTC-CCC	TTCAGAAACGATCAGTTGAAATTTCAGAAGTGAAAAGGATCTA	3145
	AACTTACCGATAACCTGAGAACACCAAAATTGGCAAAATCATA
	AATGAGTATCTGGTAGAACAGTTCTTCACTGAAAA
	TGGTGTTCTCAGGTTAT	3146
	ATAACCTGAGAACACCA	3147
Non-polyposis	TGGATGCTCCGTTTAAAGCTTGCTCCTTCATGTTCTTGCTTCTT	3148
colorectal cancer	CCTAGGAGCCAGCACCGCTCTTTGACCTTGCCATGCTTGCCT
Leu582Val	TAGATAGTCCAGAGAGTGGCTGGACAGAGGAAGATG
CTC-GTC	CATCTTCCTCTGTCCAGCCACTCTCTGGACTATCTAAGGCAA	3149
	GCATGGCAAGGTCAAAGAGCGGTGCTGGCTCCTAGGAAGAA
	GCAAGAACATGAAGGAGCAAGCTTTAACGGAGCATCCA
	CAGCACCGCTCTTTGAC	3150
	GTCAAAGAGCGGTGCTG	3151
Non-polyposis	TGCTTGCCTTAGATAGTCCAGAGAGTGGCTGGACAGAGGAAG	3152
colorectal cancer	ATGGTCCCAAAGAAGGACTTGCTGAATACATTGTTGAGTTTCT
Leu607His	GAAGAAGAAGGCTGAGATGCTTGCAGACTATTTCTC
CTT-CAT	GAGAAATAGTCTGCAAGCATCTCAGCCTTCTTCTTCAGAAACT	3153
	CAACAATGTATTCAGCAAGTCCTTCTTTGGGACCATCTTCCTC
	TGTCCAGCCACTCTCTGGACTATCTAAGGCAAGCA
	AGAAGGACTTGCTGAAT	3154
	ATTCAGCAAGTCCTTCT	3155
Non-polyposis	ACAGAGGAAGATGGTCCCAAAGAAGGACTTGCTGAATACATT	3156
colorectal cancer	GTTGAGTTTCTGAAGAAGAAGGCTGAGATGCTTGCAGACTAT
Lys618Term	TTCTCTTTGGAAATTGATGAGGTGTGACAGCCATTCT
AAG-TAG	AGTATGGCTGTCACACCTCATCAATTTCCAAAGAGAAATAGTC	3157
	TGCAAGCATCTCAGCCTTCTTCTTCAGAAACTCAACAATGTAT
	TCAGCAAGTCCTTCTTTGGGACCATCTTCCTCTGT
	TGAAGAAGAAGGCTGAG	3158
	CTCAGCCTTCTTCTTCA	3159
Non-polyposis	CAGAGGAAGATGGTCCCAAAGAAGGACTTGCTGAATACATTG	3160
colorectal cancer	TTGAGTTTCTGAAGAAGAAGGCTGAGATGCTTGCAGACTATTT
Lys618Thr	CTCTTTGGAAATTGATGAGGTGTGACAGCCATTCTT
AAG-ACG	AAGAATGGCTGTCACACCTCATCAATTTCCAAAGAGAAATAGT	3161
	CTGCAAGCATCTCAGCCTTCTTCTTCAGAAACTCAACAATGTA
	TTCAGCAAGTCCTTCTTTGGGACCATCTTCCTCTG
	GAAGAAGAAGGCTGAGA	3162
	TCTCAGCCTTCTTCTTC	3163
Non-polyposis	TACCCCTTCTGATTGACAACTATGTGCCCCCTTTGGAGGGAC	3164
colorectal cancer	TGCCTATCTTCATTCTTCGACTAGCCACTGAGGTCAGTGATCA
Arg659Leu	AGCAGATACTAAGCATTTCGGTACATGCATGTGTGC
CGA-CTA	GCACACATGCATGTACCGAAATGCTTAGTATCTGCTTGATCAC	3165
	TGACCTCAGTGGCTAGTCGAAGAATGAAGATAGGCAGTCCCT
	CCAAAGGGGGCACATAGTTGTCAATCAGAAGGGGTA
	CATTCTTCGACTAGCCA	3166
	TGGCTAGTCGAAGAATG	3167
Non-polyposis	TACCCCTTCTGATTGACAACTATGTGCCCCCTTTGGAGGGAC	3168
colorectal cancer	TGCCTATCTTCATTCTTCGACTAGCCACTGAGGTCAGTGATCA
Arg659Pro	AGCAGATACTAAGCATTTCGGTACATGCATGTGTGC
CGA-CCA	GCACACATGCATGTACCGAAATGCTTAGTATCTGCTTGATCAC	3169
	TGACGTCAGTGGCTAGTCGAAGAATGAAGATAGGCAGTCCCT
	CCTAAAGGGGGCACATAGTTGTCAATCAGAAGGGGTA
	CATTCTTCGACTAGCCA	3170
	TGGCTAGTCGAAGAATG	3171
Non-polyposis	TTACCCCTTCTGATTGACAACTATGTGCCCCCTTTGGAGGGA	3172
colorectal cancer	CTGCCTATCTTCATTCTTCGACTAGCCACTGAGGTCAGTGATC
Arg659Term	AAGCAGATACTAAGCATTTCGGTACATGCATGTGTG
CGA-TGA	CACACATGCATGTACCGAAATGCTTAGTATCTGCTTGATCACT	3173
	GACCTCAGTGGCTAGTCGAAGAATGAAGATAGGCAGTCCCTC
	CAAAGGGGGCACATAGTTGTCAATCAGAAGGGGTAA
	TCATTCTTCGACTAGCC	3174
	GGCTAGTCGAAGAATGA	3175
Non-polyposis	TTGGACCAGGTGAATTGGGACGAAGAAAAGGAATGTTTTGAA	3176
colorectal cancer	AGCCTCAGTAAAGAATGCGCTATGTTCTATTCCATCCGGAAG
Ala681Thr	CAGTACATATCTGAGGAGTCGACCCTCTCAGGCCAGC
GCT-ACT	GCTGGCCTGAGAGGGTCGACTCCTCAGATATGTACTGCTTCC	3177
	GGATGGAATAGAACATAGCGCATTCTTTACTGAGGCTTTCAAA
	ACATTCCTTTTCTTCGTCCCAATTCACCTGGTCCAA
	AAGAATGCGCTATGTTC	3178
	GAACATAGCGCATTCTT	3179
Non-polyposis	AGGCTTATGACATCTAATGTGTTTTCCAGAGTGAAGTGCCTGG	3180
colorectal cancer	CTCCATTCCPAACTCCTGGAAGTGGACTGTGGAACACATTGT
Trp712Term	CTATAAAGCCTTGCGCTCACACATTCTGCCTCCTAA
TGG-TAG	TTAGGAGGCAGAATGTGTGAGCGCAAGGCTTTATAGACAATG	3181
	TGTTCCACAGTCCACTTCCAGGAGTTTGGAATGGAGCCAGGC
	ACTTCACTCTGGAAAACACATTAGATGTCATAAGCCT
	AAACTCCTGGAAGTGGA	3182
	TCCACTTCCAGGAGTTT	3183
Non-polyposis	ATGACATCTAATGTGTTTTCCAGAGTGAAGTGCCTGGCTCCAT	3184
colorectal cancer	TCCAAACTCCTGGAAGTGGACTGTGGAACACATTGTCTATAAA
Trp714Term	GCCTTGCGCTCACACATTCTGCCTCCTAAACATTT
TGG-TAG	AAATGTTTAGGAGGCAGAATGTGTGAGCGCAAGGCTTTATAG	3185
	ACAATGTGTTCCACAGTCCACTTCCAGGAGTTTGGAATGGAG
	CCAGGCACTTCACTCTGGAAAACACATTAGATGTCAT
	CTGGAAGTGGACTGTGG	3186
	CCACAGTCCACTTCCAG	3187
Non-polyposis	TGACATCTAATGTGTTTTCCAGAGTGAAGTGCCTGGCTCCATT	3188
colorectal cancer	CCAAACTCCTGGAAGTGGACTGTGGAACACATTGTCTATAAA
Trp714Term	GCCTTGCGCTCACACATTCTGCCTCCTAAACATTTC
TGG-TGA	GAAATGTTTAGGAGGCAGAATGTGTGAGCGCAAGGCTTTATA	3189
	GACAATGTGTTCCACAGTCCACTTCCAGGAGTTTGGAATGGA
	GCCAGGCACTTCACTCTGGAAkACACATTAGATGTCA
	TGGAAGTGGACTGTGGA	3190
	TCCACAGTCCACTTCCA	3191
Non-polyposis	ATCTAATGTGTTTTCCAGAGTGAAGTGCCTGGCTCCATTCCAA	3192
colorectal cancer	ACTCCTGGAAGTGGACTGTGGAACACATTGTCTATAAAGCCTT
Val716Met	GCGCTCACACATTCTGCCTCCTAAACATTTCACAG
GTG-ATG	CTGTGAAATGTTTAGGAGGCAGAATGTGTGAGCGCAAGGCTT	3193
	TATAGACAATGTGTTCCACAGTCCACTTCCAGGAGTTTGGAAT
	GGAGCCAGGCACTTCACTCTGGAAAACACATTAGAT
	AGTGGACTGTGGAACAC	3194
	GTGTTCCACAGTCCACT	3195
Non-polyposis	GAGTGAAGTGCCTGGCTCCATTCCAAACTCCTGGAAGTGGAC	3196
colorectal cancer	TGTGGAACACATTGTCTATAAAGCCTTGCGCTCACACATTCTG
Tyr721Term	CCTCCTAAACATTTCACAGAAGATGGAAATATCCTG
TAT-TAA	CAGGATATTTCCATCTTCTGTGAAATGTTTAGGAGGCAGAATG	3197
	TGTGAGCGCAAGGCTTTATAGACAATGTGTTCCACAGTCCAC
	TTCCAGGAGTTTGGAATGGAGCCAGGCACTTCACTC
	ATTGTCTATAAAGCCTT	3198
	AAGGCTTTATAGACAAT	3199
Non-polyposis	CTAAACATTTCACAGAAGATGGAAATATCCTGCAGCTTGCTAA	3200
colorectal cancer	CCTGCCTGATCTATACAAAGTCTTTGAGAGGTGTTAAATATGG
Lys751Arg	TTATTTATGCACTGTGGGATGTGTTCTTCTTTCTC
AAA-AGA	GAGTAAGAAGAACACATCCCACAGTGCATAAATAACCATATTT	3201
	AACACCTCTCAAAGACTTTGTATAGATCAGGCAGGTTAGCAAG
	CTGCAGGATATTTCCATCTTCTGTGAAATGTTTAG
	TCTATACAAAGTCTTTG	3202
	CAAAGACTTTGTATAGA	3203
Non-polyposis	ACAGAAGATGGAAATATCCTGCAGCTTGCTAACCTGCCTGAT	3204
colorectal cancer CTATACAAAGTCTTTGAGAGGTGTTAAATATGGTTATTTATGCA
Arg755Trp	CTGTGGGATGTGTTCTTCTTTCTCTGTATTCCGAT
AGG-TGG	ATCGGAATACAGAGAAAGAAGAACACATCCCAGAGTGCATAA	3205
	ATAACCATATTTAACACCTCTCAAAGACTTTGTATAGATCAGG
	CAGGTTAGCAAGCTGCAGGATATTTCCATCTTCTGT
	TCTTTGAGAGGTGTTAA	3206
	TTAACACCTCTCAAAGA	3207

EXAMPLE 18

Human Mismatch Repair—MSH2

[0139] The human MSH2 gene is homologous to the bacterial mutS gene, which is involved in mismatch repair. Mutations in the MSH2 gene have been identified in a variety of cancers, including, for example, ovarian tumors, colorectal cancer, endometrial cancer, uterine cancer. The attached table discloses the correcting oligonucleotide base sequences for the MSH2 oligonucleotides of the invention.

TABLE 25
MSTT2 Mutations and Genome-Connecting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Non polyposis	TTTTCCACAAAAGACATTTATCAGGACCTCAACCGGTTGTTGA	3208
colorectal cancer	AAGGCAAAAAGGGAGAGCAGATGAATAGTGCTGTATTGCCAG
Gln252Term	AAATGGAGAATCAGGTACATGGATTATAAATGTGAA
CAG-TAG	TTCACATTTATAATCCATGTACCTGATTCTCCATTTCTGGCAAT	3209
	ACAGCACTATTCATCTGCTCTCCCTTTTTGCCTTTCAACAACC
	GGTTGAGGTCCTGATAAATGTCTTTTGTGGAAAA
	AGGGAGAGCAGATGAAT	3210
	ATTCATCTGCTCTCCCT	3211
Non polyposis	TCATCACTGTCTGCGGTAATCAAGTTTTTAGAACTCTTATCAG	3212
colorectal cancer	ATGATTCCAACTTTGGACAGTTTGAACTGACTACTTTTGACTT
Gln288Term	CAGCCAGTATATGAAATTGGATATTGCAGCAGTCA
CAG-TAG	TGACTGCTGCAATATCCAATTTCATATACTGGCTGAAGTCAAA	3213
	AGTAGTCAGTTCAAACTGTCCAAAGTTGGAATCATCTGATAAG
	AGTTCTAAAAACTTGATTACCGCAGACAGTGATGA
	ACTTTGGACAGTTTGAA	3214
	TTCAAACTGTCCAAAGT	3215
Non polyposis	AACTTTGGACAGTTTGAACTGACTACTTTTGACTTCAGCCAGT	3216
colorectal cancer	ATATGAAATTGGATATTGCAGCAGTCAGAGCCCTTAACCTTTT
Ala305Thr	TCAGGTAAAAAAAAAAAAAAAAAAAAAAAAAAAGG
GCA-ACA	CCTTTTTTTTTTTTTTTTTTTTTTTTTACCTGAAAAAGGTTAAG	3217
	GGCTCTGACTGCTGCAATATCCAATTTCATATACTGGCTGAAG
	TCAAAAGTAGTCAGTTCAAACTGTCCAAAGTT
	TGGATATTGCAGGAGTC	3218
	GACTGCTGCAATATCCA	3219
Non polyposis	AGCTTGCCATTCTTTCTATTTTATTTTTTGTTTACTAGGGTTCT	3220
colorectal cancer	GTTGAAGATACCACTGGCTCTCAGTCTCTGGCTGCCTTGCTG
Gly322Asp	AATAAGTGTAAAACCCCTCAAGGACAAAGACTTGT
GGC-GAC	ACAAGTCTTTGTCCTTGAGGGGTTTTACACTTATTCAGCAAGG	3221
	CAGCCAGAGACTGAGAGCCAGTGGTATCTTCAACAGAACCCT
	AGTAAACAAAAAATAAAATAGAAAGAATGGCAAGCT
	TACCACTGGCTCTCAGT	3222
	ACTGAGAGCCAGTGGTA	3223
Non polyposis	TTGCCATTCTTTCTATTTTATTTTTTGTTTACTAGGGTTCTGTTG	3224
colorectal cancer	AAGATACCACTGGCTCTCAGTCTGTGGCTGGCTTGCTGAATA
Ser323Cys	AGTGTAAAACCCCTCAAGGACAAAGACTTGTTAA
TCT-TGT	TTAACAAGTCTTTGTCCTTGAGGGGTTTTACACTTATTCAGCA	3225
	AGGCAGCCAGAGACTGAGAGCCAGTGGTATCTTCAACAGAAC
	CCTAGTAAACAAAAAATAAAATAGAAAGAATGGCAA
	CACTGGCTCTCAGTCTC	3226
	GAGACTGAGAGCCAGTG	3227
Non polyposis	GTGGAAGCTTTTGTAGAAGATGCAGAATGAGGCAGACTTTA	3228
colorectal cancer	CAAGAAGATTTACTTCGTCGATTCGCAGATCTTAACCGACTTG
Arg383Term	CCAAGAAGTTTCAAAGACAAGCAGCAAACTTACAAG
CGA-TGA	CTTGTAAGTTTGCTGCTTGTCTTTGAAACTTCTTGGCAAGTCG 3229
	GTTAAGATCTGGGAATCGACGAAGTAAATCTTCTTGTAAAGTC
	TGCCTCAATTCTGCATCTTCTACAAAAGCTTCCAC
	TACTTCGTCGATTCCCA	3230
	TGGGAATCGACGAAGTA	3231
Non polyposis	CAAGAAGATTTACTTCGTCGATTCCCAGATCTTAACCGACTTG	3232
colorectal cancer	CCAAGAAGTTTCAAAGACAAGCAGCAAACTTACAAGATTGTTA
Gln397Term	CCGACTCTATCAGGGTATAAAATCAACTACCTAATG
CAA-TAA	CATTAGGTAGTTGATTTATACCCTGATAGAGTCGGTAACAATC	3233
	TTGTAAGTTTGCTGCTTGTCTTTGAAACTTCTTGGCAAGTCGG
	TTAAGATCTGGGAATCGACGAAGTAAATCTTCTTG
	TTCAAAGACAAGCAGCA	3234
	TGCTGCTTGTCTTTGAA	3235
Non polyposis	GATCTTAACCGACTTGCCAAGAAGTTTCAAAGACAAGCAGCA	3236
colorectal cancer	AACTTACAAGATTGTTACCGACTCTATCAGGGTATAAATCAAC
Arg406Term	TACCTAATGTTATACAGGCTCTGGAAAAACATGAAG
CGA-TGA	CTTCATGTTTTTCCAGAGCCTGTATAACATTAGGTAGTTGATTT	3237
	ATACCCTGATAGAGTCGGTAACAATCTTGTAAGTTTGCTGCTT
	GTCTTTGAAACTTCTTGGCAAGTCGGTTAAGATC
	ATTGTTACCGACTCTAT	3238
	ATAGAGTCGGTAACAAT	3239
Non polyposis	GCAAACTTACAAGATTGTTACCGACTCTATCAGGGTATAAATC	3240
colorectal cancer	AACTACCTAATGTTATACAGGCTCTGGAAAATTACATGAAGGTAA
Gln419Term	CAAGTGATTTTGTTTTTTTGTTTTCTTCAACTCA
CAG-TAG	TGAGTTGAAGGAAAACAAAAAAACAAAATCACTTGTTACCTTC	3241
	ATGTTTTTCGAGAGCCTGTATAACATTAGGTAGTTGATTTATAC
	CCTGATAGAGTCGGTAACAATCTTGTAAGTTTGC
	ATGTTATACAGGCTCTG	3242
	CAGAGCCTGTATAACAT	3243
Non polyposis	TATTCTGTAAAATGAGATCTTTTTATTTGTTGTTTTACTACTTT	3244
colorectal cancer	CTTTTAGGAAAACACCAGAAATTATTGTTGGCAGTTTTTGTGA
Gln429Term	CTCCTCTTACTGATCTTCGTTCTGACTTCTCCA
GAG-TAG	TGGAGAAGTCAGAACGAAGATCAGTAAGAGGAGTCACAAAAA	3245
	CTGCCAACAATAATTTCTGGTGTTTTCCTAAAAGAAAGTAGTA
	AAACAAACAAATAAAAAGATCTCATTTTACAGAATA
	GAAAACACCAGAAATTA	3246
	TAATTTTGGTGTTTTC	3247
Non polyposis	CTCCTCTTACTGATCTTCGTTCTGACTTCTCCAAGTTTCAGGA	3248
colorectal cancer	AATGATAGAAACAACTTTAGATATGGATCAGGTATGGAATATA
Leu458Term	CTTTTTAATTTAAGCAGTAGTTATTTTTAAAAAGC
TTA-TGA	GCTTTTTAAAAATAACTACTGCTTAAATTTAAAAGTATATTGCA	3249
	TACCTGATCCATATCTAAAGTTGTTTCTATCATTTCCTGAAACT
	TGGAGAAGTCAGAACGAAGATCAGTAAGAGGAG
	AACAACTTTAGATATGG	3250
	CCATATCTAAAGTTGTT	3251
Non polyposis	TTTCTTCTTGATTATCAAGGCTTGGACCCTGGCAAAGAGATTA	3252
colorectal cancer	AACTGGATTCCAGTGCACAGTTTGGATATTACTTCGTGTAAC
Gln518Term	CTGTAAGGAAGAAAAAGTCCTTCGTAACAATAAAA
CAG-TAG	TTTTATTGTTACGAAGGACTTTTTCTTCCTTACAGGTTACACGA	3253
	AAGTAATATCCAAACTGTGCACTGGAATCCAGTTTAATCTGTT
	TGCCAGGGTCCAAGCCTTGATAATCAAGAAGAAA
	CCAGTGCACAGTTTGGA	3254
	TCCAAACTGTGCACTGG	3255
Non polyposis	GCTTGGACCCTGGCAAACAGATTAAACTGGATTCCAGTGCAC	3256
colorectal cancer	AGTTTGGATATTACTTTCGTGTAACCTGTAAGGAAGAAAAAGT
Arg524Pro	CCTTCGTAACAATAAAAACTTTAGTACTGTAGATAT
CGT-CCT	ATATCTACAGTACTTAAAGTTTTTATTGTTACGAAGGACTTTTTC	3257
	TTCCTTACAGGTTACACGTAAAGTAATATCCAAACTGTGCACTG
	GAATCCAGTTTAATCTGTTTGCCAGGGTCCAAGC
	TTACTTTCGTGTAACCT	3258
	AGGTTACACGAAAGTAA	3259
Non polyposis	TTAATATTTTTAATAAAACTGTTATTTCGATTTGCAGCAAATTGA	3260
colorectal cancer	CTTCTTTAAATGAAGAGTATACCAAAAATAAAACAGAATATGAA
Glu562Tal	GAAGCCCAGGATGCCATTGTTAAAGAAATTGT
GAG-GTG	ACAATTTCTTTAACAATGGCATCCTGGGCTTCTTCATATTCTGT	3261
	TTTATTTTTGGTATACTCTTCATTTAAAGAAGTCAATTTGCTGC
	AAATCGAAATAACAGTTTTATTAAAAATATTAA
	AAATGAAGAGTATACCA	3262
	TGGTATACTCTTCATTT	3263
Glioma	AATGAAGAGTATACCAAAAATAAAACAGAATATGAAGAAGCCC	3264
Glu580Term	AGGATGCCATTGTAAAGAAATTGTCAATATTTGTTCAGGTAAA
GAA-TAA	CTTAATAGAACTAATAATGTTCTGAATGTCACCT
	AGGTGACATTCAGAACATTATTAGTTCTATTAAGTTTACCTGAA	3265
	GAAATATTGACAATTTCTTTAAGAATGGCATCCTGGGCTTCTT
	CATATTCTGTTTTATTTTTGGTATACTCTTCATT
	TTGTTAAAGAAATTGTC	3266
	GACAATTTCTTTAACAA	3267
Non polyposis	TGTTTTTATTTTTATACAGGGTATGTAGAACCAATGCAGACACT	3268
colorectal cancer	CAATGATGTGTTAGCTCAGCTAGATGCTGTTGTCAGCTTTGCT
Gln601Term	CACGTGTCAAATGGAGCACCTGTTCCATATGTAC
CAG-TAG	GTACATATGGAACAGGTGCTCCATTTGACACGTGAGCAAAGC	3269
	TGACAACAGCATCTAGCTGAGCTAACACATCATTGAGTGTCTG
	CATTGGTTCTACATAGCCTGTATAAAAATAAAAACA
	TGTTAGCTCAGCTAGAT	3270
	ATCTAGCTGAGCTAACA	3271
Non polyposis	AGCTCAGCTAGATGCTGTTGTCAGCTTTGCTCACGTGTCAAAT	3272
colorectal cancer	GGAGCACCTGTTCCATATGTACGACCAGCCATTTTGGAGAAA
Tyr619Term	GGACAAGGAAGAATTATATTAAAAGCATCCAGGCAT
TAT-TAG	ATGCCTGGATGCTTTTAATATAATTCTTCCTTGTCCTTTCTCCA	3273
	AAATGGCTGGTCGTACATATGGAACAGGTGCTCCATTTGACA
	CGTGAGCAAAGCTGACAACAGCATCTAGCTGAGCT
	GTTCCATATGTACGACC	3274
	GGTCGTACATATGGAAC	3275
Non polyposis	CAGCTAGATGCTGTTGTCAGCTTTGCTCACGTGTCAAATGGA	3276
colorectal cancer	GCACCTGTTCCATATGTACGACCAGCCATTTTGGAGAAAGGA
Arg621Term	CAAGGAAGAATTATATTAATAGCATCCAGGCATGCTT
CGA-TGA	AAGCATGCCTGGATGCTTTTAATATAATTCTTCCTTGTCCTTTC	3277
	TCCAAAATGGCTGGTCGTACATATGGAACAGGTGCTCCATTT
	GACACGTGAGCAAAGCTGACAACAGCATCTAGCTG
	CATATGTACGACCAGCC	3278
	GGCTGGTCGTACATATG	3279
Non polyposis	TAGATGCTGTTGTCAGCTTTGCTCAGGTGTCAAATGGAGCAC	3280
colorectal cancer	CTGTTCCATATGTACGACCAGCCATTTTGGAGAAAGGACAAG
Pro622Leu	GAAGAATTATATTAAAAGCATCCAGGCATGCTTGTGT
CCA-CTA	ACACAAGCATGCCTGGATGCTTTTAATATAATTCTTCCTTGTC	3281
	CTTTCTCCAAAATGGCTGGTCGTACATATGGAACAGGTGCTC
	CATTTGACACGTGAGCAAAGCTGACAACAGCATCTA
	TGTACGACCAGCCATTT	3282
	AAATGGCTGGTCGTACA	3283
Non polyposis	CCTGTTCCATATGTACGACCAGCCATTTTGGAGAAAGGACAA	3284
colorectal cancer	GGAAGAATTATATTAAAAGCATCCAGGCATGCTTGTGTTGAAG
Ala636Pro	TTCAAGATGAAATTGCATTTATTCCTAATGACGTAT
GCA-CCA	ATACGTCATTAGGAATAAATGCAATTTCATCTTGAAGTTCAACA	3285
	CAAGCATGCCTGGATGCTTTTAATATAATTCTTCCTTGTCCTTT
	CTCCAAAATGGCTGGTCGTACATATGGAACAGG
	TATTAAAAGCATCCAGG	3286
	CCTGGATGCTTTTAATA	3287
Non polyposis	ATGTACGACCAGCCATTTTGGAGAAAGGACAAGGAAGAATTA	3288
colorectal cancer	TATTAAAAGCATCCAGGCATGCTTGTGTTGAAGTTCAAGATGA
TTis639Arg	AATTGCATTTATTCCTAATGACGTATACTTTGAAAA
CAT-CGT	TTTTCAAAGTATACGTCATTAGGAATAAATGCAATTTCATCTTG	3289
	AACTTCAACACAAGCATGCCTGGATGCTTTTAATATAATTCTTC
	CTTGTCCTTTCTCCAAAATGGCTGGTCGTACAT
	ATCCAGGCATGCTTGTG	3290
	CACAAGCATGCCTGGAT	3291
Non polyposis	TATGTACGACCAGCCATTTTGGAGAAAGGACAAGGAAGAATT	3292
colorectal cancer	ATATTAAAAGCATCCAGGCATGCTTGTGTTGAAGTTCAAGATG
TTis639Tyr	AAATTGCATTTATTCCTAATGACGTATACTTTGAAA
CAT-TAT	TTTCAAAGTATACGTCATTAGGAATAAATGCAATTTCATCTTGA 3293
	ACTTCAACACAAGCATGCCTGGATGCTTTTAATATAATTCTTC
	CTTGTCCTTTCTCCAAAATGGCTGGTCGTACATA
	CATCCAGGCATGCTTGT	3294
	ACAAGCATGCCTGGATG	3295
Non polyposis	AAAGGACAAGGAAGAATTATATTAAAAGCATCCAGGCATGGTT	3296
colorectal cancer	GTGTTGAAGTTCAAGATGAAATTGCATTTATTCCTAATGACGT
Glu647Lys	ATACTTTGAAAAAGATAAACAGATGTTCCACATCA
GAA-AAA	TGATGTGGAACATCTGThTATCTTTTTCAAAGTATACGTCATTA	3297
	GGAATAAATGCAATTTCATCTTGAACTTCAACACAAGCATGCC
	TGGATGCTTTTAATATAATTCTTCCTTGTCCTTT
	TTCAAGATGAAATTGCA	3298
	TGCAATTTCATCTTGAA	3299
Non polyposis	ATCCAGGCATGCTTGTGTTGAAGTTCAAGATGAAATTGCATTT	3300
colorectal cancer	ATTCCTAATGACGTATACTTTGAAAAAGATAAACAGATGTTCCA
Tyr656Term	CATCATTACTGGTAAAAAACCTGGTTTTTGGGCT
TAC-TAG	AGCCCAAAAACCAGGTTTTTTACCAGTAATGATGTGGAACATC	3301
	TGTTTATCTTTTTCAAAGTATACGTCATTAGGAATAAATGCAAT
	TTCATCTTGAACTTCAACACAAGCATGCCTGGAT
	GACGTATACTTTGTAAAA	3302
	TTTTCAAAGTATACGTC	3303
Non polyposis	GAAAGAAGTTTAAAATCTTGCTTTCTGATATAATTTGTTTTGTA	3304
colorectal cancer	GGCCCCAATATGGGAGGTTAATCAACATATATTCGACAAACT
Gly674Asp	GGGGTGATAGTACTCATGGCCCAAATTGGGTGTTT
GGT-GAT	AAACACCCAATTTGGGCCATGAGTAGTATCACCCCAGTTTGTC	3305
	GAATATATGTTGATTTACCTCCCATATTGGGGCCTACAAAACA
	AATTATATCAGAAAGCAAGATTTTAAACTTCTTTTC
	TATGGGAGGTAAATCAA	3306
	TTGATTTACCTCCCATA	3307
Non polyposis	TTGCTTTCTGATATAATTTGTTTTGTAGGCCCCAATATGGGAG	3308
colorectal cancer	GTAAATCAACATATATTCGACAAACTGGGGTGATAGTACTCAT
Arg680Term	GGCCCAAATTGGGTGTTTTGTGCCATGTGAGTCAG
CGA-TGA	CTGACTCACATGGCACAAAACACCCAATTTGGGCCATGAGTA	3309
	CTATCACCCCAGTTTGTCGAATATATGTTGATTTACCTCCCAT
	ATTGGGGCCTACAAAACAAATTATATCAGAAAGCAA
	CATATATTCGACAAACT	3310
	AGTTTGTCGAATATATG	3311
Non polyposis	ATGGGAGGTAAATCAACATATATTCGACAAAACTGGGGTGATA	3312
colorectal cancer	GTACTCATGGCCCAAATTGGGTGTTTTGTGCCATGTGAGTCA
Gly692Arg	GCAGAAGTGTCCATTGTGGACTGCATCTTAGCCCGAG
GGG-CGG	CTCGGGCTAAGATGCAGTCCACAATGGACACTTCTGCTGACT	3313
	CACATGGCACAAAACACCCAATTTGGGCCATGAGTACTATCA
	CCCCAGTTTGTCGAATATATGTTGATTTACCTCCCAT
	CCCAAATTGGGTGTTTT	3314
	AAAACACCCAATTTGGG	3315
Non polyposis	ACATATATTCGACAAACTGGGGTGATAGTACTCATGGCCCAAA	3316
colorectal cancer	TTGGGTGTTTTGTGCCATGTGAGTCAGCAGAAGTGTCCATTG
Cys697Arg	TGGACTGCATCTTAGCCCGAGTAGGGGCTGGTGACA
TGT-CGT	TGTCACCAGCCCCTACTCGGGCTAAGATGCAGTCCACAATGG	3317
	ACACTTCTGCTGACTCACATGGCACAAAACACCCAATTTGGG
	CCATGAGTACTATCACCCCAGTTTGTCGAATATATGT
	TTGTGCCATGTGAGTCA	3318
	TGACTCACATGGCACAA	3319
Non polyposis	CATATATTCGACAAACTGGGGTGATAGTACTCATGGCCCAAAT	3320
colorectal cancer	TGGGTGTTTTGTGCCATGTGAGTCAGCAGAAGTGTCCATTGT
Cys697Phe	GGACTGCATCTTAGCCCGAGTAGGGGCTGGTGACAG
TGT-TTT	CTGTCACCAGCCCCTACTCGGGCTAAGATGCAGTCCACAATG	3321
	GACACTTCTGCTGACTCACATGGCACAAAACACCCAATTTGG
	GCCATGAGTACTATCACCCCAGTTTGTCGAATATATG
	TGTGCCATGTGAGTCAG	3322
	CTGACTCACATGGCACA	3323
Non polyposis	GAGTCAGCAGAAGTGTCCATTGTGGACTGCATCTTAGCCCGA	3324
colorectal cancer	GTAGGGGCTGGTGACAGTCAATTGAAAGGAGTCTCCACGTTC
Gln718Term	ATGGCTGAAATGTTGGAAACTGCTTCTATCCTCAGGT
CAA-TAA	ACCTGAGGATAGAAGCAGTTTCCAACATTTCAGCCATGAACG	3325
	TGGAGACTCCTTTCAATTGACTGTCACCAGCCCCTACTCGGG
	CTAAGATGCAGTCCACAATGGACACTTCTGCTGACTC
	GTGACAGTCAATTGAAA	3326
	TTTCAATTGACTGTCAC	3327
Non polyposis	CCAATCAGATACCAACTGTTAATAATCTACATGTCACAGCACT	3328
colorectal cancer	CACCACTGAAGAGACCTTAACTATGCTTTATCAGGTGAAGAAA
Leu811Term	GGTATGTACTATTGGAGTACTCTTAAATTCAGAACT
TTA-TGA	AGTTCTGAATTTAGAGTACTCCAATAGTACATACCTTTCTTCAC	3329
	CTGATTAAAGCATAGTTAAGGTCTCTTCAGTGGTGAGTGCTGT
	GACATGTAGATTATTAACAGTTGGTATCTGATTGG
	AGAGACCTTAACTATGC	3330
	GCATAGTTAAGGTCTCT	3331
Non polyposis	TTCCCCAAATTTCTTATAGGTGTCTGTGATCAAAGTTTTGGGA	3332
colorectal cancer	TTCATGTTGCAGAGCTTGCTAATTTCCCTAAGCATGTAATAGA
Ala834Thr	GTGTGCTAAACAGAAAGCCCTGGAACTTGAGGAGT
GCT-ACT	ACTCCTCAAGTTCCAGGGCTTTCTGTTTAGCACACTCTATTAC	3333
	ATGCTTAGGGAAATTAGCAAGCTCTGCAACATGAATCCCAAAA
	CTTTGATCACAGACACCTATAAGAAATTTGGGGAA
	CAGAGCTTGCTAATTTC	3334
	GAAATTAGCAAGCTCTG	3335
Non polyposis	ATAGAGTGTGCTAAACAGAAAGCCCTGGAACTTGAGGAGTTT	3336
colorectal cancer	CAGTATATTGGAGAATCGCAAGGATATGATATCATGGAACCAG
Gln861Term	CAGCAAAGAAGTGCTATCTGGAAAGAGAGGTTTGTC
CAA-TAA	GACAAACCTCTCTTTCCAGATAGCACTTCTTTGCTGCTGGTTC	3337
	CATGATATCATATCCTTGCGATTCTCCAATATACTGAAACTCCT
	CAAGTTCCAGGGCTTTCTGTTTAGCACACTCTAT
	GAGAATCGCAAGGATAT	3338
	ATATCCTTGCGATTCTC	3339
Non polyposis	AGGAGTTCCTGTCCAAGGTGGAACAAATGCCCTTTACTGAAAT	3340
colorectal cancer	GTCAGAAGAAAACATCACAATAAAGTTAAAACAGCTAAAAGCT
Thr905Arg	GAAGTAATAGCAAAGAATAATAGCTTTGTAAATGA
ACA-AGA	TCATTTACAAAGCTATTATTCTTTGCTATTACTTCAGCTTTTAG	3341
	CTGTTTTAACTTTATTGTGATGTTTTCTTCTGACATTTCAGTAA
	AGGGCATTTGTTTCACCTTGGACAGGAACTCCT
	AAACATCACAATAAAGT	3342
	ACTTTATTGTGATGTTT	3343

