METHODS FOR DETECTING AND PREDICTING CANCER AND/OR CIN3

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Jun. 9, 2021, is named ‘Sequence listing as filed 17 Jun. 2021 N417234WO MGW JAS.txt’ and is 564,410 bytes in size.

FIELD OF THE INVENTION

The present invention relates to assays for predicting the presence, absence or development of cancer and/or grade 3 cervical intra-epithelial neoplasia (CIN3) in an individual, particularly endometrial, ovarian and cervical cancer, by determining the methylation status of certain CpGs in a population of DNA molecules in a sample which has been taken from the individual, deriving an index value based on the methylation status of the certain CpGs, and predicting the presence, absence or development of cancer in the individual based on the cancer index value. The invention further relates to a method of treating and/or preventing cancer in an individual, particularly endometrial, ovarian and cervical cancer, and CIN3, the method comprising assessing the presence, absence or development of cancer in an individual by performing the assays of the invention, followed by administering one or more therapeutic or preventative treatments or measures to the individual based on the assessment. The invention further provides a method of monitoring the cancer status of an individual according to changes in the individual's cancer index value over the course of time. The invention further relates to arrays which are suitable for performing the assays of the invention.

The project leading to this application has been funded by the European Commission's Horizon 2020 Research and Innovation Action, H2020 FORECEE under Grant Agreement No. 634570, the European Commission's Horizon 2020 European Research Council Executive Agency, H2020 BRCA-ERC under Grant Agreement No. 742432 as well as the charity, The Eve Appeal.

BACKGROUND TO THE INVENTION

Endometrial cancer has become the most frequently occurring gynaecological cancer in developed countries. By 2030, it is expected that endometrial cancer will be the third most common cancer affecting women in the US after that of breast and thyroid. Approximately 20% of women with endometrial cancer present with high-risk and/or more advanced disease characteristics with an increased incidence of distant metastases and cancer-related death and hence in addition to surgery require adjuvant chemo- and radiotherapy which are associated with a high morbidity.

Therefore, a tool with which to diagnose earlier and predict specifically high-risk endometrial cancers is urgently required.

Imaging-based screening for endometrial cancers is not efficient. The performance characteristics of endometrial thickness and abnormalities for detection of endometrial cancer within one year of transvaginal ultrasound in a population-based nested case-control study of postmenopausal women showed a sensitivity of only 54.1% and a positive predictive value of 6.1%.

Recent evidence has shown that an assay (called PapSEEK) for mutations in 18 genes as well as an assay for aneuploidy in cervical brush samples is able to identify 81% of women presenting with endometrial cancer. However, in this study, the average age of cases and controls was 62 and 34 years, respectively. The consistent observation of a high allele frequency of pathogenic driver mutations in DNA from non-malignant normal endometrium with increasing age combined with the fact that the cases were almost twice as old as the controls makes it impossible to judge the true specificity of the PapSEEK test.

The inventors, along with other scientists, have shown in the past that DNA methylation in vaginal fluid or cervical smears may be able to identify women with endometrial cancer. All of these studies were relatively small and did not validate the findings in a large data set. In addition, none of these studies focused specifically on high risk endometrial cancers and, most importantly, none assessed cohort-based samples from women prior to the diagnosis of the disease.

Here, the inventors have developed and validated a DNA methylation signature in samples, particularly cervical smear samples, which is capable of both diagnosing and predicting the risk of developing cancer.

SUMMARY OF THE INVENTION

The current inventors set out to understand whether DNAme (DNA methylation) profiles may be used to detect the presence or absence of cancer, particularly endometrial and ovarian cancer. The inventors also set out to understand whether said DNAme profiles may be associated with the development of cancer, and therefore whether such profiles may be capable of functioning as surrogate markers for individual stratification purposes in connection with cancer.

In this regard the inventors have succeeded in developing assays involving “cancer index values” which are derived from and associated with DNAme profiles established from samples from tissue comprising epithelial cells from a given individual. The sample may particularly be derived from the cervix, the vagina, the buccal area, blood and/or urine. The sample is preferably a cervical liquid-based cytology sample, and more preferably a cervical smear sample. Subsequent DNAme profiles from a given individual, and which values can be used to stratify the individual in connection with cancer and/or CIN3 status. A preferred sample for use in any of the assays described and defined herein is a cervical liquid-based cytology sample. A particularly preferred sample for use in any of the assays described and defined herein is a cervical smear sample.

Accordingly, in contrast to prior art assays, the inventors have surprisingly determined that it is possible to derive “cancer index values” derived from and associated with DNAme profiles established from samples, wherein the samples are free of tumor-derived DNA. Thus the tissue(s) from which DNAme profiles of the present assays are established may act to provide surrogate markers for the presence, absence or development of cancer, wherein tumor cells, if present, or cells at risk of transforming into tumor cells, are located at an anatomical site distinct from the site from which the sample was taken.

The cancer index value is determined from data relating to the methylation status of one or more CpGs in a panel of CpGs as further defined and described herein. CpGs of the panel are methylation sites in DNA from cells derived from/obtained from samples comprising epithelial cells. The sample may particularly be derived from the cervix, the vagina, the buccal area, blood and/or urine. The sample is preferably a cervical liquid-based cytology sample, and more preferably a cervical smear sample.

For the purposes of the present invention, the cancer index value may be used interchangeably herein with “WID-EC-Index”, “WID-Index”, “cancer index”, “index” or “index value” (WID=women's risk identification). Furthermore, any reference to a cancer index value in the context of the present invention, may be equally used for the assessment of the presence, absence or development of endometrial cancer and/or ovarian cancer in an individual.

Based on studies with patients known to be free of endometrial cancer, the inventors have established cancer index values, using specific panels of CpGs, which have been determined to be associated with/characteristic of endometrial tissue which is negative for endometrial cancer, i.e. normal endometrial tissue which is free of endometrial cancer. Based on studies with patients known to possess endometrial cancer, the inventors have established cancer index values which have been determined to be associated with/characteristic of endometrial tissue which is positive for endometrial cancer.

The inventors have further established that the same specific panels of CpGs that associate with endometrial tissue which is negative or positive for endometrial cancer may likewise be associated with ovarian tissue that is negative or positive for ovarian cancer and/or cervical tissue that is negative or positive for CIN3. Based on studies with patients known to be free of ovarian cancer and/or CIN3, the inventors have established cancer index values, using specific panels of CpGs, which have been determined to be associated with/characteristic of ovarian tissue which is negative for ovarian cancer, i.e. normal ovarian tissue which is free of ovarian cancer, and/or of cervical tissue which is negative for CIN3. Based on studies with patients known to possess ovarian cancer and/or CIN3, the inventors have established cancer index values which have been determined to be associated with/characteristic of ovarian tissue which is positive for ovarian cancer and or cervical tissue which is positive for CIN3.

Thus, the inventors have been able to establish cancer index values, using specific panels of CpGs, which can characterize an individual as having cancer and/or CIN3 or not having cancer and/or CIN3, or having a high risk of cancer and/or CIN3 development.

By determining the methylation profile-based cancer index value from a sample derived from the individual, the individual may be seen to possess a cancer index value which correlates with those possessed by individuals which are known, via the inventor's studies described herein, to be cancer positive or negative. Such correlations have been determined with a high degree of statistical accuracy, particularly with respect to parameters relevant to biological assays such as receiver operating characteristics (ROC) sensitivity and specificity, as well as area under the curve (AUC). Accordingly, by determining the cancer index value from a sample from a given individual, the individual may be determined to possess endometrial and/or ovarian tissue which is positive for cancer, i.e, the individual is diagnosed as having endometrial and/or ovarian cancer and/or CIN3, most preferably endometrial cancer. Conversely, by determining the cancer index value from a sample from a given individual, the individual may be determined to possess endometrial and/or ovarian tissue which is negative for cancer, i.e, the individual is diagnosed as not having endometrial and/or ovarian cancer, most preferably endometrial cancer.

Assessing the development of cancer in accordance with the assays of the invention may refer to assessing an increased or decreased likelihood of cancer development. Assessing of the development of cancer in accordance with the assays of the invention may refer to assessing progression or worsening of a pre-existing cancer lesion in an individual. Assessment of the development of cancer in accordance with the assays of the invention may refer to predicting the likelihood of recurrence of cancer.

The observation that the cancer index value discussed herein correlates with the stage and severity of cancer in women indicates that the cancer index value can act as a surrogate marker for indicating the severity of cancer in an individual. These observations from the current inventors further establish that the cancer index value, as further described and defined herein, is dynamic and can change according to, at least, the stage and severity of the cancer. The cancer index value may therefore be used to monitor an individual's cancer status and risk of cancer development. Moreover, the cancer index value may be used to monitor the efficacy of cancer treatments being administered to an individual, including therapeutic treatments and preventative treatments.

Accordingly, in the context of the present invention, by determining the cancer index value from a sample from a given individual it is possible to assess the presence, absence or development of cancer in an individual, or in other words to stratify the individual for cancer. In the context of the present invention, stratification for cancer is the process of categorizing the individual as being a member of a group of individuals who possess a phenotype in connection with cancer, including the presence or absence of cancer in the individual, or the development of cancer, i.e. by having epithelial cells, particularly derived from the cervix, the vagina, the buccal area, blood and/or urine which is more characteristic of endometrial or ovarian tissue which is cancer positive than endometrial or ovarian tissue which is cancer negative, or which is more characteristic of cervical tissue which is CIN3 positive than cervical tissue which is CIN3 negative. The sample is preferably a cervical liquid-based cytology sample, and more preferably a cervical smear sample.

As explained herein, the assays methods of the invention are based on a cancer index value derived from a methylation profile from DNA originating from samples comprising epithelial cells. The sample may particularly be derived from the cervix, the vagina, the buccal area, blood and/or urine. The sample is preferably a cervical liquid-based cytology sample, and more preferably a cervical smear sample. Accordingly, the assays provide means for correlating samples derived from the cervix, the vagina, the buccal area, blood and/or urine-derived DNA methylation profile with a status connected with endometrial or ovarian cancer ranging from the individual being cancer negative, to the individual being cancer positive, or with cervical tissue ranging from the individual being CIN3 positive to CIN3 negative, with high statistical accuracy. Because the assays of the invention provide a correlation between the methylation profile and the disease status, the skilled person will appreciate that as part of the stratification process and outcome, disease status is assigned on the basis of a likelihood. As such, the methods of the invention provide assays which are predictive of an individual's status with respect to cancer. The assays of the invention accordingly provide means for predicting the presence or absence of cancer and/or CIN3 in an individual. The assays of the invention accordingly also provide means for predicting the development of cancer and or CIN3 in an individual. The assays of the invention can provide means for predicting the development of cancer in an individual since the inventors have demonstrated that specific cancer index values can define endometrial and ovarian tissue which is cancer negative, whilst others can define endometrial and ovarian tissue which is cancer positive, and since the specific cancer index values may be dynamic and thereby increased in association with known risk factors associated with endometrial and ovarian cancer, in addition to CIN3 status, the values may be subject to change along a scale of cancer and/or CIN3 risk.

Whilst disease status may be assigned on the basis of a likelihood, the inventors have demonstrated herein that correlations between DNA methylation profile and cancer status using cancer index values can be achieved with a very high degree of statistical accuracy using parameters relevant to biological assays, as described further herein. As such, the assays of the invention provide means for predicting the presence or absence of cancer and/or CIN3 in an individual and for predicting the development of cancer in an individual, and for stratifying an individual for cancer, and wherein the prediction/stratification can be defined to be statistically highly reliable and robust. This in turn means that the prediction/stratification can be made with a high level of confidence. The assays of the invention can be defined to be statistically accurate by means known in the art, as further described and defined herein. The assays of the invention can be defined according to parameters relating to their statistical specificity and sensitivity. These parameters define the likelihood of false positive and false negative test results. The lower the proportion of false positive and false negative test results the more statistically accurate the assay becomes. In this regard the inventors have established CpG panels, as described and defined further herein, wherein the methylation status of CpGs in the panel can be used to establish cancer index values such that the assays produce statistically accurate predictions of cancer status. Accordingly, the inventors have determined that the assays described herein may be defined according to statistical parameters such as percentage specificity and sensitivity and also by receiver operating characteristics (ROC) area under the curve (AUC). All such means are known in the art and are known to be defined measures of statistical accuracy for biological assays such as those described and defined herein.

Thus the methods of the invention provide assays which can be used, with a high degree of statistical accuracy, to predict the presence, absence or development of cancer. The methods of the invention provide assays which can be used, with a high degree of statistical accuracy, to stratify an individual with respect to cancer status. Accordingly, the methods of the invention provide useful information to individuals and their physicians concerning patient cancer status. This information may help inform actual therapeutic treatment measures if the presence of cancer is identified in the individual. The information may help to monitor the progress of therapeutic treatment measures in the individual by monitoring changes in the cancer index value over the course of a period of time. The information may help to monitor the progress of prophylactic or preventative treatment measures in the individual by monitoring changes in the cancer index value over the course of a period of time. As such the methods of the invention offer significant advantages in the personalized prevention and early detection as well as treatment and management of cancer in individuals.

Accordingly, the invention provides an assay for assessing the presence, absence or development of cancer and/or grade 3 cervical intra-epithelial neoplasia (CIN3) in an individual, the assay comprising:

- 1. providing a sample which has been taken from the individual, the sample comprising a population of DNA molecules;
- 2. determining in the population of DNA molecules in the sample the methylation status of a panel of:
  - i. one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
  - ii. one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG;
- 3. deriving a cancer index value based on the methylation status of the one or more CpGs in the panel; and
- 4. assessing the presence, absence or development of cancer and/or CIN3 in the individual based on the cancer index value;
- wherein the assay is characterised as having an area under the curve (AUC) of 0.60 or more as determined by receiver operating characteristics (ROC).

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least 50 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.90.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having an AUC of at least 0.95.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least 100 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having an AUC of at least 0.96.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least 150 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93.

The assay of the invention may be performed above and additionally the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having an AUC of at least 0.96.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least 200 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having an AUC of at least 0.96.

The assay of the invention may be performed above and additionally wherein the panel of one or more CpGs comprises at least the 500 CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and further wherein the assay is characterised as having an AUC of at least 0.97.

The assay of the invention may be performed above and additionally wherein the step of determining in the population of DNA molecules in the sample the methylation status of the one or more CpGs in the panel comprises determining a β value of each CpG.

The assay of the invention may be performed above and additionally wherein the step of deriving the cancer index value based on the methylation status of the one or more CpGs in the panel comprises:

- 1. providing a methylation β-value data set comprising the methylation β-values for each CpG in the panel;
- 2. providing a mathematical model capable of generating the cancer index from the methylation β-value data set; and
- 3. applying the mathematical model to the methylation β-value data set, thereby generating the cancer index.

The assay of the invention may be performed above and additionally wherein the cancer index value is a WID-EC-Index cancer index value, and wherein the mathematical model which is applied to the methylation β-value data set to generate the cancer index is an algorithm according to the following formula:

$WID - EC - index = \sum_{i = 1}^{n} \frac{w_{i} β_{i} - μ}{σ}$

wherein:

- 1. β₁, . . . , β_nare methylation beta-values (between 0 and 1);
- 2. w₁, . . . , w₅₀₀are real valued coefficients;
- 3. μ and σ are real valued parameters used to scale the index; and
- 4. n refers to the number of CpGs in the panel of one or more CpGs;
- preferably wherein the cancer is endometrial cancer.

The assay of the invention may be performed above and additionally wherein when the cancer index value for the individual is about −0.201 or more, the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about −0.201, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein:

- 1, the panel of one or more CpGs comprises at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 76%;
- 2, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 80%;
- 3, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 92% and specificity is at least 79%; or
- 4, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 93% and specificity is at least 80%;
- preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, more preferably wherein the cancer is endometrial cancer.