EXAMPLE 19

Human Mismatch Repair—MSH6

[0140] The human MSH6 gene is homologous to the bacterial mutS gene, which is involved in mismatch repair. Mutations in the MSH6 gene have been identified in a variety of cancers, including particularly hereditary nonpolyposis colorectal cancer. The attached table discloses the correcting oligonucleotide base sequences for the MSH6 oligonucleotides of the invention.

TABLE 26
MSH6 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Non-polyposis	GGAAATCAGTCCGTGTTCATGTACAGTTTTTTGATGACAGCCC	3344
colorectal cancer	AACAAGGGGCTGGGTTAGCAAAAGGCTTTTAAAGCCATATAC
Ser144lle	AGGTAAGAGTCACTACTGCCATGTGTGTGTGTTTGT
AGC-ATC
	ACAAACACACACACATGGCAGTAGTGACTCTTACCTGTATATG	3345
	GCTTTAAAAGCCTTTTGCTAACCCAGCCCCTTGTTGGGCTGT
	CATCAAAAAACTGTACATGAACACGGACTGATTTCC
	CTGGGTTAGCAAAAGGC	3346
	GCCTTTTGCTAACCCAG	3347
Endometrial cancer	CGTGAGCCTCTGCACCCGGCCCTTATTGTTTATAAATACATTT	3348
Ser156Term	CTTTCTAGGTTCAAAATCAAAGGAAGCCCAGAAGGGAGGTCA
TCA-TGA	TTTTTACAGTGCAAAGCCTGAAATACTGAGAGCAAT
	ATTGCTCTCAGTATTTCAGGCTTTGCACTGTAAAAATGACCTC	3349
	CCTTCTGGGCTTCCTTTGATTTTGAACCTAGAAAGAAATGTAT
	TTATAAACAATAAGGGCCGGGTGCAGAGGCTCACG
	TTCAAAATCAAAGGAAG	3350
	CTTCCTTTGATTTTGAA	3351
Early onset colorectal	TTCCAAATTTTGATTTGTTTTTAAATACTCTTTCCTTGCCTGGC	3352
cancer	AGGTAGGCACAACTTACGTAACAGATAAGAGTGAAGAAGATA
Tyr214Term	ATGAAATTGAGAGTGAAGAGGAAGTACAGCCTAAG
TAC-TAG
	CTTAGGCTGTACTTCCTCTTCACTCTCAATTTCATTATCTTCTT	3353
	CACTCTTATCTGTTACGTAAGTTGTGCCTACCTGCCAGGCAA
	GGAAAGAGTATTTAAAAACAAATCAAAATTTGGAA
	ACAACTTACGTAACAGA	3354
	TCTGTTACGTAAGTTGT	3355
Endometrial cancer	GAAGAGGAAGTACAGCCTAAGACACAAGGATCTAGGCGAAGT	3356
Arg248Term	AGCCGCCAAATXAATTAAACGAAGGGTCATATCAGATTCTGAG
CGA-TGA	AGTGACATTGGTGGCTCTGATGTGGAATTTAAGCCAG
	CTGGCTTAAATTCCACATCAGAGCCACCAATGTCACTCTCAGA	3357
	ATCTGATATGACCCTTCGTTTTTTTATTTGGCGGCTACTTCGC
	CTAGATCCTTGTGTCTTAGGCTGTACTTCCTCTTC
	TAAAAAAACGAAGGGGTC	3358
	GACCCTTCGTTTTTTTA	3359
Colorectal cancer	TTAAGCCAGACACTAAGGAGGAAGGAAGCAGTGATGAAATAA	3360
Ser285lle	GCAGTGGAGTGGGGGATAGTGAGAGTGAAGGCCTGAACAGC
AGT-ATT	CCTGTCAAAGTTGCTCGAAAGCGGAAGAGAATGGTGAC
	GTCACCATTCTCTTCCGCTTTCGAGCAACTTTGACAGGGCTG	3361
	TTCAGGCCTTCACTCTCACTATCCCCCACTCCACTGCTTATTT
	CATCACTGCTTCCTTCCTCCTTAGTGTCTGGCTTAA
	GGGGGATAGTGAGAGTG	3362
	CACTCTCACTATCCCCC	3363
Colorectal cancer	GAGGAAGATTCTTCTGGCCATACTCGTGCATATGGTGTGTGC	3364
Gly566Arg	TTTGTTGATACTTCACTGGGAAAGTTTTTCATAGGTCAGTTTTC
GGA-AGA	AGATGATCGCCATTGTTCGAGATTTAGGACTCTAG
	CTAGAGTCCTAAATCTCGAACJAATGGCGATCATCTGAAAACTG	3365
	ACCTATGAAAAACTTTCCCAGTGAAGTATCAACAAAGCACACA
	CCATATGCACGAGTATGGCCAGAAGAATCTTCCTC
	CTTCACTGGGAAAGTTT	3366
	AAACTTTCCCAGTGAAG	3367
Non-polyposis	GAATTGGCCCTCTCTGCTCTAGGTGGTTGTGTCTTCTACCTC	3368
colorectal cancer	AAAAAATGCCTTATTGATCAGGAGCTTTTATCAATGGCTAATTT
Gln698Glu	TGAAGAATATATTCCCTTGGATTCTGACACAGTCA
CAG-GAG
	TGACTGTGTCAGAATCCAAGGGAATATATTCTTCAAAATTAGC	3369
	CATTGATAAAAGCTCCTGATCAATAAGGCATTTTTTGAGGTAG
	AAGACACAACCACCTAGAGCAGAGAGGGCCAATTC
	TTATTGATCAGGAGCTT	3370
	AAGCTCCTGATCAATAA	3371
Endometrial cancer	CCCTTGGATTCTGACACAGTCAGCACTACAAGATCTGGTGCT	3372
Gln731Term	ATCTTCACCAAAGCCTATCAACGAATGGTGCTAGATGCAGTG
CAA-TAA	ACATTAAACAACTTGGAGATTTTTCTGAATGGAACAA
	TTGTTCCATTCAGAAAAATCTCCAAGTTGTTTAATGTCACTGCA	3373
	TCTAGCACCATTCGTTGATAGGCTTTGGTGAAGATAGCACCA
	GATCTTGTAGTGCTGACTGTGTCAGAATCCAAGGG
	AAGCCTATCAACGAATG	3374
	CATTCGTTGATAGGCTT	3375
Colorectal cancer	GCCCCACTCTGTAACCATTATGCTATTAATGATCGTCTAGATG	3376
Val800Leu	CCATAGAAGACCTCATGGTTGTGCCTGACAAAATCTCCGAAG
GTT-CTT	TTGTAGAGCTTCTAAAGAAGCTTCCAGATCTTGAGA
	TCTCAAGATCTGGAAGCTTCTTTAGAAGCTCTACAACTTCGGA	3377
	GATTTTGTCAGGCACAACCATGAGGTCTTCTATGGCATCTAGA
	CGATCATTAATAGCATAATGGTTACAGAGTGGGGC
	ACCTCATGGTTGTGCCT	3378
	AGGCACAACCATGAGGT	3379
Colorectal cancer	GTAACCATTATGCTATTAATGATCGTCTAGATGGCATAGAAGA	3380
Asp803Gly	CCTCATGGTTGTGCCTGACAAAATCTCCGAAGTTGTAGAGCT
GAC-GGC	TCTAAAGAAGCTTCCAGATCTTGAGAGGCTACTCAG
	CTGAGTAGCCTCTCAAGATCTGGAAGCTTCTTTAGAAGCTCTA 3381
	CAACTTCGGAGATTTTGTCAGGCACAACCATGAGGTCTTCTAT
	GGCATCTAGACGATCATTAATAGCATAATGGTTAC
	TGTGCGTGACAAAATCT	3382
	AGATTTTGTCAGGCACA	3383
Non-polyposis	CTCCCCTGAAGAGTCAGAACCACCCAGACAGCAGGGCTATAA	3384
colorectal cancer	TGTATGAAGAAACTACATACAGCAAGAAGAAGATTATTGATTT
Tyr850Cys	TCTTTCTGCTCTGGAAGGATTCAAAGTAATGTGTAA
TAC-TGC
	TTACACATTACTTTGAATCCTTCCAGAGCAGAAAGAAATCAA	3385
	TAATCTTCTTCTTGCTGTATGTAGTTTCTTCATACATTATAGCC
	CTGCTGTCTGGGTGGTTCTGACTCTTCAGGGGAG
	AACTACATACAGCAAGA	3386
	TCTTGCTGTATGTAGTT	3387
Colorectal cancer	TATAGTCGAGGGGGTGATGGTCCTATGTGTCGCCCAGTAATT	3388
Pro1087Thr	CTGTTGCCGGAAGATACCCCCCCCTTCTTAGAGCTTAAAGGA
CCC-ACC	TCACGCCATCCTTGCATTACGAAGACTTTTTTTGGAG
	CTCCAAAAAAAGTCTTCGTAATGCAAGGATGGCGTGATCCTTT	3389
	AAGCTCTAAGAAGGGGGGGGTATCTTCCGGCAACAGAATTAC
	TGGGCGACACATAGGACCATCACCCCCTCGACTATA
	AAGATACCCCCCCCTTC	3390
	GAAGGGGGGGGTATCTT	3391
Non-polyposis	ACTATAAAATGTCGTACATTATTTFCAACTCACTACCATTCATT	3392
colorectal cancer	AGTAGAAGATTATTCTCAAAATGTTGCTGTGCGCCTAGGACAT
Gln1258Term	ATGGTATGTGCAAATTGTTTTFTTCCACAAATTC
CAA-TAA
	GAATTTGTGGAAAAAAACAATTTGCACATACCATATGTCCTAG	3393
	GCGCACAGCAACATTTTGAGAATAATCTTCTACTAATGAATGG
	TAGTGAGTTGAAAATAATGTACGACATTTTATAGT
	ATTATTCTCAAAATGTT	3394
	AACATTTTGAGAATAAT	3395

EXAMPLE 20

Hyperlipidemia—APOE

[0141] Hyperlipidemia is the abnormal elevation of plasma cholesterol and/or triglyceride levels and it is one of the most common diseases. The human apolipoprotein E protein is involved in the transport of endogenous lipids and appears to be crucial for both the direct removal of cholesterol-rich LDL from plasma and conversion of IDL particles to LDL particles. Individuals who either lack apolipoprotein E or who are homozygous for particular alleles of apoE may have have a condition known as dysbetalipoproteinemia, which is characterized by elevated plasma cholesterol and triglyceride levels and an increased risk for atherosclerosis.

[0142] In a comprehensive review of apoE variants, de Knijff et al., Hum. Mutat. 4:178-194 (1994) found that 30 variants had been characterized, including the most common variant, apoE3. To that time, 14 apoE variants had been found to be associated with familial dysbetalipoproteinemia. The attached table discloses the correcting oligonucleotide base sequences for the APOE oligonucleotides of the invention.

TABLE 27
APOE Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Apolipoprotein	TTGTTCCACACAGGATGCCAGGCCAAGGTGGAGCAAGCGGT	3396
Glu13Lys	GGAGACAGAGCCGGAGCCCGAGCTGCGCCAGCAGACCGAG
cGAG-AAG	TGGCAGAGCGGCCAGCGCTGGGAACTGGCACTGGGTCGCT
	AGCGACCCAGTGCCAGTTCCCAGCGCTGGCCGCTCTGCCAC	3397
	TCGGTCTGCTGGCGCAGCTCGGGCTCCGGCTCTGTCTCCAC
	CGCTTGCTCCACCHGGCCTGGCATCCTGTGTGGAACAA
	CGGAGCCCGAGCTGCGC	3398
	GCGCAGCTCGGGCTCCG	3399
Apolipoprotein E	CAAGGTGGAGCAAGCGGTGGAGACAGAGCCGGAGCCCGAG	3400
Trp20Term	CTGCGCCAGCAGACCGAGTGGCAGAGCGGCCAGCGCTGGG
TGGc-TGA	AACTGGCACTGGGTCGCTTFTGGGATTACCTGCGCTGGGTG
	CACCCAGCGCAGGTAATCCCAAAAGCGACCCAGTGCCAGTT	3401
	CCCAGCGCTGGCCGCTCTGCCACTCGGTCTGCTGGCGCAGC
	TCGGGCTCCGGCTCTGTCTCCACCGCTTGCTGCACCTTG
	ACCGAGTGGCAGAGCGG	3402
	CCGCTCTGCCACTCGGT	3403
Apolipoprotein E	CAGAGCCGGAGCCCGAGCTGCGCCAGCAGACCGAGTGGCA	3404
Leu28Pro	GAGCGGCCAGCGCTGGGAACTGGCACTGGGTCGCTTTTGGG
CTG-CCG	ATTACCTGCGCTGGGTGCAGACACTGTCTGAGCAGGTGCA
	TGCACCTGCTCAGACAGTGTCTGCACCCAGCGCAGGTAATCC	3405
	CAAAAGCGACCCAGTGCCAGTTCCCAGCGCTGGCCGCTCTG
	CCACTCGGTGTGCTGGCGCAGCTCGGGCTCCGGCTCTG
	CTGGGAACTGGCACTGG	3406
	CCAGTGCCAGTTCCCAG	3407
Apolipoprotein E	CGGCTGTCCAAGGAGCTGCAGGCGGCGCAGGCCCGGCTGG	3408
Cys112Arg	GCGCGGACATGGAGGACGTGTGCGGCCGCCTGGTGCAGTA
gTGC-CGC	CCGCGGCGAGGTGCAGGCCATGCTCGGCCAGAGCACCGAGG
	CCTCGGTGCTCTGGCCGAGCATGGCCTGCACCTCGCCGCGG	3409
	TACTGCACCAGGCGGCCGCACACGTCCTCCATGTCCGCGCC
	CAGCCGGGCCTGCGCCGCCTGCAGCTCCTTGGACAGCCG
	AGGACGTGTGCGGCCGC	3410
	GCGGCCGCACACGTCCT	3411
Apolipoprotein E	ACATGGAGGACGTGTGCGGCCGCCTGGTGCAGTACCGCGG	3412
Gly127Asp	CGAGGTGCAGGCCATGCTCGGCCAGAGCACCGAGGAGCTGT
GGC-GAC	CGGGTGCGCCTCGCCTCCCACCTGCGCAAGCTGCGTAAGCG
	CGCTTACGCAGCTTGCGCAGGTGGGAGGCGAGGCGCACCC	3413
	GCAGCTCCTCGGTGCTCTGGCCGAGCATGGCCTGCACCTCG
	CCGCGGTACTGCACCAGGCGGCCGCACACGTCCTCCATGT
	CATGCTCGGCCAGAGCA	3414
	TGCTCTGGCCGAGCATG	3415
Apolipoprotein E	GTGCAGTACCGCGGCGAGGTGCAGGCCATGCTCGGCCAGA	3416
Arg136Cys	GCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCG
gCGC-TGC	CAAGCTGCGTAAGCGGCTCCTCCGCGATGCCGATGACCTGC
	GCAGGTCATGGGCATCGCGGAGGAGCCGCTTACGCAGCTTG	3417
	CGCAGGTGGGAGGCGAGGCGCACCCGCAGCTCCTCGGTGC
	TCTGGCCGAGCATGGCCTGCACCTCGCCGCGGTACTGCAC
	TGCGGGTGCGCCTCGCC	3418
	GGCGAGGCGCACCCGCA	3419
Apolipoprotein E	TGCAGTACCGCGGCGAGGTGCAGGCCATGCTCGGCCAGAG	3420
Arg136His	CACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCGC
CGC-CAC	AAGCTGCGTAAGCGGCTCCTCCGCGATGCCGATGACCTGCA
	TGCAGGTCATCGGCATCGCGGAGGAGCCGCTTACGCAGCTT	3421
	GCGCAGGTGGGAGGCGAGGCGCACCCGCAGCTCCTCGGTG
	CTCTGGCCGAGCATGGCCTGCACCTCGCCGCGGTACTGCA
	GCGGGTGCGCCTCGCCT	3422
	AGGCGAGGCGCACCCGC	3423
Apolipoprotein E	GTGCAGTACCGCGGCGAGGTGCAGGCCATGCTCGGCCAGA	3424
Arg136Ser	GCACCGAGGAGCTGCGGGTGCGCCTCGCCTCGCACCTGCG
gCGC-AGC	CAAGCTGCGTAAGCGGCTCCTCCGCGATGCCGATGACCTGC
	GCAGGTCATCGGCATCGCGGAGGAGCCGCTTACGCAGTTG	3425
	CGCAGGTGGGAGGCGAGGCGCACCCGCAGCTCCTCGGTGC
	TCTGGCCGAGCATGGCCTGCACCTCGCCGCGGTACTGCAC
	TGCGGGTGCGCCTCGCC	3426
	GGCGAGGCGCACCCGCA	3427
Apolipoprotein E	GTGCAGGCCATGCTCGGCCAGAGCACCGAGGAGCTGCGGG	3428
Arg142Cys	TGCGCCTCGCCTCCCACCTGCGCAAGCTGCGTAAGCGGCTC
gCGC-TGC	CTCCGCGATGCCGATGACCTGCAGAAGCGCCTGGCAGTGT
	ACACTGCCAGGCGCTTCTGCAGGTCATCGGCATCGCGGAGG	3429
	AGCCGCTTACGCAGCTTGCGCAGGTGGGAGGCGAGGCGCA
	CCCGCAGCTCCTCGGTGCTCTGGCCGAGCATGGCCTGCAC
	CCCACCTGCGCAAGCTG	3430
	CAGCTTGCGCAGGTGGG	3431
Apolipoprotein E	TGCAGGCCATGCTCGGCCAGAGCACCGAGGAGCTGCGGGT	3432
Arg142Leu	GCGCCTCGCCTCCCACCTGCGCAAGCTGCGTAAGCGGCTCC
CGC-CTC	TCCGCGATGCCGATGACCTGCAGAAGCGCCTGGCAGTGTA
	TACACTGCCAGGCGCTTCTGCAGGTCATCGGCATCGCGGAG	3433
	GAGCCGCTTACGCAGCTTGCGCAGGTGGGAGGCGAGGCGC
	ACCCGCAGCTCCTCGGTGCTCTGGCCGAGCATGGCCTGCA
	CCACCTGCGCAAGCTGC	3434
	GCAGCTTGCGCAGGTGG	3435
Apolipoprotein E	ATGCTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCG	3436
Arg145Cys	CCTCCCACCTGCGCAAGCTGCGTAAGCGGCTCCTCCGCGAT
gCGT-TGT	GCCGATGACCTGCAGAAGCGCCTGGCAGTGTACCAGGCCG
	CGGCCTGGTACACTGCCAGGCGCTTCTGCAGGTCATCGGCA	3437
	TCGCGGAGGAGCCGCTTACGCAGCTTGCGCAGGTGGGAGG
	CGAGGCGCACCCGCAGGTCCTCGGTGCTCTGGCCGAGCAT
	GCAAGCTGCGTAAGCGG	3438
	CCGCTTACGCAGCTTGC	3439
Apolipoprotein E	TGCTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCGC	3440
Arg145Pro	CTCCCACCTGCGCAAGCTGCGTAAGCGGCTCCTCCGCGATG
CGT-CCT	CCGATGACCTGCAGAAGCGCCTGGCAGTGTACCAGGCCGG
	CCGGCCTGGTACACTGCCAGGCGCTTCTGCAGGTCATCGGC	3441
	ATCGCGGAGGAGCCGCTTACGCAGCTTGCGCAGGTGGGAG
	GCGAGGCGCACCCGCAGCTCCTCGGTGCTCTGGCCGAGCA
	CAAGCTGCGTAAGCGGC	3442
	GCCGCTTACGCAGCTTG	3443
Apolipoprotein E	CTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCGCCT	3444
Lys146Gln	CCCACCTGCGCAAGCTGCGTAAGCGGCTCCTCCGCGATGCC
tAAG-CAG	GATGACCTGCAGAAGCGCCTGGCAGTGTACCAGGCCGGGG
	CCCCGGCCTGGTACACTGCCAGGCGCTTCTGCAGGTCATCG	3445
	GCATCGCGGAGGAGCCGCTTACGCAGCTTGCGCAGGTGGGA
	GGCGAGGCGCACCCGCAGCTCCTCGGTGCTGTGGCCGAG
	AGCTGCGTAAGCGGCTC	3446
	GAGCCGCTTACGCAGCT	3447
Apolipoprotein E	CTCGGCCAGAGCACCGAGGAGCTGCGGGTGCGCCTCGCCT	3448
Lys146Glu	CCCACCTGCGCAAGCTGCGTAAGCGGCTCCTCCGCGATGCC
tAAG-GAG	GATGACCTGCAGAAGCGCCTGGCAGTGTACCAGGCCGGGG
	CCCCGGCCTGGTACACTGCCAGGCGCTTCTGCAGGTCATCG	3449
	GCATCGCGGAGGAGCCGCTTACGCAGCTTGCGCAGGTGGGA
	GGCGAGGCGCACCCGCAGCTCCTCGGTGCTCTGGCCGAG
	AGCTGCGTAAGCGGCTC	3450
	GAGCCGCTTACGCAGCT	3451
Apolipoprotein E	GCCTCCCACCTGCGCAAGCTGCGTAAGCGGCTCCTCCGCGA	3452
Arg158Cys	TGCCGATGACCTGCAGAAGCGCCTGGCAGTGTACCAGGCCG
gCGC-TGC	GGGCCCGCGAGGGCGCCGAGCGCGGCCTCAGCGCCATCC
	GGATGGCGCTGAGGCCGCGCTCGGCGCCCTCGCGGGCCCC	3453
	GGCCTGGTACACTGCCAGGCGCTTCTGCAGGTCATCGGCAT
	CGCGGAGGAGCCGCTTACGCAGCTTGCGCAGGTGGGAGGC
	TGCAGAAGCGCCTGGCA	3454
	TGCCAGGCGCTTCTGCA	3455
Apolipoprotein E	CGCGAGGGCGCCGAGCGCGGCCTCAGCGCCATCCGCGAGC	3456
Gln187Glu	GCCTGGGGCCCCTGGTGGAACAGGGCCGCGTGCGGGCCGC
aCAG-GAG	CACTGTGGGCTCCCTGGCCGGCCAGCCGCTACAGGAGCGGG
	CCCGCTCCTGTAGCGGCTGGCCGGCCAGGGAGCCCACAGT	3457
	GGCGGCCCGCACGCGGCCCTGTTCCACCAGGGGCCCCAGG
	CGCTCGCGGATGGCGCTGAGGCCGCGCTCGGCGCCCTCGCG
	TGGTGGAACAGGGCCGC	3458
	GCGGCCCTGTTCCACCA	3459
Apolipoprotein E	TGCGGGCCGCCACTGTGGGCTCCCTGGCCGGCCAGCCGCT	3460
Trp210Term	ACAGGAGCGGGCCCAGGCCTGGGGCGAGCGGCTGCGCGC
TGG-TAG	GCGGATGGAGGAGATGGGCAGCCGGACCCGCGACCGCCTGGA
	TCCAGGCGGTCGCGGGTCCGGCTGCCCATCTCCTCCATCCG	3461
	CGCGCGCAGCCGCTCGCCCCAGGCCTGGGCCCGCTCCTGT
	AGCGGCTGGCCGGCCAGGGAGCCCACAGTGGCGGCCCGCA
	CCAGGCCTGGGGCGAGC	3462
	GCTCGCCCCAGGCCTGG	3463
Apolipoprotein E	CAGGCCTGGGGCGAGCGGCTGCGCGCGCGGATGGAGGAGA	3464
Arg228Cys	TGGGCAGCCGGACCCGCGACCGCCTGGACGAGGTGAAGGA
cCGC-TGC	GCAGGTGGCGGAGGTGCGCGCCAAGCTGGAGGAGCAGGCCC
	GGGCCTGCTCCTCCAGCTTGGCGCGCACCTCCGCCACCTGC	3465
	TCCTTCACCTCGTCCAGGCGGTCGCGGGTCCGGCTGCCCAT
	CTCCTCCATCCGCGCGCGCAGCCGCTCGCCCCAGGCCTG
	CCCGCGACCGCCTGGAC	3466
	GTCCAGGCGGTCGCGGG	3467
Apolipoprotein E	CGGACCCGCGACCGCCTGGACGAGGTGAAGGAGCAGGTGG	3468
Glu244Lys	CGGAGGTGCGCGCCAAGCTGGAGGAGCAGGCCCAGCAGAT
gGAG-AAG	ACGCCTGCAGGCCGAGGCCTTCCAGGCCCGCCTCAAGAGCT
	AGCTCTTGAGGCGGGCCTGGAAGGCCTCGGCCTGGAGGCGT	3469
	ATCTGCTGGGCCTGCTCCTCCAGCTTGGCGCGCACCTCCGC
	CACCTGCTCCTTCACCTCGTCCAGGCGGTCGCGGGTCCG
	CCAAGCTGGAGGAGCAG	3470
	CTGCTCCTCCAGCTTGG	3471

EXAMPLE 21

Familial Hypercholesterolemia—LDLR

[0143] Familial hypercholesterolemia is characterized by elevation of serum cholesterol bound to low density lipoprotein (LDL) and is, hence, one of the conditions producing a hyperlipoproteinemia phenotype. Familial hypercholesterolemia is an autosomal dominant disorder characterized by elevation of serum cholesterol bound to low density lipoprotein (LDL). Mutations in the LDL receptor (LDLR) gene cause this disorder. The attached table discloses the correcting oligonucleotide base sequences for the LDLR oligonucleotides of the invention.