The assay of the invention may be performed above and additionally wherein when the cancer index value for the individual is about 0.269 or more, the individual is assessed as having cancer and/or CIN3, or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about 0.269, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein:

- 1, the panel of one or more CpGs comprises at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 75% and the specificity is at least 94%;
- 2, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 98%;
- 3, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 98%; or
- 4, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%;
- preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, more preferably wherein the cancer is endometrial cancer.

The assay of the invention may be performed above and additionally wherein when the cancer index value for the individual is about 1.072 or more, the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about 1.072, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein:

- 1, the panel of one or more CpGs comprises at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and the specificity is at least 99%;
- 2, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is 100%;
- 3, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 63% and specificity is 100%; or
- 4, the panel of one or more CpGs comprises at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, more preferably wherein the cancer is endometrial cancer.

The assay of the invention may be performed above and additionally wherein when the cancer index value for the individual is:

- 1. less than about −0.660 the individual is assessed as not having cancer and/or CIN3;
- 2. about −0.660 or more and less than about −0.430 the individual is assessed as having a low risk of cancer and/or CIN3 development;
- 3. about −0.430 or more and less than about −0.230 the individual is assessed as having a moderate risk of cancer and/or CIN3 development; or
- 4. about −0.230 or more the individual is assessed as having a high risk of cancer and/or CIN3 development;
- preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, more preferably wherein the cancer is endometrial cancer.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of a panel of one or more CpGs comprises determining the methylation status of one or more CpGs denoted by CG identified in a panel of one or more DMRs defined by SEQ ID NOs 501 to 808, optionally wherein the panel of one or more CpGs comprises two or more CpGs denoted by CG identified in the panel of DMR(s), three or more CpGs denoted by CG identified in the panel of DMR(s), four or more CpGs denoted by CG identified in the panel of DMR(s), or all CpGs denoted by CG identified in the DMR(s) defined by SEQ ID NOs 501 to 808.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of a panel of the one or more CpGs comprises determining the methylation status of five or more, six or more, seven or more, eight or more, or nine or more, or all of the CpGs denoted by CG within any one or more of the DMRs defined by SEQ ID NOs 501 to 808.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of a panel of one or more CpGs comprises determining the methylation status of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more, or all of the CpGs denoted by CG within:

- 1. any combination of two, three, four, five, six, seven, eight, or nine or more of DMRs 1 to 308;
- 2. any combination of ten, twenty, thirty, forty, fifty, sixty, seventy, eighty, or ninety or more of DMRs 1 to 308;
- 3. all 308 of DMRs 1 to 308;
- 4. one DMR defined by SEQ ID NO: 501, two DMRs defined by SEQ ID NOs: 501 to 502, three DMRs defined by SEQ ID NOs: 501 to 503, four DMRs defined by SEQ ID NOs: 501 to 504, five DMRs defined by SEQ ID NOs: 501 to 505, six DMRs defined by SEQ ID NOs: 501 to 506, seven DMRs defined by SEQ ID NOs: 501 to 507, eight DMRs defined by SEQ ID NOs: 501 to 508, or nine DMRs defined by SEQ ID NOs: 501 to 509; or
- 5. ten DMRs defined by SEQ ID NOs: 501 to 510, twenty DMRs defined by SEQ ID NOs: 501 to 520, thirty DMRs defined by SEQ ID NOs: 501 to 530, forty DMRs defined by SEQ ID NOs: 501 to 540, fifty DMRs defined by SEQ ID NOs: 501 to 550, sixty DMRs defined by SEQ ID NOs: 501 to 560, seventy DMRs defined by SEQ ID NOs: 501 to 570, eighty DMRs defined by SEQ ID NOs: 501 to 580, or ninety DMRs defined by SEQ ID NOs: 501 to 590; or
- 6. ten DMRs defined by SEQ ID NOs: 501 to 510, SEQ ID NOs: 511 to 520, SEQ ID NOs: 521 to 530, SEQ ID NOs: 531 to 540, SEQ ID NOs: 541 to 550, SEQ ID NOs: 551 to 560, SEQ ID NOs: 561 to 570, SEQ ID NOs: 571 to 580, SEQ ID NOs: 581 to 590, SEQ ID NOs: 591 to 600, SEQ ID NOs: 601 to 610, SEQ ID NOs: 611 to 620, SEQ ID NOs: 621 to 630, SEQ ID NOs: 631 to 640, SEQ ID NOs: 641 to 650, SEQ ID NOs: 651 to 660, SEQ ID NOs: 661 to 670, SEQ ID NOs: 671 to 680, SEQ ID NOs: 681 to 690, SEQ ID NOs: 691 to 700, SEQ ID NOs: 701 to 710, SEQ ID NOs: 711 to 720, SEQ ID NOs: 721 to 730, SEQ ID NOs: 731 to 740, SEQ ID NOs: 741 to 750; SEQ ID NOs: 751 to 760; SEQ ID NOs: 761 to 770; SEQ ID NOs: 771 to 780; SEQ ID NOs: 781 to 790; SEQ ID NOs: 791 to 800 or SEQ ID NOs: 801 to 808.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of a panel of one or more CpGs comprises determining the methylation status of one or more CpGs within any one or more DMRs selected from the group of DMRs consisting of DMRs 1 to 308 as defined by SEQ ID NOs 501 to 808, including:

- a. one or more CpGs within DMR 1 as defined by SEQ ID NO: 501 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.911, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- b. one or more CpGs within DMR 2 as defined by SEQ ID NO: 502 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.903, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- c. one or more CpGs within DMR 3 as defined by SEQ ID NO: 503 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- d. one or more CpGs within DMR 4 as defined by SEQ ID NO: 504 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- e. one or more CpGs within DMR 5 as defined by SEQ ID NO: 505 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- f. one or more CpGs within DMR 6 as defined by SEQ ID NO: 506 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.897, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- g. one or more CpGs within DMR 7 as defined by SEQ ID NO: 507 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.894, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- h. one or more CpGs within DMR 8 as defined by SEQ ID NO: 508 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.894, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- i. one or more CpGs within DMR 9 as defined by SEQ ID NO: 509 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.892, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]]; or
- j. one or more CpGs within DMR 10 as defined by SEQ ID NO: 510 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.891, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]].

The assay of the invention may be performed above and additionally wherein:

- 1. when the cancer index for the individual is about 0.025 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development; or
- 2. when the cancer index for the individual is less than about 0.025 the individual is classified as not having cancer and/or CIN3;
- preferably wherein the assay has a specificity of 95% or more, more preferably wherein the assay comprises determining mean β-values for each CpG in the panel of one or more CpGs.

The assay of the invention may be performed above and additionally wherein:

- 1. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 1 defined by SEQ ID NO: 501, and wherein when the cancer index for the individual is about 0.209 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 70.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 1, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [[CG]] in SEQ ID NO: 501;
- 2. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 1 defined by SEQ ID NO: 501, and wherein when the cancer index for the individual is less than about 0.209 the individual is classified as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 70.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 1, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [[CG]] in SEQ ID NO: 501;
- 3. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 2 defined by SEQ ID NO: 502, and wherein when the cancer index for the individual is about 0.271 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 77.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least one CpG from DMR 2, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 502;
- 4. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 2 defined by SEQ ID NO: 502, and wherein when the cancer index for the individual is less than about 0.271 the individual is classified as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 77.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least one CpGs from DMR 2, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 502;
- 5. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 3 defined by SEQ ID NO: 503, and wherein when the cancer index for the individual is about 0.123 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 3, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 503;
- 6. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 3 defined by SEQ ID NO: 503, and wherein when the cancer index for the individual is less than about 0.123 the individual is classified as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 3, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [[CG]] in SEQ ID NO: 503;
- 7. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 4 defined by SEQ ID NO: 504, and wherein when the cancer index for the individual is about 0.123 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 4, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [[CG]] in SEQ ID NO: 504;
- 8. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 4 defined by SEQ ID NO: 504, and wherein when the cancer index for the individual is less than about 0.123 the individual is classified as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 73.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least three CpGs from DMR 4, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 504;
- 9. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 5 defined by SEQ ID NO: 505, and wherein when the cancer index for the individual is about 0.105 or more the individual is classified as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least five CpGs from DMR 5, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 505; or
- 10. CpGs denoted by CG whose cancer index value is determined are located within at least DMR 5 defined by SEQ ID NO: 505, and wherein when the cancer index for the individual is less than about 0.105 the individual is classified as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the sensitivity of the assay is at least 71.00% and the specificity of the assay is at least 95.00%, preferably wherein the panel of one or more CpGs comprises at least five CpGs from DMR 5, and more preferably wherein the cancer index value is the mean β-value for the CpGs denoted by [CG] in SEQ ID NO: 505.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of the one or more CpGs in the panel further comprises or additionally comprises determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809 to 919.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of the one or more CpGs in the panel comprises determining each CpG within:

- a. SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883 and wherein when the cancer index value is about 0.282 or more the individual is classified as having endometrial cancer or as having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883;
- b. SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883 and wherein when the cancer index value is less than about 0.282 the individual is classified as not having endometrial cancer or as having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 809 and/or SEQ ID NO 846 and/or SEQ ID NO 883;
- c. SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884 and wherein when the cancer index value is about 0.212 or more the individual is classified as having endometrial cancer or as having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 883;
- d. SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884 and wherein when the cancer index value is less than about 0.212 the individual is classified as not having endometrial cancer or as having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 55.00%, the specificity of the assay is about 100.00%, and the AUC is about 1.00, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 810 and/or SEQ ID NO 847 and/or SEQ ID NO 884;
- e. SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885 and wherein when the cancer index value is about 0.002 or more the individual is classified as having endometrial cancer or as having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 740 and/or SEQ ID NO 777 and/or SEQ ID NO 814;
- f. SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885 and wherein when the cancer index value is less than about 0.002 the individual is classified as not having endometrial cancer or as having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 90.00%, the specificity of the assay is about 80.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 811 and/or SEQ ID NO 848 and/or SEQ ID NO 885;
- g. SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886 and wherein when the cancer index value is about 0.026 or more the individual is classified as having endometrial cancer or as having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 90.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886;
- h. SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886 and wherein when the cancer index value is less than about 0.026 the individual is classified as not having endometrial cancer or as having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 90.00%, and the AUC is about 0.98, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 812 and/or SEQ ID NO 849 and/or SEQ ID NO 886;
- i. SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887 and wherein when the cancer index value is about 0.003 or more the individual is classified as having endometrial cancer or as having a high risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887; and/or
- j. SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887 and wherein when the cancer index value is less than about 0.003 the individual is classified as not having endometrial cancer or as having a low risk of endometrial cancer development, and wherein the sensitivity of the assay is at least 85.00%, the specificity of the assay is about 85.00%, and the AUC is about 0.97, preferably wherein the cancer index value is the percent methylated reference for sequence defined by SEQ ID NO 813 and/or SEQ ID NO 850 and/or SEQ ID NO 887.

The assay of the invention may be performed above and additionally wherein the step of determining in the population of DNA molecules in the sample the methylation status of each CpG in the panel of one or more CpGs comprises:

- 1. performing a sequencing step to determine the sequence of each CpG;
- 2. hybridising DNA to an array comprising probes capable of discriminating between methylated and non-methylated forms of the CpGs and applying a detection system to the array so as to determine the methylation status of each CpG; and/or
- 3. performing a PCR step using methylation-specific primers, wherein the methylation status of the CpG is determined by the presence or absence of a PCR product.

The assay of the invention may be performed above and additionally wherein the step of determining the methylation status of each CpG in the panel of one or more CpGs comprises:

- 1. bisulphite converting the DNA; or
- 2. performing the steps of oxidising 5-methylcytosine bases (5mC) to 5-carboxylcytosine bases (5caC), preferably by ten-eleven translocation (TET), and/or oxidising 5-hydroxymethylcytosine bases (5hmC) to 5-carboxylcytosine bases (5caC), preferably by ten-eleven translocation (TET); followed by reducing 5-carboxylcytosine bases (5caC) to dihydrouracil bases (DHU), optionally with pyridine borane.

The invention also provides a method of treating or preventing cancer in an individual, the method comprising:

- 1. assessing the cancer status of the individual by assessing the presence, absence or development of cancer in the individual by performing the assay of any one of the assays of the invention;
- 2. administering one or more therapeutic or preventative treatments to the individual based on the assessment.

The method of the invention may be performed above and additionally wherein the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, and wherein the cancer index value is about −0.660 or more and less than about −0.430, and preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, the individual is subjected to one or more treatments according to their cancer index value, the one or more treatments comprise:

- 1. a transvaginal ultrasound to assess endometrium and ovaries;
- 2. a repeat assay according to any one of the assays of the invention, preferably wherein the repeat assay is performed about two years after the previous assay.

The method of the invention may be performed above and additionally wherein the individual is assessed as having a moderate risk of having cancer and/or CIN3 or as having a moderate risk of cancer and/or CIN3 development, and wherein the cancer index value is about −0.430 or more and less than about −0.230, and preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, the individual is subjected to one or more treatments according to their cancer index value, the one or more treatments comprise any of:

- 1. a transvaginal ultrasound to assess endometrium and ovaries;
- 2. intensified screening, preferably wherein the intensified screening comprises one or more of:
  - i. a colposcopy;
  - ii. a HPV test;
  - iii. a cervical cytology test;
  - iv. a test for CA125, preferably wherein the test is repeated six-monthly;
  - v. a test for cell-free tumour DNA methylation in plasma/serum, preferably wherein the test is repeated annually;
  - vi. a test for cell-free tumour DNA methylation in vaginal fluid, preferably wherein the test is repeated annually
  - vii. a pelvic MRI scan, preferably wherein the individual being subjected to the pelvic MRI scan is post-menopausal, and preferably wherein the scan is repeated annually;
  - viii. a repeat assay according to any one of the assays of the invention, preferably wherein the repeat assay is performed about one year after the previous assay
- 3. administration of one or more of progestogens, particularly wherein the progestogens are delivered locally or systemically, Aspirin, Metformin, aromatase-inhibitors, weight-loss regimen.

The method of the invention may be performed above and additionally wherein when the colposcopy, HPV and cytology tests are negative, the intensified screening further comprises a hysteroscopy and endocervical and endometrial biopsy.

The method of the invention may be performed above and additionally wherein when the transvaginal ultrasound and intensified screening are both negative:

- 1, the transvaginal ultrasound, the test for CA125, the test for cell-free tumour DNA methylation in plasma/serum, and the test for cell-free tumour DNA methylation in vaginal fluid is repeated about six months after the previous assay; and
- 2, the colposcopy, the HPV test, and the cervical cytology test, is repeated about one year after the previous assay.

The method of the invention may be performed above and additionally wherein the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, and wherein the cancer index value is about −0.230 or more, and preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, the individual is subjected to one or more treatments according to their cancer index value, the one or more treatments comprise any of:

- 1. a transvaginal ultrasound to assess endometrium and ovaries;
- 2. intensified screening, preferably wherein the intensified screening comprises one or more of:
  - i. a colposcopy;
  - ii. a HPV test;
  - iii. a cervical cytology test;
  - iv. a test for CA125, preferably wherein the test is repeated six-monthly;
  - v. a test for cell-free tumour DNA methylation in plasma/serum, preferably wherein the test is repeated annually;
  - vi. a test for cell-free tumour DNA methylation in vaginal fluid, preferably wherein the test is repeated annually
  - vii. a pelvic MRI scan, preferably wherein the individual being subjected to the pelvic MRI scan is post-menopausal, and preferably wherein the scan is repeated annually;
  - viii. a repeat assay according to any one of the assays of the invention, preferably wherein the repeat assay is performed about one year after the previous assay;
- 3. administration of one or more of progestogens, particularly wherein the progestogens are delivered locally or systemically, Aspirin, Metformin, aromatase-inhibitors, weight-loss regimen;
- 4. a total hysterectomy and bilateral salpingo-oophorectomy.