TABLE 28
LDLR Mutations and Genome-Correcting Oligos
Cilnical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Hypercholesterolaemia	GCGTTGAGAGACCCTTTCTCCTTTTCCTCTCTCTCAGTGGGC	3472
Glu10Term	GACAGATGCGAAAGAAACGAGTTCCAGTGCCAAGACGGGAA
cGAG-TAG	ATGCATCTCCTACAAGTGGGTCTGCGATGGCAGCGCTG
	CAGCGCTGCCATCGCAGACCCACTTGTAGGAGATGCATTTCC	3473
	CGTCTTGGCACTGGAACTCGTTTCTTTCGCATCTGTCGCCCA
	CTGAGAGAGAGGAAAAGGAGAAAGGGTCTCTCAACGC
	AAAGAAACGAGTTCCAG	3474
	CTGGAACTCGTTTCTTT	3475
Hypercholesterolaemia	AGAGACCCTTTCTCCTTTTCCTCTCTCTCAGTGGGCGACAGA	3476
Gln12Term	TGCGAAAGAAACGAGTTCCAGTGCCAAGACGGGAAATGCATC
cCAG-TAG	TCCTACAAGTGGGTCTGCGATGGCAGCGCTGAGTGCC
	GGCACTCAGCGCTGCCATCGCAGACCCACTTGTAGGAGATG	3477
	CATTTCCCGTCTTGGCACTGGAAGTCGTTTCTTTCGCATCTGT
	CGCCCACTGAGAGAGAGGAAAAGGAGAAAGGGTCTCT
	ACGAGTTCCAGTGCCAA	3478
	TTGGCACTGGAACTCGT	3479
Hyperchoiesterolaemia	CCTTTCTCCTTTTCCTCTCTCTCAGTGGGCGACAGATGCGAA	3480
Gln14Term	AGAAACGAGTTCCAGTGCCAAGACGGGAAATGCATCTCCTAC
cCAA-TAA	AAGTGGGTCTGCGATGGCAGCGCTGAGTGCCAGGATG
	CATCCTGGCACTCAGCGCTGCCATCGCAGACCCACTTGTAG	3481
	GAGATGCATTTCCCGTCTTGGCACTGGAACT
	CATCTGTCGCCCACTGAGAGAGAGGAAAAGGAGAAAGG
	TCCAGTGCCAAGACGGG	3482
	CCCGTCTTGGCACTGGA	3483
Hypercholesterolaemia	GCGACAGATGCGAAAGAAACGAGTTCCAGTGCCAAGACGGG	3484
Trp23Term	AAATGCATCTCCTACAAGTGGGTCTGCGATGGCAGCGCTGAG
TGG-TAG	TGCCAGGATGGCTCTGATGAGTCCCAGGAGACGTGCTG
	CAGCACGTCTCCTGGGACTCATCAGAGCCATCCTGGCACTCA	3485
	GCGCTGCCATCGCAGACCCACTTGTAGGAGATGCATTTCCCG
	TCTTGGCACTGGAACTCGTTTCTTTCGCATCTGTCGC
	CTACAAGTGGGTCTGCG	3486
	CGCAGACCCACTTGTAG	3487
Hypercholesterolaemia	AACGAGTTCCAGTGCCAAGACGGGAAATGCATCTCCTACAAG	3488
Ala29Ser	TGGGTCTGCGATGGCAGCGCTGAGTGCCAGGATGGCTCTGA
cGCT-TCT	TGAGTCCCAGGAGACGTGCTGTGAGTCCCCTTTGGGCA
	TGCCCAAAGGGGACTCACAGCACGTCTCCTGGGACTCATCA	3489
	GAGCCATCCTGGCACTCAGCGCTGCCATCGCAGACCCACTT
	GTAGGAGATGCATTTCCCGTCTTGGCACTGGAACTCGTT
	ATGGCAGCGCTGAGTGC	3490
	GCACTCAGCGCTGCCAT	3491
Hypercholesterolaemia	TCCAGTGCCAAGACGGGAAATGCATCTCCTACAAGTGGGTCT	3492
Cys31Tyr	GCGATGGCAGCGCTGAGTGCCAGGATGGCTCTGATGAGTCC
TGC-TAC	CAGGAGACGTGCTGTGAGTCCCCTTTGGGCATGATATG
	CATATCATGCCCAAAGGGGACTCACAGCACGTCTCCTGGGAC	3493
	TCATCAGAGCCATCCTGGCACTCAGCGCTGCCATCGCAGAC
	CCACTTGTAGGAGATGCATTTCCCGTCTTGGCACTGGA
	CGCTGAGTGCCAGGATG	3494
	CATCCTGGCACTCAGCG	3495
Hypercholesterolaemia	AATCCTGTCTCTTCTGTAGTGTCTGTCACCTGCAAATCCGGG	3496
Arg57Cys	GACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCATTCCTCA
cCGT-TGT	GTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACAACG
	CGTTGTCGCAGTCCACTTGGCCATCGCACCTCCAGAACTGAG	3497
	GAATGCAGCGGTTGACACGGCCCCCACAGCTGAAGTCCCCG
	GATTTGCAGGTGACAGACACTACAGAAGAGACAGGATT
	GTGGGGGCCGTGTCAAC	3498
	GTTGACACGGCCCCCAC	3499
Hypercholesterolaemia	TCTGTCACCTGCAAATCCGGGGACTTCAGCTGTGGGGGCCG	3500
Gln64Term	TGTCAACCGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCA
tCAG-TAG	AGTGGACTGCGACAACGGCTCAGACGAGCAAGGCTGTC
	GACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCCACTTGGC	3501
	CATCGCACCTCCAGAACTGAGGAATGCAGCGGTTGACACGG
	CCCCCACAGCTGAAGTCCCCGGATTTGCAGGTGACAGA
	GCATTCCTCAGTTCTGG	3502
	CCAGAACTGAGGAATGC	3503
Hypercholesterolaemia	ACCTGCAAATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAA	3504
Trp66Gly	CCGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGG
cTGG-GGG	ACTGCGACAACGGCTCAGACGAGCAAGGCTGTCGTAAGT
	ACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCCA	3505
	CTTGGCCATCGCACCTCCAGAACTGAGGAATGCAGCGGTTG
	ACACGGCCCCCACAGCTGAAGTCCCCGGATTTGCAGGT
	CTCAGTTCTGGAGGTGC	3506
	GCACCTCCAGAACTGAG	3507
Hypercholesterolaemia	CCTGCAAATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAAC	3508
Trp66Term	CGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGA
TGG-TAG	CTGCGACAACGGCTCAGACGAGCAAGGCTGTCGTAAGTG
	CACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCC	3509
	ACTTGGCCATCGCACCTCCAGAACTGAGGAATGCAGCGGTG
	ACACGGCCCCCACAGCTGAAGTCCCCGGATTTGCAGG
	TCAGTTCTGGAGGTGCG	3510
	CGCACCTCCAGAACTGA	3511
Hypercholesterolaemia	AAATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTG	3512
Cys68Arg	CATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGA
gTGC-CGC	CAACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCC
	GGCCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGC	3513
	AGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAATGCAG
	CGGTTGACACGGCCCCCACAGCTGAAGTCCCCGGATTT
	TCTGGAGGTGCGATGGC	3514
	GCCATCGCACCTCCAGA	3515
Hypercholesterolaemia	ATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCA	3516
Cys68Trp	TTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACA
TGCg-TGG	ACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCCT
	AGGGCCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTC	3517
	GCAGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAATGCA
	GCGGTTGACACGGCCCCCACAGCTGAAGTCCCCGGAT
	TGGAGGTGCGATGGCCA	3518
	TGGCCATCGCACCTCCA	3519
Hypercholesterolaemia	AATCCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTGC	3520
Cys68Tyr	ATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGAC
TGC-TAC	AACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCC
	GGGCCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTC	3521
	GCAGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAATGCA
	GCGGTTGACACGGCCCCCACAGCTGAAGTCCCCGGATT
	CTGGAGGTGCGATGGCC	3522
	GGCCATCGCACCTCCAG	3523
Hypercholesterolaemia	TCCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCAT	3524
Asp69Asn	TCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACA
cGAT-AAT	ACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCCTG
	CAGGGCCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGT	3525
	CGCAGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAATG
	CAGCGGTTGACACGGCCCCCACAGCTGAAGTCCCCGGA
	GGAGGTGCGATGGCCAA	3526
	TTGGCCATCGCACCTCC	3527
Hypercholesterolaemia	CCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCATT	3528
Asp69Gly	CCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACAA
GAT-GGT	CGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCCTGC
	GCAGGGCCACACTTACGACAGCCTTGGTCGTCTGAGCCGTT	3529
	GTCGCAGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAAT
	GCAGCGGTTGACACGGCCCCCACAGCTGAAGTCCCCGG
	GAGGTGCGATGGCCAAG	3530
	CTTGGCCATCGCACCTC	3531
Hypercholesterolaemia	TCCGGGGACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCAT	3532
Asp69Tyr	TCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACA
cGAT-TAT	ACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCCTG
	CAGGGCCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGT	3533
	CGCAGTCCACTTGGCCATCGCACCTCCAGAACTGAGGAATG
	CAGCGGTTGACACGGCCCCCACAGCTGAAGTCCCCGGA
	GGAGGTGCGATGGCCAA	3534
	TTGGCCATCGCACCTCC	3535
Hypercholesterolaemia	GACTTCAGCTGTGGGGGCCGTGTCAACCGCTGCATTCCTCA	3536
Gln71Glu	GTTCTGGAGGTGCGATGGCCAAGTGGACTGCGACAACGGCT
cCAA-GAA	CAGACGAGCAAGGCTGTCGTAAGTGTGGCCCTGCCTTTG
	CAAAGGCAGGGCCACACTTACGACAGCCTTGCTCGTCTGAG	3537
	CCGTTGTCGCAGTCCACTTGGCCATCGCACCTCCAGAACTGA
	GGAATGCAGCGGTTGACACGGCCCCCACAGCTGAAGTC
	GCGATGGCCAAGTGGAC	3538
	GTCCACTTGGCCATCGC	3539
Hypercholesterolaemia	TGTGGGGGCCGTGTCAACCGCTGCATTCCTCAGTTCTGGAG	3540
Cys74Gly	GTGCGATGGCCAAGTGGACTGCGACAACGGCTCAGACGAGC
cTGC-GGC	AAGGCTGTCGTAAGTGTGGCCCTGCCTTTGCTATTGAGC
	GCTCAATAGCAAAGGCAGGGCCACACTTACGACAGCCTTGCT	3541
	CGTCTGAGCCGTTGTCGCAGTCCACTTGGCCATCGCACCTC
	CAGAACTGAGGAATGCAGCGGTTGACACGGCCCCCACA
	AAGTGGACTGCGACAAC	3542
	GTTGTCGCAGTCCACTT	3543
Hypercholesterolaemia	TCAACCGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAG	3544
Ser78Term	TGGACTGCGACAACGGCTCAGACGAGCAAGGCTGTCGTAAG
TCA-TGA	TGTGGCCCTGCGTTTGCTATTGAGCCTATCTGAGTCCT
	AGGACTCAGATAGGCTCAATAGCAAAGGCAGGGCCACACTTA	3545
	CGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCCACTTGG
	CCATCGCACCTCCAGAACTGAGGAATGCAGCGGTTGA
	CAACGGCTCAGACGAGC	3546
	GCTCGTCTGAGCCGTTG	3547
Hypercholesterolaemia	CGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGA	3548
Glu80Lys	CTGCGACAACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTG
cGAG-AAG	GCCCTGCCTTTGCTATTGAGCCTATCTGAGTCCTGGGGA
	TCCCCAGGACTCAGATAGGCTCAATAGCAAAGGCAGGGCCA	3549
	CACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCC
	ACTTGGCCATCGCACCTCCAGAACTGAGGAATGCAGCG
	GCTCAGACGAGCAAGGC	3550
	GCCTTGCTCGTCTGAGC	3551
Hypercholesterolaemia	CGCTGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGA	3552
GTu80Term	CTGCGACAACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTG
cGAG-TAG	GCCCTGCCTTTGCTATTGAGCCTATCTGAGTCCTGGGGA
	TCCCCAGGACTCAGATAGGCTCAATAGCAAAGGCAGGGCCA	3553
	CACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAGTCC
	ACTTGGCCATCGCACCTCCAGAACTGAGGAATGCAGCG
	GCTCAGACGAGCAAGGC	3554
	GCCTTGCTCGTCTGAGC	3555
Hypercholesterolaemia	TGCATTCCTCAGTTCTGGAGGTGCGATGGCCAAGTGGACTGC	3556
Gln81Term	GACAACGGCTCAGACGAGCAAGGCTGTCGTAAGTGTGGCCC
gCAA-TAA	TGCCTTTGCTATTGAGCCTATCTGAGTCCTGGGGAGTG
	CACTCCCCAGGACTCAGATAGGCTCAATAGCAAAGGCAGGG	3557
	CCACACTTACGACAGCCTTGCTCGTCTGAGCCGTTGTCGCAG
	TCCACTTGGCCATCGCACCTCCAGAACTGAGGAATGCA
	CAGACGAGCAAGGCTGT	3558
	ACAGCCTTGCTCGTCTG	3559
Hypercholesterolaemia	TGGGAGACTTCACACGGTGATGGTGGTCTCGGCCCATCCAT	3560
Cys88Arg	CCCTGCAGCCCCCAAGACGTGCTCCCAGGACGAGTTTCGCT
gTGC-CGC	GCCACGATGGGAAGTGCATCTCTCGGCAGTTCGTCTGTG
	CACAGACGAACTGCCGAGAGATGCAGTTCCCATCGTGGCAG	3561
	CGAAACTCGTCCTGGGAGCACGTCTTGGGGGCTGCAGGGAT
	GGATGGGCCGAGACCACCATCACCGTGTGAAGTCTCCCA
	CCAAGACGTGCTCCCAG	3562
	CTGGGAGCACGTCTTGG	3563
Hypercholesterolaemia	CACGGTGATGGTGGTCTCGGCCCATCCATCCCTGCAGCCCC	3564
Glu92Term	CAAGACGTGCTCCCAGGACGAGTTTCGCTGCCACGATGGGA
cGAG-TAG	AGTGCATCTCTCGGCAGTTCGTCTGTGACTCAGACCGGG
	CCCGGTCTGAGTCACAGACGAACTGCCGAGAGATGCACTTC	3565
	CCATCGTGGCAGCGTAAACTCGTCCTGGGAGCACGTCTTGGG
	GGCTGCAGGGATGGATGGGCCGAGACCACCATCACCGTG
	CCCAGGACGAGTTFCGC	3566
	GCGAAACTCGTCCTGGG	3567
Hypercholesterolaemia	GGTGGTCTCGGCCCATCCATCCCTGCAGCCCCCAAGACGTG	3568
Cys95Arg	CTCCCAGGACGAGTTTCGCTGCCACGATGGGAAGTGCATCT
cTGC-CGC	CTCGGCAGTTCGTCTGTGACTCAGACCGGGACTGCTTGG
	CCAAGCAGTCCCGGTCTGAGTCACAGACGAACTGCCGAGAG	3569
	ATGCACTTCCCATCGTGGCAGCGAAACTCGTCCTGGGAGCA
	CGTCTTGGGGGCTGCAGGGATGGATGGGCCGAGACCACC
	AGTTTCGCTGCCACGAT	3570
	ATCGTGGCAGCGAAACT	3571
Hypercholesterolaemia	CTCGGCCCATCCATCCCTGCAGCCCCCAAGACGTGCTCCCA	3572
Asp91Tyr	GGACGAGTTTCGCTGCCACGATGGGAAGTGCATCTCTCGGC
cGAT-TAT	AGTTCGTCTGTGACTCAGACCGGGACTGCTTGGACGGCT
	AGCCGTCCAAGCAGTCCCGGTCTGAGTCACAGACGAACTGC	3573
	CGAGAGATGCACTTCCCATCGTGGCAGCGAAACTCGTCCTG
	GGAGCACGTCTTGGGGGCTGCAGGGATGGATGGGCCGAG
	GCTGCCACGATGGGAAG	3574
	CTTCCCATCGTGGCAGC	3575
Hypercholesterolaemia	GGGTCGGGACACTGCCTGGCAGAGGCTGCGAGCATGGGGC	3576
Trp(−12)Arg	CCTGGGGCTGGAAATTGCGCTGGACCGTCGCCTTGCTCCTC
cTGG-AGG	GCCGCGGCGGGGACTGCAGGTAAGGCTTGCTCCAGGCGCC
	GGCGCCTGGAGCAAGCCTTACCTGCAGTCCCCGCCGCGGC	3577
	GAGGAGCAAGGCGACGGTCCAGCGCAATTCCAGCCCCAGG
	GCCCCATGCTCGCAGCCTCTGCCAGGCAGTGTCCCGACCC
	AATTGCGCTGGACCGTC	3578
	GACGGTCCAGCGCAATT	3579
Hypercholesterolaemia	CAGCAGGTCGTGATCCGGGTCGGGACACTGCCTGGCAGAGG	3580
Trp(−18)Term	CTGCGAGCATGGGGCCCTGGGGCTGGAAATTGCGCTGGACC
TGGg-TGA	GTCGCCTTGCTCCTCGCCGCGGCGGGGACTGCAGGTAAG
	CTTACCTGCAGTCCCCGCCGCGGCGAGGAGCAAGGCGACG	3581
	GTCCAGCGCAATTTCCAGCCCCAGGGCCCCATGCTCGCAGC
	CTCTGCCAGGCAGTGTCCCGACCCGGATCACGACCTGCTG
	GGGCCCTGGGGCTGGAA	3582
	TTCCAGCCCCAGGGCCC	3583
Hypercholesterolaemia	CAGCTAGGACACAGCAGGTCGTGATCCGGGTCGGGACACTG	3584
Met(−21)Leu	CCTGGCAGAGGCTGCGAGCATGGGGCCCTGGGGCTGG
cATG-TTG	TTGCGCTGGACCGTCGCCTTGCTCCTCGCCGCGGCGGGGA
	TCCCCGCCGCGGCGAGGAGCAAGGCGACGGTCCAGCGCAA	3585
	TTTCCAGCCCCAGGGCCCCATGCTCGCAGCCTCTGCCAGGC
	AGTGTGCCGACCCGGATCACGACCTGCTGTGTCCTAGCTG
	CTGCGAGCATGGGGCCC	3586
	GGGCCCCATGCTCGCAG	3587
Hypercholesterolaemia	CAGCTAGGACACAGCAGGTCGTGATCCGGGTCGGGACACTG	3588
Met(−21 )Val	CCTGGCAGAGGCTGCGAGCATGGGGCCCTGGGGCTGG
cATG-GTG	TTGCGCTGGACCGTCGCCTTGCTCCTCGCCGCGGCGGGGA
	TCCCCGCCGCGGCGAGGAGCAAGGCGACGGTCCAGCGCAA	3589
	TTTCCAGCCCCAGGGCCCCATGCTCGCAGCCTCTGCCAGGC
	AGTGTCCCGACCCGGATCACGACCTGCTGTGTCCTAGCTG
	CTGCGAGCATGGGGCCC	3590
	GGGCCCCATGCTCGCAG	3591
Hypercholesterolaemia	ATCCCTGCAGCCCCCAAGACGTGCTCCCAGGACGAGTTTCG	3592
lle101Phe	CTGCCACGATGGGAAGTGCATCTCTCGGCAGTTCGTCTGTGA
cATC-TTC	CTCAGACCGGGACTGCTTGGACGGCTCAGACGAGGCCT
	AGGCCTCGTCTGAGCCGTCCAAGCAGTCCCGGTCTGAGTCA 3593
	CAGACGAACTGCCGAGAGATGCACTTCCCATCGTGGCAGCG
	AAACTCGTCCTGGGAGCACGTCTTGGGGGCTGCAGGGAT
	GGAAGTGCATCTCTCGG	3594
	CCGAGAGATGCACTTCC	3595
Hypercholesterolaemia	GCCCCCAAGACGTGCTCCCAGGACGAGTTTCGCTGCCACGA	3596
Gln104Term	TGGGAAGTGCATCTCTCGGCAGTTCGTCTGTGACTCAGACCG
gCAG-TAG	GGACTGCTTGGACGGCTCAGACGAGGCCTCCTGCCCGG
	CCGGGCAGGAGGCCTCGTCTGAGCCGTCCAAGCAGTCCCG	3597
	GTCTGAGTCACAGACGAACTGCCGAGAGATGCACTTCCCATC
	GTGGCAGCGAAACTCGTCCTGGGAGCACGTCTTGGGGGC
	TCTCTCGGCAGTTCGTC	3598
	GACGAACTGCCGAGAGA	3599
Hypercholesterolaemia	TTFCGCTGCCACGATGGGAAGTGCATCTCTCGGCAGTTCGTC	3600
Cys113Arg	TGTGACTCAGACCGGGACTGCTTGGACGGCTCAGACGAGGC
cTGC-CGC	CTCCTGCCCGGTGCTCACCTGTGGTCCCGCCAGCTTCC
	GGAAGCTGGCGGGACCACAGGTGAGCACCGGGCAGGAGGC	3601
	CTCGTCTGAGCCGTCCAAGCAGTCCCGGTCTGAGTCACAGA
	CGAACTGCCGAGAGATGCACTTCCCATCGTGGCAGCGAAA
	ACCGGGACTGCTTGGAC	3602
	GTCCAAGCAGTCCCGGT	3603
Hypercholesterolaemia	AAGTGCATCTCTCGGCAGTTCGTCTGTGACTCAGACCGGGAC	3604
Glu119Lys	TGCTTGGACGGCTCAGACGAGGCCTCCTGCCCGGTGCTCAC
cGAG-AAG	CTGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCT
	AGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACAGGTG	3605
	AGCACCGGGCAGGAGGCCTCGTCTGAGCCGTCCATTAGCAGTC
	CCGGTCTGAGTCACAGACGAACTGCCGAGAGATGCACTT
	GCTCAGACGAGGCCTCC	3606
	GGAGGCCTCGTCTGAGC	3607
Hypercholesterolaemia	AAGTGCATCTCTCGGCAGTTCGTCTGTGACTCAGACCGGGAC	3608
Glu119Term	TGCTTGGACGGCTCAGACGAGGCCTCCTGCCCGGTGCTCAC
cGAG-TAG	CTGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCT
	AGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACAGGTG	3609
	AGCACCGGGCAGGAGGCCTCGTCTGAGCCGTCCAAGCAGTC
	CCGGTCTGAGTCACAGACGAACTGCCGAGAGATGCACTT
	GCTCAGACGAGGCCTCC	3610
	GGAGGCCTCGTCTGAGC	3611
Hypercholesterolaemia	TCGGCAGTTCGTCTGTGACTCAGACCGGGACTGCTTGGACG	3612
Cys122Term	GCTCAGACGAGGCCTCCTGCCCGGTGCTCACCTGTGGTCCC
TGCc-TGA	GCCAGCTFCCAGTGCAACAGCTCCACCTGCATCCCCCAG
	CTGGGGGATGCAGGTGGAGCTGTTGCACTGGAAGCTGGCGG	3613
	GACCACAGGTGAGCACCGGGCAGGAGGCCTCGTCTGAGCC
	GTCCAAGCAGTCCCGGTCTGAGTCACAGACGAACTGCCGA
	GCCTCCTGCCCGGTGCT	3614
	AGCACCGGGCAGGAGGC	3615
Hypercholesterolaemia	TGACTCAGACCGGGACTGCTTGGACGGCTCAGACGAGGCCT	3616
Cys127Trp	CCTGCCCGGTGCTCACCTGTGGTCCCGCCAGCTTCCAGTGC
TGTg-TGG	AACAGCTCCACCTGCATCCCCCAGCTGTGGGCCTGCGAC
	GTCGCAGGCCCACAGCTGGGGGATGCAGGTGGAGCTGTTGC	3617
	ACTGGAAGCTGGCGGGACCACAGGTGAGCACCGGGCAGGA
	GGCCTCGTCTGAGCCGTCCAAGCAGTCCCGGTCTGAGTCA
	CTCACCTGTGGTCCCGC	3618
	GCGGGACCACAGGTGAG	3619
Hypercholesterolaemia	TGCTTGGACGGCTCAGACGAGGCCTCCTGCCCGGTGCTCAC	3620
Gln133Term	CTGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCAT
cCAG-TAG	CCCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCG
	CGCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGGAT	3621
	GCAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACAGG
	TGAGCACCGGGCAGGAGGCCTCGTCTGAGCCGTCCAAGCA
	CCAGCTTCCAGTGCAAC	3622
	GTTGCACTGGAAGCTGG	3623
Hypercholesterolaemia	TTGGACGGCTCAGACGAGGCCTCCTGCCCGGTGCTCACCTG	3624
Cys134Gly	TGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCATCC
gTGC-GGC	CCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAG
	CTTCGCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGG	3625
	ATGCAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACA
	GGTGAGCACCGGGCAGGAGGCCTCGTCTGAGCCGTCCAA
	GCTTCCAGTGCAACAGC	3626
	GCTGTTGCACTGGAAGC	3627
Hypercholesterolaemia	GAGGCCTCCTGCCCGGTGCTCACCTGTGGTCCCGCCAGCTT	3628
Cys139Gly	CCAGTGCAACAGCTCCACCTGCATCCCCCAGCTGTGGGCCT
cTGC-GGC	GCGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGT
	ACTCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCGCAG	3629
	GCCCACAGCTGGGGGATGCAGGTGGAGCTGTTGCACTGGAA
	GCTGGCGGGACCACAGGTGAGCACCGGGCAGGAGGCCTC
	GCTCCACCTGCATCCCC	3630
	GGGGATGCAGGTGGAGC	3631
Hypercholesterolaemia	AGGCCTCCTGCCCGGTGCTCACCTGTGGTCCCGCCAGCTTC	3632
Cys139Tyr	CAGTGCAACAGCTCCACCTGCATCCCCCAGCTGTGGGCCTG
TGC-TAC	CGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGTG
	CACTCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCGCA	3633
	GGCCCACAGCTGGGGGATGCAGGTGGAGCTGTTGCACTGGA
	AGCTGGCGGGACCACAGGTGAGCACCGGGCAGGAGGCCT
	CTCCACCTGCATCCCCC	3634
	GGGGGATGCAGGTGGAG	3635
Hypercholesterolaemia	CTGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCAT	3636
Cys146Term	CCCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAG
TGCg-TGA	ATGGCTCGGATGAGTGGCCGCAGCGCTGTAGGGGTCTT
	AAGACCCCTACAGCGCTGCGGCCACTCATCCGAGCCATCTTC	3637
	GCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGGATG
	CAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACAG
	TGGGCCTGCGACAACGA	3638
	TCGTTGTCGCAGGCCCA	3639
Hypercholesterolaemia	TGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCATC	3640
Asp147Asn	CCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAGA
cGAC-AAC	TGGCTCGGATGAGTGGCCGCAGCGCTGTAGGGGTCTTT
	AAAGACCCCTACAGCGCTGCGGCCACTCATCCGAGCCATCTT	3641
	CGCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGGAT
	GCAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACA
	GGGCCTGCGACAACGAC	3642
	GTCGTTGTCGCAGGCCC	3643
Hypercholesterolaemia	TGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCATC	3644
Asp147His	CCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAGA
cGAC-CAC	TGGCTCGGATGAGTGGCCGCAGCGCTGTAGGGGTCTTT
	AAAGACCCCTACAGCGCTGCGGCCACTCATCCGAGCCATCTT	3645
	CGCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGGAT
	GCAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACA
	GGGCCTGCGACAACGAC	3646
	GTCGTTGTCGCAGGCCC	3647
Hypercholesterolaemia	TGTGGTCCCGCCAGCTTCCAGTGCAACAGCTCCACCTGCATC	3648
Asp147Tyr	CCCCAGCTGTGGGCCTGCGACAACGACCCCGACTGCGAAGA
cGAC-TAC	TGGCTCGGATGAGTGGCCGCAGCGCTGTAGGGGTCTTT
	AAAGACCCCTACAGCGCTGCGGCCACTCATCCGAGCCATCTT	3649
	CGCAGTCGGGGTCGTTGTCGCAGGCCCACAGCTGGGGGAT
	GCAGGTGGAGCTGTTGCACTGGAAGCTGGCGGGACCACA
	GGGCCTGCGACAACGAC	3650
	GTCGTTGTCGCAGGCCC	3651
Hypercholesterolaemia	TTCCAGTGCAACAGCTCCACCTGCATCCCCCAGCTGTGGGC	3652
Cys152Arg	CTGCGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGT
cTGC-CGC	GGCCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGG
	CCCCTTGGAACACGTAAAGACCCCTACAGCGCTGCGGCCAC	3653
	TCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCGCAGGC
	CCACAGCTGGGGGATGCAGGTGGAGCTGTTGCACTGGAA
	ACCCCGACTGCGAAGAT	3654
	ATCTTCGCAGTCGGGGT	3655
Hypercholesterolaemia	TTCCAGTGCAACAGCTCCACCTGCATGCCCCAGCTGTGGGC	3656
Cys152Gly	CTGCGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGT
cTGC-GGC	GGCCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGG
	CCCCTTGGAACACGTAAAGACCCCTACAGCGCTGCGGCCAC	3657
	TCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCGCAGGC
	CCACAGCTGGGGGATGCAGGTGGAGCTGTTGCACTGGAA
	ACCCCGACTGCGAAGAT	3658
	ATCTTCGCAGTCGGGGT	3659
Hypercholesterolaemia	CCAGTGCAACAGCTCCACCTGCATCCCCCAGCTGTGGGCCT	3660
Cys152Trp	GCGACAACGACCCCGACTGCGAAGATGGCTCGGATGAGTGG
TGCg-TGG	CCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGGAC
	GTCCCCTFGGAACACGTAAAAGACCCCTACAGCGCTGCGGCC	3661
	ACTCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCGCAG
	GCCCACAGCTGGGGGATGCAGGTGGAGCTGTTGCACTGG
	CCCGACTGCGAAGATGG	3662
	CCATCTTCGCAGTCGGG	3663
Hypercholesterolaemia	TGCAACAGCTCCACCTGCATCCCCCAGCTGTGGGCCTGCGA	3664
Asp154Asn	CAACGACCCCGACTGCGAAGATGGCTCGGATGAGTGGCCGC
aGAT-AAT	AGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGGACAGTA
	TACTGTCCCCTTGGAACACGTAAAGACCCCTACAGCGCTGCG	3665
	GCCACTCATCCGAGCCATCTTCGCAGTCGGGGTCGTTGTCG
	CAGGCCCACAGCTGGGGGATGCAGGTGGAGCTGTTGCA
	ACTGCGAAGATGGCTCG	3666
	CGAGCCATCTTCGCAGT	3667
Hypercholesterolaemia	GCTCCACCTGCATCCCCCAGCTGTGGGCCTGCGACAACGAC	3668
Ser156Leu	CCCGACTGCGAAGATGGCTCGGATGAGTGGCCGCAGCGCTG
TCG-HG	TAGGGGTCTTFACGTGTTCCAAGGGGACAGTAGCCCCTG
	CAGGGGCTACTGTCCCCTTGGAACACGTAAAGACCCCTACAG	3669
	CGCTGCGGCCACTCATCCGAGCCATCTTCGCAGTCGGGGTC
	GTTGTCGCAGGCCCACAGCTGGGGGATGCAGGTGGAGC
	AGATGGCTCGGATGAGT	3670
	ACTCATCCGAGCCATCT	3671
Hypercholesterolaemia	TGTGGGCCTGCGACAACGACCCCGACTGCGAAGATGGCTCG	3672
Cys163Tyr	GATGAGTGGCCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAA
TGT-TAT	GGGGACAGTAGCCCCTGCTCGGCCTTCGAGTTCCACTG
	CAGTGGAACTCGAAGGCCGAGCAGGGGCTACTGTCCCCTTG	3673
	GAACACGTAAAGACCCCTACAGCGCTGCGGCCACTCATCCG
	AGCCATCTTCGCAGTCGGGGTCGTTGTCGCAGGCCCACA
	GCAGCGCTGTAGGGGTC	3674
	GACCCCTACAGCGCTGC	3675
Hypercholesterolaemia	CAACGACCCCGACTGCGAAGATGGCTCGGATGAGTGGCCGC	3676
Tyr167Term	AGCGCTGTAGGGGTCTTTACGTGTTCCAAGGGGACAGTAGC
TACg-TAG	CCCTGCTCGGCCTTCGAGTTCCACTGCCTAAGTGGCGAG
	CTCGCCACTTAGGCAGTGGAACTCGAAGGCCGAGCAGGGGC	3677
	TACTGTCCCCTTGGAACACGTAAAGACCCCTACAGCGCTGCG
	GCCACTCATCCGAGCCATCTTCGCAGTCGGGGTCGTTG
	GGTCTTTACGTGTTCCA	3678
	TGGAACACGTAAAGACC	3679
Hypercholesterolaemia	CCCGACTGCGAAGATGGCTCGGATGAGTGGCCGCAGCGCTG	3680
Gln170Term	TAGGGGTCTTTACGTGTTCCAAGGGGACAGTAGCCCCTGCTC
cCAA-TAA	GGCCHCGAGTTCCACTGCCTAAGTGGCGAGTGCATCC
	GGATGCACTCGCCACTTAGGCAGTGGAACTCGAAGGCCGAG	3681
	CAGGGGCTACTGTCCCCTTGGAACACGTAAAGACCCCTACAG
	CGCTGCGGCCACTCATCCGAGCCATCTTCGCAGTCGGG
	ACGTGTTCCAAGGGGAC	3682
	GTCCCCTTGGAACACGT	3683
Hypercholesterolaemia	CGGATGAGTGGCCGCAGCGCTGTAGGGGTCTTTACGTGTTC	3684
Cys176Phe	CAAGGGGACAGTAGCCCCTGCTCGGCCTTCGAGTTCCACTG
TGC-TTC	CCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGA
	TCACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGCA	3685
	GTGGAACTCGAAGGCCGAGCAGGGGCTACTGTCCCCTTGGA
	ACACGTAAAGACCCCTACAGCGCTGCGGCCACTCATCCG
	TAGCCCCTGCTCGGCCT	3686
	AGGCCGAGCAGGGGCTA	3687
Hypercholesterolaemia	CGGATGAGTGGCCGCAGCGCTGTAGGGGTCTTTACGTGTTC	3688
Cys176Tyr	CAAGGGGACAGTAGCCCCTGCTCGGCCTFCGAGTTCCACTG
TGC-TAC	CCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGA
	TCACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGCA	3689
	GTGGAACTCGAAGGCCGAGCAGGGGCTACTGTCCCCTTGGA
	ACACGTAAAGACCCCTACAGCGCTGCGGCCACTCATCCG
	TAGCCCCTGCTCGGCCT	3690
	AGGCCGAGCAGGGGCTA	3691
Hypercholesterolaemia	ATGAGTGGCCGCAGCGCTGTAGGGGTCTTTACGTGTTCCAAG	3692
Ser177Leu	GGGACAGTAGCCCCTGCTCGGCCTTCGAGTTCCACTGCCTA
TCG-TTG	AGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGATGG
	CCATCACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAG	3693
	GCAGTGGAACTCGAAGGCCGAGCAGGGGCTACTGTCCCCTT
	GGAACACGTAAAGACCCCTACAGCGCTGCGGCCACTCAT
	CCCCTGCTCGGCCTTCG	3694
	CGAAGGCCGAGCAGGGG	3695
Hypercholesterolaemia	TACGTGTTCCAAGGGGACAGTAGCCCCTGCTCGGCCTTCGA	3696
Glu187Lys	GTTCCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGC
cGAG-AAG	GCTGTGATGGTGGCCCCGACTGCAAGGACAAATCTGACG
	CGTCAGATTTGTCCTTGCAGTCGGGGCCACCATCACAGCGC	3697
	CAGCTGGAGTGGATGCACTCGCCACTTAGGCAGTGGAACTC
	GAAGGCCGAGCAGGGGCTACTGTCCCCTTGGAACACGTA
	TAAGTGGCGAGTGCATC	3698
	GATGCACTCGCCACTTA	3699
Hypercholesterolaemia	CAAGGGGACAGTAGCCCCTGCTCGGCCTTCGAGTTCCACTG	3700
His190Tyr	CCTPAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGATG
cCAC-TAC	GTGGCCCCGACTGCAAGGACAAATCTGACGAGGAAAACT
	AGTTTTCCTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCAT	3701
	CACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGCAG
	TGGAACTCGAAGGCCGAGCAGGGGCTACTGTCCCCTTG
	AGTGCATCCACTCCAGC	3702
	GCTGGAGTGGATGCACT	3703
Hypercholesterolaemia	CCTTCGAGTFCCACTGCCTAAGTGGCGAGTGCATCCACTCCA	3704
Gly198Asp	GCTGGCGCTGTGATGGTGGCCCCGACTGCAAGGACAAATCT
GGC-GAC	GACGAGGAAAACTGCGGTATGGGCGGGGCCAGGGTGGG
	CCCACCCTGGCCCCGCCCATACCGCAGTTTTCCTCGTCAGAT	3705
	TTGTCCTTGCAGTCGGGGCCACCATCACAGCGCCAGCTGGA
	GTGGATGCACTCGCCACTTAGGCAGTGGAACTCGAAGG
	TGATGGTGGCCCCGACT	3706
	AGTCGGGGCCACCATCA	3707
Hypercholesterolaemia	GAGTTCCACTGCCTAAGTGGCGAGTGCATCCAGTCCAGCTG	3708
Asp200Asn	GCGCTGTGATGGTGGCCCCGACTGCAAGGACAAATCTGACG
cGAC-AAC	AGGAAAACTGCGGTATGGGCGGGGCCAGGGTGGGGGCGG