The method of the invention may be performed above and additionally wherein when the transvaginal ultrasound and intensified screening are both negative:

- 1, the transvaginal ultrasound, the test for CA125, the test for cell-free tumour DNA methylation in plasma/serum, the test for cell-free tumour DNA methylation in vaginal fluid, the colposcopy, the HPV test, and the cervical cytology test is repeated about six months after the previous assay; and
- 2, the pelvic MRI scan is repeated about one year after the previous assay.

The method of the invention may be performed above and additionally wherein the progestogens are delivered locally via an intrauterine device.

The method of the invention may be performed above and additionally wherein the one or more treatments that the individual is subjected to are repeated on a monthly, three monthly, six monthly, yearly or two yearly basis following an initial administration.

The invention also provide a method of monitoring the cancer status of an individual according to the individual's cancer index value, the method comprising: (a) assessing the presence, absence or development of cancer in an individual by performing the assay according to any one of the assays of the invention at a first time point; (b) assessing the presence, absence or development of cancer in the individual by performing the assay according to any one of the assays of the invention at one or more further time points; and (c) monitoring any change in the cancer index value and/or cancer status and/or CIN3 status of the individual between time points.

The method of the invention may be performed above and additionally the further time points are monthly, three monthly, six monthly, yearly or two yearly basis following an initial assessment.

The method of the invention may be performed above and additionally wherein depending on the cancer index value and/or cancer status and/or CIN3 status of the individual, one or more treatments are administered to the individual according to any one of the methods of the invention, or when the cancer index value of the individual is less than about −0.660 no treatment is administered to the individual.

The method of the invention may be performed above and additionally wherein an increase in the cancer index value indicates a negative response to the one or more treatments.

The method of the invention may be performed above and additionally wherein changes are made to the one or more treatments if a negative response is identified.

The method of the invention may be performed above and additionally wherein a decrease in the cancer index value indicates a positive response to the one or more treatments.

The method of the invention may be performed above and additionally wherein changes are made to the one or more treatments if a positive response is identified.

The assay of the invention may be performed above and additionally wherein the sample is obtained from a tissue comprising epithelial cells, preferably wherein the sample is not obtained from ovarian or endometrial tissue.

The assay of the invention may be performed above and additionally wherein the sample is obtained from:

- 1. cervical tissue;
- 2. vaginal tissue;
- 3. cervicovaginal tissue;
- 4. buccal tissue;
- preferably wherein the sample is obtained from cervical tissue, most preferably wherein the sample is obtained from tissue from a cervical smear.

The assay of the invention may be performed above and additionally wherein the assay is for assessing the presence, absence or development of:

- 1. endometrial cancer, preferably wherein the endometrial cancer is an endometroid cancer, uterine carcinosarcoma, squamous cell carcinoma, small cell carcinoma, transitional carcinoma, serous carcinoma, clear-cell carcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma or serous adenocarcinoma;
- 2. ovarian cancer, particularly wherein the ovarian cancer is serious carcinoma, mucinous carcinoma, endometrioid carcinoma, clear cell carcinoma, lop malignant potential (LMP) tumor, borderline epithelial ovarian cancer, teratoma, dysgerminoma, endodermal sinus tumor, Choriocarcinoma, granulosa-theca tumor, Sertoli-Leydig tumor, granulosa cell tumor, small cell carcinoma of the ovary or primary peritoneal carcinoma;
- 3. grade 3 cervical epithelial neoplasia (CIN3) and/or cervical cancer, particularly wherein the cervical cancer is squamous cell cancer, an adenocarcinoma or an adenosquamous carcinoma.

The invention also provides an array capable of discriminating between methylated and non-methylated forms of CpGs; the array comprising oligonucleotide probes specific for a methylated form of each CpG in a CpG panel and oligonucleotide probes specific for a non-methylated form of each CpG in the panel; wherein the panel consists of at least 50 CpGs selected from the CpGs identified in SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and identified in SEQ ID NOs 501 to 808 and denoted by CG.

The array of the invention may be performed above and additionally provided that the array is not an Infinium MethylationEPIC BeadChip array or an Infinium HumanMethylation450, and/or provided that the number of CpG-specific oligonucleotide probes of the array is 482,000 or less, 480,000 or less, 450,000 or less, 440,000 or less, 430,000 or less, 420,000 or less, 410,000 or less, or 400,000 or less.

The array of the invention may be performed above and additionally wherein the panel comprises any panel of CpGs defined in the assays of any one of the assays of the invention.

The array of the invention may be performed above and additionally further comprising one or more oligonucleotides comprising any set of CpGs defined in the assays of any one of the assays of the invention, wherein the one or more oligonucleotides are hybridized to corresponding oligonucleotide probes of the array.

The invention also provides a hybridized array, wherein the array is obtainable by hybridizing to an array of the invention a group of oligonucleotides comprising any panel of CpGs defined in the assays of the invention.

The invention also provides process for making the hybridized array of the invention, comprising contacting an array of the invention with a group of oligonucleotides comprising any panel of CpGs defined in the assays of the invention.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the experimental design underpinning the discovery and validation of the WID-EC-index.

FIG. 2 shows ROC curve of the WID-EC-index in the internal validation set (Panel A). Box plot of the WID-EC index in the internal validation set (Panel B).

FIG. 3 shows WID-EC-index in endometrial cancer cases and healthy controls in the external validation dataset (Panel A). ROC curve in the external validation set (Panel C). WID-EC-index versus time-to-event in prospectively collected validation samples (Panel D). ROC curve corresponding to the prospective samples (Panel E).

FIG. 4 shows the WID-EC-index versus age in samples from the internal and external validation datasets (Panel A). Correlation with body mass index (BMI) in controls (Panel B). Menopause (Panel C). Parity (Panel D). Stage (Panel E). Grade (Panel F). Histology (Panel G). Panels A to D are based on controls from the internal and external validation datasets. Panels E to G are based on cases from the internal and external validation datasets.

FIG. 5 shows WID-EC-index versus the estimated proportion of tumor DNA (Panel A). The estimated proportion of tumor DNA in each cervical smear sample as estimated using the EpiDISH algorithm for controls (Panel B) and endometrial cancers (Panel C).

FIG. 6 shows the distribution of p-values obtained by comparing cases and controls at each CpG site and after controlling for immune cell proportion and age (Panel A). Distribution of different cell types in the discovery dataset inferred using the HEpiDISH algorithm (*p<0.05, **p<0.01, ***p<0.001) (Panel B). Area under the receiver operating characteristic curve (AUROC) in the internal validation set as a function of the number of CpGs used to train the classifier (Panel C). Distribution of the WID-EC-index with respect to immune cell proportion in the internal validation set (Panel D).

FIG. 7 shows the distribution of different cell types in the external validation dataset inferred using the HEpiDISH algorithm (*p<0.05, **p<0.01, ***p<0.001) (Panel A). Cell type distribution in the prospective validation dataset (Panel B). The mean delta-beta (difference between mean beta values in control samples from the prospective and discovery datasets) across different genomic regions (Panel C). Odds ratios corresponding to the genomic annotation of the 500 CpGs comprising the WID-EC-index (when compared to the 776,725 CpGs in the dataset; ***p<0.001) (Panel D).

FIG. 8 shows the distribution of the WID-EC-index in controls that volunteered from the general population and women that presented at hospitals for benign women-specific conditions (Discovery set) (Panel A). The WID-EC-index versus the number of days between sample collection and DNA extraction.

FIG. 9 shows the inferred tumour DNA proportion versus the inferred epithelial cell proportion in the discovery set as determined using the HEpiDISH algorithm.

FIG. 10 shows the WID-EC-index versus immune cell proportion in the ovarian cancer validation dataset (Panel A) and the corresponding ROC curve (Panel B).

FIG. 11 shows cutpoints applied to the patient data, and consequent specificity and sensitivity for cancer status discrimination achieved when these cutpoints are applied.

DETAILED DESCRIPTION OF THE INVENTION
Identification of CpGs

The present inventors sought to identify CpG methylation-based assays capable of assessing the presence, absence or development of cancer in an individual. Any of the assays described herein for assessing the presence, absence or development of cancer in an individual are capable of being utilised for assessing the presence, absence or development of endometrial cancer and/or ovarian cancer, particularly endometrial cancer. The present inventors compared CpG methylation levels in non-cancerous epithelial tissue, particularly cervical tissue, vaginal tissue or cervicovaginal tissue across groups of women that were either known to be both endometrial and ovarian cancer negative, and/or CIN3 negative, or known to be endometrial and/or ovarian cancer positive, and/or CIN3 positive. This led to the surprising establishment of a “cancer index”, used interchangeable herein with “index”, “index value”, “WID-EC-Index” or “WID-Index” (WID=women's risk identification).

A CpG as defined herein refers to the CG dinucleotide motif identified in relation to each SEQ ID NO., wherein the CG dinucleotide of interest is denoted by CG. Thus by determining the methylation status of any panel of one or more CpGs defined by or identified in a given SEQ ID NO, it is meant that a determination is made as to the methylation status of the cytosine of the CG dinucleotide motif identified in square brackets in the panel of one or more CpGs in each sequence shown below, accepting that variations in the sequence upstream and downstream of any given CpG may exist due to sequencing errors or variation between individuals.

As set out in more detail in the Examples, the methylation status of sub-selections of the 500 CpGs, as identified in SEQ ID NOs 1 to 500, may be determined in order to assess an individual for the presence, absence or development of cancer with high sensitivity and specificity. The cancer is preferably endometrial cancer or ovarian cancer, most preferably endometrial cancer. A panel of one or more of the CpGs identified in SEQ ID NOs 1 to 500 may be utilised to derive a cancer index for an individual in accordance with the invention described herein.

The methylation status of a panel of one or more CpGs of the 500 CpGs defined according to SEQ ID NOs: 1 to 500 may be assessed by any suitable technique. As explained in more detail in the Examples below, one particular exemplary technique which the inventors have used is an array-based analysis technique coupled with beta value analysis. SEQ ID NOs 1 to 500 correspond to the sequences of commercial probes utilised in said array.

The inventors further identified 308 differentially methylated regions (DMRs) with relevance to cancer, particularly endometrial or ovarian cancer. The nucleotide sequences of the 308 DMRs are defined respectively by the nucleotide sequences of SEQ ID NO: 501 to 808 as set out in Table 1 below, accepting that variation in the nucleotide sequence of any given DMR may exist due to sequencing errors and/or variation between individuals. In each sequence shown below the cytosine of the CG dinucleotide motif identified in square brackets or double square brackets is a cytosine of a CpG which may be included in a panel of CpGs when performing the assays of the invention.

The inventors further defined 37 regions within a select number of the 308 DMRs with particular relevance to cancer and CIN3, particularly endometrial and ovarian cancer. The nucleotide sequence of the 37 regions are defined respectively by the nucleotide sequence of SEQ ID NOs: 809 to 919 as set out in Table 10 below, accepting that variation in the nucleotide sequence of any given DMR may exist due to sequencing errors and/or variation between individuals. When any one or more of the 37 regions are included in a panel of CpGs when performing the assays of the invention, the methylation status of every cytosine within a CG dinucleotide in the region is determined. The amplicon sequences generated by the 37 primer and probe reactions as set out Table 10 are described and defined by SEQ ID NOs 920 to 956 and in Table 12. In any of the assays described herein, the step of determining the methylation status of a panel of one or more CpGs may comprise determining the methylation status of one or more CpGs within any one or more the amplicons defined by SEQ ID NOs 920 to 956 and denoted by CG. More preferably, in any of the assays described herein, the step of determining the methylation status of a panel of one or more CpGs may comprise determining the methylation status of one or more CpGs within any one or more the amplicons defined by SEQ ID NOs 920, 922 and 924 and denoted by CG, yet more preferably all of the CpGs denoted by CG in the amplicons defined by SEQ ID NOS 920, 922 and 924.

TABLE 10

SEQ ID

SEQ ID

NO of

NO of

SEQ ID

forward

reverse

NO of

gene_name
Forward.Primer
primer
Reverse.Primer
primer
Probe
probe

custom-character

AGAGCGGTCGCGGAAGT
809
AACCGAAAACGACCACGAAA
846
CGTTTCGCGCGGGTTGGTTTT
883

HCG4
TCGATAGCGACGTTACGAGTTTT
810
TCCGACCCCTCCTACTCCAT
847
ATGGAGTCGCGGGCGTCGTG
884

custom-character

TTTGGTTAGTTTTCGCGGTTTT
811
CGACGAATACTCACCGAAACTAAA
848
TCGGGTTGACGTTTAGGAATGTGGTCG
885

RASSF1
CGGGTTTCGATTTTAGCGTTT
812
CCATTACGCGACTCTCCTCAA
849
TAGGATTTAGATTGGGCGGCGGGAAG
886

custom-character

TGCGGGTCGCGGTTT
813
CCCAACAACACGACGTAACCT
850
TTTTTTTTACGGGGGGTATTTATCGAGGTTG
887

TRH
GATGTGTTCGCGTCGTGTTTT
814
CGATACACAAACGAACGCTATACTC
851
CGTCGGGTTTTCGGTTTGCGTTC
888

PTGER4
AGGTTGCGTATCGTTAGTTATTATTATGTT
815
CACCGCCGAAATAATCACTAAAC
852
TTAATTCGTTCGTTTTTTTGAGTTTCGATCGG
889

FAIM2
GAGGAGAGGGTCGGGTTTG
816
TTACCCCGAACTCGCGAAT
853
AAGATGTTGCGGAGGACGTTGCG
890

DMRTA2
CGAGTTGTAGTTGTTTTACGGTATTGTC
817
TCGTAAACGAACCTCGAAAAAATAA
854
TTGGCGTTGGTCGTCGTTAACGGT
891

NA
GAGTTGGTGAGGTCGTTTAGTTAGG
818
GCCCGCTACGCTATACGAAA
855
TTGGTTAGCGTGCGATATAGGCGCG
892

TRABD
GTCGGGTTTTTTTGGAGGTTT
819
ACCCCCGACCTCACGAA
856
CGGACGATCGGAAGTGATTGAGCG
893

TCP11
GAGGAGGAGGTGACGGTTTG
820
AAAACGTAAAAAAACCCCTTCCTT
857
TTTGGGTCGGCGTTTCGGGC
894

GATA3
CGCGAGTATAGTCGAGGTTATGG
821
CCCGTTAAACACGACGAAATAAT
858
ACGGCGGATTAGTCGCGTTGGG
895

NA
GGCGGTGATGGTTTTGGA
822
AACGTACGACATAAACGCGAAA
859
CGCGCGGTCGTAGTGTGTCGTT
896

SPDYA
GTTGGTTAGCGATCGACGAGTA
823
CCGAACAACGACGATCAAAA
860
TCGTTTGAGGTTAGGAGCGTTGCGA
897

NA
GCGTAGCGGGCGGTATATT
824
CCCAACTATACGCATCGCTAACT
861
TAGAGTTATTATCGTTAGGAGGACGTATTCGGCG
898

KIAA1383
AGTAGGTTGTAGGCGGAAGAGGTA
825
GCCGAACCGTAACCCGATA
862
TTTGTCGCGATCGAAGCGGATG
899

CDH4
CGGCGGGAGTTGTAGGAATT
826
ACAACAACGCTACCCGAAAAA
863
TTTTTCGTGGTCGATCGGTTTCGTTG
900

EPHX3
GGCGGGTTTAGCGGTTTC
827
CAAACGTACAAAAACGAACTAACGA
864
TTCGGCGTCGTTTTTTTGTTGGTTTAATAGG
901

NEFM
TTTTCGGTCGTCGTTTTTACG
828
CGCCGCAACCCATTTATAA
865
TTTTGGTTCGGGATTAGCGTCGCG
902

SORCS3
CGTCGGGCGTAGTTTTTAATTATT
829
ACCCTTAACAAAAAAACGACTTCCT
866
ACGTTTGGGTTATTGTTTCGGTCGATGG
903

ZNF718
CGTTTCGTCGTTGTTCGTATTTC
830
AAAAACGAATCCGCGACGTA
867
CGCGTTCGGAGTTTAGCGTAGTATAGAGGAGTC
904

TRH
CGGGATTCGTAGTCGGTAGGT
831
GACCCATCTAAAAAAAACTCGACAA
868
AGTTTGTAGCGTTGAGGATTTCGGGCG
905

DMRT1
ACGCGTTTTCGGCGTTT
832
ACAACGACGACGCTTAAAATCC
869
ATCGGCGATGTAGCGTGGTCGG
906

MYO3A
TTTTTGCGTTGTTTCGATACGT
833
GTAACCAACGCCCCCGTAA
870
TTTGGGCGGGAAGTCGGGC
907

NA
TTCGGTTTTGCGGAGTAGTTG
834
ACTCGCTACGCCACGAAAAT
871
ATTCGAAGGGCGGCGCGG
908

FAM38B
GCGTTTTTTTTTAAGGTTTCGGTAT
835
CCTACGACCGACCCATTTAATATAA
872
TTTTGAAGAAGTCGTCGTCGTTGTCGG
909

NA
CGGAGGCGACGGAGATATTA
836
AATAACGACAAACGACAACAACAAA
873
CGAGAATTAGATGTTCGTCGTTCGCGTG
910

DMRTA2
CGTTATGATACGTTGGCGTTTC
837
CAAAAACCACAAACGCTACTATCG
874
CGATGAGCGTGTATTTGGCGTATAGGTAGTTTT
911

LBX2
CGGATTGGGAGTCGAGTATTG
838
TCGCGTCCCGAATTCATAA
875
CGGATAGTCGGATCGTTTTAGTTCGGTCG
912

NA
GCGTGGTGTCGTCGTTGTT
839
ACGCACAACTAAACCGTACAATAACT
876
CGGATTAGCGTTTTGGTTGTCGCG
913

NA
CGTATAGTTGGGTCGTGTAGTGGTT
840
ACTAACGTAATACCGCCGCTACTAA
877
CGCGGTAGTTAGAGCGTTGGTTCGC
914

NA
TTGCGTTAGGATTTTGTAGATTCG
841
CCGTACAACCCTAATATTACAAACGTAA
878
TCGCGGTCGGGTCGAGTGTTTT
915

GDF6
GTTAGTCGGGTTGGAGTTTTGC
842
CCACTCGTATTAAAACCTCGAAACA
879
TTTCGGTTTTTTTGTTTTAGCGTGGTGTTTTC
916

GAD2
GGAAGAGCGTTACGGTTTTAGAGT
843
ACGAAACCTACCCGCTAAATCC
880
TTTTTGGAGTTTCGAGGTTAGGTTCGGG
917

NA
TTATTAATTCGGTTGCGTAAATCG
844
CCGACAACTCACAAATAAAATAATCC
881
TTTGGTTGAGCGGTCGTTGTGCG
918

FOXE1
GGGTAATTATTGGGCGTTTGATT
845
GCTTACGACGACGCAAAAAACT
882
TAACGCGGAGGATATGTTCGAGAGCG
919

TABLE 12

Amplicon.
Amplicon
Amplicon

rxn_name
gene_name
Chromosome
Rxn.Start
Rxn.Finish
Location
Length
SEQ ID NO
amplicon_sequence_5_to_3

ML_cg25060829_ii
ZSCAN12
6
28367535
28367599
chr6:
65
920
GGC[[CG]]GAAG[[CG]]GCCA]]CG]]GGGGGT

28367535-

CTAAGAACCAGCC[[CG]][[CG]][[CG]]GGG[[C

28367599

G]]CACTTC[[CG]][[CG]]GC[[CG]]CTCT

ML_cg14443519_i
HCG4
6
29760319
29760385
chr6:
67
921
T[[CG]]ACAG[[CG]]A[[CG]]CCA[[CG]]AGTCC

29760319-

CAGGATGGAGC[[CG]][[CG]]GG[[CG]]C[[CG]

29760385

]TGGATGGAGCAGGAGGGGC[[CG]]GA

ML_cg15975865_i
GYPC
2
127413797
127413902
chr2:
106
922
CCTGGCCAGTCCC[[CG]][[CG]]GTCTCTGCC[[

127413797-

CG]]GGCTGA[[CG]]CCCAGGAATGTGGT[[CG

127413902

]]A[[CG]AGAAGCCCCAACAGCA[CG]G[CG]TG

GCCTCTCAGCCT[[CG]]GTGAGTACC[[CG]][[

CG]]

ML_cg27569446_i
RASSF1
3
50378305
50378379
chr3:
75
923
[[CG]GGCCC[[CG]ACTTCAG[[CG]]CCTCCCC

50378305-

CAGGATCCAGACTGGG[[CG]]G[[CG]]GGAA

50378379

GGAGCTGAGGAGAGC[[CG]][[CG]]CAATGG

ML_cg15768103_ii
GYPC
2
127413858
127413944
chr2:
87
924
CCCAACAGCA[[CG]]G[[CG]]TGGCCTCTCAG

127413858-

CCT[[CG]]GTGAGTACC[[CG]]C[[CG]]TGGGG

127413944

AAGGGTCCTGGGGACCCACTGGAGGC[[CG]]

[[CG]]GCC[[CG]CA

ML_cg05835982_ii
TRH
3
129693780
129693868
chr3:
89
925
[[CG]]GTGCACAGG[[CG]]GG[[CG]]CTGTGCT

129693780-

[[CG]]CACCCC[CG]]GGTCCTCCC[[CG]]AG

129693868

[[CG]]CAGGC[[CG]]GGGACC[[CG]]A[[CG]]

GGAGGCA[[CG]]G[[CG]][[CG]]GGCACATC

ML_cg05971966_i
PTGER4
5
40681071
40681173
chr5:
103
926
AGGCTG[[CG]]CAC[[CG]]CCAGCCACTATCAT

40681071-

GTCCACTCC[[CG]]GGGTCAATT[[CG]]TC[[CG]]

40681173

CCTCCTTGAGCCC[[CG]]AC[[CG]]GCTGAACA

GCCCAGTGACCATCC[[CG]][G[CG]]GTG

ML_cg06947913_i
FAIM2
12
50297727
50297790
chr12:
64
927
GAGGAGAGGGC[[CG]]GGCCTGGGAAGATG

50297727-

CTG[[CG]]GAGGA[[CG]]CTG[CG]]GATT[[CG]]

50297790

CG]]AGCC[[CG]]GGGTAA

ML_cg16732616_ii
DMRTA2
1
50886745
50886828
chr1:
84
928
T[[CG]]TAGG[[CG]]GGCCT[[CG]]GGGGGAT

50886745-

GATGC[[CG]]TTGG[[CG]]G[[CG]]GCCAG[[C

50886828

G]]CCAGCCCCT[[CG]]GCAGTGC[[CG]]TAGAG

CAGCTGCAGCT[[CG]]

ML_cg22305167_i
N/A
6
29521375
29521459
chr6:
85
929
GCC[[CG]]CTG[[CG]]CTATG[[CG]]GGGCT[[C

29521375-

G]]TCTCCC[[CG]][[CG]]CCTATGT[[CG]]CA

29521459

[[CG]]CTGGCCAG[[CG]]CCTCCTGGCTAAG

[[CG]]GCCTCACCAACTC

ML_cg05297854_i
N/A
22
50623618
50623686
chr22:
69
930
GC[[CG]]GGTCCCCCTGGAGGCCTC[[CG]]GA

50623618-

[[CG]]AT[[CG]]GAAGTGACTGAG[[CG]]TC[[CG

50623686

]]]GGTC[[CG]]TGAGGC[[CG]]GGGGT

ML_cg13423262_i
TCP11
6
35108892
35108990
chr6:
99
931
GAAG[[CG]]TGGGAAGGCCCCTTCCTT[[CG]][[C

35108892-

G]]G[[CG]]AGGTGCCCCCCT[[CG]]CC[[CG]]

35108990

AAA[[CG]]C[[CG]]GCCCAGGCC[[CG]CCTC[CG]

GCTCCCAGGC[CG[[TCACCTCCTCCTC

ML_cg15267232_i
GATA3
10
8097600
8097681
chr10:
82
932
[CG]][[CG[[AGCACAGC[CG]AGGCCATGG

8097600-

AGGTGA[[CG]]G[[CG]]GACCAGC[CG]][[CG[

8097681

]CTGGGTGAGCCACCACCACCC[[CG]]C[CG]]

TGCTCAA[[CG]]GG

ML_cg21632158_i
N/A
6
29521337
29521423
chr6:
87
933
GG[CG]]GTGATGGCTCTGGAC[[G][CG]][[

29521337-

CG[[GC[CG[[CAGTGTGC[CG[[CC[CG[CTG[

29521423

CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[[

G[[CCTATGT[CG[[CA[CG[CT

ML_cg14920003_i
SPDYA
2
29033710
29033782
chr2:
73
934
GCTGGCTAG[CG[[AC[CG[[A[CG[[AGCAAC

29033710-

[[CG[TCTGAGGCCAGGAG[CG[[CTG[[CG[[A

29033782

[CG[GAGCCTTGAC[CG[C[CG[TTGCC[CG[

[G

ML_cg21632158_ii
N/A
6
29521288
29521385
chr6:
98
935
CCCAGCTGTG[CG[[CAT[CG[CTGGCTCTGG

29521288-

GTTC[CG[C[CG[AATG[CG[[TCCTCCTGG[

29521385

[CG[[GTGATGGCTCTGGAC[CG[[CG[[CG[GC[

CG[CAGTGTGC[CG[[CC[CG[CTG[CG[C

ML_cg16430166_ii
MAP10
1
232941433
232941501
chr1:
69
936
GC[CG[AAC[CG[TGGCC[CG[GTGTCATC[

232941433-

[CG[[CTT[CG[[GT[CG[[[[CG[GCAAGTCCTG

232941501

CCTCTTC[CG[[CCTGCAGCCTGCT

ML_cg16619425_i
CDH4
20
59828486
59828556
chr20:
71
937
[CG[G[CG[[GGAGTTGCAGGAACCCCCTCT[

59828486-

[CG[[TGGC[CG[[AT[CG[GCCT[CG[CTGCC

59828556

TTCTCC[CG[GGCAG[CG[[CTGTTGT

ML_cg24520342_i
N/A
19
15344240
15344316
chr19:
77
938
GG[CG[[GGTCCAG[CG[GCCT[CG[GCC[CG

15344240-

[[G[CG[[[[CG[[TCCTCCTGCTGGCCCAACA

15344316

GGCC[CG[[CCAGCC[CG[[CCCCTGTA[CG[[

TCTG

ML_cg07552803_i
NEFM
8
24771188
24771260
chr8:
73
939
TCCT[CG[[GC[CG[[C[CG[CCTCCA[CG[[G

24771188-

GG[CG[GGGCCCTGGCC[CG[GGACCAG[[C

24771260

G[[C[[CG[[[[CG[GCTATAAATGGGCTG[CG[[

G[CG[[

ML_cg01874697_i
SORCS3
10
106401479
106401574
chr10:
96
940
[CG[[C[CG[[GG[CG[CAGCCCCCAATCACC

106401479-

CAGGAA[CG[[CG[GGGA[CG[[CCTGGGCCA

106401574

CTGCTC[CG[[GC[CG[[ATGGTTCCAGAGGA

AGC[CG[[TCCCCTTGCTAAGGGT

ML_cg26894523_ii
ZNF718/
4
107714
107802
chr4:
89
941
AGGGG[CG[[GGTC[CG[[[CG[G[CG[TG[C

ZNF595

107714-

G[GGGCCCTGG[CG[GCTCCTCTGTGCTG[[CG

107802

[[CTGGGCTC[CG[[GG[CG[[[[CG[[[CG[GGA

TG[CG[[GGCAG[CG[[G[CG[GGA[[CG[[

ML_cg02700891_ii
TRH
3
129693544
129693621
chr3:
78
942
GGCCCATCTGAAGAGGGCT[CG[GCAGG[C

129693544-

G[[CC[[CG[[GGGTCCTCAG[CG[CTGCAGAC

129693621

TCCTGACCTGC[CG[ACTG[CG[GATCC[[CG

]]

ML_cg07528692_ii
DMRT1
9
842623
842694
chr9:
72
943
ACAG[CG[[G[CG[[G[CG[CTTGGGGTCCTG

842623-

GGCTCC[CG[GCCA[CG[[CTACAT[CG[[[[

842694

CG[[GTCTGGGAG[CG[[C[CG[[GAGA[CG]][

[CG[[T

ML_cg15843567_ii
MYO3A
10
26223207
26223281
chr10:
75
944
GTAGCCAG[CG[[CCCC[[CG]]TAAAGAAATA

26223207-

AGGAGG[CG[CC[CG[[GCTTCC[CG[[CCCAG

26223281

GTA[CG[[TGT[CG[[GGACAG[CG[[CAGGG

G

ML_cg17759274_ii
N/A
19
39260951
39261015
chr19:
65
945
GCT[[CG]]CTG[[CG]]CCA[[CG]]GAAATCC[C

39260951-

G[[[[CG[C[CG[CCCTT[CG[AGTCCTCCCA

39261015

GCTGCTC[CG[[CAGAGC[CG[[GG

ML_cg03602280_ii
PIEZO2
18
11148842
11148934
chr18:
93
946
CCTG[CG[[GC[CG[[GCCCATTTAGTGTGAAT

11148842-

CCTGGATC[CG[[GCAG[CG[[G[[CG[[G[CG[

11148934

]GCTTCTTCAGGGGTAGCTGATGC[[CG[[GGG

CCTTGGAGAGGGA[CG[[C

ML_cg00370229_i
N/A
6
29521559
29521637
chr6:
79
947
[CG[[GAGG[CG[[A[[CG[[GAGACACTAC[[C

29521559-

G[]AGAACCAGATGTT[CG[[CG[CC[CG[[

29521637

[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC

[CG[TCATC

ML_cg25191628_i
DMRTA2
1
50886879
50886963
chr1:
85
948
[CG[CCATGACA[CG[[CTGG[CG[CTC[CG[[

50886879-

[CG[[ATGAG[CG[[TGCACTTGG[CG[[CACA

50886963

GGCAGTCCTTCCAG[CG[[ACAGTAG[CG[[T

TTGTGGCCCTTG

ML_cg25040225_ii
LBX2
2
74726648
74726747
chr2:
100
949
T[CG[[[[CG[[TCC[CG[[AGTTCATGGT[CG[[

74726648-

GC[CG[[GGCTGGGG[CG[[GTC[CG[[GCTGT

74726747

C[[CG[[TTG[CG[CTAGGCTC[CG[CAAA[CG[C

CTGGGCCCCAGTGCT[CG[GCTCCCAATC[[C

G[[

ML_cg10491628_i
N/A
6
29521219
29521300
chr6:
82
950
G[CG[TGGTGC[CG[[C[[CG[CTGCTGGCCA

29521219-

ACCTG[CG[[CG[[GACCAG[CG[CTCTGGCT

29521300

GC[CG[[[[CG[[CAGCCACTGCA[CG[[GCCCA

GCTGTG[CG[C

ML_cg10491628_ii
N/A
6
29521215
29521299
chr6:
85
951
ACTAG[CG[TGGTGC[CG[C[CG[CTGCTG

29521215-

GCCAACCTG[CG[[[CG[[GACCAG[CG[[CTCT

29521299

GGCTGC[CG[[[[CG[[CAGCCACTGCA[CG[[G

CCCAGCTGTG[[CG[[

ML_cg10210594_i
N/A
1
208132750
208132848
chr1:
99
952
CTG[CG[[CCAGGACCCTGCAGACC[CG[[GC[

208132750-

[CG[[[[CG[GC[CG[GGC[CG[AGTGCCTCC[

208132848

CG[C[CG[GGGCCTTA[CG[CCCA[CG[GTCCA[[

CG[[CTTGCAACACCAGGGCTGTA[CG[[G

ML_cg11073558_ii
GDF6
8
97171863
97171947
chr8:
85
953
CCACT[CG[[TGTTGAGGCCT[CG[[GAGCAG

97171863-

C[CG[GGAGCACCA[[CG[[CTGGAGCAAAAAA

97171947

GC[CG[GAGGG[CG[CAGGGCTCCAGCC[C

G[[GCTGAC

ML_cg27206674_ii
GAD2
10
26507075
26507154
chr10:
80
954
G[[CG[[GGACCTGCC[CG[CTGGGTCCAAGC

26507075-

CCC[CG[[AACCTGGCCT[CG[[GAGCTCCAA

26507154

GAGGGCTCTGAGGC[CG[[TGG[CG[CTCTT

CC

ML_cg21133153_i
N/A
6
29521450
29521539
chr6:
90
955
TCACCAACT[CG[[GTTG[CG[CAAAC[CG[[[

29521450-

CG[CTCCTGGCTGAG[CG[[GC[CG[[CTGTG[[

29521539

CG[[[CG[CCC[CG[CCTGCTGGACCACTTCATC

TGTGAGCTGC[[CG[[G

ML_cg13791254_i
FOXE1
9
100616565
100616638
chr9:
74
956
GGGCAACTACTGGG[CG[[CTTGACCCCAA[[

100616565-

CG[[[[CG[[GAGGACATGTT[CG[[AGAG[[CG[

100616638

]GCAGCTTCCTG[CG[[[[CG[C[CG[[CAAGC

TABLE 1

The nucleotide sequences of the 308 DMRs are defined respectively by the

nucleotide sequences of SEQ ID NO: 501 to 808.