	CCGCCCCCACCCTGGCCCCGCCCATACCGCAGTTTTCCTCG	3709
	TCAGATTTGTCCTTGCAGTCGGGGCCACCATCACAGCGCCAG
	CTGGAGTGGATGCACTCGCCACTTAGGCAGTGGAACTC
	GTGGCCCCGACTGCAAG	3710
	CTTGCAGTCGGGGCCAC	3711
Hypercholesterolaemia	AGTTCCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGC	3712
Asp200Gly	GCTGTGATGGTGGCCCCGACTGCAAGGACAAATCTGACGAG
GAC-GGC	GAAAACTGCGGTATGGGCGGGGCCAGGGTGGGGGCGGG
	CCCGCCCCCACCCTGGCCCCGCCCATACCGCAGJTFTCCTC	3713
	GTCAGATTTGTCCTTGCAGTCGGGGCCACCATCACAGCGCCA
	GCTGGAGTGGATGCACTCGCCACTTAGGCAGTGGAACT
	TGGCCCCGACTGCAAGG	3714
	CCTTGCAGTCGGGGCCA	3715
Hypercholesterolaemia	GAGTTCCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTG	3716
Asp200Tyr	GCGCTGTGATGGTGGCCCCGACTGCAAGGACAAATCTGACG
cGAC-TAC	AGGAAAACTGCGGTATGGGCGGGGCCAGGGTGGGGGCGG
	CCGCCCCCACCCTGGCCCCGCCCATACCGCAGTTTFCCTCG	3717
	TCAGATTTGTCCTTGCAGTGGGGGCCACCATCACAGCGCCAG
	CTGGAGTGGATGCACTCGCCACTTAGGCAGTGGAACTC
	GTGGCCCCGACTGCAAG	3718
	CTTGCAGTCGGGGCCAC	3719
Hypercholesterolaemia	CCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCT	3720
Cys201Term	GTGATGGTGGCCCCGACTGCAAGGACAAATCTGACGAGGAA
TGCa-TGA	AACTGCGGTATGGGCGGGGCCAGGGTGGGGGCGGGGCGT
	ACGCCCCGCCCCCACCCTGGCCCCGCCCATACCGCAGTTTT	3721
	CCTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCATCACAGC
	GCCAGCTGGAGTGGATGCACTCGCCACTTAGGCAGTGG
	CCCGACTGCAAGGACAA	3722
	TTGTCCTTGCAGTCGGG	3723
Hypercholesterolaemia	TCCACTGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGC	3724
Cys201Tyr	TGTGATGGTGGCCCCGACTGCAAGGACAAATCTGACGAGGA
TGC-TAC	AAACTGCGGTATGGGCGGGGCCAGGGTGGGGGCGGGGCG
	CGCCCCGCCCCCACCCTGGCCCCGCCCATACCGCAGTTTTC	3725
	CTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCATCACAGCG
	CCAGCTGGAGTGGATGCACTCGCCACTTAGGCAGTGGA
	CCCCGACTGCAAGGACA	3726
	TGTCCTTGCAGTCGGGG	3727
Hypercholesterolaemia	TGCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGA	3728
Asp203Asn	TGGTGGCCCCGACTGCAAGGACAAATCTGACGAGGAAAACT
gGAC-AAC	GCGGTATGGGCGGGGCCAGGGTGGGGGCGGGGCGTCGTA
	TAGGACGCCCCCGCCCCCACCCTGGCCCCGCCCATACCGCA	3729
	GTTTTCCTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCATC
	ACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGCA
	ACTGCAAGGACAAATCT	3730
	AGATTTGTCCTTGCAGT	3731
Hypercholesterolaemia	GCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGAT	3732
Asp203Gly	GGTGGCCCCGACTGCAAGGACAAATCTGACGAGGAAAACTG
GAC-GGC	CGGTATGGGCGGGGCCAGGGTGGGGGCGGGGCGTCCTAT
	ATAGGACGCCCCGCCCCCACCCTGGCCCCGCCCATACCGCA	3733
	GTTTTCCTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCATC
	ACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGC
	CTGCAAGGACAAATCTG	3734
	CAGATTTGTCCTTGCAG	3735
Hypercholesterolaemia	GCCTAAGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGAT	3736
Asp203Val	GGTGGCCCCGACTGCAAGGACAAATCTGACGAGGAAAACTG
GAC-GTC	CGGTATGGGCGGGGCCAGGGTGGGGGCGGGGCGTCCTAT
	ATAGGACGCCCCGCCCCCACCCTGGCCCCGCCCATACCGCA	3737
	GTTTTCCTCGTCAGATTTGTCCTTGCAGTCGGGGCCACCATC
	ACAGCGCCAGCTGGAGTGGATGCACTCGCCACTTAGGC
	CTGCAAGGACAAATCTG	3738
	CAGATTTGTCCTTGCAG	3739
Hypercholesterolaemia	AGTGGCGAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGG	3740
Ser205Pro	CCCCGACTGCAAGGACAAATCTGACGAGGAAAACTGCGGTAT
aTCT-CCT	GGGCGGGGCCAGGGTGGGGGCGGGGCGTCCTATCACCT
	AGGTGATAGGACGCCCCGCCCCCACCCTGGCCCCGCCCATA	3741
	CCGCAGTTTTCCTCGTCAGATTTGTCCTTGCAGTCGGGGCCA
	CCATCACAGCGCCAGCTGGAGTGGATGCACTCGCCACT
	AGGACAAATCTGACGAG	3742
	CTGGTCAGATTTGTCCT	3743
Hypercholesterolaemia	CGAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGGCCCCG	3744
Asp206Glu	ACTGCAAGGACAAATCTGACGAGGAAAACTGCGGTATGGGC
GACg-GAG	GGGGCCAGGGTGGGGGCGGGGCGTCCTATCACCTGTCCC
	GGGACAGGTGATAGGACGCCCCGCCCCCACCCTGGCCCCG	3745
	CCCATACCGCAGTTTTCCTCGTCAGATTTGTCCTTGCAGTCG
	GGGCCACCATCACAGCGCCAGCTGGAGTGGATGCACTCG
	AAATCTGACGAGGAAAA	3746
	TTTTCCTCGTCAGATTT	3747
Hypercholesterolaemia	GAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGGCCCCGA	3748
Glu207Gln	CTGCAAGGACAAATCTGACGAGGAAAACTGCGGTATGGGCG
cGAG-CAG	GGGCCAGGGTGGGGGCGGGGCGTCCTATCACCTGTCCCT
	AGGGACAGGTGATAGGACGCCCCGCCCCCACGCTGGCCCC	3749
	GCCCATACCGCAGTTTTCCTCGTCAGATTTGTCCTTGCAGTC
	GGGGCCACCATCACAGCGCCAGCTGGAGTGGATGCACTC
	AATCTGACGAGGAAAAC	3750
	GTTTTCCTCGTCAGATT	3751
Hypercholesterolaemia	GAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGGCCCCGA	3752
Glu207Lys	CTGCAAGGACPAATCTGACGAGGAAAACTGCGGTATGGGCG
cGAG-AAG	GGGCCAGGGTGGGGGCGGGGCGTCCTATCACCTGTCCCT
	AGGGACAGGTGATAGGACGCCCCGCCCCCACCCTGGCCCC	3753
	GCCCATACCGCAGTTTTCCTCGTCAGATTTGTCCTTGCAGTC
	GGGGCCACCATCACAGCGCCAGCTGGAGTGGATGCACTC
	AATCTGACGAGGAAAAC	3754
	GTTTTCCTCGTCAGATT	3755
Hypercholesterolaemia	GAGTGCATCCACTCCAGCTGGCGCTGTGATGGTGGCCCCGA	3756
Glu207Term	CTGCAAGGACAAATCTGACGAGGAAAACTGCGGTATGGGCG
cGAG-TAG	GGGCCAGGGTGGGGGCGGGGCGTCCTATCACCTGTCCCT
	AGGGACAGGTGATAGGACGCCCCGCCCCCACCCTGGCCCC	3757
	GCCCATACCGCAGTTTTCCTCGTCAGATTTGTCCTTGCAGTC
	GGGGCCACCATCACAGCGCCAGCTGGAGTGGATGCACTC
	AATCTGACGAGGAAAAC	3758
	GTTTTCCTCGTCAGATT	3759
Hypercholesterolaemia	TCTTGAGAAAATCAACACACTCTGTCCTGTTTTCCAGCTGTGG	3760
Glu219Lys	CCACCTGTCGCCCTGACGAATTCCAGTGCTCTGATGGAAACT
cGAA-AAA	GCATCCATGGCAGCCGGCAGTGTGACCGGGAATATG
	CATATTCCCGGTCACACTGCCGGCTGCCATGGATGCAGTTTC	3761
	CATCAGAGCACTGGAATTCGTCAGGGCGACAGGTGGCCACA
	GCTGGAAAACAGGACAGAGTGTGTTGATTTTCTCAAGA
	GCCCTGACGAATTCCAG	3762
	CTGGAATTCGTCAGGGC	3763
Hypercholesterolaemia	GAAAATCAACACACTCTGTCCTGTTYFCCAGGTGTGGCCACCT	3764
Gln221Term	GTCGCCCTGACGAATTCCAGTGCTCTGATGGAAACTGCATCC
cCAG-TAG	ATGGCAGCCGGCAGTGTGACCGGGAATATGACTGCA
	TGCAGTCATATTCCCGGTCACACTGCCGGCTGCCATGGATGC	3765
	AGTTTCCATCAGAGCACTGGAATTCGTCAGGGCGACAGGTGG
	CCACAGCTGGAAAACAGGACAGAGTGTGTTGATTTTC
	ACGAATTCCAGTGCTCT	3766
	AGAGCACTGGAATTCGT	3767
Hypercholesterolaemia	CCTGTTTTCCAGCTGTGGCCACCTGTCGCCCTGACGAATTCC	3768
Cys227Phe	AGTGCTCTGATGGAAACTGCATCCATGGCAGCCGGCAGTGT
TGC-TTC	GACCGGGAATATGACTGCAAGGACATGAGCGATGAAGT
	ACTTCATCGCTCATGTCCTTGCAGTCATATTCCCGGTCACACT	3769
	GCCGGCTGCCATGGATGCAGTTTCCATCAGAGCACTGGAATT
	CGTCAGGGCGACAGGTGGCCACAGCTGGAAAACAGG
	TGGAAACTGCATCCATG	3770
	CATGGATGCAGTTTCCA	3771
Hypercholesterolaemia	TCGCCCTGACGAATTCCAGTGCTCTGATGGAAACTGCATCCA	3772
Asp235Glu	TGGCAGCCGGCAGTGTGACCGGGAATATGACTGCAAGGACA
GACc-GAA	TGAGCGATGAAGTTGGTTAATGGTGAGCGCTGG
	CCAGCGCTCACCATTAACGCAGCCAACTTCATCGCTCATGTC	3773
	CTTGCAGTCATATTCCCGGTCACACTGCCGGCTGCCATGGAT
	GCAGTTTCCATCAGAGCACTGGAATTCGTCAGGGCGA
	CAGTGTGACCGGGAATA	3774
	TATTCCCGGTCACACTG	3775
Hypercholesterolaemia	GTCGCCCTGACGAATTCCAGTGCTCTGATGGAAACTGCATCC	3776
Asp235Gly	ATGGCAGCCGGCAGTGTGACCGGGAATATGACTGCAAGGAC
GAC-GGC	ATGAGCGATGAAGTTGGCTGCGTTAATGGTGAGCGCTG
	CAGCGCTCACCATTAACGCAGCCAACTTCATCGCTCATGTCC	3777
	TTGCAGTCATATTCCCGGTCACACTGCCGGCTGCCATGGATG
	CAGTTTCCATCAGAGCACTGGAATFCGTCAGGGCGAC
	GCAGTGTGACCGGGAAT	3778
	ATTCCCGGTCACACTGC	3779
Hypercholesterolaemia	CCTGACGAATTCCAGTGCTCTGATGGAAACTGCATCCATGGC	3780
Glu237Lys	AGCCGGCAGTGTGACCGGGAATATGACTGCAAGGACATGAG
gGAA-AAA	CGATGAAGTTGGCTGCGTTAATGGTGAGCGCTGGCCAT
	ATGGCCAGCGCTCACCATTAACGCAGCCAACTTCATCGCTCA	3781
	TGTCCTTGCAGTCATATTCCCGGTCACACTGCCGGCTGCCAT
	GGATGCAGTTTCCATCAGAGCACTGGAATTCGTCAGG
	GTGACCGGGAATATGAC	3782
	GTCATATTCCCGGTCAC	3783
Hypercholesterolaemia	TCCAGTGCTCTGATGGAAACTGCATCCATGGCAGCCGGCAGT	3784
Cys240Phe	GTGACCGGGAATATGACTGCAAGGACATGAGCGATGAAGTTG
TGC-TTC	GCTGCGTTAATGGTGAGCGCTGGCCATCTGGTTFTCC
	GGAAAACCAGATGGCCAGCGCTCACCABAACGCAGCCAACT	3785
	TCATCGCTCATGTCCTTGCAGTCATATTCCCGGTCACACTGC
	CGGCTGCCATGGATGCAGTTTCCATCAGAGCACTGGA
	ATATGACTGCAAGGACA	3786
	TGTCCTTGCAGTCATAT	3787
Hypercholesterolaemia	AAACTGCATCCATGGCAGCCGGCAGTGTGACCGGGAATATG	3788
Asp245Glu	ACTGCAAGGACATGAGCGATGAAGTTGGCTGCGTTAATGGTG
GATg-GAA	AGCGCTGGCCATCTGGTTTTCCATCCCCCATTCTCTGT
	ACAGAGAATGGGGGATGGAAAACCAGATGGCCAGCGCTCAC	3789
	CATTAACGGAGCCAACTTCATCGCTCATGTCCTTGCAGTCATA
	TTCCCGGTCACACTGCCGGCTGCCATGGATGCAGTTT
	ATGAGCGATGAAGTTGG	3790
	CCAACTTCATCGCTCAT	3791
Hypercholesterolaemia	ATGGCAGCCGGCAGTGTGACCGGGAATATGACTGCAAGGAC	3792
Cys249Tyr	ATGAGCGATGAAGTTGGCTGCGTTAATGGTGAGCGCTGGCC
TGC-TAC	ATCTGGTTTTCCATCCCCCATTCTCTGTGCCTTGCTGCT
	AGCAGCAAGGCACAGAGAATGGGGGATGGAAAACCAGATGG	3793
	CCAGCGCTCACCATTAACGCAGCCAACTTCATCGCTCATGTC
	CTTGCAGTCATATTCCCGGTCACACTGCCGGCTGCCAT
	AGTTGGCTGCGTTAATG	3794
	CATTAACGCAGCCAACT	3795
Hypercholesterolaemia	AGGCTCAGACACACCTGACCTTCCTCCTTCCTCTCTCTGGCT	3796
Glu256Lys	CTCACAGTGACACTCTGCGAGGGACCCAACAAGTTCAAGTGT
cGAG-AAG	CACAGCGGCGAATGCATCACCCTGGACAAAGTCTGCA
	TGCAGACTTTGTCCAGGGTGATGCATTCGCCGCTGTGACACT	3797
	TGAACTTGTTGGGTCCCTCGCAGAGTGTCACTGTGAGAGCCA
	GAGAGAGGAAGGAGGAAGGTCAGGTGTGTCTGAGCCT
	CACTCTGCGAGGGACCC	3798
	GGGTGCCTCGCAGAGTG	3799
Hypercholesterolaemia	CCTCTCTCTGGCTCTCACAGTGACACTCTGCGAGGGACCCAA	3800
Ser265Arg	CAAGTTCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAA
AGCg-AGA	AGTCTGCAACATGGCTAGAGACTGCCGGGACTGGTCA
	TGACCAGTCCCGGCAGTCTCTAGCCATGTTGCAGACTTTGTC	3801
	CAGGGTGATGCATTCGCCGCTGTGACACTTGAACTTGTFGGG
	TCCCTCGCAGAGTGTCACTGTGAGAGCCAGAGAGAGG
	TGTCACAGCGGCGAATG	3802
	CATTCGCCGCTGTGACA	3803
Hypercholesterolaemia	TCTCTGGCTCTCACAGTGACACTCTGCGAGGGACCCAACAAG	3804
Glu267Lys	TTCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAAAGTC
cGAA-AAA	TGCAACATGGCTAGAGACTGCCGGGACTGGTCAGATG
	CATCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGCAGACTT	3805
	TGTCCAGGGTGATGCATTCGCCGCTGTGACACTTGAACTTGT
	TGGGTCCCTCGCAGAGTGTCACTGTGAGAGCCAGAGA
	ACAGCGGCGAATGCATC	3806
	GATGCATTCGCCGCTGT	3807
Hypercholesterolaemia	TCTCTGGCTCTGACAGTGACACTCTGCGAGGGACCCAACAAG	3808
Glu267Term	TTCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAAAGTC
cGAA-TAA	TGCAACATGGCTAGAGACTGCCGGGACTGGTCAGATG
	CATCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGCAGACTT	3809
	TGTCCAGGGTGATGCATTCGCCGCTGTGACACTTGAACTFGT
	TGGGTCCCTCGCAGAGTGTCACTGTGAGAGCCAGAGA
	ACAGCGGCGAATGCATC	3810
	GATGCATTCGCCGCTGT	3811
Hypercholesterolaemia	ACACTCTGCGAGGGACCCAACAAGTTCAAGTGTCACAGCGG	3812
Lys273Glu	CGAATGCATCACCCTGGACAAAGTCTGCAACATGGCTAGAGA
cAAA-GAA	CTGCCGGGACTGGTCAGATGAACCCATCAAAGAGTGCG
	CGCACTCTTTGATGGGTTCATCTGACCAGTCCCGGCAGTCTC	3813
	TAGCCATGTTGCAGACTTTGTCCAGGGTGATGCATTCGCCGC
	TGTGACACTTGAACTTGTTGGGTCCCTCGCAGAGTGT
	CCCTGGACAAAGTCTGC	3814
	GCAGACTTTGTCCAGGG	3815
Hypercholesterolaemia	CGAGGGACCCAACAAGTTCAAGTGTCACAGCGGCGAATGCA	3816
Cys275Term	TCACCCTGGACAAAGTCTGCAACATGGCTAGAGACTGCCGG
TGCa-TGA	GACTGGTCAGATGAACCCATCAAAGAGTGCGGTGAGTCT
	AGACTCACCGCACTCTTTGATGGGTTCATCTGACCAGTCCCG	3817
	GCAGTCTCTAGCCATGTTGCAGACTTFGTCCAGGGTGATGCA
	TTCGCCGCTGTGACACTTGAACTTGTTGGGTCCCTCG
	AAAGTCTGCAACATGGC	3818
	GCCATGTTGCAGACTTT	3819
Hypercholesterolaemia	AGTTCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAAAG	3820
Asp280Gly	TCTGCAACATGGCTAGAGACTGCCGGGACTGGTCAGATGAA
GAC-GGC	CCCATCAAAGAGTGCGGTGAGTCTCGGTGCAGGCGGCT
	AGCCGCCTGCACCGAGACTCACCGCACTCTTTGATGGGTTCA	3821
	TCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGCAGACTTTG
	TCCAGGGTGATGCATTCGCCGCTGTGACACTTGAACT
	GGCTAGAGACTGCCGGG	3822
	CCCGGCAGTCTCTAGCC	3823
Hypercholesterolaemia	TCAAGTGTCACAGCGGCGAATGCATCACCCTGGACAAAGTCT	3824
Cys281Tyr	GCAACATGGCTAGAGACTGCCGGGACTGGTCAGATGAACCC
TGC-TAC	ATCAAAGAGTGCGGTGAGTCTCGGTGCAGGCGGCTTGC
	GCAAGCCGCCTGCACCGAGACTCACCGCACTCTTTGATGGG	3825
	TTCATCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGCAGAC
	TTTGTCCAGGGTGATGCATTCGCCGCTGTGACACTTGA
	TAGAGACTGCCGGGACT	3826
	AGTCCCGGCAGTCTCTA	3827
Hypercholesterolaemia	TGTCACAGCGGCGAATGCATCACCCTGGACAAAGTCTGCAAC	3828
Asp283Asn	ATGGCTAGAGACTGCCGGGACTGGTCAGATGAACCCATCAAA
gGAC-AAC	GAGTGCGGTGAGTCTCGGTGCAGGCGGCTTGCAGAGT
	ACTCTGCAAGCCGCCTGCACCGAGACTCACCGCACTCTTTGA	3829
	TGGGTTCATCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGC
	AGACTTTGTCCAGGGTGATGCATTCGCCGCTGTGACA
	ACTGCCGGGACTGGTCA	3830
	TGACCAGTCCCGGCAGT	3831
Hypercholesterolaemia	TCACAGCGGCGAATGCATCACCCTGGACAAAGTCTGCAACAT	3832
Asp283Glu	GGCTAGAGACTGCCGGGACTGGTCAGATGAACCCATCAAAG
GACt-GAG	AGTGCGGTGAGTCTCGGTGCAGGCGGCTTGCAGAGTTT
	AAACTCTGCAAGCCGCCTGCACCGAGACTCACCGCACTCTTT	3833
	GATGGGTTCATCTGACCAGTCCCGGCAGTCTCTAGCCATGTT
	GCAGACTTTGTCCAGGGTGATGCATTCGCCGCTGTGA
	TGCCGGGACTGGTCAGA	3834
	TCTGACCAGTCCCGGCA	3835
Hypercholesterolaemia	TGTCACAGCGGCGAATGCATCACCCTGGACAAAGTCTGCAAC	3836
Asp283Tyr	ATGGCTAGAGACTGCCGGGACTGGTCAGATGAACCCATCAAA
gGAC-TAC	GAGTGCGGTGAGTCTCGGTGCAGGCGGCTTGCAGAGT
	ACTCTGCAAGCCGCCTGCACCGAGACTCACCGCACTCTTTGA	3837
	TGGGTTCATCTGACCAGTCCCGGCAGTCTCTAGCCATGTTGC
	AGACTTTGTCCAGGGTGATGCATTCGCCGCTGTGACA
	ACTGCCGGGACTGGTCA	3838
	TGACCAGTCCCGGCAGT	3839
Hypercholesterolaemia	CAGCGGCGAATGCATCACCCTGGACAAAGTCTGCAACATGG	3840
Trp284Term	CTAGAGACTGCCGGGACTGGTCAGATGAACCCATCTAAAGAGT
TGGt-TGA	GCGGTGAGTCTCGGTGCAGGCGGCTTGCAGAGTTTGTG
	CACTAAACTCTGCAAGCCGCCTGCACCGAGACTGACCGCACT	3841
	CTTTGATGGGTTCATCTGACCAGTCCCGGCAGTCTCTAGCCA
	TGTTGCAGACTTFGTCCAGGGTGATGCATTCGCCGCTG
	CGGGACTGGTCAGATGA	3842
	TCATCTGACCAGTCCCG	3843
Hypercholesterolaemia	GCGGCGAATGCATCACCCTGGACAAAGTCTGCAACATGGCTA	3844
Ser285Leu	GAGACTGCCGGGACTGGTCAGATGAACCCATCAAAGAGTGC
TCA-TTA	GGTGAGTCTCGGTGCAGGCGGCTTGCAGAGTTTGTGGG
	CCCACAAACTCTGCAAGCCGCCTGCACCGAGACTCACCGCA	3845
	CTCTTTGATGGGTTCATCTGACCAGTCCCGGCAGTCTCTAGC
	CATGTTGCAGACTTTGTCCAGGGTGATGCATTCGCCGC
	GGACTGGTCAGATGAAC	3846
	GTTCATCTGACCAGTCC	3847
Hypercholesterolaemia	CCCTGGACTAAAGTCTGCAACATGGCTAGAGACTGCCGGGAC	3848
Lys290Arg	TGGTCAGATGAACCCATCAAAGAGTGCGGTGAGTCTCGGTG
AAA-AGA	CAGGCGGCTTGCAGAGTTTGTGGGGAGCCAGGAAAGGGA
	TCCCTTTCGTGGCTCCCCACAAACTCTGCAAGCCGCCTGCAC	3849
	CGAGACTCACCGCACTCTTTGATGGGTTCATCTGACCAGTCC
	CGGCAGTCTCTAGCCATGTTGCAGACTTTGTCCAGGG
	ACCCATCAAAGAGTGCG	3850
	CGCACTCTTTGATGGGT	3851
Hypercholesterolaemia	GGGTAGGGGCCCGAGAGTGACCAGTCTGCATCCCCTGGCCC	3852
Cys297Phe	TGCGCAGGGACCAACGAATGCTTGGACAACAACGGCGGCTG
TGC-TTC	TTCCCACGTCTGCAATGACCTTAAGATCGGCTACGAGTG
	CACTCGTAGCCGATCTTAAGGTCATTGCAGACGTGGGAACAG	3853
	CCGCCGTTGTTGTCCAAGCATTCGTTGGTCCCTGCGCAGGG
	CCAGGGGATGCAGACTGGTCACTCTCGGGCCCCTACCC
	CAACGAATGCTTGGACA	3854
	TGTCCAAGCATTCGTTG	3855
Hypercholesterolaemia	GGGTAGGGGCCCGAGAGTGACCAGTCTGCATCCCCTGGCCC	3856
Cys297Tyr	TGCGCAGGGACCAACGAATGCTTGGACAACAACGGCGGCTG
TGC-TAC	TTCCCACGTCTGCAATGACCTTAAGATCGGCTACGAGTG
	CACTCGTAGCCGATCTTAAGGTCATTGCAGACGTGGGAACAG	3857
	CCGCCGTTGTTGTCCAAGCATTCGTTGGTCCCTGCGCAGGG
	CCAGGGGATGCAGACTGGTCACTCTCGGGCCCCTACCC
	CAACGAATGCTTGGACA	3858
	TGTCCAAGCATTCGTTG	3859
Hypercholesterolaemia	TGCATCCCCTGGCCCTGCGCAGGGACCAACGAATGCTTGGA	3860
His306Tyr	CAACAACGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGAT
cCAC-TAC	CGGCTACGAGTGCCTGTGCCCCGACGGCTTCCAGCTGG
	CCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTAGCCGATC	3861
	TTAAGGTCATTGCAGACGTGGGAACAGCCGCCGTTGTTGTCC
	AAGCATTCGTTGGTCCCTGCGCAGGGCCAGGGGATGCA
	GCTGTTCCCACGTCTGC	3862
	GCAGACGTGGGAACAGC	3863
Hypercholesterolaemia	CCCTGGCCCTGCGCAGGGACCAACGAATGCTTGGACAACAA	3864
Cys308Gly	CGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGCTA
cTGC-GGC	CGAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCCC
	GGGCCACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTA	3865
	GCCGATCTTAAGGTCATTGCAGACGTGGGAACAGCCGCCGT
	TGTTGTCCAAGCATTCGTTGGTCCCTGCGCAGGGCCAGGG
	CCCACGTCTGCAATGAC	3866
	GTCATTGCAGACGTGGG	3867
Hypercholesterolaemia	CCTGGCCCTGCGCAGGGACCAACGAATGCTTGGACAACAAC	3868
Cys308Tyr	GGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGCTAC
TGC-TAC	GAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCCCA
	TGGGCCACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTA	3869
	GCCGATCTTAAGGTCATTGCAGACGTGGGAACAGCCGCCGTT
	GTTGTCCAAGCATTCGTTGGTCCCTGCGCAGGGCCAGG
	CCACGTCTGCAATGACC	3870
	GGTCATTGCAGACGTGG	3871
Hypercholesterolaemia	ACCAACGAATGCTTGGACAACAACGGCGGCTGTTCGCACGTC	3872
Gly314Ser	TGCAATGACCTTAAGATCGGCTACGAGTGGCTGTGCCCCGAC
cGGC-AGC	GGCTTCCAGCTGGTGGCCCAGCGAAGATGCGAAGGTG
	CACCTTCGCATCTTCGCTGGGCCACCAGCTGGAAGCCGTCG	3873
	GGGCACAGGCACTCGTAGCCGATCTTAAGGTCATTGCAGAC
	GTGGGAACAGCCGCCGTTGTTGTCCAAGCATTCGTTGGT
	TTAAGATCGGCTACGAG	3874
	CTCGTAGCCGATCTTAA	3875
Hypercholesterolaemia	CCAACGAATGCTTGGACAACAACGGCGGCTGTTCCCACGTCT	3876
Gly314Val	GCAATGACCTTAAGATCGGCTACGAGTGCCTGTGCCCCGAC
GGC-GTC	GGCTTCCAGCTGGTGGCCCAGCGAAGATGCGAAGGTGA
	TCACCTTCGCATCTTCGCTGGGCCACCAGCTGGAAGCCGTC	3877
	GGGGCACAGGCACTCGTAGCCGATCTTAAGGTCATTGCAGA
	CGTGGGAACAGCCGCCGTTGTTGTCCAAGCATTCGTTGG
	TAAGATCGGCTACGAGT	3878
	ACTCGTAGCCGATCTTA	3879
Hyperchoesterolaemia	CGAATGCTTGGACAACAACGGCGGCTGTTCCCACGTCTGCAA	3880
Tyr315Term	TGACCTTAAGATCGGCTACGAGTGCCTGTGCCCCGACGGCTT
TACg-TAA	CCAGCTGGTGGCCCAGCGAAGATGCGAAGGTGATTTC
	GAAATCACCTTCGCATCTTCGCTGGGCCACCAGCTGGAAGCC	3881
	GTCGGGGCACAGGCACTCGTAGCCGATCTTAAGGTCATTGCA
	GACGTGGGAACAGCCGCCGTTGTTGTCCAAGCATTCG
	ATCGGCTACGAGTGCCT	3882
	AGGCACTCGTAGCCGAT	3883
Hypercholesterolaemia	TGCTTGGACAACTAACGGCGGCTGTTCCCACGTCTGCAATGAC	3884
Cys317Gly	CTTAAGATCGGCTACGAGTGCCTGTGCCCCGACGGCTTCCA
gTGC-GGC	GCTGGTGGCCCAGCGAAGATGCGAAGGTGATTTCCGGG
	CCCGGAAAATCACCTTCGCATCTTCGCTGGGCCACCAGCTGG	3885
	AAGCCGTCGGGGCACAGGCACTCGTAGCCGATCTTAAGGTC
	ATTGCAGACGTGGGAACAGCCGCCGTTGTTGTCCAAGCA
	GCTACGAGTGCCTGTGC	3886
	GCACAGGCACTCGTAGC	3887
Hypercholesterolaemia	TGCTTGGACAACAACGGCGGCTGTTCCCACGTCTGCAATGAC	3888
Cys317Ser	CTTAAGATCGGCTACGAGTGCCTGTGCCCCGACGGCTTCCA
gTGC-AGC	GCTGGTGGCCCAGCGAAGATGCGAAGGTGATTTCCGGG
	CCCGGAAATCACCTFCGCATCTTCGCTGGGCCACCAGCTGG	3889
	AAGCCGTCGGGGCACAGGCACTCGTAGCCGATCTTAAGGTC
	ATTGCAGACGTGGGAACAGCCGCCGTTGTTGTCCAAGCA
	GCTACGAGTGCCTGTGC	3890
	GCACAGGCACTCGTAGC	3891
Hypercholesterlaemia	ACAACGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCG 3892
Pro320Arg	GCTACGAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCC
CCC-CGC	CAGCGAAGATGCGAAGGTGATTTCCGGGTGGGACTGAG
	CTCAGTCCCACCCGGAAATCACCTTCGCATCTTCGCTGGGCC	3893
	ACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTAGCCGAT
	CTTAAGGTCATTGCAGACGTGGGAACAGCCGCCGTTGT
	CCTGTGCCCCGACGGCT	3894
	AGCCGTCGGGGCACAGG	3895
Hypercholesterolaemia	AACGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGC	3896
Asp321Asn	TACGAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCCCA
cGAC-AAC	GCGAAGATGCGAAGGTGATTTCCGGGTGGGACTGAGCC
	GGCTCAGTCCCACCCGGAAATCACCTTCGCATCTTCGCTGGG	3897
	CCACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTAGCCG
	ATCTTAAGGTCATTGCAGACGTGGGAACAGCCGCCGTT
	TGTGCCCCGACGGCTTC	3898
	GAAGCCGTCGGGGCACA	3899
Hypercholesterolaemia	CGGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGCTA	3900
Asp321Glu	CGAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCCCAGC
GACg-GAG	GAAGATGCGAAGGTGATTTCCGGGTGGGACTGAGCCCT
	AGGGCTCAGTCCCACCCGGAAATCACCTTCGCATCTTCGCTG	3901
	GGCCACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTAG
	CCGATCTTAAGGTCATTGCAGACGTGGGAACAGCCGCCG
	TGCCCCGACGGCTTCCA	3902
	TGGAAGCCGTCGGGGCA	3903
Hypercholesterolaemia	GGCGGCTGTTCCCACGTCTGCAATGACCTTAAGATCGGCTAC	3904
Gly322Ser	GAGTGCCTGTGCCCCGACGGCTTCCAGCTGGTGGCCCAGCG
cGGC-AGC	AAGATGCGAAGGTGATTTCCGGGTGGGACTGAGCCCTG
	CAGGGCTCAGTCCCACCCGGAAATCACCTTCGCATCTTCGCT	3905
	GGGCCACCAGCTGGAAGCCGTCGGGGCACAGGCACTCGTA
	GCCGATCTTAAGGTCATTGCAGACGTGGGAACAGCCGGC
	GCCCCGACGGCTTCCAG	3906
	CTGGAAGCCGTCGGGGC	3907
Hypercholesterolaemia	TGTTCCCACGTCTGCAATGACCTTAAGATCGGCTACGAGTGC	3908
Gln324Term	CTGTGCCCCGACGGCTTCCAGCTGGTGGCCCAGCGAAGATG
cCAG-TAG	CGAAGGTGATTTCCGGGTGGGACTGAGCCCTGGGCCCC
	GGGGCCCAGGGCTCAGTCCCACCCGGAAATCACCTTCGCAT	3909
	CTTCGCTGGGCCACCAGCTGGAAGCCGTCGGGGCACAGGCA
	CTCGTAGCCGATCTTAAGGTCATTGCAGACGTGGGAACA
	ACGGCTTCCAGCTGGTG	3910
	CACCAGCTGGAAGCCGT	3911
Hypercholesterolaemia	ATGACCTTAAGATCGGCTACGAGTGCCTGTGCCCCGACGGC	3912
Arg329Pro	TTCCAGCTGGTGGCCCAGCGAAGATGCGAAGGTGATTTCCG
CGA-CCA	GGTGGGACTGAGCCCTGGGCCCGCTCTGCGCTTCCTGAC
	GTCAGGAAGCGCAGAGGGGGCCCAGGGCTCAGTCCCACCC	3913
	GGAAATCACCTTCGCATCTTCGCTGGGCCACCAGCTGGAAG
	CCGTCGGGGCACAGGCACTCGTAGCCGATCTTAAGGTCAT
	GGCCCAGCGAAGATGCG	3914
	CGCATCTTCGCTGGGCC	3915
Hypercholesterolaemia	AATGACCTTAAGATCGGCTACGAGTGCCTGTGCCCCGACGG	3916
Arg329Term	CTTCCAGCTGGTGGCCCAGCGAAGATGCGAAGGTGATTTCC
gCGA-TGA	GGGTGGGACTGAGCCCTGGGCCCCCTCTGCGCTTCCTGA
	TCAGGAAGCGCAGAGGGGGCCCAGGGCTCAGTCCCACCCG	3917
	GAAATCACCTTCGCATCTTCGCTGGGCCACCAGCTGGAAGCC
	GTCGGGGCACAGGCACTCGTAGCCGATCTTAAGGTCATT
	TGGCCCAGCGAAGATGC	3918
	GCATCTTCGCTGGGCCA	3919
Hypercholesterolaemia	TCTAGCCATTGGGGAAGAGCCTCCCCACCAAGCCTCTTTCTC	3920
Glu336Lys	TCTCTTCCAGATATCGATGAGTGTCAGGATCCCGACACCTGC
tGAG-AAG	AGCCAGCTCTGCGTGAACCTGGAGGGTGGCTACAAGT
	ACTTGTAGCCACCCTCCAGGTTCACGCAGAGCTGGCTGCAG	3921
	GTGTCGGGATCCTGACACTCATCGATATCTGGAAGAGAGAGA
	AAGAGGCTTGGTGGGGAGGCTCTTCCCCAATGGCTAGA
	ATATCGATGAGTGTCAG	3922
	CTGACACTCATCGATAT	3923
Hypercholesterolaemia	CATTGGGGAAGAGCCTCCCCACCAAGCCTCTTTCTCTCTCTT	3924
Gln338Term	CCAGATATCGATGAGTGTCAGGATCCCGACACCTGCAGCCAG
tCAG-TAG	CTCTGCGTGAACCTGGAGGGTGGCTACAAGTGCCAGT
	ACTGGCACTTGTAGCCACCCTCCAGGTTCACGCAGAGCTGG	3925
	CTGCAGGTGTCGGGATCCTGACACTCATCGATATCTGGAAGA
	GAGAGAAAGAGGCTTGGTGGGGAGGCTCTTCCCCAATG
	ATGAGTGTCAGGATCCC	3926
	GGGATCCTGACACTCAT	3927
Hypercholesterolaemia	TCCCCACCAAGCCTCTTFCTCTCTCTTCCAGATATCGATGAGT	3928
Cys343Arg	GTCAGGATCCCGACACCTGCAGCCAGCTCTGCGTGAACCTG
cTGC-CGC	GAGGGTGGCTACAAGTGCCAGTGTGAGGAAGGCTTCC
	GGAAGCCTTCCTCACACTGGCACTTGTAGCCACCCTCCAGGT	3929
	TCACGCAGAGCTGGCTGCAGGTGTCGGGATCCTGACACTCA
	TCGATATCTGGAAGAGAGAGAAAGAGGCTTGGTGGGGA
	CCGACACCTGCAGCCAG	3930
	CTGGCTGCAGGTGTCGG	3931
Hypercholesterolaemia	CAAGCCTCTTTCTCTCTCTTCCAGATATCGATGAGTGTCAGGA	3932
Gln345Arg	TCCCGACACCTGCAGCCAGCTCTGCGTGAACCTGGAGGGTG
CAG-CGG	GCTACAAGTGCCAGTGTGAGGAAGGCTTCCAGCTGGA
	TCCAGCTGGAAGCCTTCCTCAGACTGGCACTTGTAGCCACCC	3933
	TCCAGGTTCACGCAGAGCTGGCTGCAGGTGTCGGGATCCTG
	ACACTCATCGATATCTGGAAGAGAGAGAAAGAGGCTTG
	CTGCAGCCAGCTCTGCG	3934
	CGCAGAGCTGGCTGCAG	3935
Hypercholesterolaemia	TCTTTCTCTCTCTTCCAGATATCGATGAGTGTCAGGATCCCGA	3936
Cys347Tyr	CACCTGCAGCCAGCTCTGCGTGAACCTGGAGGGTGGCTACA
TGC-TAC	AGTGCCAGTGTGAGGAAGGCTTCCAGCTGGACCCCCA
	TGGGGGTCCAGCTGGAAGCCTTCCTCACACTGGCACTTGTA	3937
	GCCACCCTCCAGGTTCACGCAGAGCTGGCTGCAGGTGTCGG
	GATCCTGACAGTCATCGATATCTGGAAGAGAGAGAAAGA
	CCAGCTCTGCGTGAACC	3938
	GGTTCACGCAGAGCTGG	3939
Hypercholesterolaemia	CTCTTTCTCTCTCTTCCAGATATCGATGAGTGTCAGGATCCCG	3940
Cys347Arg	ACACCTGCAGCCAGCTCTGCGTGAACCTGGAGGGTGGCTAC
cTGC-CGC	AAGTGCCAGTGTGAGGAAGGCTTCCAGCTGGACCCCC
	GGGGGTCCAGCTGGAAGCCTTCCTCACACTGGCACTTGTAG	3941
	CCACCCTCCAGGTTCACGCAGAGCTGGCTGCAGGTGTCGGG
	ATCCTGACACTCATCGATATCTGGXAGAGAGAGAAAGAG
	GCCAGCTCTGCGTGAAC	3942
	GTTCACGCAGAGCTGGC	3943
Hypercholesterolaemia	CAGATATCGATGAGTGTCAGGATCCCGACACCTGCAGCCAGC	3944
Gly352Asp	TCTGCGTGAACCTGGAGGGTGGCTACAAGTGCCAGTGTGAG
GGT-GAT	GAAGGCTTCCAGCTGGACCCCCACACGAAGGCCTGCAA
	TTGCAGGCCTTCGTGTGGGGGTCCAGCTGGAAGCCTTCCTC	3945
	ACACTGGCACTTGTAGCCACCCTCCAGGTTCACGCAGAGCTG
	GCTGCAGGTGTCGGGATCCTGACACTCATCGATATCTG
	CCTGGAGGGTGGCTACA	3946
	TGTAGCCACCCTCCAGG	3947
Hypercholesterolaemia	TCGATGAGTGTCAGGATCCCGACACCTGCAGCCAGCTCTGC	3948
Tyr354Cys	GTGAACCTGGAGGGTGGCTACAAGTGCCAGTGTGAGGAAGG
TAC-TGC	CTTCCAGCTGGACCCCCACACGAAGGCCTGCAAGGCTGT
	ACAGCCTTGCAGGCCTTCGTGTGGGGGTCCAGCTGGAAGCC	3949
	TTCCTCACACTGGCACTTGTAGCCACCCTCCAGGTTCACGCA
	GAGCTGGCTGCAGGTGTCGGGATCCTGACACTCATCGA
	GGGTGGCTACAAGTGCC	3950
	GGCACTTGTAGCCACCC	3951
Hypercholesterolaemia	CAGGATCCCGACACCTGCAGCCAGGTCTGCGTGAACCTGGA	3952
Cys358Arg	GGGTGGCTACAAGTGCCAGTGTGAGGAAGGCTTCCAGCTGG
gTGT-CGT	ACCCCCACACGAAGGCCTGCAAGGCTGTGGGTGAGCACG
	CGTGCTCACCCACAGCCTTGCAGGCCTTCGTGTGGGGGTCC	3953
	AGCTGGAAGCCTTCCTCACACTGGCACTTGTAGCCACCCTCC
	AGGTTCACGCAGAGCTGGCTGCAGGTGTCGGGATCCTG
	AGTGCCAGTGTGAGGAA	3954
	TTCCTCACACTGGCACT	3955
Hypercholesterolaemia	TGCAGCCAGCTCTGCGTGAACCTGGAGGGTGGCTACAAGTG	3956
Gln363Term	CCAGTGTGAGGAAGGCTTCCAGCTGGACCCCCACACGAAGG
cCAG-TAG	CCTGCAAGGCTGTGGGTGAGCACGGGAAGGCGGCGGGTG
	CACCCGCCGCCTTCCCGTGCTCACCCACAGCCTTGCAGGCC	3957
	TTCGTGTGGCGGTCCAGCTGGAAGCCTTCCTCACACTGGCA
	CTTGTAGCCACCCTCCAGGTTCACGCAGAGCTGGCTGCA
	AAGGCTTCCAGCTGGAC	3958
	GTCCAGCTGGAAGCCTT	3959