SEQ ID NO: 501

TGAAGCTGCT[CG]AGG[CG[AGGCCACTG[CG[CACCC[CG[[CG[CTG[CG[[CG[CTGGCCT[CG[TGCTG[CG[G[CG[TCT

GGGC[CG[TGG[CG[CTGCTGGC[CG[GCCTGCCCTCCCTGGTCTAC[CG[GGGGTTGCAGCCCCTGCCTGGGGGCCAG

GACAGCCAGTG[CG[G[CG]AGGAGCCCTCCCA[[CG[CCTTCCAGGGCCTCAGCTTGCTGCTGCTGCTGCTGACCTT[

CG[TGCTGCCCCTGGT[G[TCACCTCTTCTGCTACTG[CG[CATCT[G[[G[[G[CCTG[CG[A[CG[GC[CG[C[CG[

CA[CG[TGGGT[CG[GGCC[CG[GAGGAACT[CG[CTG[CG[CATCATCTT[CG[CCAT[CG]AGAGCA[CG[TTTGTGGGCT

CCTGGCTGCCCTTCAG[CG[CCCTG[CG[GGC[CG[TCTTCCACCTGG[CG[[CG[TCTGGGGG[CG[CTGC[CG[CTGC[CG[

TGCCCCCTGCTGCTGG[CG[CTG[CG[CTGGGGCCTCACCATTGCCACCTGCCTGGCCTT[CG[TCAACAGCTG[CG[CC

AACC[CG[CTCATCTACCTCCTGCTGGAC[CG[CTCATTC[CG[AGCC[CG[GG[CG[CTGGA[CG[GGGCCTG[CG[GG[CG[

CAC[CG[GC[CG[CCTGG[CG[[CG[AAGGATCAGCTCAGCCTCCT[CG[CTCTCCAGGG

SEQ ID NO: 502

CC[CG]AGCACCCA[CG[TGCAGCTTC[CG[ATCACAGCCCTGG[CG[TGGCTTCTCTGTCCC[CG[GCTAAGGCC[CG[[C

G[GT[CG[CTGCAGGGTGCCT[CG[C[CG]AGGGTG[CG[GGCT[CG[GGGCTCACAGTGCTCCCAGCCTCTCCCACCCCA

ACCC[CG[CCATTAAGGGGAGCCCCAG[CG[A[CG[CCCTGAACCCTGAAAGTCACACTGGGGC[CG[GGGCTGCACTT

GG[CG[TC[CG[CTTCCCCTCC[CG[TCACAGTGACCAGGGCTAGGGC[CG[[CG[GT[CG[GGGC[CG[T[CG[GGGAGAG[C

AGCTGCTC[CG[CAGAGC[CG[GGGC[CG[CTGCCAT[CG[[CG[TCTGCCC[CG[AGGGTG[CG[CAGG[CG[GGTACCTGT

CC[CG[ACT[CG[GGGAACAG[CG[GGAGCC[CG[GAGA[CG[CC[CG[T[CG[GGCTTCCCAGCCCCACCTGGGA[CG[TCT

CTAGGGG[CG[GGAGGCCAGGAGAGAAGAGGGTGGGAGAGATGAGCTGCAGGGGGATA[CG[GGACCCAGGGACC[

CG[GGATCTTATAACA[CG[CTTTCCACC[CG[TAGGATTGGGGCCCACAAATGACCA

SEQ ID NO: 503

GGTTAGAAAAG[CG[TGGTTCTTG[CG[CAGGAAAGTTGGAGCAAAGAAGAGTTCAGAAGTGGG[CG[GGTGTGTGTT

TAAAAAAAAAAAAGGGGGTGGAAACCCCACCAGCCAAGTCTGCAGAAAAAAAATAAATGAAGTCTGCCTATCTC[

CG[GGCCAGAGCCCCCCCT[G[GCC[G[[CG[[CG[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[CG[C[CG[C