EXAMPLE 22

UDP-Glucuronosyltransferase—UGT1

[0144] Mutations in the human UGT1 gene result in a range of disease syndromes, ranging from relatively common diseases such as Gilbert's syndrome, which effects up to 7% of the population, to rare disorders such as Crigler-Najjar syndrome. Symptoms of these diseases are the result of diminished bilirubin conjugation and typically present with jaundice or, when mild, as an incidental finding during routing laboratory analysis. Severe cases of Crigler-Najar syndrome are caused by an absence of UGT1 activity and the majority of these patents die in the neonatal period. The only known treatment is liver transplant. The attached table discloses the correcting oligonucleotide base sequences for the UGT1 oligonucleotides of the invention.

TABLE 29
UGT1 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Crigler-Najjar	GCAGGAGCAAAGGCGCCATGGCTGTGGAGTCCCAGGGCGG	3960
syndrome 2	ACGCCCACTTGTCCTGGGCCTGCTGCTGTGTGTGCTGGGCC
Leu15Arg	CAGTGGTGTCCCATGCTGGGAAGATACTGTTGATCCCAGT
CTG-CGG
	ACTGGGATCAACAGTATCTTCCCAGCATGGGACACCACTGGGCGTCC	3961
	CCCAGCACACACAGCAGCAGGCCCAGGACAAGTGGGCGTCC
	GCCCTGGGACTCCACAGCCATGGCGCCTTTGCTCCTGC
	CCTGGGCCTGCTGCTGT	3962
	ACAGCAGCAGGCCCAGG	33963
Crigler-Najjar	GGGAAGATACTGTTGATCCCAGTGGATGGCAGCCACTGGCT	3964
syndrome 1	GAGCATGCTTGGGGCCATCCAGCAGCTGCAGCAGAGGGGAC
Gln49Term	ATGAAATAGTTGTCCTAGCACCTGACGCCTCGTTGTACA
CAG-TAG
	TGTACAACGAGGCGTCAGGTGCTAGGACAACTATTTCATGTC	3965
	CCCTCTGCTGCAGCTGCTGGATGGCCCCAAGCATGCTCAGC
	CAGTGGCTGCCATCCACTGGGATCAACAGTATGTTCCC
	GGGCCATCCAGCAGCTG	3966
	CAGCTGCTGGATGGCCC	3967
Crigler-Najjar	CAGCAGAGGGGACATGAAATAGTTGTCCTAGCACCTGACGCC	3968
syndrome 1	TCGTTGTACATCAGAGACGGAGCATTTTACACCTTGAAGACGT
Gly71Arg	ACCCTGTGCCATTCCAAAGGGAGGATGTGAAAGAGT
GGA-AGA
	ACTCTTTCACATCCTCCCTTTGGAATGGCACAGGGTACGTCTT	3969
	CAAGGTGTAAAATGCTCCGTCTCTGATGTACAACGAGGCGTC
	AGGTGCTAGGACAACTATTTCATGTCCCCTCTGCTG
	TCAGAGACGGAGCATTT	3970
AAATGCTCCGTCTCTGA	3971
Gilbert syndrome	GGGTGAAGAACATGCTCATTGCCVTTTCACAGAACTTTCTGTG	3972
Pro229Gln	CGACGTGGTTTATTCCCCGTATGCAACCCTTGCCTCAGAATT
CCG-CAG	CCTTCAGAGAGAGGTGACTGTCCAGGACCTATTGAG
	CTCAATAGGTCCTGGACAGTCACCTCTCTCTGAAGGAATTCT	3973
	GAGGCAAGGGTTGCATACGGGGAATAAACCACGTCGCACAG
	AAGTTCTGTGAAAAGGCAATGAGCATGTTCTTCACCC
	TTATTCCCCGTATGCAA	3974
	TTGCATACGGGGAATAA	3975
Crigler-Najjar	TGTGAAGGATTACCCTAGGCCCATCATGCCCAATATGGTTTTT	3976
syndrome 1	GTTGGTGGTAATCAACTGCCTTCACCAAAATCCACTATCCCAG
Cys280Term	GTGTGTATTGGAGTGGGACTTTTACATGCGTATATT
TGC-TGA
	AATATACGCATGTAAAAGTCCCACTCCAATACACACCTGGGAT	3977
	AGTGGATTTTGGTGAAGGCAGTTGATTCCACCAACAAAAAC
	ATATTGGGCATGATGGGCCTAGGGTAATCCTTCACA
	ATCAAACTGCCTTCACCA	3978
	TGGTGAAGGCAGTTGAT	3979
Crigler-Najjar	ATCAAAGAATATGAGAAAAAATTAACTGAAAATTTTTCTTCTGG	3980
syndrome 1	CTCTAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACATG
Ala292Val	GAATTGTGGTTTTCTCTTTGGGATCAATGGTCTC
GCC-GTC
	GAGACCATTGATCCCAAAGAGAAAACCACAATTCCATGTTCTC	3981
	CAGAAGCATTAATGTAGGCTTCAAATTCCTAGAGCCAGAAGAA
	AAATTTTCAGTTAATTTTTTCTCATATTCTTTGAT
	ATTTGAAGCCTACATTA	3982
	taatgtagGCTTCAAAT	3983
Crigler-Najjar	AGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACATGGAAT	3984
syndrome 1	TGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAG
Gly308Glu	AAGAAAGCTATGGCAATTGCTGATGCTTTGGGCAA
GGA-GAA
	TTGCCCAAAGCATCAGCAATTGCCATAGCTTTCTTCTCTGGAA	3985
	TTTCTGAGACCATTGATCCCAAAGAGAAAACCACAATTCCATG
	TTCTCCAGAAGCATTAATGTAGGCTTCAAATTCCT
	CTCTTTGGGATCAATGG	3986
	CCATTGATCCCAAAGAG	3987
Crigler-Najjar	GTCTCAGAAATTCCAGAGAAGAAAGCTATGGCAATTGCTGAT	3988
syndrome 1	GCTTTGGGCAAAATCCCTCAGACAGTAAGAAGATTCTATACCA
Gln331Term	TGGCCTCATATCTATTTTCACAGGAGCGCTAATCCC
CAG-TAG
	GGGATTAGCGCTCCTGTGAAAATAGATATGAGGCCATGGTAT	3989
	AGAATCTTCTTACTGTCTGAGGGATTTTGCCCAAAGCATCAGC
	AATTGCCATAGCTTTCTTCTCTGGAATTTCTGAGAC
	AAATCCCTCAGACAGTA	3990
	TACTGTCTGAGGGATTT	3991
Crigler-Najjar	TCTAATCATATTATGTTCTTTCTTTACGTTCTGCTCTTTTTGCC	3992
syndrome 1	CCTCCCAGGTCCTGTGGCGGTACACTGGAACCCGACCATCG
Trp335Term	AATCTTGCGAACAACACGATACTTGTTAAGTGGCTA
TGG-TGA
	TAGCCACTTAACAAGTATCGTGTTGTTCGCAAGATTCGATGGT	3993
	CGGGTTCCAGTGTACCGCCACAGGACCTGGGAGGGGCAAAA
	AGAGCAGAACGTAAAGAAAGAACATAATATGATTAGA
	GTCCTGTGGCGGTACAC	3994
	GTGTACCGCCACAGGAC	3995
Crigler-Najjar	ACACTGGAACCCGACCATCGAATCTTGCGAACAACACGATAC	3996
syndrome 1	TTGTTAAGTGGCTACCCCAAAACGATCTGCTTGGTATGTTGG
Gln357Arg	GCGGATTGGATGTATAGGTCAAACCAGGGTCAAATTA
CAA-CGA
	TAATTTGACCCTGGTTTGACCTATACATCCAATCCGCCCAACA	3997
	TACCAAGCAGATCGTTTTGGGGTAGCCACTTAACAAGTATCGT
	GTTGTTCGCAAGATTCGATGGTCGGGTTCCAGTGT
	GCTACCCCAAAACGATC	3998
	GATCGTTTTGGGGTAGC	3999
Crigler-Najjar	TACACTGGAACCCGACCATCGAATCTTGCGAACAACACGATA	4000
syndrome 1	CTTGTTAAGTGGCTACCCCAAAACGATCTGCTTGGTATGTTG
Gln357Term	GGCGGATTGGATGTATAGGTCAAACCAGGGTCAAATT
CAA-TAA
	AATTTGACCCTGGTTTGACCTATACATCCAATCCGCCCAACAT	4001
	ACCAAGCAGATCGTTTTGGGGTAGCCACTTAACAAGTATCGT
	GTTGTTCGCAAGATTCGATGGTCGGGTTCCAGTGTA
	GGCTACCCCAAAACGAT	4002
	ATCGTTTTGGGGTAGCC	4003
Gilbert syndrome	AACTCAGAGATGTAACTGCTGACATCCTCCCTATTTTGCATCT	4004
Arg367Gly	CAGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTT
CGT-GGT	CCCATGGTGTTTATGAAAGCATATGCAATGGCGTTC
	GAACGCCATTGCATATGCTTTCATAAACACCATGGGAACCAG	4005
	CATGGGTGATAAAGGCACGGGTCATCGGGTGACCTGAGATG
	CAAAATAGGGAGGATGTCAGCAGTTACATCTCTGAGTT
	CGATGACCCGTGCCTTT	4006
	AAAGGCACGGGTCATCG	4007
Crigler-Najjar	TCAGAGATGTAACTGCTGACATCCTCCCTATTTTGCATCTCAG	4008
syndrome 1	GTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCC
Ala368Thr	ATGGTGTTTATGAAAGCATATGCAATGGCGTTCCCA
GCC-ACC
	TGGGAACGCCATTGCATATGCTTTCATAAACACCATGGGAAC	4009
	CAGCATGGGTGATAAAGGCACGGGTCATCGGGTGACCTGAG
	ATGCAAAATAGGGAGGATGTCAGCAGTTACATCTCTGA
	TGACCCGTGCCTTTATC	4010
	GATAAAGGCACGGGTCA	4011
Crigler-Najjar	CCTCCCTATTTTTGCATCTCAGGTCACCCGATGACCCGTGCCT	4012
syndrome 1	TTATCACCCATGCTGGTTCCCATGGTGTTTATGAAAGCATATG
Ser375Phe	CAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGG
TCC-TTC
	CCAAACAAGGGCATCATCACCATGGGAACGCCATTGCATATG	4013
	CTTTCATAAACACCATGGGAACCAGCATGGGTGATAAAGGCA
	CGGGTCATCGGGTGACCTGAGATGCAAAATAGGGAGG
	TGCTGGTTCCCATGGTG	4014
	CACCATGGGAACCAGCA	4015
Crigler-Najjar	AGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTC	4016
syndrome 1	CCATGGTGTTTATGAAAGCATATGCAATGGCGTTCCCATGGT
Ser381Arg	GATGATGCCCTTGTTTGGTGATCAGATGGACAATGCA
AGC-AGG
	TGCATTGTCCATCTGATCACCAAACAAGGGCATCATCACCAT	4017
	GGGAACGCCATTGCATATGCTTTCATAAACACCATGGGAACC
	AGCATGGGTGATAAAGGCACGGGTCATCGGGTGACCT
	TATGAAAGCATATGCAA	4018
	TTGCATATGCTTTCATA	4019
Crigler-Najjar	AGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTT	4020
syndrome 1	GGTGATCAGATGGACAATGCAAAGCGCATGGAGACTAAGGG
Ala401Pro	AGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCTG
GCA-CCA
	CAGAAGTCATTTCCAGAACATTCAGGGTCACTCCAGCTCCCT	4021
	TAGTCTCCATGCGCTTTGCATTGTCCATCTGATCACCAAACAA
	GGGCATCATCACCATGGGAACGCCATTGCATATGCT
	TGGACAATGCAAAGCGC	4022
	GCGCTTTGCATTGTCCA	4023
Crigler-Najjar	GGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCTGAA	4024
syndrome 1	GATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGGT
Lys428Glu	AAGAAAGAAGATACAGAAGAATACTTTGGTCATGGC
AAA-GAA
	GCCATGACCAAAGTATTCTTCTGTATCTTCTTCTTTACCTTTTG	4025
	TCATTGATGACTGCTTTTAGAGCATTTTCTAAATGTTCAGAAGT
	CATTTCCAGAACATTCAGGGTCACTCCAGCTCC
	ATGCTCTAAAAGCAGTC	4026
	GACTGCTTTTAGAGCAT	4027
Crigler-Najjar	ATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCC	4028
syndrome 1	ACGACCTCACCTGGTACCAGTACCATTCCTTGGACGTGATTG
Tyr486Asp	GTTTCCTCTTGGCCGTCGTGCTGACAGTGGCCTTCATCA
TAC-GAC
	TGATGAAGGCCACTGTCAGCACGACGGCCAAGAGGAAACCA	4029
	ATCACGTCCAAGGAATGGTACTGGTACCAGGTGAGGTCGTG
	GGCTGCGGGGCGCAGGTGTGGCGCGCCCTTGTGCCTCAT
	GGTACCAGTACCATTCC	4030
	GGAATGGTACTGGTACC	4031
Crigler-Najjar	ACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCACGACCT	4032
syndrome 1	CACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCT
Ser488Phe	CTTGGCCGTCGTGCTGACAGTGGCCTTCATCACCTTTAA
TCC-UC
	TTAAAGGTGATGAAGGCCACTGTCAGCACGACGGCCAAGAG	4033
	GAAACCAATCACGTCCAAGGAATGGTACTGGTACCAGGTGAG
	GTCGTGGGCTGCGGGGCGCAGGTGTGGCGCGCCCTTGT
	GTACCATTCCTTGGACG	4034
	CGTCCAAGGAATGGTAC	4035

EXAMPLE 23

Alzheimer's Disease—Amyloid Precursor Protein (APP)

[0145] Over the past few decades Alzheimer's disease (AD), once considered a rare disorder, has become recognized as a major public health problem. Although there is no agreement on the exact prevalence of Alzheimer's disease, in part due to difficulties of diagnosis, studies consistently point to an exponential rise in prevalence of this disease with age. After age 65, the percentage of affected people approximately doubles with every decade of life, regardless of definition. Among people age 85 or older, studies suggest that 25 to 35 percent have dementia, including Alzheimer's disease; one study reports that 47.2 percent of people over age 85 have Alzheimer's disease, exclusive of other dementias.

[0146] Alzheimer's disease progressively destroys memory, reason, judgment, language, and, eventually, the ability to carry out even the simplest tasks. Anatomic changes associated with Alzheimer's disease begin in the entorhinal cortex, proceed to the hippocampus, and then gradually spread to other regions, particularly the cerebral cortex. Chief among such anatomic changes are the presence of characteristic extracellular plaques and internal neurofibrillary tangles.

[0147] At least four genes have been identified to date that contribute to development of Alzheimer's disease: AD1 is caused by mutations in the amyloid precursor gene (APP); AD2 is associated with a particular allele of APOE (see Example 20); AD3 is caused by mutation in a gene encoding a 7-transmembrane domain protein, presenilin-1 (PSEN1), and AD4 is caused by mutation in a gene that encodes a similar 7-transmembrane domain protein, presenilin-2 (PSEN2). The attached table discloses

TABLE 30
APP Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Alzheimer disease	CTGCATACTTTAATTATGATGTAATACAGGTTCTGGGTTGACA	4036
Glu665Asp	AATATCAAGACGGAGGAGATCTCTGAAGTGAAGATGGATGCA
GAG-GAC	GAATTCCGACATGACTCAGGATATGAAGTTCATCAT
	ATGATGAACTTCATATCCTGAGTCATGTCGGAATTCTGCATCC	4037
	ATCTTCACTTCAGAGATCTCCTCCGTCTTGATATTTGTCAACC
	CAGAACCTGTATTACATCATAATTAAAGTATGCAG
	ACGGAGGAGATCTCTGA	4038
	TCAGAGATCTCCTCCGT	4039
Alzheimer disease	ATTATATTGCATTTAGAAATTAAAATTCTTTTTCTTAATTTGTTTT	4040
Ala692Gly	CAAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACAAAGGTGC
GCA-GGA	AATCATTGGACTCATGGTGGGCGGTGTTGTCAT
	ATGACAACACCGCCCACCATGAGTCCAATGATTGCACCTTTG	4041
	TTTGAACCCACATCTTCTGCAAAGAACACCTTGAAAACAAATT
	AAGAAAAAGAATTTTAATTTCTAAATGCAATATAAT
	GTTCTTTGCAGAAGATG	4042
	CATCTTCTGCAAAGAAC	4043
Alzheimer disease	TATATTGCATTTAGAAATTAAAATTCTTTTTCTTAATTTGTTTTC	4044
Glu693Gln	AAGGTGTTCTTTGCAGAAGATGTGGGTTCAAACAAAGGTGCA
GAA-CAA	ATCATTGGACTCATGGTGGGCGGTGTTGTCATAG
	CTATGACAACACCGCCCACCATGAGTCCAATGATTGCACCTT	4045
	TGTTTGAACCCACATCTTCTGCAAAGAACACCTTGAAAACAAA
	TTAAGAAAAAGAATTTTAATTTCTAAATGCAATATA
	TCTTTGCAGAAGATGTG	4046
	CACATCTTCTGCAAAGA	4047
Alzheimer disease	ATATTGCATTTAGAAATTAAAATTCTTTTTCTTAATTTGTTTTCA	4048
Glu693Gly	AGGTGTTCTTTGCAGAAGATGTGGGTTCAAACAAAGGTGCAA
GAA-GGA	TCATTGGACTCATGGTGGGCGGTGTTGTCATAGC
	GCTATGACAACACCGCCCACCATGAGTCCAATGATTGCACCT	4049
	TTGTTTGAACCCACATCTTCTGCAAAGAACACCTTGAAAACAA
	ATTAAGAAPAAGAATTTTAATTTCTAAATGCAATAT
	CTTTGCAGAAGATGTGG	4050
	CCACATCTTCTGCAAAG	4051
Alzheimer disease	GAAGATGTGGGTTCAAACAAAGGTGCAATCATTGGACTCATG	4052
Ala713Thr	GTGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTG
GCG-ACG	GTGATGCTGAAGAAGAAACAGTACACATCCATTCATC
	GATGAATGGATGTGTACTGTTTCTTCTTCAGCATCACCAAGGT	4053
	GATGACGATCACTGTCGCTATGACAACACCGCCCACCATGAG
	TCCAATGATTGCACCTTTGTTTGAACCCACATCTT
	TTGTCATAGCGACAGTG	4054
	CACTGTCGCTATGACAA	4055
Schizophrenia	AAGATGTGGGTTCAAACAAAGGTGCAATCATTGGACTCATGG	4056
Ala713Val	TGGGCGGTGTTGTCATAGCGACAGTGATCGTCATCACCTTGG
GCG-GTG	TGATGCTGAAGAAGAAACAGTACACATCCATTCATCA
	TGATGAATGGATGTGTACTGTTTCTTCTTCAGCATCACCAAGG	4057
	TGATGACGATCACTGTCGCTATGACAACACCGCCCACCATGA
	GTCCAATGATTGCACCTTTGTTTGAACCCACATCTT
	TGTCATAGCGACAGTGA	4058
	TCACTGTCGCTATGACA	4059
Alzheimer disease	GTGGGTTCAAACAAAGGTGCAATCATTGGACTCATGGTGGGC	4060
Val715Met	GGTGTTGTCATAGCGACAGTGATCGTCATCACCTTGGTGATG
GTG-ATG	CTGAAGAAGAAACAGTACACATCCATTCATCATGGTG
	CACCATGATGAATGGATGTGTACTGTTTCTTCTTCAGCATCAC	4061
	CAAGGTGATGACGATCACTGTCGCTATGACAACACCGCCCAC
	CATGAGTCCAATGATTGCACCTTTGTTTGAACCCAC
	TAGCGACAGTGATCGTC	4062
	GACGATCACTGTCGCTA	4063
Alzheimer disease	GGTTCAAACAAAGGTGCAATCATTGGACTCATGGTGGGCGGT	4064
lle716Val	GTTGTCATAGCGACAGTGATCGTCATCACCTTGGTGATGCTG
ATC-GTC	AAGAAGAAACAGTACACATCCATTCATCATGGTGTGG
	CCACACCATGATGAATGGATGTGTACTGTTTCTTCTTCAGCAT	4065
	CACCAAGGTGATGACGATCACTGTCGCTATGACAACACCGCC
	CACCATGAGTCCAATGATTGCACCTTTGTTTGAACC
	CGACAGTGATCGTCATC	4066
	GATGACGATCACTGTCG	4067
Alzheimer disease	CAAACAAAGGTGCAATCATTGGACTCATGGTGGGCGGTGTTG	4068
Val717Gly	TCATAGCGACAGTGATCGTCATCACCTTGGTGATGCTGAAGA
GTC-GGC	AGAAACAGTACACATCCATTCATCATGGTGTGGTGGA
	TCCACCACACCATGATGAATGGATGTGTACTGTTTCTTCTTCA	4069
	GCATCACCAAGGTGATGACGATCACTGTCGCTATGACAACAC
	CGCCCACCATGAGTCCAATGATTGCACCTTTGTTTG
	AGTGATCGTCATCACCT	4070
	AGGTGATGACGATCACT	4071
Aizheimer disease	TCAAACAAAGGTGCAATCATTGGACTCATGGTGGGCGGTGTT	4072
Val17lle	GTCATAGCGACAGTGATCGTCATCACCTTGGTGATGCTGAAG
GTC-ATC	AAGAAACAGTACACATCCATTCATCATGGTGTGGTGG
	CCACCACACCATGATGAATGGATGTGTACTGTTTCTTCTTCAG	4073
	CATCACCAAGGTGATGACGATCACTGTCGCTATGACAACACC
	GCCCACCATGAGTCCAATGATTGCACCTTTGTTTGA
	CAGTGATCGTCATCACC	4074
	GGTGATGACGATCACTG	4075
Alzheimer disease	TCAAACAAAGGTGCAATCATTGGACTCATGGTGGGCGGTGTT	4076
Val717Phe	GTCATAGCGACAGTGATCGTCATCACCTTGGTGATGCTGAAG
GTC-TTC	AAGAAACAGTACACATCCATTCATCATGGTGTGGTGG
	CCACCACACCATGATGAATGGATGTGTACTGTTTCTTCTTCAG	4077
	CATCACCAAGGTGATGACGATCACTGTCGCTATGACAACACC
	GCCCACCATGAGTCCAATGATTGCACCTTTGTTTGA
	CAGTGATCGTCATCACC	4078
	GGTGATGACGATCACTG	4079
Alzheimer disease	TTGGACTCATGGTGGGCGGTGTTGTCATAGCGACAGTGATCG	4080
Leu723Pro	TCATCACCTTGGTGATGCTGAAGAAGAAACAGTACACATCCAT
CTG-CCG	TCATCATGGTGTGGTGGAGGTAGGTAAACTTGACTG
	CAGTCAAGTTTACCTACCTCCACCACACCATGATGAATGGAT	4081
	GTGTACTGTTTCTTCTTCAGCATCACCAAGGTGATGACGATCA
	CTGTCGCTATGACAACACCGCCCACCATGAGTCCAA
	GGTGATGCTGAAGAAGA	4082
	TCTTCTTCACCATCACC	4083

EXAMPLE 24

Alzheimer's Disease—Presenilin-1 (PSEN1)

[0148] The attached table discloses the correcting oligonucleotide base sequences for the PSEN1 oligonucleotides of the invention.

TABLE 31
PSEN1 Mutations and Genome-Correcting Oligos
Clinical Phenotype &		SEQ ID
Mutation	Correcting Oligos	NO:
Alzheimer disease	CCCGGCAGGTGGTGGAGCAAGATGAGGAAGAAGATGAGGAG	4084
Ala79Val	CTGACATTGAAATATGGCGCCAAGCATGTGATCATGCTCTTTG
GCC-GTC	TCCCTGTGACTCTCTGCATGGTGGTGGTCGTGGCTAC
	GTAGCCACGACCACCACCATGCAGAGAGTCACAGGGACAAA	4085
	GAGCATGATCACATGCTTGGCGCCATATTTCAATGTCAGCTC
	CTCATCTTCTTCCTCATCTTGCTCCACCACCTGCCGGG
	ATATGGCGCCAAGCATG	4086
	CATGCTTGGCGCCATAT	4087
Alzheimer disease	GTGGTGGAGCAAGATGAGGAAGAAGATGAGGAGCTGACATT	4088
Val82Leu	GAAATATGGCGCCAAGCATGTGATCATGCTCTTTGTCCCTGT
tGTG-CTG	GACTCTCTGCATGGTGGTGGTCGTGGCTACCATTAAGT
	ACTTAAGGTAGCCACGACCACCACCATGCAGAGAGTCACAG	4089
	GGACAAAGAGCATGATCACATGCTTGGCGCCATATTTCAATG
	TCAGCTCCTCATCTTCTTCCTCATCTTGCTCCACCAC
	CCAAGCATGTGATCATG	4090
	CATGATCACATGCTTGG	4091
Alzheimer disease	AAATATGGCGCCAAGCATGTGATCATGCTCTTTGTCCCTGTG	4092
Val96Phe	ACTCTCTGCATGGTGGTGGTCGTGGCTACCATTAAGTCAGTC
gGTC-TTC	AGCTTTTATACCCGGAAGGATGGGCAGCTGTACGTAT
	ATACGTACAGCTGCCCATCCTTCCGGGTATAAAAGCTGACTG	4093
	ACTTAATGGTAGCCACGACCACCACCATGCAGAGAGTCACAG
	GGACAAAGAGCATGATCACATGCTTGGCGCCATATTT
	TGGTGGTGGTCGTGGCT	4094
	AGCCACGACCACCACCA	4095
Alzheimer disease	CTTTGTCCCTGTGACTCTCTGCATGGTGGTGGTCGTGGCTAC	4096
Phe105Leu	CATTAAGTCAGTCAGCTTTTATACCCGGAAGGATGGGCAGCT
TTTt-TTG	GTACGTATGAGTTTTGTTTTATTATTCTCAAAGCCAG
	CTGGCTTTGAGAATAATAAAACAAAACTCATACGTACAGCTGC	4097
	CCATCCTTCCGGGTATAAAAGCTGACTGACTTAATGGTAGCC
	ACGACCACCACCATGCAGAGAGTCACAGGGACAAAG
	GTCAGCTTTTATACCCG	4098
	CGCGTATAAAAGCTGAC	4099
Alzheimer disease	TGGTGATCTCCATTAACACTGACCTAGGGCTTTTGTGTTTGTT	4100
Thr116Asn	TTATTGTAGAATCTATACCCCATTCACAGAAGATACCGAGACT
ACC-AAC	GTGGGCCAGAGAGCCCTGCACTCAATTCTGAATGC
	GCATTCAGAATTGAGTGCAGGGCTCTCTGGCCCACAGTCTCG	4101
	GTATCTTCTGTGAATGGGGTATAGATTCTACAATAAAACAAAC
	ACAAAAGCCCTAGGTCAGTGTTAATGGAGATCACCA
	AATCTATACCCCATTCA	4102
	TGAATGGGGTATAGATT	4103
Alzheimer disease	TGATCTCCATTAACACTGACCTAGGGCTTTTGTGTTTGTTTTAT	4104
Pro117Leu	TGTAGAATCTATACCCCATTCACAGAAGATACCGAGACTGTG
CCA-CTA	GGCCAGAGAGCCCTGCACTCAATTCTGAATGCTGC
	GCAGCATTCAGAATTGAGTGCAGGGCTCTCTGGCCCACAGTC	4105
	TCGGTATCTTCTGTGAATGGGGTATAGATTCTACAATAAAACA
	AACACAAAAGCCCTAGGTCAGTGTTAATGGAGATCA
	CTATACCCCATTCACAG	4106
	CTGTGAATGGGGTATAG	4107
Alzheimer disease	TAACACTGACCTAGGGCTTTTGTGTTTGTTTTATTGTAGAATCT	4108
Glu120Asp	ATACCCCATTCACAGAAGATACCGAGACTGTGGGCCAGAGAG
GAAg-GAT	CCCTGCACTCAATTCTGAATGCTGCCATCATGATC
	GATCATGATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCTG	4109
	GCCCACAGTCTCGGTATCTTCTGTGAATGGGGTATAGATTCT
	ACAATAAAACAAACACAAAAGCCCTAGGTCAGTGTTA
	TTCACAGAAGATACCGA	4110
	TCGGTATCTTCTGTGAA	4111
Alzheimer disease	TAACACTGACCTAGGGCTTTTGTGTTTGTTTTATTGTAGAATCT	4112
Glu120Asp	ATACCCCATTCACAGAAGATACCGAGACTGTGGGCCAGAGAG
GAAg-GAC	CCCTGCACTCAATTCTGAATGCTGCCATCATGATC
	GATCATGATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCTG	4113
	GCCCACAGTCTCGGTATCTTCTGTGAATGGGGTATAGATTCT
	ACAATAAAACAAACACAAAAGCCCTAGGTCAGTGTTA
	TTCACAGAAGATACCGA	4114
	TCGGTATCTTCTGTGAA	4115
Alzheimer disease	ATTAACACTGACCTAGGGCTTTTGTGTTTGTTTATTGTAGAAT	4116
Glu120Lys	CTATACCCCATTCACAGAAGATACCGAGACTGTGGGCCAGAG
aGAA-AAA	AGCCCTGCACTCAATTCTGAATGCTGCCATCATGA
	TCATGATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCTGGC	4117
	CCACAGTCTCGGTATCTTCTGTGAATGGGGTATAGATTCTACA
	ATAAAACAAACACAAAAGCCCTAGGTCAGTGTTAAT
	CATTCACAGAAGATACC	4118
	GGTATCTTCTGTGAATG	4119
Alzheimer disease	GACCTAGGGCTTTTGTGTTTGTTTTATTGTAGAATCTATACCC	14120
Glu123Lys	CATTCACAGAAGATACCGAGACTGTGGGCCAGAGAGCCCTGT
cGAG-AAG	CACTCAATTCTGAATGCTGCCATCATGATCACTGTCA
	TGACACTGATCATGATGGCAGCATTCAGAATTGAGTGCAGGG	4121
	CTCTCTGGCCCACAGTCTCGGTATCTTCTGTGAATGGGGTAT
	AGATTCTACAATAAAACAAACACAAAAGCCCTAGGTC
	AAGATACCGAGACTGTG	4122
	CACAGTCTCGGTATCTT	4123
Alzheimer disease	TATACCCCATTCACAGAAGATACCGAGACTGTGGGCCAGAGA	4124
Asn13SAsp	GCCCTGCACTCAATTCTGAATGCTGCCATCATGATCAGTGTC
gAAT-GAT	ATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTATA
	TATACAGAACCACCAGGAGGATAGTCATGACAACAATGACAC	4125
	TGATCATGATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCT
	GGCCCACAGTCTCGGTATCTTCTGTGAATGGGGTATA
	CAATTCTGAATGCTGCC	4126
	GGCAGCATTCAGAATTG	4127
Alzheimer disease	AGAAGATACCGAGACTGTGGGCCAGAGAGCCCTGCACTCAA	4128
Met139lle	TTCTGAATGCTGCCATCATGATCAGTGTCATTGTTGTCATGAC
ATGa-ATA	TATCCTCCTGGTGGTTCTGTATAAATACAGGTGCTAT
	ATAGCACCTGTATTTATACAGAACCACCAGGAGGATAGTCATG	4129
	ACAACAATGACACTGATCATGATGGCAGCATTCAGAATTGAGT
	GCAGGGCTCTCTGGCCCACAGTCTCGGTATCTTCT
	GCCATCATGATCAGTGT	4130
	ACACTGATCATGATGGC	4131
Alzheimer disease	CAGAAGATACCGAGACTGTGGGCCAGAGAGCCCTGCACTCA	4132
Met139Lys	ATTCTGAATGCTGCCATCATGATCAGTGTCATTGTTGTCATGA
ATG-AAG	CTATCCTCCTGGTGGTTCTGTATAAATACAGGTGCTA
	TAGCACCTGTATTTATACAGAACCACCAGGAGGATAGTCATGA	4133
	CAACAATGACACTGATCATGATGGCAGCATTCAGAATTGAGT
	GCAGGGCTCTCTGGCCCACAGTCTCGGTATCTTCTG
	TGCCATCATGATCAGTG	4134
	CACTGATCATGATGGCA	4135
Alzheimer disease	CAGAAGATACCGAGACTGTGGGCCAGAGAGCCCTGCACTCA	4136
Met139Thr	ATTCTGAATGCTGCCATCATGATCAGTGTCATTGTTGTCATGA
ATG-ACG	CTATCCTCCTGGTGGTTCTGTATAAATACAGGTGCTA
	TAGCACCTGTATTTATACAGAACCACCAGGAGGATAGTCATGA	4137
	CAACAATGACACTGATCATGATGGCAGCATTCAGAATTGAGT
	GCAGGGCTCTCTGGCCCACAGTCTCGGTATCTTCTG
	TGCCATCATGATCAGTG	4138
	CACTGATCATGATGGCA	4139
Alzheimer disease	ACAGAAGATACCGAGACTGTGGGCCAGAGAGCCCTGCACTC	4140
Met139Val	AATTCTGAATGCTGCCATCATGATCAGTGTCATTGTTGTCATG
cATG-GTG	ACTATCCTCCTGGTGGTTCTGTATAAATACAGGTGCT
	AGCACCTGTATTTATACAGAACCACCAGGAGGATAGTCATGA	4141
	CAACAATGACACTGATCATGATGGCAGCATTCAGAATTGAGT
	GCAGGGCTCTCTGGCCCACAGTCTCGGTATCTTCTGT
	CTGCCATCATGATCAGT	4142
	ACTGATCATGATGGCAG	4143
Alzheimer disease	GAGACTGTGGGCCAGAGAGCCCTGCACTCAATTCTGAATGCT	4144
lle143Phe	GCCATCATGATCAGTGTCATTGTTGTCATGACTATCCTCCTGG
cATT-TTT	TGGTTCTGTATAAATACAGGTGCTATAAGGTGAGCA
	TGCTCACCTTATAGCACCTGTATTTATACAGAACCACCAGGAG	4145
	GATAGTCATGACAACAATGACACTGATCATGATGGCAGCATTC
	AGAATTGAGTGCAGGGCTCTCTGGCCCACAGTCTC
	TCAGTGTCATTGTTGTC	4146
	GACAACAATGACACTGA	4147
Alzheimer disease	AGACTGTGGGCCAGAGAGCCCTGCACTCAATTCTGAATGCTG	4148
lle143Thr	CCATCATGATCAGTGTCATTGTTGTCATGACTATCCTCCTGGT
ATT-ACT	GGTTCTGTATAAATACAGGTGCTATAAGGTGAGCAT
	ATGCTCACCTTATAGCACCTGTATTTATACAGAACCACCAGGA	4149
	GGATAGTCATGACAACAATGACACTGATCATGATGGCAGCAT
	TCAGAATTGAGTGCAGGGCTCTCTGGCCCACAGTCT
	CAGTGTCATTGTTGTCA	4150
	TGACAACAATGACACTG	4151
Alzheimer disease	CCAGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATGAT	4152
Met146lle	CAGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTAT
ATGa-ATA	AAATACAGGTGCTATAAGGTGAGCATGAGACACAGA
	TCTGTGTCTCATGCTCACCTTATAGCACCTGTATTTATACAGA	4153
	ACCACCAGGAGGATAGTCATGACAACAATGACACTGATCATG
	ATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCTGG
	GTTGTCATGACTATCCT	4154
	AGGATAGTCATGACAAC	4155
Alzheimer disease	CCAGAGAGCCCTGCACTCAATTCTGAATGGTGCCATCATGAT	4156
Met146lle	CAGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTAT
ATGa-ATC	AAATACAGGTGCTATAAGGTGAGCATGAGACACAGA
	TCTGTGTCTCATGCTCACCTTATAGCACCTGTATTTATACAGA	4157
	ACCACCAGGAGGATAGTCATGACAACAATGACACTGATCATG
	ATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCTGG
	GTTGTCATGACTATCCT	4158
	AGGATAGTCATGACAAC	4159
Alzheimer disease	GGCCAGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATG	4160
Met146Leu	ATCAGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGT
cATG-UG	ATAAATACAGGTGCTATAAGGTGAGCATGAGACACA
	TGTGTCTCATGCTCACCUATAGCACCTGTATTTATACAGAAC	4161
	CACCAGGAGGATAGTCATGACAACAATGACACTGATCATGAT
	GGCAGCATTCAGAATTGAGTGCAGGGCTCTCTGGCC
	TTGTTGTCATGACTATC	4162
	GATAGTCATGACAACAA	4163
Alzheimer disease	GGCCAGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATG	4164
Met146Val	ATCAGTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGT
cATG-GTG	ATAAATACAGGTGCTATAAGGTGAGCATGAGACACA
	TGTGTCTCATGCTCACCTTATAGCACCTGTATTTATACAGAAC	4165
	CACCAGGAGGATAGTCATGACAACAATGACACTGATCATGAT
	GGCAGCATTCAGAATTGAGTGCAGGGCTCTCTGGCC
	TTGTTGTCATGACTATC	4166
	GATAGTCATGACAACAA	4167
Alzheimer disease	AGAGAGCCCTGCACTCAATTCTGAATGCTGCCATCATGATCA	4168
Thr147lle	GTGTCATTGTTGTCATGACTATCCTCCTGGTGGTTCTGTATAA
ACT-ATT	ATACAGGTGCTATAAGGTGAGCATGAGACACAGATC
	GATCTGTGTCTCATGCTCACCTTATAGCACCTGTATTTATACA	4169
	GAACCACCAGGAGGATAGTCATGACAACAATGACACTGATCA
	TGATGGCAGCATTCAGAATTGAGTGCAGGGCTCTCT
	TGTCATGACTATCCTCC	4170
	GGAGGATAGTCATGACA	4171
Alzheimer disease	CTTTTTAAGGGTTGTGGGACCTGTTAATTATATTGAAATGCTTT	4172
His163Arg	CTTTTCTAGGTCATCCATGCCTGGCTTATTATATCATCTCTATT
CAT-CGT	GTTGCTGTTCTTTTTTTCATTCATTTACTTGGG
	CCCAAGTAAATGAATGAAAAAAAGAACAGCAACAATAGAGATG	4173
	ATATAATAAGCCAGGCATGGATGACCTAGAAAAGAAAGCATTT
	CAATATAATTAACAGGTCCCACAACCCTTAAAAAG
	GGTCATCCATGCCTGGC	4174
	GCCAGGCATGGATGACC	4175
Alzheimer disease	ACTTTTTAAGGGTTGTGGGACCTGTTAATTATATTGAAATGCTT	4176
His163Tyr	TCTTTTCTAGGTCATCCATGCCTGGCTTATTATATCATCTCTAT
cCAT-TAT	TGTTGCTGTTTCTTTTTTTCATTCATTTACTTGG
	CCAAGTAAATGAATGAAAAAAAGAACAGCAACAATAGAGATGA	4177
	TATAATAAGCCAGGCATGGATGACCTAGAAAAGAAAGCATTTC
	AATATAATTAACAGGTCCCACAACCCTTAAAAAGT
	AGGTCATCCATGCCTGG	4178
	CCAGGCATGGATGACCT	4179
Alzheimer disease	AGGGTTGTGGGACCTGTTAATTATATTGAAATGCTTTCTTTTCT	4180
Trp165Cys	AGGTCATCCATGCCTGGCTTATTATATCATCTCTATTGTTGCT
TGGc-TGC	GTTCTTTTTTTCATTCATTTACTTGGGGTAAGTT
	AACTTACCCCAAGTAAATGAATGAAAAAAAGAACAGCAACAAT	4181
	AGAGATGATATAATAAGCCAGGCATGGATGACCTAGAAAAGA
	AAGCATTTCAATATAATTAACAGGTCCCACAACCCT
	CATGCCTGGCTTATTAT	4182
	ATAATAAGCCAGGCATG	4183
Alzheimer disease	ACCTGTTAATTATATTGAAATGCTTTCTTTTCTAGGTCATCCAT	4184
Ser169Leu	GCCTGGCTTATTATATCATCTCTATTGTTGCTGTTCTTTTTTTC
TCA-TTA	ATTCATTTACTTGGGGTAAGTTGTGAAATTTTT
	AAAAATTTCACAACTTACCCCAAGTAAATGAATGAAAAAAAGAA	4185
	CAGCAACAATAGAGATGATATAATAAGCCAGGCATGGATGAC
	CTAGAAAAGAAAGCATTTCAATATAATTAACAGGT
	TATTATATCATCTCTAT	4186
	ATAGAGATGATATAATA	4187
Alzheimer disease	TAATTATATTGAAATGCTTTCTTTTCTAGGTCATCCATGCCTGG	4188
Leu171Pro	CTTATTATATCATCTCTATTGTTGCTGTTCTTTTTTTCATTCATT
CTA-CCA	TACTTGGGGTAAGTTGTGAAATTTTTGGTCTG
	CAGACCAAAAATTTCACAACTTACCCCAAGTAAATGAATGAAA	4189
	AAAAGAACAGCAACAATAGAGATGATATAATAAGCCAGGCAT
	GGATGACCTAGAAAAGAAAGCATTTCAATATAATTA
	ATCATCTCTATTGTTGC	4190
	GCAACAATAGAGATGAT	4191
Alzheimer disease	TATTGAAATGCTTTCTTTTCTAGGTCATCCATGCCTGGCTTATT	4192
Leu173Trp	ATATCATCTCTATTGTTGCTGTTCTTTTTTTCATTCATTTACTTG
TTG-TGG	GGGTAAGTTGTGAAATTTTTGGTCTGTCTTTC
	GAAAGACAGACCAAAAATTTCACAACTTACCCCAAGTAAATGA	4193
	ATGAAAAAAAGAACAGCAACAATAGAGATGATATAATAAGCCA
	GGCATGGATGACCTAGAAAAGAAAGCATTCAATA
	TCTATTGTTGCTGTTCT	4194
	AGAACAGCAACAATAGA	4195
Alzheimer disease	TATAACGTTGCTGTGGACTACATTACTGTTGCACTCCTGATCT	4196
Gly209Arg	GGAATTTTGGTGTGGTGGGAATGATTTCCATTCACTGGAAAG
gGGA-AGA	GTCCACTTCGACTCCAGCAGGCATATCTCATTATGA
	TCATAATGAGATATGCCTGCTGGAGTCGAAGTGGACCTTTCC	4197
	AGTGAATGGAAATCATTCCCACCACACCAAAATTCCAGATCAG
	GAGTGCAACAGTAATGTAGTCCACAGCAACGTTATA
	GTGTGGTGGGAATGATT	4198
	AATCATTCCCACCACAC	4199
Alzheimer disease	ATAACGTTGCTGTGGACTACATTACTGTTGCACTCCTGATCTG	4200
Gly209Val	GAATTTTGGTGTGGTGGGAATGATTTCCATTCACTGGAAAGGT
GGA-GTA	CCACTTCGACTCCAGCAGGCATATCTCATTATGAT
	ATCATAATGAGATATGCCTGCTGGAGTCGAAGTGGACCTTTC	4201
	CAGTGAATGGAAATCATTCCCACCACACCAAAATTCCAGATCA
	GGAGTGCAACAGTAATGTAGTCCACAGCAACGTTAT
	TGTGGTGGGAATGATTT	4202
	AAATCATTCCCACCACA	4203
Alzheimer disease	TGGACTACATTACTGTTGCACTCCTGATCTGGAATTTTGGTGT	4204
lle213Thr	GGTGGGAATGATTTCCATTCACTGGAAAGGTCCACTTCGACT
ATT-ACT	CCAGCAGGCATATCTCATTATGATTAGTGCCCTCAT
	ATGAGGGCACTAATCATAATGAGATATGCCTGCTGGAGTCGA	4205
	AGTGGACCTTTCCAGTGAATGGAAATCATTCCCACCACACCA
	AAATTCCAGATCAGGAGTGCAACAGTAATGTAGTCCA
	GATTTCCATTCACTGGA	4206
	TCCAGTGAATGGAAATC	4207
Alzheimer disease	CACTCCTGATCTGGAATTTTGGTGTGGTGGGAATGATTTCCAT	4208
Leu219Pro	TCACTGGAAAGGTCCACTTCGACTCCAGCAGGCATATCTCAT
CTT-CCT	TATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAA
	TTGATAAACACCAGGGCCATGAGGGCACTAATCATAATGAGA	4209
	TATGCCTGCTGGAGTCGAAGTGGACCTTTCCAGTGAATGGAA
	ATCATTCCCACCACACCAAAATTCCAGATCAGGAGTG
	AGGTCCACTTCGACTCC	4210
	GGAGTCGAAGTGGACCT	4211
Alzheimer disease	ATTTCCATTCACTGGAAAGGTCCACTTCGACTCCAGCAGGCA	4212
Ala231Thr	TATCTCATTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCA
tGCC-ACC	AGTACCTCCCTGAATGGACTGCGTGGCTCATCTTGG
	CCAAGATGAGCCACGCAGTCCATTCAGGGAGGTACTTGATAA	4213
	ACACCAGGGCCATGAGGGCACTAATCATAATGAGATATGCCT
	GCTGGAGTCGAAGTGGACCTTTCCAGTGAATGGAAAT
	TGATTAGTGCCCTCATG	4214
	CATGAGGGCACTAATCA	4215
Alzheimer disease	TTTCCATTCACTGGAAAGGTCCACTTCGACTCCAGCAGGCAT	4216
Ala231Val	ATCTCATTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAA
GCC-GTC	GTACCTCCCTGAATGGACTGCGTGGCTCATCTTGGC
	GCCAAGATGAGCCACGCAGTCCATTCAGGGAGGTACTTGATA	4217
	AACACCAGGGCCATGAGGGCACTAATCATAATGAGATATGCC
	TGCTGGAGTCGAAGTGGACCTTTCCAGTGAATGGAAA
	GATTAGTGCCCTCATGG	4218
	CCATGAGGGCACTAATC	4219
Alzheimer disease	TTCACTGGAAAGGTCCACTTCGACTCCAGCAGGCATATCTCA	4220
Met233Thr	TTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAAGTACCT
ATG-ACG	CCCTGAATGGACTGCGTGGCTCATCTTGGCTGTGAT
	ATCACAGCCAAGATGAGCCACGCAGTCCATTCAGGGAGGTAC	4221
	TTGATAAACACCAGGGCCATGAGGGCACTAATCATAATGAGA
	TATGCCTGCTGGAGTCGAAGTGGACCTTCCAGTGAA
	TGCCCTCATGGCCCTGG	4222
	CCAGGGCCATGAGGGCA	4223
Alzheimer disease	GGAAAGGTCCACTTCGACTCCAGCAGGCATATCTCATTATGA	4224
Leu235Pro	TTAGTGCCCTCATGGCCCTGGTGTTTATCAAGTACCTCCCTG
CTG-CCG	AATGGACTGCGTGGCTCATCTTGGCTGTGATTTCAGT
	ACTGAAATCACAGCCAAGATGAGCCACGCAGTCCATTCAGGG	4225
	AGGTACTTGATAAACACCAGGGCCATGAGGGCACTAATCATA
	ATGAGATATGCCTGCTGGAGTCGAAGTGGACCTTTCC
	CATGGCCCTGGTGTTTA	4226
	TAAACACCAGGGCCATG	4227
Alzheimer disease	TCATTATGATTAGTGCCCTCATGGCCCTGGTGTTTATCAAGTA	4228
Ala246Glu	CCTCCCTGAATGGACTGCGTGGCTCATCTTGGCTGTGATTTC
GCG-GAG	AGTATATGGTAAAACCCAAGACTGATAATTTGTTTG
	CAAACAAATTATCAGTCTTGGGTTTTACCATATACTGAAATCAC	4229
	AGCCAAGATGAGCCACGCAGTCCATTCAGGGAGGTACTTGAT
	AAACACCAGGGCCATGAGGGCACTAATCATAATGA
	ATGGACTGCGTGGCTCA	4230
	TGAGCCACGCAGTCCAT	4231
Alzheimer disease	GTGCCCTCATGGCCCTGGTGTTTATCAAGTACCTCCCTGAAT	4232
Leu250Ser	GGACTGCGTGGCTCATCTTGGCTGTGATTTCAGTATATGGTA
TTG-TCG	AAACCCAAGACTGATAATTTGTTTGTCACAGGAATGC
	GCATTCCTGTGACAAACAAATTATCAGTCTTGGGTTTTACCAT	4233
	ATACTGAAATCACAGCCAAGATGAGCCACGCAGTCCATTCAG
	GGAGGTACTTGATAAACACCAGGGCCATGAGGGCAC
	GCTCATCTTGGCTGTGA	4234
	TCACAGCCAAGATGAGC	4235
Alzheimer disease	AGTTTAGCCCATACATTTTATTAGATGTCTTTTATGTTTTTCTTT	4236
Ala260Val	TTCTAGATTTAGTGGCTGTTTTGTGTCCGAAAGGTCCACTTCG
GCT-GTT	TATGCTGGTTGAAACAGCTCAGGAGAGAAATGA
	TCATTTCTCTCCTGAGCTGTTTCAACCAGCATACGAAGTGGAC	4237
	CTTTCGGACACAAAACAGCCACTAAATCTAGAAAAAGAAAAAC
	ATAAAAGACATCTAATAAAATGTATGGGCTAAACT
	TTTAGTGGCTGTTTTGT	4238
	ACAAAACAGCCACTAAA	4239
Alzheimer disease	CCCATACATTTTATTAGATGTCTTTTATGTTTTTCTTTTTCTAGA	4240
Leu262Phe	TTTAGTGGCTGTTTTGTGTCCGAAAGGTCCACTTCGTATGCTG
TTGt-TTC	GTTGAAACAGCTCAGGAGAGAAATGAAACGCTT
0
	AAGCGTTTCATTTCTCTCCTGAGCTGTTTCAACCAGCATACGA	4241
	AGTGGACCTTTCGGACAe,uns b Cl ee AAAACAGCCACTAAATCTAGAAAAA
	GAAAAACATAAAAGACATCTAATAAAATGTATGGG
0
	GCTGTTTTe,uns b Gl ee TGTCCGAA	4242
0
	TTCGGACAe,uns b Cl ee AAAACAGC	4243
0
Alzheimer disease	CCATACATTTTATTAGATGTCTTTTATGTTTTCTTTTTCTAGAT	4244
Cys263Arg	TTAGTGGCTGTTTTGe,uns b Tl ee GTCCGAAAGGTCCACTTCGTATGCTG
gTGT-CGT	GTTGAAACAGCTCAGGAGAGAAATGAAACGCTTT
0
	AAAGCGTTTCATTTCTCTCCTGAGCTGTTTCAACCAGCATACG	4245
	AAGTGGACCTTTCGGACe,uns b Al ee CAAAACAGCCACTAAATCTAGAAA
	AAGAAAAACATAAAAGACATCTAATAAAATGTATGG
0
	CTGTTTTGTGe,uns b Tl ee CCGAAA	4246
0
	TTTCGGACe,uns b Al ee CAAAACAG	4247
0
Alzheimer disease	ACATTTTATTAGATGTCTTTTATGTTTTTCTTTTTCTAGATTTAG	4248
Pro264Leu	TGGCTGTTTTGTGTCe,uns b Cl ee GAAAGGTCCACTTCGTATGCTGGTTG
CCG-CTG	AAACAGCTCAGGAGAGAAATGAAACGCTTTTTCC
0
	GGAAAAAGCGTTTCATTTCTCTCCTGAGCTGTTTCAACCAGCA	4249
	TACGAAGTGGACCTTTCe,uns b Gl ee GACACAAAACAGCCACTAAATCTA
	GAAAAAGAAAAACATAAAAGACATCTAATAAAATGT
0
	TTTGTGTCe,uns b Cl ee GAAAGGTC	4250
0
	GACCTTTCe,uns b Gl ee GACACAAA	4251
0
Alzheimer disease	GTCTTTTATGTTTTTCTTTTTCTAGATTTAGTGGCTGTTTTGTG	4252
Arg269Gly	TCCGAAAGGTCCACTTe,uns b Cl ee GTATGCTGGTTGAAACAGCTCAGGA
tCGT-GGT	GAGAAATGAAACGCTTTTTCCAGCTCTCATTTACT
0
	AGTAAATGAGAGCTGGAAAAAGCGTTTCATTTCTCTCCTGAGC	4253
	TGTTTCAACCAGCATACe,uns b Gl ee AAGTGGACCTTTCGGACACAAAAC
	AGCCACTAAATCTAGAAAAAGAAAAACATAAAAGAC
0
	GTCCACTTe,uns b Cl ee GTATGCTG	4254
0
	CAGCATACe,uns b Gl ee AAGTGGAC	4255
0
Alzheimer disease	TCTTTTATGTTTTTCTTTTTCTAGATTTAGTGGCTGTTTTGTGTC	4256
Arg269His	CGAAAGGTCCACTTCe,uns b Gl ee TATGCTGGTTGAAACAGCTCAGGAGA
CGT-CAT	GAAATGAAACGCTTTTTCCAGCTCTCATTTACTC
0
	GAGTAAATGAGAGCTGGAAAAAGCGTTTCATTTCTCTCCTGAG	4257
	CTGTTTCAACCAGCATAe,uns b Cl ee GAAGTGGACCTTTCGGACACAAAA
	CAGCCACTAAATCTAGAAAAAGAAAAACATAAAAGA
0
	TCCACTTCe,uns b Gl ee TATGCTGG	4258
0
	CCAGCATAe,uns b Cl ee GAAGTGGA	4259
0
Alzheimer disease	TAGTGGCTGTTTTGTGTCCGAAAGGTCCACTTCGTATGCTGG	4260
Arg278Thr	TTGAAACAGCTCAGGAGAe,uns b Gl ee AAATGAAACGCTTTTTCCAGCTCT
AGA-ACA	CATTTACTCCTGTAAGTATTTGAGAATGATATTGAA
0
	TTCAATATCATTCTCAAATACTTACAGGAGTAAATGAGAGCTG	4261
	GAAAAAGCGTTTCATTTe,uns b Cl ee TCTCCTGAGCTGTTTCAACCAGCAT
	ACGAAGTGGACCTTTCGGACACAAAACAGCCACTA
0
	TCAGGAGAe,uns b Gl ee AAATGAAA	4262
0
	TTTCATTTe,uns b Cl ee TCTCCTGA	4263
0
Alzheimer disease	CTGTTTTGTGTCCGAAAGGTCCACTTCGTATGCTGGTTGAAAC	4264
Glu280Ala	AGCTCAGGAGAGAAATGe,uns b Al ee AACGCTTTTTCCAGCTCTCATTTAC
GAA-GCA	TCCTGTAAGTATTTGAGAATGATATTGAATTAGTA
0
	TACTAATTCAATATCATTCTCAAATACTTACAGGAGTAAATGAG	4265
	AGCTGGAAAAAGCGTTe,uns b Tl ee CATTTCTCTCCTGAGCTGTTTCAACC
	AGCATACGAAGTGGACCTTTCGGACACAAAACAG
0
	GAGAAATGe,uns b Al ee AACGCTTT	4266
0
	AAAGCGTTe,uns b Tl ee CATTTCTC	4267
0
Alzheimer disease	CTGTTTTGTGTCCGAAAGGTCCACTTCGTATGCTGGTTGAAAC	4268
Glu280Gly	AGCTCAGGAGAGAAATGe,uns b Al ee AACGCTTTTTCCAGCTCTCATTTAC
GAA-GGA	TCCTGTAAGTATTTGAGAATGATATTGAATTAGTA
0
	TACTAATTCAATATCATTCTCAAATACTTACAGGAGTAAATGAG	4269
	AGCTGGAAAAAGCGTTe,uns b Tl ee CATTTCTCTCCTGAGCTGTTTCAACC
	AGCATACGAAGTGGACCTTTCGGACACAAAACAG
0
	GAGAAATGe,uns b Al ee AACGCTTT	4270
0
	AAAGCGTTe,uns b Tl ee CATTTCTC	4271
0
Alzheimer disease	TGTGTCCGAAAGGTCCACTTCGTATGCTGGTTGAAACAGCTC	4272
Leu282Arg	AGGAGAGAAATGAAACGCe,uns b Tl ee TTTTCCAGCTCTCATTTACTCCTG
CTT-CGT	TAAGTATTTGAGAATGATATTGAATTAGTAATCAGT
0
	ACTGATTACTAATTCAATATCATTCTCAAATACTTACAGGAGTA	4273
	AATGAGAGCTGGAAAAe,uns b Al ee GCGTTTCATTTCTCTCCTGAGCTGTT
	TCAACCAGCATACGAAGTGGACCTTTCGGACACA
0
	TGAAACGCe,uns b Tl ee TTTTCCAG	4274
0
	CTGGAAAAe,uns b Al ee GCGTTTCA
0
Alzheimer disease	AAGGTCCACTTCGTATGCTGGTTGAAACAGCTCAGGAGAGAA	4276
ATa285Val	ATGAAACGCTTTTTCCAGe,uns b Cl ee TCTCATTTACTCCTGTAAGTATTTG
GCT-GTT	AGAATGATATTGAATTAGTAATCAGTGTAGAATTT
0
	AAATTCTACACTGATTACTAATTCAATATCATTCTCAAATACTTA	4277
	CAGGAGTAAATGAGAe,uns b Gl ee CTGGAAAAAGCGTTTCATTTCTCTCCT
	GAGCTGTTTCAACCAGCATACGAAGTGGACCTT
0
	TTTTCCAGe,uns b Cl ee TCTCATTT	4278
0
	AAATGAGAe,uns b Gl ee CTGGAAAA	4279
0
Alzheimer disease	GGTCCACTTCGTATGCTGGTTGAAACAGCTCAGGAGAGAAAT	4280
Leu286Val	GAAACGCTTTTTCCAGCTe,uns b Cl ee TCATTTACTCCTGTAAGTATTTGA
tCTC-GTC	GAATGATATTGAATTAGTAATCAGTGTAGAATTTAT
0
	ATAAATTCTACACTGATTACTAATTCAATATCATTCTCAAATACT	4281
	TACAGGAGTAAATGAe,uns b Gl ee AGCTGGAAAAAGCGTTTCATTTCTCTC
	CTGAGCTGTTTCAACCAGCATACGAAGTGGACC
0
	TTCCAGCTe,uns b Cl ee TCATTTAC	4282
0
	GTAAATGAe,uns b Gl ee AGCTGGAA	4283
0
Alzheimer disease	GTGACCAACTTTTTAATATTTGTAACCTTTCCTTTTTAGGGGGA	4284
Gly384Ala	GTAAAACTTGGATTGGe,uns b Gl ee AGATTTCATTTTCTACAGTGTTCTGG
GGA-GCA	TTGGTAAAGCCTCAGCAACAGCCAGTGGAGACTG
0
	CAGTCTCCACTGGCTGTTGCTGAGGCTTTACCAACCAGAACA	4285
	CTGTAGAAAATGAAATCTe,uns b Cl ee CCAATCCAAGTTTTACTCCCCCTA
	AAAAGGAAAGGTTACAAATATTAAAAAGTTGGTCAC
0
	TGGATTGGe,uns b Gl ee AGATTTCA	4286
0
	TGAAATCTe,uns b Cl ee CCAATCCA	4287
0
Alzheimer disease	TTTGTAACCTTTCCTTTTTAGGGGGAGTAAAACTTGGATTGGG	4288
Ser390lle	AGATTTCATTTTCTACAe,uns b Gl ee TGTTCTGGTTGGTAAAGCCTCAGCA
AGT-ATT	ACAGCCAGTGGAGACTGGAACACAACCATAGCCTG
0
	CAGGCTATGGTTGTGTTCCAGTCTCCACTGGCTGTTGCTGAG	4289
	GCTTTACCAACCAGAACAe,uns b Cl ee TGTAGAAAATGAAATCTCCCAATC
	CAAGTTTTACTCCCCCTAAAAAGGAAAGGTTACAAA
0
	TTTCTACAe,uns b Gl ee TGTTCTGG	4290
0
	CCAGAACAe,uns b Cl ee TGTAGAAA	4291
0
Alzheimer disease	AACCTTTCCTTTTTAGGGGGAGTAAAACTTGGATTGGGAGATT	4292
Leu392Val	TCATTTTCTACAGTGTTe,uns b Cl ee TGGTTGGTAAAGCCTCAGCAACAGC
tCTG-GTG	CAGTGGAGACTGGAACACAACCATAGCCTGTTTCG
0
	CGAAACAGGCTATGGTTGTGTTCCAGTCTCCACTGGCTGTTG	4293
	CTGAGGCTTTACCAACCAe,uns b Gl ee AACACTGTAGAAAATGAAATCTCC
	CAATCCAAGTTTTACTCCCCCTAAAAAGGAAAGGTT
0
	ACAGTGTTe,uns b Cl ee TGGTTGGT	4294
0
	ACCAACCAe,uns b Gl ee AACACTGT	4295
0
Alzheimer disease	ATTTCATTTTCTACAGTGTTCTGGTTGGTAAAGCCTCAGCAAC	4296
Asn405Ser	AGCCAGTGGAGACTGGAe,uns b Al ee CACAACCATAGCCTGTTTCGTAGC
AAC-AGC	CATATTAATTGTAAGTATACACTAATAAGAATGTGT
0
	ACACATTCTTATTAGTGTATACTTACAATTAATATGGCTACGAA	4297
	ACAGGCTATGGTTGTGe,uns b Tl ee TCCAGTCTCCACTGGCTGTTGCTGA
	GGCTTTACCAACCAGAACACTGTAGAAAATGAAAT
0
	AGACTGGAe,uns b Al ee CACAACCA	4298
0
	TGGTTGTGe,uns b Tl ee TCCAGTCT	4299
0
Alzheimer disease	TACAGTGTTCTGGTTGGTAAAGCCTCAGCAACAGCCAGTGGA	4300
Ala409Thr	GACTGGAACACAACCATAe,uns b Gl ee CCTGTTTCGTAGCCATATTAATTG
aGCC-ACC	TAAGTATACACTAATAAGAATGTGTCAGAGCTCTTA
0
	TAAGAGCTCTGACACATTCTTATTAGTGTATACTTACAATTAAT	4301
	ATGGCTACGAAACAGGe,uns b Cl ee TATGGTTGTGTTCCAGTCTCCACTG
	GCTGTTGCTGAGGCTTTACCAACCAGAACACTGTA
0
	CAACCATAe,uns b Gl ee CCTGTTTC	4302
0
	GAAACAGGe,uns b Cl ee TATGGTTG	4303
0
Alzheimer disease	GTGTTCTGGTTGGTAAAGCCTCAGCAACAGCCAGTGGAGACT	4304
Cys410Tyr	GGAACACAACCATAGCCTe,uns b Gl ee TTTCGTAGCCATATTAATTGTAAG
TGT-TAT	TATACACTAATAAGAATGTGTCAGAGCTCTTAATGT
0
	ACATTAAGAGCTCTGACACATTCTTATTAGTGTATACUACAAT	4305
	TAATATGGCTACGAAAe,uns b Cl ee AGGCTATGGTTGTGTTCCAGTCTCCA
	CTGGCTGTTGCTGAGGCTTTACCAACCAGAACAC
0
	CATAGCCTe,uns b Gl ee TTTCGTAG	4306
0
	CTACGAAAe,uns b Cl ee AGGCTATG	4307
0
Alzheimer disease	TGTGAATGTGTGTCTTTCCCATCTTCTCCACAGGGTTTGTGCC	4308
Ala426Pro	TTACATTATTACTCCTTe,uns b Gl ee CCATTTTCAAGAAAGCATTGCCAGCT
tGCC-CCC	CTTCCAATCTCCATCACCTTTGGGCTTGTTTTCT
0
	AGAAAACAAGCCCAAAGGTGATGGAGATTGGAAGAGCTGGCA	4309
	ATGCTTTCTTGAAAATGGe,uns b Cl ee AAGGAGTAATAATGTAAGGCACAA
	ACCCTGTGGAGAAGATGGGAAAGACACACATTCACA
0
	TACTCCTTe,uns b Gl ee CCATTTTC	4310
0
	GAAAATGGe,uns b Cl ee AAGGAGTA	4311
0
Alzheimer disease	AGGGTTTGTGCCTTACATTATTACTCCTTGCCAVTTTCAAGAA	4312
Pro436Gln	AGCATTGCCAGCTCTTCe,uns b Cl ee AATCTCCATCACCTTTGGGCTTGTT
CCA-CAA	TTCTACTTTGCCACAGATTATCTTGTACAGCCTTT
0
	AAAAGGCTGTACAAGATAATCTGTGGCAAAGTAGAAAACAAGC	4313
	CCAAAGGTGATGGAGATTe,uns b Gl ee GAAGAGCTGGCAATGCTTTCTTG
	AAAATGGCAAGGAGTAATAATGTAAGGCACAAACCCT
0
	AGCTCTTCe,uns b Cl ee AATCTCCA	4314
0
	TGGAGATTe,uns b Gl ee GAAGAGCT	4315
0
Alzheimer disease	CAGGGTTTGTGCCTTACATTATTACTCCTTGCCATTTTCAAGA	4316
Pro436Ser	AAGCATTGCCAGCTCTTe,uns b Cl ee CAATCTCCATCACCTTTGGGCTTGT
tCCA-TCA	TTTCTACTTTGCCACAGATTATCTTGTACAGCCTT
0
	AAGGCTGTACAAGATAATCTGTGGCAAAGTAGAAAACAAGCC	4317
	CAAAGGTGATGGAGATTGe,uns b Gl ee AAGAGCTGGCAATGCTTTCTTGA
	AAATGGCAAGGAGTAATAATGTAAGGCACAAACCCTG
0
	CAGCTCTTe,uns b Cl ee CAATCTCC	4318
0
	GGAGATTGe,uns b Gl ee AAGAGCTG	4319tz,1/48
ps

EXAMPLE 26

Plant Cells

[0149] The oligonucleotides of the invention can also be used to repair or direct a mutagenic event in plants and animal cells. Although little information is available on plant mutations amongst natural cultivars, the oligonucleotides of the invention can be used to produce “knock out” mutations by modification of specific amino acid codons to produce stop codons (e.g., a CAA codon specifying Gln can be modified at a specific site to TAA; a MG codon specifying Lys can be modified to UAG at a specific site; and a CGA codon for Arg can be modified to a UGA codon at a specific site). Such base pair changes will terminate the reading frame and produce a defective truncated protein, shortened at the site of the stop codon. Alternatively, frameshift additions or deletions can be directed into the genome at a specific sequence to interrupt the reading frame and produce a garbled downstream protein. Such stop or frameshift mutations can be introduced to determine the effect of knocking out the protein in either plant or animal cells.

[0150] All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims

1. An oligonucleotide for targeted alteration(s) of genetic sequence, comprising a single-stranded oligonucleotide having a DNA domain, said DNA domain having at least one mismatch with respect to the genetic sequence to be altered, and further comprising chemical modifications within the oligonucleotide, said targeted alteration(s) occurring more frequently than alteration(s) of the genetic sequence by a double-stranded double hairpin chimeric oligonucleotide containing RNA and DNA nucleotides.

2. The oligonucleotide according to claim one that comprises at least one phosphorothioate linkage within the oligonucleotide.

3. The oligonucleotide according to claim one that comprises a 2′-O-methyl analog.

4. The oligonucleotide according to claim one that comprises a locked nucleotide analog.

5. The oligonucleotide according to claim one that comprises a combination of at least two modifications selected from the group of a phosphorothioate linkage, a 2′-O-methyl analog, a locked nucleotide analog and a ribonucleotide.

6. The oligonucleotide according to any one of claims 1 to 5 that comprises at least one unmodified ribonucleotide.

7. The oligonucleotide according to any one of claims 1 to 6, wherein the sequence of said oligonucleotide is selected from the group consisting of SEQ ID NOS: 1-4339.

8. A method of targeted alteration of genetic material, comprising combining the target genetic material with an oligonucleotide according to any one of claims 1 to 7 in the presence of purified proteins.

9. A method of targeted alteration of genetic material, comprising administering to a cell extract an oligonucleotide of any one of claims 1 to 7.

10. A method of targeted alteration of genetic material, comprising administering to a cell an oligonucleotide of any one of claims 1 to 7.

11. A method of targeted alteration of genetic sequence in a subject, comprising administering to the subject an oligonucleotide of any one of claims 1 to 7.

12. A method of targeted alteration of genetic sequence, comprising combining target genetic material with an oligonucleotide according to any one of claims 1 to 7, said target genetic material being a non-transcribed DNA strand of a duplex DNA.

13. The genetic material obtained by any one of the methods of claim 8, 9 or claim 10.

14. A cell comprising the genetic material of claim 13.

15. A non-human organism comprising the cell according to claim 14.

16. A pharmaceutical composition comprising the oligonucleotide according to any one of claims 1 to 7.

17. A method of targeted chromosomal genomic alteration, comprising administering the pharmaceutical composition of claim 16 to a subject.

18. A non-human organism produced by the method of claim 11 or claim 17.

19. A method of optimizing an oligonucleotide for targeted alteration of a genetic sequence, which comprises: (a) comparing the efficiency of alteration of a targeted genetic sequence by an oligonucleotide of any one of claims 1 to 7 with the efficiency of alteration of the same targeted genetic sequence by a second oligonucleotide, said second oligonucleotide selected from the group of (1) an oligonucleotide that is fully complementary to the target and lacks the mismatch, (2) a fully modified phosphorothiolated oligonucleotide, (3) a fully modified 2′-O-methylated oligonucleotide and (4) a chimeric double-stranded double hairpin containing RNA and DNA nucleotides.

20. The method of claim 19 in which the alteration is produced in a cell extract.

21. The method of claim 20 in which the cell extract is selected from the group of a fungal cell extract, a plant cell extract, a rodent cell extract, a primate cell extract and a human cell extract.

22. The method of claim 19 in which the alteration is produced in a cell.

23. The method of claim 21 in which the cell is selected from the group of a fungal cell, a plant cell, a rodent cell, a primate cell and a human cell.

24. A kit comprising the oligonucleotide according to any one of claims 1 to 7 and a second oligonucleotide selected from the group of (1) an oligonucleotide that is fully complementary to the target and lacks the mismatch, (2) a fully modified phosphorothiolated oligonucleotide, (3) a fully modified 2-O-methylated oligonucleotide and (4) a chimeric double stranded double hairpin containing RNA and DNA nucleotides.