[G[AGGGTAGGAGCC[G[GGAG[CG[[CG[ACCCTCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGCCAGTCCC[CG[

[CG[GTCTCTGCC[CG[GGCTGA[[CG[[CCCAGGAATGTGGT[CG[A[CG[AGAAGCCCCAACAGCA[CG[G[CG[TGGCCT

AGCCAGGGGC[CG[AGCCA[CG[GCCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG[GGCCTCCAGG[CG[GAG

GAGG[CG[TC[CG[CTGGGCTCAGATCCC[CG[ACTCCAGCCC[CG[GTTCCC[CG[G[CG[CCTGGGCTG[CG[[CG[GAGT

CCCTGTCC[G[[G[TCC[G[GACCCCTA[G[[CG[CAGCCTCCA[CG[[CG[CTC[CG]AGC

SEQ ID NO: 504

G[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[CG[C[CG[C[CG]AGGGTCAGGAGCC[CG[GGAG[CG[[CG[ACCC

TCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGCCAGTCCC[CG[[CG[GTCTCTGCC[CG[GGCTGA[[CG[CCCAGGAAT

GTGGT[CG[A[CG[AGAAGCCCCAACAGCA[CG[G[CG[TGGCCTCTCAGCCT[CG[GTGAGTACC[CG[C[CG[TGGGGAA

GGGTCCTGGGGACCCACTGGAGGC[CG[[CG[[GCC[CG[CAGCAGCCAGGGGC[CG]AGCCA[CG[GCCA[CG[GA[CG[

CCCTGGTGTCC[CG[GTC[CG[TGC[CG[GGCCTCCAGG[CG[GAGGAGG[CG[TC[CG[CTGGGCTCAGATCCC[CG[ACT

[[CAGCCTCCA[CG[[CG[CTC[CG[AGCTGGAGAAGC[CG[CCAGCC[CG[CCCTCCCAGGG[CG[TGT[CG[CC[CG[CTTTC

TGTTTCTTTGTG[CG[GGGCATGTGAAATGTGTGGGGCCAGAATTGTCTCCCTAAAGAACA

SEQ ID NO: 505

CG[GAAGGC[CG[CCTG[CG[CCTG[CG[ACCAGAAGCCCTGCAGCTGCTCCAAAGTGGATGTCAACTA[CG[[CG[TTT

CTCCATGCAACAGGTAAAGACTCAG[CG[[GGGAGCCC[CG[GGG[CG[CCCCTGCCCCTCTCTCTGCCC[CG[CCCAC[

[G[GC[G[GTG[CG[GGTC[CG[G[CG[CTGAGAGC[CG[GACAGGGG[CG[T[CG]AGGTGGCAG[CG[GAGG[CG[[G

GACCTGCCAGAATCTTCAGATAAAAG[CG[AGAAATG[CG[[GGACCTGCC[CG[CTGGGTCCAAGCCCC[CG[AACCT

GGCCT[CG[GAGCTCCAAGAGGGCTCTGAGGC[CG[TGG[CG[CTCTTCCCCCAG[CG[[CG[GCCCTTGGGATGG[CG[G

GTGGC[G[A[G[ATCCAGG[CG[CT[CG[TG[CG[CTCACTGAAT[CG[ATGA[CG[GCTGGCTTCCCTAGGC[CG[CTGG

GGCCT[CG[GGTGGGACTCAGTTTCCAAATAC[CG[TGCC[CG[AGAATTCAGAATTGCATTTTTTTTAGGTCTTTAGA

TCA[[CG[[AGAGTGATTTGTAGCTGCAATTGCACAAGAGAA[CG[ATTCCATTCACATGAA

SEQ ID NO: 506

GCA[CG]AGCTGTCCC[CG[GGACCCAGCTCC[CG[GCTTCC[CG[CCCCT[CG[AGGGT[CG[[CG[CT[CG[CAGGGG[CG[[

CG[CAC[CG[AT[CG]AGGGTCCCAGACTC[CG[GAACTGCCCTCTCCAGGC[CG[[CG[GGG[CG[CCCTCCTG[CG[[CG[C

G][CG[CCCTTCCTC[CG[[CG[GGCTCCCACCCCCATTTC[CG[GGGTCTCCTCCCTCT[CG[CC[CG[CACCTTCC[CG[[CG

CTCCCCCC[G[CCCCCC[G[[G[[G[CC[CG[[CG[[CTCACCTGGTTGTTTTTGCAGAGATCAGCCCACATG

CTGGTGC[CG[TCCCCTC[CG[[CG[CATCAGGA[CG[TGGTAGGTGAAGAAGTAGATGCC[CG[GGATGGAGCAGGTGA

ACTTGC[CG[GTGGTGGGGT[CG[TAGTGGTTTC[CG[AGGTTGGTGACCA[CG[T[CG[[T[CG[AACTTGAGCACCT[CG[

TAGCCTTCATGCTGC[CG[CTTGAGGC[CG[G[CG[TAGAAGG[CG[ATCTTGGGCAC[CG[TGCTGTAGGTGG[CG[G[CG

CTGATGGCCC[G[[G[[G[TTCAGG[G[GG[CG[CCC[CG[GG[CG[GGCC[CG[GCAGGCCTT

SEQ ID NO: 507

CCC[CG[AGAGGGCAGAA[CG[ACCATCCAAAA[CG[AACTG[CG[CCAG[CG[AGTGCTGC[CG[CCCTCCCCAA[CG[GC

CCTGGAAGACCAC[CG[CCC[CG[GGCCCCAGG[CG[[CG[TCCTGTCC[CG[TGCCTACCTC[CG[ACACCACCTCCAAG

AG[G[CCAC[CG[[CG[GAG[CG[GG[CG[CCTCCTGGA[CG[CTG[CG[GGGCCACT[CG[GGCT[CG[GTAGGCCACT[CG[

GGCT[CG[GTAGACTT[CG[GG[CG[GGCCCTGAGGGCTGAGCCAGGCTTAAGAGGG[CG[GG[CG[GGGC[CG[[[[CG[[

GGGCAT[CG[ACAGGT[CG[AGGGTAGGGAATTGACC[CG[[GCCCA[CG[CAGATCCC[CG[[CG[T[CG[TCTTCTCCC[[

CG[[CCCAC[CG[CAGCCATTGGC[CG[ACTCT[CG[ACT[CG[CCCTCTGTCCCCTGGGGT[CG[CTCACTTAACTCATCA

GTTTTCCAAACCCTCCCTGGGACCCTAGTGG[CG[AGCACT[CG[C[CG[CTGGCCTTCTAGGGCAGGCAGTATTGC[[C

G[[CTCCAGG[CG[TG[CG[GAGT[CG[GGGAGAAAAAAAC[CG[AACA[CG[TGTGCTACCCAGGGCCCCCAGATAAGC

CCCC[G[[CG[[CG[CACACACACCCTGAAC[CG[GAGTCCAGAAGGC[CG[GACT[CG[[CG[TCC

SEQ ID NO: 508

GGCCCCACTCCCTTCT[G[C[CG[GGCTC[CG[GGCCAAGGAAG[CG[[CG[GC[CG[GAGTCC[CG[GGAAGCCCCT[CG

]GCAGCCAGCCAAGGGCCCTG[CG[AGGATGTGGATGG[CG[[[CG[GATGG[CG[[CG[GCCTCCACCTG[CG[GGCAGT

GGAGAGAG[CG[G[CG[AGAGGAAGAATATTCCC[CG[[CG[AGC[CG[GGATAAGGGGCCCCTT[CG[GCT[CG[[GTTG

ACCCAGGTCAGATCCTCC[CG[C[CG[ACCTT[CG[GCC[CG[CCCTCTACAGG[CG[GCCCAGTTCTTCCCCTGCT[CG[G

CTGCCCCTGC[G[CCCCT[G[AGGGAG[CG[CC[CG[TAGCCAG[CG[CCCC[CG[TAAAGAAATAAGGAGG[CG[CC

[CG[GCTTCC[CG[CCCAGGTA[CG[TGT[CG[GGACAG[CG[CAGGGGACTGGCTTGGGG[CG[G[CG[GTGGGTAG[CG[G

[G[[G[[G[[CG[G[CG[CTGGAAA[CG[GCCC[CG[CTTCCTTGGACCC[CG[GGGCTTGCAGGG[CG[GGCC[CG[G

GGCTTCTAG[C[[G[AGGCTG[G[[CG[AC[CG[CC[CG[CC[CG[CCCAGGTCAGATC[CG[GAGGACCTGTGTGT

TTGT[CG[GGGCCTGGGGTGAGAGAGGGGACT[CG[AGGGGAGAAGTAGAG[CG[GGAAACCAAGAGGGGG

SEQ ID NO: 509

ACCT[CG[TATTCTGGGGGTCTCT[CG[GGGCATTGGAGGGTCTGGCCAAGGCAGGAATGGGGG[CG[GCTGAGGGGG

ACAGT[CG[CATTCACTTGG[CG]AG[CG[GGCCCAGGGATTCTGCAGGAATTGGAGGGAGGGTTGGGC[CG[GGGCTG

[CG[CTCACCTGC[CG[AGTAGGG[CG[[CG[GGCTGGTGGT[CG[[CG[TAGGG[CG[CCAAGTG[CG[CAGTTGGAGGAGC

[CG[AG[CG[[CG[GGGCAGGG[CG[GCCCTGC[CG[[CG[GGGAAAG[CG[GGC[CG[CAGGGGGCTGTATTGGAAGC[CG[

[G[GGCTGGCTGCAGG[G[CCAAAGT[G[[CG[TAGG[CG[GA[CG[CCTCCATGGC[CG[CCA[CG[CA[CG]AGT[

CG[TA[CG[AATTGAGGTAGGAGTAGTCCAT[CG[GCC[CG[GGGGG[CG[GGGG[CG[GGGGC[CG[GGCCAGGC[CG[GG

T[CG[GGGT[CG[GGGTC[CG[GGTGGAGGT[CG[[GAAGGGAGGTT[CG[AG[CG[CCAGGCTC[CG]AGGACC[CG[AGG

CCAGCTCTAG[G[[G[AGAGT[G[[G[[G[[CG[[CG[GC[CG[CACTCAGCC[CG[GGTGCAA[CG[C

AAGTGAGCCAGCC[G[GCC[CG[[CG[[CG[CCTTTTAA[CG[[CG[CAGGACCC[CG[[CG[GAGGGGGG[CG[GGG[CG[

G

SEQ ID NO: 510

[G[[CG[[CC[CG[GCAGAGCCC[CG[GGACTCCTAGTTTTTGC[CG[C[CG[CTGAGGA[CG[[CG[G[CG[[CG[GGCTGC

TGGC[CG[[CG[T[CG[C[CG[AGGGAGGGCC[CG[GACAGCCCTGCAG[CG[[CG[TCTCAG[CG[GAGCCCTGGGGGC[C

G[[CG[C[CG[CTCCTCCAAACATGATTCAGAAC[CG[CC[CG[TCAGCCTTGGCTCCAG[CG[CCTGG[CG[[CG]AG[CG[A

G[CTG[G[CCAGGACCTGAGA[G[[G[[G[GC[CG[GGC[CG[AGTGCCTCC[CG[C[CG[GGGCCTTA[CG[C

CCA[CG[GTCCA[CG[CTTGCAACACCAGGGCTGTA[CG[G[CG[GGTC[CG[CAGCTGGGTCTG[CG[CCTGGGACT[CG[

GGGCTCCCTG[CG[CTCCT[CG[TGC[CG[CACCCCTTGCCTTAACCCCAAG[CG[GA[CG[GGTCCTGGGGCTTCAC[CG[

GCCAGGC[CG[GAGCCCCAGCCCCACAACTCCCCCCCTCCCAC[CG[CACTGCCCCCTCTG[CG[CTGTGG[CG[GGAGT

TGGGGACTGGGGC[CG[GAGAAAGGAGA[CG[[CG[C[CG[GTCCTCAAGTCTCTTGAGCCATTT[CG[GTTC

SEQ ID NO: 511

GGAAGATCCCAGCCTGCC[CG[AAGG[CG[G[CG[TCTGACC[CG[CTGGTGGACCTGGTGGGTGTCTGTTCCTGATAC

CTGGGGA[[CG[[AGG[CG[GGAG[CG[CCTTGAG[CG[CTGGGAAGCTT[CG[CCT[CG[[CG[AGTCCC[CG[GCAGTGACA

[CG[TGGGAG[CG[TTGGGCC[CG[GCACCCC[CG[A[CG[CTTC[CG[AGGTTT[CG[GGTGGT[CG[TTTTGCTCTCT[CG[G

GGGCTTTTATTCCTTAAGTGGCTTTAAA[G[A[G[AGGATGGGCCTCC[G[[CG[C[CG[C[CG[CAGCTGTCACTTC

CTT[CG[GGAAAGGCTAG[CG[ACCTTGGA[CG[[CG[CAGGCTCTGAAAACCAAGGTCCAGACCCATAC[CG]AG[CG[

CCCAAAGAC[CG[CATTTGAATTCTCCT[CG[C[CG[[GCCATTGAGGGAGAGAAAGGAA[CG[CTTAGTTCCATTCAC

ATTCACAGAAAGAAG[CG[C[CG[AGGGTGGGGGAAA[CG[CAGTCTTGC[CG[GGTGAGC[CG[GGACAGGTTCCT[CG

]CCTGCCCCC[CG[GC[CG[CTGCTTCCTCTTAGCTGAATGGGGAG[CG[ACC[CG[CCC[CG[GG[CG[[CG[GCCTT[CG[

GGGCTGAAGACTGAGGTGCAGCCTCACCCC[CG[GCCTGGCAG[CG[GCTTGGAAGA

SEQ ID NO: 512

TGGGCTGAGGACAGGGGAGGATTAGGGTGGGTGGCCTGGGCTGGGACAAAGGTTTGAGA[CG[GGGAACCAGGAG

GAGAGAGGTGAGGAAAAGGCTAAGTCAGAGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGCTGCAGA

G[G[[G[[CG[[CG[TCAAGTC[CG[[CG[GAAAGTTTTACTAGTCAGCTCCTCCAG[CG[[CG[CACAG[CG[G[CG[A[CG

[TTGGACC[CG[GACC[CG[ACTCTGGAAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAG

GATGTCTG[G[ATGTTAAGAGTGTC[G[GGGTGTT[G[GGGCT[CG[[CG[TCC[CG]AGTTCATGGT[CG[GC[C

G[GGCTGGGG[CG[GTC[CG[GCTGTC[CG[TTG[CG[[CTAGGCTC[CG[CAAA[CG[CCTGGGCCCCAGTGCT[CG[[GC

TCCCAATC[CG[GGCCCCCAGCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG]AGTCC[CG[TGTGCCCCTCCTCCT

G[CG[CCCCCACCTCTCCACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTAC

AGGCTGGGGCAGG[CG[[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGG

SEQ ID NO: 513

CAGGAGGAGAGAGGTGAGGAAAAGGCTAAGTCAGAGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGC

TGCAGAG[G[[CG[[CG[[CG[TCAAGTC[CG[[CG[GAAAGTTTTACTAGTCAGCTCCTCCAG[CG[[CG[CACAG[CG[G[

CG[A[CG[TTGGACC[CG[GACC[CG[ACTCTGGAAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[G

GGCTAGGATGTCTG[G[ATGTTAAGAGTGT[G[GGGTGTT[CG[GGGCT[CG[[CG[TCC[CG[AGTTCATGGT[

CG[GC[CG[GGCTGGGG[CG[GTC[CG[GCTGTC[CG[TTG[CG[[CTAGGCTC[CG[CAAA[CG[CCTGGGCCCCAGTGCT

[CG[GCTCCCAATC[CG[GGCCCCCAGCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG[AGTCC[CG[TGTGCCCCT

CCTCCTG[CG[CCCCCACCTCTCCACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTAT

TTCTACAGGCTGGGGCAGG[CG[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGG

CTGCTC[CG[[CG[CTG[CG[GGG[CG[CTGCAC[CG[TGCACAGTCAGGC[CG[GGCCATACCTCCAGA

SEQ ID NO: 514

CTC[G[GGTAAGTTG[G[CCTCC[G[CCCC[CG[C[CG[TT[CG[GAAGCCC[CG[GGCAG[CG[GGAGGT[CG[TCCC[C

GCATCCAGCC[G[[G[[G[[G[CT[CG[G[CG[AAGCTGCCTG[CG[GT[CG[GCAGGAG[CG[GGAAGC[CG[CCTG

GGCAG[CG[GGGAG[CG[G[CG[GAGCAGGGTGGGAGTGGGGCT[CG[GTGGAGGACC[CG[GGGAGCTC[CG[CCTGCA

[G[GACC[CG[C[CG[AGCCTCCCT[CG[AA[CG[CCCAAAGCC[CG[TAGC[CG[CTACC[CG[GAGCT[CG[GCTTGCCT

GGGGTTGC[G[AGCCCAGCCC[G[GC[CG[TGGCTGAAGG[CG[TGGGG[CG[CC[CG[G[CG[GCTG[CG[GGCCAGG

GATC[CG[[CG[AGTG[CG[GGG[CG[CCTGCC[CG[ACCTCTCCTGCCCAAGGCCTGGGGGTC[CG[TCTAG[CG[G[CG[C[

CG[CTCAGTTCTGTGGGTGC[CG[GCAGGACC[CG[[CG[CTG[CG[GGTGGG[CG[G[CG[GGGTAGGACTG[CG[GGGCA

CTCTCA

SEQ ID NO: 515

AC[G[GTGCC[CG[CAGTCCC[CG[CCTCCT[CG[GC[CG[C[CG[CCTCCA[CG[GGG[CG[GGGCCCTGGCC[CG[GGACC

AG[G[[G[[G[GCTATAAATGGGCTG[G[G[CG[[AGGC[CG[[GCAGAA[CG[[CTGTGACAGCCACA[CG[CCCC

AAGGCCTCCAAGATGAGCTACA[CG[TTGGACT[CG[CTGGGCAACC[CG[TC[CG[CCTAC[CG[G[CG[GGTAAC[CG[

AGACC[CG[CT[CG]AGCTTCAGC[CG[[CG[TCAG[CG[GCTCCC[CG[TCCAGTGGCTTC[CG[CT[CG[CAGT[CG[TGGTC

C[CG[[CG[GCT[CG[CCCAGCAC[CG[TGTCCTCCTCCTATAAG[CG[CAGCATGCT[CG[CCC[CG[[CG[CCT[CG[CTTA

CAGCT[CG[GCCATGCTCAGCTC[CG[C[CG]AGAGCAGCCTTGACTTCAGCCAGTCCT[CG[TCCCTGCTCAA[CG[G[C

GGCTC[G[GACC[CG[G[CG[G[CG[ACTACAAGCTGTCC[CG[CTCCAA[CG]AGAAGGAGCAGCTGCAGGGGCTGAA

[CG[AC[CG[CTTTGC[CG[[GCTACATAGAGAAGGTGCACTACCTGGAGCAGCAGAATAAGGAGATTGAGG[CG[GA

GATCCAGG[G[CTG[G[GCAGAAGCAGGCCT[G[CA[G[CCCAGCTGGG[CG[A[CG[[CG[TA[CG[ACCAGGAG

SEQ ID NO: 516

GAGGATTAGGGTGGGTGGCCTGGGCTGGGACAAAGGTTTGAGA[CG[GGGAACCAGGAGGAGAGAGGTGAGGAA

AAGTC[CG[[CG[GAAAGTTTTACTAGTCAGCTCCTCCAG[CG[[CG[CACAG[CG[G[CG[A[CG[TTGGACC[CG[GACC[C

G]ACTCTGGAAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAGGATGTCTG[CG[ATGCT

TAAGAGTGT[G[GGGTGTT[G[GGGCT[CG[[CG[TCC[CG[AGTTCATGGT[CG[GC[CG[GGCTGGGG[CG[GTC[

CG[GCTGTC[CG[TTG[CG[[CTAGGCTC[CG[CAAA[CG[CCTGGGCCCCAGTGCT[CG[[GCTCCCAATC[CG[GGCCC

CCAGCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG]AGTCC[CG[TGTGCCCCTCCTCCTG[CG[CCCCCACCTCTC

CACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTACAGGCTGGGGCAGG[[C

G[[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGGCTGCTCC

SEQ ID NO: 517

TTTCTGTACCCA[CG[CTCCATACC[CG[AGGCTGGG[CG[AG[CG[GTGAACCCTAGCAGT[CG[[CG[G[CG[ACTGGAC

A[CG[GGGGTTCTACTCTTTCTGAAC[CG[AGACAAGCCCCTGGGCCC[CG[TGCCCCAGAGCTA[CG[ATCCTGCTGCC

GG[G[CTC[G[CTCCAGGTCCCC[G[[G[[G[G[CG[G[CG[CACACTGAAC[CG]AAGACCT[CG[TAGG[CG[GG

CCT[G[GGGGGATGTG[G[TTGG[G[G[CG[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[TAGAGCAGCTGC

AGCT[CG[[CG[[CG[CCT[CG[TTCTCCTCCTG[CG[CCTGCTGCCTG[CG[CAG[CG[CCACCTG[CG[C[CG[CCATGACA[C

G[CTGG[G[CTC[CG[[CG[ATGAG[CG[TGCACTTGG[CG[[CACAGGCAGTCCTTCCAG[CG[ACAGTAG[CG[TTTGT

GGCCCTTGAGGGC[[CG[[ACACCA[CG[CCATGGTTG[CG[ACAG[CG[[CG[[CG[CACTTGGGGGTC[CG[[CG[GGTACT

TCT[CG[GCTGCC[CG[CAGCAACAGTGG[CG[GCCCC[CG[CAGCAAGC[CG[CCTGCCA[CG[CTCAC

SEQ ID NO: 518

GT[G[G[CG[G[CG[CACACTGAAC[CG[AAGACCT[CG[TAGG[CG[GGCCT[CG[GGGGGATGATGC[CG[TTGG[CG[G[

[CG[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[TAGAGCAGCTGCAGCT[CG[[CG[[CG[CCT[CG[TTCTCCTCCTG[

CGCCTGCTGCCTG[G[CAG[G[CCACCTG[G[[CG[CCATGACA[CG[CTGG[CG[CTC[CG[[CG]ATGAG[CG[TGCA

CTTGG[CG[CACAGGCAGTCCTTCCAG[CG[ACAGTAG[CG[TTTGTGGCCCTTGAGGGC[CG[[ACACCA[CG[CCAT

GGTTG[CG[ACAG[CG[[CG[[CG[CACTTGGGGGTC[CG[[CG[GGTACTTCT[CG[GCTGCC[CG[CAGCAACAGTGG[CG[

CG[GGCA[CG[CTGGGCAGCTC[CG[AG[CG[CAGCTCCATGACAGGACCTGA[CG[GGAAAGAAGGTGGGAGAGGGG

AGAGA

SEQ ID NO: 519

G[CG[TC[CG[TGGGC[CG[TGATTCCCACTCA[CG[C[CG[GGGGCCCAGGCAGGCAGAGAAGAGTTAATGAG[CG[[C

G[CAAGTGCAGG[CG[GTCACTCCTGGGCCTGAAACTCC[CG[[CG[CTGTGCATTCAGGGCCCT[CG[TGGCTCTCAGA

GG[CG[[CG[TCCCAGGGG[CG[CACACTGCACCTTGGGCTGGGCAGCTC[CG[C[CG[GGTTGTGG[CG]AG[CG[GATGA

GGGAAGGA[CG[CAGAAACCAGGG[CG[GAGGAGC[CG[[CG[AGGGGCAGGA[CG[AGGCTGCATGGGCCAG[CG[AG

GGGGT[CG[ACAC[CG]AGCCAGAGTGAG[CG[[[CG[[GGGCCTGGGG[CG[CAGAGCC[CG[CCCAGGGAGC[CG[GGAG

AGCCCTGGTCCCTCAGCTGCAC[CG[GACTGAGC[CG[[CG[AC[CG[CTCAGCA[CG[[CG[CTGCTTATAAATCAGGG

GTG[CG[CTTCCCAAGCCC[CG[GGTGAGGTCCCCTA[CG[T[CG[GCACAGCCTTAGGAGCTGCAAAGCAG[CG[[CG[[

CG[CCTC[CG[GGGCTCCTG[CG[[CG[CCCCTTGAACCC[CG[CCTCC[CG[CATCCTCCTGCAACAGCCTG

SEQ ID NO: 520

GGGGCC[CG[[CG[GCCCTCTCCCTCCTCTCTCC[CG[CTG[CG[CCCC[CG[C[CG[CTTGCTCCCTGGGTA[CG[GCCTGA

GGCTGGA[G[GAG[CG[C[CG[TC[CG[GG[CG[TCCAGGACTCAGGCCTGGCCACTC[CG]AGCCCCCCACCCCC[[CG[[

[G[[G[[G[GCC[CG[[CG[CACCCTGCTTCC[CG[CAACTTGCAGCAAA[CG[CAG[CG[GCCTCTGGAGAGCCT

AG[CG[A[CG[GGTAGCAAACTTTGTCCCCTTAAG[CG[CAAGAGCAATCCT[CG[CAAAGTTTGTG[CG[[G[CG[GAGC

CCACTCCCTACCTGAGCTGGGGAAGCT[G[CC[CG[[CG[C[CG[TGTGGCTGC[CG[GGGC[CG[[CG[GGGAGCAG

G][CG[[CG[GAGCCTC[CG[CCTCCT[CG[GAAGGGGGGAGGGGTCT[CG[GAACCC[CG[GGG[CG[GGGG[CG[GGAG[C

AAGCT[G[[G[[G[[CG[[CG[CTCCAG[CG[GGGAGC[CG[G[CG[ACAACTAATGGAGACATTTCCAGG[CG[GAGC

ACCT

SEQ ID NO: 521

GAGGTGAGGAAAAGGCTAAGTCAGAGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGCTGCAGAG[[CG[[

[G[[CG[[CG[TCAAGTC[CG[[CG[GAAAGTTTTACTAGTCAGCTCCTCCAG[CG[[CG[CACAG[CG[G[CG[A[CG[TTGG

ACC[CG[GACC[CG[ACTCTGGAAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAGGATGT

CTG[G[ATGTTAAGAGTGT[G[GGGTGTT[G[GGGCT[CG[[[CG[TCC[CG[AGTTCATGGT[CG[GC[CG[GGCT

GGGG[CG[GTC[CG[GCTGTC[CG[TTG[CG[[CTAGGCTC[CG[CAAA[CG[CCTGGGCCCCAGTGCT[[CG[[GCTCCCAA

TC[CG[GGCCCCCAGCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG[AGTCC[CG[TGTGCCCCTCCTCCTG[CG[CC

CCCACCTCTCCACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTACAGGCTG

GGGCAGG[CG[[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGGCTGCTC[CG[[CG[

CTG[CG[GGG[CG[CTGCAC[CG[TGCACAGTCAGGC[CG[GGCCATACCTCCAGA[CG[[CTGTATGC

SEQ ID NO: 522

[G[[G[CTGGTGTGTGG[G[GTG[CG[[CG[[ACC[CG[[CG[CCTGCACA[CG[[CCCATGTACTACTTCCTCT

GCCACCTGGCCTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[[C[CG[CTGCTGGCCAACCTG[CG[[

CG[GACCAG[CG[CTCTGGCTGC[CG[[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTT

[CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[G

GCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[[GAGACACTAC[

CG]AGAACCAGATGTT[G[[CG[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[[CG[TCATCCTGGCCT

CCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[GAGGAGGG[CG[GTGGG

CA[CG[TGTG

SEQ ID NO: 523

CCC[CG[CAGACAGACCCAAGCTCTGGGACAGA[CG[CCCAG[CG[TCCCAGACAG[CG[CCTTCCTCTGGGCCATGC

TGGTAGGCC[CG[GGTCCAGGGC[CG[GGTGA[CG[AGAC[CG[TAGCCCCCCATTGGTTCT[CG[CAGAAACCA[CG[T

GCTAGCTCTGCACCTTCCTCCCCCAG[G[CTTTCTTCC[CG[[CG[CC[CG[T[CG[AATCCTCTCCAGTCCCCAGT[CG[C

CTTCCTGGGAGGTTTGGTT[CG[TATTGA[CG[GTTCTCAAAGCAAAGAAAA[CG[TGGAGAGACAGTGCTG[CG[[CG[[

CG[GCTTGGATCTC[CG[TCAATA[[CG[[GTACTAG[CG[GGAGCTTC[CG]AGGTCAACCTAGGGTCCA[CG[GGGACCC

TCCTAGTGGACATG[CG[GGGATTGGAGGTGGAGTCCTTGCTGTGCAACC[CG[ATC[CG[[GTCCATCCAGCCTGGTC

TTAGCTCAACTCTGCATTCTTATGG[CG[[GAGGAAAGCTAAGATAGAGACAGCTGGGACC[CG[[CG[GAATTTGAG

G[G[[CG[[CG[CTGGGATCTTA[CG[TG[CG[CAGAGGC[CG[GAC[CG[CAGAGTAGAAGTGAGTCTTGACCCACCAG

GGCCTATATTGAGATGGAAACCTCTCTCTTTGAACAGAATCC

SEQ ID NO: 524

TCCCTGCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTG

GTGTGTGG[G[GTG[G[[G[[ACC[CG[[CG[[CCTGCACA[CG[[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[C

G[CTCTGGCTGC[CG[[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AA

TG[G[TCCTCCTGG[G[GTGATGGTCTGGAC[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[C

GGGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[[CCTCCTGGCTAAG[CG[GCCTCACCAA

CTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACACTAC[CG]AGAACC

AGATGT[G[[G[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCCTGGCCTCCTA[CG[GT

GCC

SEQ ID NO: 525

TGTCCCAA[CG[CACTTTGGGGAGGGAGAGCTTCC[CG[[CG[GATC[CG[CCTGGGTTTGGGAGGAC[CG[GGGTCCA

CTCTGCAC[CG[GCCAGGGCCTGAGGGGCCCAGCAGCTGGAATACAGCAATCTCC[G[CCCACCTGCT[G[CAG[[C

G[[TACAGAGCACAACAT[CG[CTCACCTG[CG[GCCCCCAGGGCCAGAAGAGAACTCCCTCCTA[CG[GAG[CG[[AAG

GCAAGAGGCCT[CG[AACCCTTTTGGGACC[CG[GAACCCATCAAAAGTGACCCACAAAGGC[CG[GAAG[CG[GCCA[

CGGGGGGTTAAGAACCAGCC[G[[G[[G[GGG[CG[CACTTC[CG[[CG[GC[CG[CTCTAGGAAGGGAG[CG[AAA

GGGGCTTTCAACT[CG[GTAGTGTTTC[CG[[CG[[CG[[TCTA[CG[TGAGAGGAAGGTTGATGGCTTTCAGGCC[CG[CT

GGTAAATGGAA[CG[GGTTTATCTTCTCCTCTTCTTTACCCAGCCATTGTCCACACTTCCCC[CG[ACC[CG[[ATGGGT

GGT[CG[AGGCTTGTAGAACTGATCTTAAGACAGGGAAATCCCTTG[CG[TCTCCATTCACTTTGGGATTCTGTGTCT

CTGAGGTTAGAGATGCCTCAAAGGGATGTTCTC[CG[GGGGA

SEQ ID NO: 526

CC[CG[[CG[GTCTCTGCC[CG[GGCTGA[CG[[CCCAGGAATGTGGT[CG[A[CG[AGAAGCCCCAACAGCA[CG[G[CG[T

G[CAGCAGCCAGGGGC[CG]AGCCA[CG[GCCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG[GGCCTCCAGG[

G[GAGTCCCTGTCC[CG[[CG[TCC[CG[GACCCCTA[CG[[CG[[CAGCCTCCA[CG[[CG[CTC[CG]AGCTGGAGAAGC[C

G]CCAGCC[CG[CCCTCCCAGGG[CG[TGT[CG[CC[CG[CTTTCTGTTTCTTTGTG[CG[GGGCATGTGAAATGTGTGGGG

CCAGAATTGTCTCCCTAAAGAACAGTTAGGTGAGAGTTCACATCACAAGTTGCTTCTGTGCTGCTCCCCAGCCAGG

GTC[CG[AC[CG[GCCAGGCTC[CG[GTGAACTCCAGGCAACTCCAGCCTTGCCCAGGGACTTGCT[CG[CTC[CG[CTGG

G[CG[C[CG[CAAAGGCACACAGATG[CG[[AGGGAATCCTG[CG[GCCTGGATCCTT

SEQ ID NO: 527

CTGGCCTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GAC

CAG[CG[CTCTGGCTGC[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

ATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTCA

ACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACACTAC[CG]AG

AACCAGATGTT[G[[CG[CC[CG[[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[[TCATCCTGGCCTCCTA[

CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG[[GAGGAGGG[CG[GTGGGCA[CG

]TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[[GCT[CG[GCCATCTACACCTACCTGAG[G[[[[C

G[[CAG

SEQ ID NO: 528

GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCTGGCTGC[CG[[[

CG[[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCTCCTGG[C

GGTGATGGTCTGGAC[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT[CG[TCTCCC[

CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GTTG[CG[CAAA

[C[[G[CTCCTGGCTAG[G[GC[G[CTGTG[G[[CG[CCC[CG[[CCTGCTGGACCACTTCATCTGTGAGCTG

C[CG[[[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCCTGGCCTCCTA[CG[GTGC[CG[TGGCC[CG[AG

CTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG[[GAGGAGGG[CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAG

C[CG[TCTGCCTGTTCTA[CG[GCT[CG[GCCATCTACACCTACCTGCAGCC[CG[[CG[CAG[CG[CTACAACCAG

GCA[CG[[G

SEQ ID NO: 529

AGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGCTGCAGAG[G[[CG[[CG[[CG[TCAAGTC[CG[[CG[GA

AAGTTTTACTAGTCAGCTCCTCCAG[G[[CG[CACAG[CG[G[CG[A[CG[TTGGACC[CG[GACC[CG[ACTCTGGAAGC

TG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAGGATGTCTG[CG[ATGCTTAAGAGTGTC[[CG

GGGTGTT[G[GGGCT[CG[[CG[TCC[CG[AGTTCATGGT[CG[GC[CG[GGCTGGGG[CG[GTC[CG[GCTGTC[CG[TT

G[[CG[[CTAGGCTC[CG[CAAA[CG[CCTGGGCCCCAGTGCT[CG[GCTCCCAATC[CG[GGCCCCCAGCCT[CG[GAC

C[CG[CCCC[CG[GCTCTGGGCC[CG]AGTCC[CG[TGTGCCCCTCCTCCTG[CG[CCCCCACCTCTCCACCC[CG[GGC[CG

][CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTACAGGCTGGGGCAGG[CG[[[CG[GAGAGCAG

AAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGGCTGCTC[CG[[CG[CTG[CG[GGG[CG[CTGCAC[CG[TG

CACAGTCAGGC[CG[GGCCATACCTCCAGA[CG[CTGTATGC[CG[C[CG[ACTCCC[CG[CCTAGC[CG[C

SEQ ID NO: 530

A[CG[[CG[GGCTTCACTACTAG[CG[[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCTGGC

TGC[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCT

CCTGG[G[GTGATGGTCTGGAC[G[[G[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT[CG

ITCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GTTG[

CG[CAAAC[G[[G[CTCCTGGCTGAG[G[GC[G[CTGTG[G[[CG[CCC[CG[[CCTGCTGGACCACTTCATCTG

TGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACACTAC[CG[AGAACCAGATGTT[[C

GC[G[CC[CG[[CG[[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCCTGGCCTCCTA[CG[GTGC[CG[TGGC

C[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG[GAGGAGGG[CG[GTGGGCA[CG[TGTGGGTCCCACC

TGACAGC[CG[TCTGCCTGTTCTA[CG[[GCT[CG[GCCATCTACACCTACCTGCAGCC[CG[[CG[CAG[CG[[CTAC

AACCAGG

SEQ ID NO: 531

AGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCT

GGCTGC[CG[[CG[[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[T

CCTCCTGG[G[GTGATGGCTTGGA[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT

[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GT

TG[G[CAAAC[G[[G[CTCCTGGCTAG[G[[G[CTGTG[CG[[CG[[CCC[CG[CCTGCTGGACCACTTCATC

TGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACACTAC[CG[AGAACCAGATGTT

[G[[G[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCCTGGCCTCCTA[CG[GTGC[CG[TG

GCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG[GAGGAGGG[CG[GTGGGCA[CG[TGTGGGTCCCA

CCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[GCCATCTACACCTACCTGCAGCC[CG[[CG[CAG[CG[CT

ACAACCA

SEQ ID NO: 532

ACCCCTCCC[CG[CTGACCTCACT[CG]AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCATCTGAAGAG

GGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[[GATCC[CG[AGT

CCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCTCTCCTTC[CG[CAG

A[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCACCTT[CG[GTTCTCTGAGAGCTTCCT

GGAGAACAGGGC[CG[GTGCACAGG[CG[GG[CG[CTGTGCT[CG[CACCCC[CG[GGTCCTCCC[CG]AG[CG[CAGGC[

CG[GGGACC[CG[A[CG[GGAGGCA[CG[G[CG[[CG[GGCACAT[CG[GAGGCTCT[CG[CTGCTGGGCACTCAGGT[CG[C

CAGAGTC[CG[CAG[CG[[CG[GGGTGGGAGCTC[CG[[CG[GCACCCCCTGCCTGGGTGC[CG[C[CG[GACAGAGCTGGG

TATTCAGGG[CG[T[CG[GCCTGAGAACCTGGGAGTT[CG[AATCCCAATCTCAA[CG[CTAGAAATAGAATTTTAG[CG

[TTGAAGTTAGGATTTTAG[[CG[[TTAGAATCAGATTCCTGGCTTAGTCATGAAAG

SEQ ID NO: 533

TGTG[CG[CAGCAGG[CG[AGT[CG[GGAGCACCATCCCCTGAG[CG[CAACCTGGTGGGCCCCCTGGGGC[CG[CCCC

TTTGG[CG[CC[CG[CTAGTG[CG[GGAGGGGCTATGCTCC[CG[GAGGTA[CG[TGG[CG[CCCCTGCCACCCTGAGAGC

TATTTTCTATTCCCAGGTGGT[CG[[CG[TTATCCTCATCCCC[CG[CCCTGCACCTT[CG[TCATCAGCTTTGCCTCTCC

[CG[TGTC[CG[TGTGTAGCTCCATCCT[CG[TGCT[CG[CCTTCTTCATTGG[CG[GAAGCTGGGAGC[CG[AGAGAGTGA

GC[CG[TG[CG[CAGATGTG[CG[G[CG[[GTGGAGGTGGCTTTTGTTTCTCCTC[CG[[CG[CCCCCTCCCCCCC[CG[CCC[

CG[CACATTGCCTGT[CG[CTCTTCCCACCTAGGACCCTCAAACTGGTTCCCCCTGTACACAGAACCTGG[CG[ACCA[

CG[GATCATCCCCTCTCTCTTCCTT[CG[ATG[CG[ATCATATAACATTTAGATTTTGCCAGGCCCCTTTAAATCATTGC

TTCTTTGAACCCTCCCAACAATCCTAAAGGGAAATACTGTTTATGAACC[CG[TTTTACTAATCTGACAATTATAGC

ATAAAGTTTAAGTAACTTGCTCAACATC

SEQ ID NO: 534

T[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCTCCTGG[CG[GTGATGGCTCTGGAC[CG[[CG[[CG[GC[CG[CA

GTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[[

CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GTTG[CG[CAAAC[CG[[CG[CTCCTGGCTGAG[CG[GC[CG[CTGTG[[

CG[[[CG[CCC[CG[CCTGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[C

GC[CG[[TCATCCTGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG

[[GAGGAGGG[CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCT

ACACCTACCTGCAGCC[CG[[CG[[CAG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACA

C[CG[TGGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGG

SEQ ID NO: 535

AATG[G[TCCTCCTG[G[GTGATGGCTCTGGAC[CG[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG

[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[[CCTCCTGGCTAAG[CG[GCCTCACCA

ACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACACTAC[CG[AGAAC

CAGATGT[G[[G[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCCTGGCCTCCTA[CG[G

TGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[CG[GTGGGCA[CG[TGT

AG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[TGGTCACACCTGCTCTCAACC

[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG]AGGAGGCTGCTG[CG[GAGTCTGGGGA

SEQ ID NO: 536

GCAAGGGG[CG[CA[CG[CAG[CG[GGAGCCACTGGGCCCAGCAGCA[CG[CAA[CG[A[CG[CCTCCTGCTGTTGAACT

TGTTGGGGTCCAGGATGTCCAGTAC[CG]AGAAGGAGGTGGGG[CG[CAGGGG[CG[CTG[CG[GGC[CG[GGC[CG[CT

CCAGCCCCCT[G[[G[[G[CAGGCACAGTGT[G[CTGGC[CG[[CG]AG[CG[G[CG[GGGCTCCAG[CG[[CG[GGG

AAAGGC[G[GCAGCT[G[G[CG[[CG[CC[CG[TCCATAGCTTCCTGGGCAG[CG[G[CG[G[CG[GGAG[CG[GG[CG[GTG

[CG[GGCCC[CG[AACCTGGCTGGGGAGG[CG[G[CG[GTAG[CG[[[CG[GGAATGTCCCCAGGAGCCT[CG[GGGC[CG[

TAG[G[CTCATG[G[GCCTCC[G[[G[CTC[G[[CG[GCT[CG[GGCCC[CG[CCACCTACTGGGCTCCCAT

[G[[G[CATTTATGGCAGCCC[G[[G[GAGG[G[CCCA[CG[[CG[CCCACA[CG[C[CG[AACACA[CG[TG[CG[CC[

CG[CAGG[CG[GC

SEQ ID NO: 537

TGCTCACCATTGGCTCAGGGTC[CG[CCCTGAGTGGTCCTAGTCAGAGAT[CG[CAC[CG[TCACCACTACCCTACACA

CACACACAAG[G[[G[[G[[CG[[CG[[CG[GTGT[CG[GCTAGCCAGG[CG[GTGAAGGGGTGCTGGCTAGGCC[CG[G

AGCACCC[CG[GGGT[CG[GGGGTGGAGTCT[CG[GTGGCCTCACCC[CG[C[CG[CCATGTGCTGCAGGTCTGGTTCCA

TTC[G[CAGTC[G[[CG[C[CG[GATG[CG[GC[CG[CTGGTGGAC[CG[CCTGGAGC[CG[GG[CG[AGCTCATCCCCAA

TGGTCCCTTCTCCTTCTA[G[GAGGTGGGTG[CG[[CG[C[CG[AATGG[CG[GGGCA[CG[GCCAGGT[CG[GGG[CG[GG

CTT[CG[TTGGAAG[CG[GGTGGCAG[CG[[CG[GGGGGGCA[CG[CCT[CG[CTCTCTGTAAGCCACTGGAGAGTTGGGG

[CG]AGTAGGGAGAAGGCTGGGAGTAAATCAAGGGGAGG[CG[G[CG[AGAC[CG]AGGACCCAATTCA[CG[GCCCTG

AATAA[CG[GGGGTAGCTGGTAAGGGGCAGCTCC[CG[GGCTTG[CG[CCCAGCCTCCTCC

SEQ ID NO: 538

CCTCCTGG[CG[GTGATGGCTCTGGAC[CG[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT

[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GT

TG[G[CAAAC[G[[G[CTCCTGGCTGAG[CG[GC[G[CTGTG[CG[[CG[[CCC[CG[CCTGCTGGACCACTTCATC

TGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[[GAGACACTAC[CG[AGAACCAGATGTT

[G[[G[[CG[[CG[TGGTCATCCTGCTGCTGC[CG[[TTTGC[CG[TCATCCTGGCCTCCTA[CG[GTGC[CG[TG

GCC[CG[AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[[CG[[GAGGAGGG[CG[GTGGGCA[CG[TGTGGGTCCCA

CCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTACCTGCAGCC[CG[[CG[CAG[CG[CT

ACAACCAGGCA[[CG[[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[TGGTCACACCTGCTCTCAACC[CG[CTCAT

CTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG]AGGAGGCTGCTG[CG[GAGTCTGGGGAGAGGCCA

SEQ ID NO: 539

AG[CG[GC[CG[TCCTTCCCCAGCT[CG[AAGCC[CG[TAGCACATT[CG[CAGGCAAAGCCTCCCAAGT[CG[TCTAGGC

AGTTAGGGAGCTCTG[CG[CATTTGCCAGCA[CG[GAGGTACCTCC[CG[GGGCAGGGACACAACACAT[CG[CC[CG[A

GAGTTTGTCCCAG[G[A[G[[G[ATTT[G[TC[CG[[CG[ATGCAAGTAACTGAGAT[CG[GGAGCTGTCCC[CG[G

CAGAG[CG[CACTCACCT[CG[GTCCCAGGTGGACTGAAGTCCAGAG[CG[G[CG[CTGTGCAGCTGGAAGGG[CG[[[[C

G[[G[ATAGCTCAAGTTAGAGG[G[GCC[G[GGG[CG[[CG[G[CG[CAGGACACAAGACCTCAAACTGGTACTTG

CACAGGTAGC[CG[TTGG[CG[[CG[CAGGTGGCAT[CG[CATCTCCTTCCAGCCTG[CG[GGCT[CG[ACCCCAC[CG[GTG

GCCTGGAGTAC[CG[[CG[CATCTC[CG[[CG[[CG[GTGCAGGAG[CG[TTGGGGCTCCTCCACCCACTGCAG[CG[TGT[C

G[CTTT[CG[AGAC[CG[C[CG[GGGT[CG[GAGGACAGCCAGGAGAAACCC[CG[CAAAGGCT[CG[TTCTCCAGGGTGC

AGTGGGAA[CG[CCTG[CG[CTCCAGTG[[CG[[ACCCAGAACAGCAGGTCTTTGGAGCCCC

SEQ ID NO: 540

GCTGTCCTTCCCCACTGGTCACACAAGAG[CG[GC[CG[TCCTTCCCCAGCT[CG[AAGCC[CG[TAGCACATT[CG[CAG

GCAAAGCCTCCCAAGT[CG[TCTAGGCAGTTAGGGAGCTCTG[CG[CATTTGCCAGCA[CG[GAGGTACCTCC[CG[GG

GCAGGGACACAACACAT[G[CC[CG[AGAGTTTGTCCCAG[G[AG[CG[C[CG[ATTT[CG[TC[CG[[CG[ATGCAAGTA

ACTGAGAT[CG[GGAGCTGTCCC[CG[GCAGAG[CG[CACTCACCT[CG[GTCCCAGGTGGACTGAAGTCCAGAG[CG[G

GACACAAGACCTCAAACTGGTACTTGCACAGGTAGC[CG[TTGG[CG[[CG[CAGGTGGCAT[CG[CATCTCCTTCCAG

CCT[G[GGCT[G[ACCCCAC[G[GTGGCCTGGAGTAC[CG[[CG[CATCTC[CG[[CG[[CG[GTGCAGGAG[CG[TTGG

GGCTCCTCCACCCACTGCAG[CG[TGT[CG[CTTT[CG[AGAC[CG[C[CG[GGGT[CG[GAGGACAGCCAGGAGAAACCC

[CG[CAAAGGCT[CG[TTCTCCAGGGTGCAGTGGGAA[CG[CCTG[CG[CTCCAGTG[[CG[[A

SEQ ID NO: 541

AGTTTCTGGACTCAAAGGGTGCTCCTCCAAAGCTC[CG[[GGCCTC[CG[GGCTACCCCTACTTGAAGC[CG[CTATGC

CCCTCTCCTGTGCC[CG]AGGTGGC[CG[CTGGGTGGCAGGGGAGGCC[CG[GGC[CG[A[CG[G[CG[GTCCCAC[CG[CA

CTGT[CG[[CG[AAGGCAGG[CG[AAGAACAGGGCCACACTGAGTGGGGACAACTGGGCC[[CG[[GGCCCAGAGGACA

[CG[AAGGAAGGTC[CG[GGAGAAGGAATTCCTAGTTTCAGGGAAGAAAAGGTGGCT[CG[AGTGAGGAAACTG[CG[

GGGGCAA[G[GTCTCT[G[[G[[G[GGACCC[CG[C[CG[TGTGC[CG[CCCAGGGA[CG[[CG[AGGGGG[CG[CTG

CTGC[CG[[CG[CCAGGGG[CG[AGGGTCC[CG[[GGGCCTCCTGAGCACCTCC[[CG[GCCCTGCC[CG[GCCAACTCAG

ACTACACC[CG[GACTCTGCCCAC[CG[[CG[TTTC[CG[CCCT[CG[GCCT[CG[GGTCCCTGGAGGGCT[CG[[CG[GGTAG

GAAGAGT[CG[GGGTGG[CG[GGACTTT[CG[C[CG[ACACC[CG[GCTCCC[CG[CCTGGTGGCTG[CG[CACA[CG]AGGC

[G[G[CG[A[CG[GGACTTGCC[CG[[CG[TCTCAG[CG[CCTCCTGTGTGAAG[CG[GGAC[CG[CTGC

SEQ ID NO: 542

TGCTCCCAGGCTTCCACTCCTTGAGGTATTTCCACACCACCATGT[G[GCC[G[GC[CG[[CG[[CG[GATCCC[CG[

CTTCCTCTC[G[TGGG[G[A[G[TGGA[G[ACA[G[CAGTG[CG[TG[CG[GCT[CG[ACAG[CG[A[CG[CCA[CG[AGT

CCCAGGATGGAGC[CG[[CG[GG[CG[C[CG[TGGATGGAGCAGGAGGGGC[CG[GAATATTGGGAAGAGGAGACAGG

GAC[CG[CCAAGGCCAAAGCACAGTTTTAC[CG[AGTGAACCTG[CG[[GACCCTGAG[CG[GCTACTACAACCAGA

GTGAGGCCTGTGAGTGACAC[CG[GC[CG[GGGG[[CG[CAGGTCACTACCCCTCCACATCCCCCA[CG[GAC[CG[CC[

CG[GGTCTCCC[CG[AGTCTCTGGGTC[CG[AGATCCA[CG[C[CG]AGGCAG[CG[GGACCTGGAGACCCTTGACC[[CG[[

GGAGAGGCCCAGGAGC[CG[TTACC[CG[GTTTCATTTTCAGCCAAAATCCC[CG[CAGGTTGGTCCTGG[CG[[AGGG[

CG[GGGCT[[CG[[GTGGG[[CG[GGGCTGGC[CG[[CG[GGGG[CG[GGGCCAGGGTCTCACACCCATCTAGAGGATGTC

TGTCTG[CG[A[CG[[TGGGGT[CG[GA[CG[GG[CG[CCTACTC[CG[[CG[GGTATCACCAGCTTGCTTA

SEQ ID NO: 543

GTTCT[G[GGG[G[CCCCC[G[GTGGGTCCC[G[[CG[AAGC[CG[C[CG[C[CG[CACACCTTCCTCAG[CG[TAGCC[C

G[CCAGTGGAAAC[CG[GGGGAGGTTCTGCCTCCAGCACCCAAG[CG[G[CG[GC[CG[CACCT[CG[CAGTGAGACCCT[

CG[CAAG[G[[G[[CG[CCTCCCT[CG[CCC[CG[[CG[TCCCCTCTGCCC[CG[[CG[AGCCCCCCTGGG[CG[C[CG]AG

TAG[G[[G[CTG[G[[G[[CG[C[CG[[CG[GTGGAGGC[CG[CTGCTTTCC[CG[C[CG[GGAGCC[CG[GCACAGTC

GGCCCTTCCCCAGATGAG[G[[G[[G[[CG[GC[CG[CCCCCCAGTG[CG[C[CG[GTGCCTCCCTGGG[CG[C[CG[

AGG[G[CAGG[G[[G[[G[TGAAGAC[G[A[G[TG[CG[C[CG[GGCT[CG]AG[CG[[CG[GTCTGAG[CG[[CG[

[CG[G[CG[CCTG[CG[G[CG[GC

SEQ ID NO: 544

TTTTG[CG[CCTAGTCCCTGCCTGACCTTTCCTCCTCCTCTCCCAGGGCTTTAGGTACTCTTAGTCCCTGTGTCATAG

GGACTGGGAGCAGATAGGCCCCTC[CG[CCCACCCCACCCCTCCCCCACCCCT[CG[CCCACCCCTCCCCCACCCCTC

[CG[[CG[TTCCTACTCTAATCTCCTACCCTGATCTG[CG[GTGCAGGG[CG[G[CG[CTGGAGAGGGTGGCTTG[CG[GCT

GATCC[CG[[CG[GTCTGGTTTG[CG[GCTAGGTGTGTGTCCC[CG[GACTGG[CG[TGGGTCC[CG[GGCCAGG[[CG[[TGG

TCCTGGG[G[[CG[[CG[GCC[CG[TGACAGGACC[CG[A[CG[CCTCCTGGTGGGCATTT[CG[CTCCAAGC[CG[GGA

GAGGGCTCCCAAGGCCC[CG[AGGACAGTCCCACCCTCAC[CG]ACAGGAC[CG[TCCCTG[CG[CATCCCCCACCCTT

CTTCATCTT[CG[GG[CG[CT[CG[GGCCAACCTGGACAGCAGGG[CG[GAAGCTTCCAGAAAGGACAGAGATGGAGA

AGGTGGGAAGGGTGGGGCTCAGGCAGGGGACACCA[CG[GCC

SEQ ID NO: 545

CAG[G[[G[[G[[G[CTCCCCT[G[[G[GC[CG[[CG[[CG[GAGCCTC[CG[CCTCCT[CG[GAAGGGGGGAG

GGGTCT[CG[GAACCC[CG[GGG[CG[GGGG[CG[GGAG[CG[GGGGACCTCACCTACCTG[CG[GTGG[CG[CTGGGC[[C

G[[CTC[G[GCAGCC[G[[G[AGGGCTC[G[[G[[G[GAAGCT[G[[G[[CG[[CG[[CG[CTCCAG[CG[GGGAGC[

TGCCCCCC[G[[G[CCCATTAA[G[CTTTCTCC[G[[G[GG[CG[C[CG[[CG[CTCTTGCCAACTTTCCCCTC[C

GTC[G[GTCTG[G[[G[[G[G[CG[[CG[C[CG[GGTGCAGGAGCTGGGGTGAGGG[CG[CCC[CG[GGTGCCAGCAGG

GG[CG[[CTGGGAGCTGTTTGGG[[CG[GGGA[CG[TAGGGCTC[[CG[GGAGGTCACACAGCCCTAACAGGACAGTG

GGAAGG[G[[CG[[CG]AGCCAGATTTGGCCAAA[CG[CTAAGCT[CG[CTG[CG[GCCT[CG[GGCCCT[CG[GCCCA[C

G[GGGCCCCTCTCCC[CG[TTTGGG

SEQ ID NO: 546

TTTGCAGCCTT[CG[CCAAGGCCCCAG[CG[ACT[CG[GT[CG[CTGCCCAGAAATTC[CG[C[CG[AGGGC[CG[GCAGT[C

TCAGTAACCT[CG[AGACT[CG[[CG]AGC[CG[CCCCCAGGT[CG[C[CG[GAGCAGGAGCTG[CG[CT[CG[GGCCA[CG[G

AGGACTCAGG[G[GCCCTTAG[G[GGTCA[G[[CG[CC[CG[CAAGCA[CG[ATATTTGAAAGCATGGTC[CG[CTGGA

CAGAGTAAGGC[CG[AAACCTGGG[CG[CCT[CG[GGC[CG[GACTC[CG[GAGC[CG[CAGCTGAATGCT[CG[GCTCCT

CTCAGAGG[G[CAGTGA[G[[CG[GACCCT[CG[[CG[CCCCA[CG[CCAATGCAGG[CG]AGCACACAGCC[CG[CTC[

SEQ ID NO: 547

AGGTGGC[CG[CTGGGTGGCAGGGGAGGCC[CG[GGC[CG[A[CG[G[CG[GTCCCAC[CG[CACTGT[CG[[CG[AAGGCA

GG[CG[AAGAACAGGGCCACACTGAGTGGGGACAACTGGGCC[[CG[[GGCCCAGAGGACA[CG[AAGGAAGGTC[CG[

GGAGAAGGAATTCCTAGTTTCAGGGAAGAAAAGGTGGCT[CG]AGTGAGGAAACTG[CG[GGGGCAA[CG[GTCTCT[

CGT[G[[G[GGACCC[CG[C[CG[TGTGC[CG[CCCAGGGA[CG[[CG[AGGGGG[CG[CTGCTGC[CG[[CG[CCAGGG

G[CG[AGGGTCC[CG[GGGCCTCCTGAGCACCTCC[[CG[[GCCCTGCC[CG[GCCAACTCAGACTACACC[CG[GACTC

TGCCCAC[CG[[CG[TTTC[CG[CCCT[CG[GCCT[CG[GGTCCCTGGAGGGCT[CG[[CG[GGTAGGAAGAGT[CG[GGGTG

G[CG[GGACTTT[CG[C[CG]ACACC[CG[GCTCCC[CG[CCTGGTGGCTG[CG[CACA[CG]AGGC[CG[G[CG[A[CG[GGAC

TTGCC[CG[[CG[TCTCAG[CG[CCTCCTGTGTGAAG[CG[GGAC[CG[CTG[CG[GTACCTGCCCCAGGGAAGGC[CG[[C

G[[GGGAGGGTTACAGAGCC[CG[TAGGCACTGG[CG[GGGATCTTTATACACCCCCAAAACACACACAT

SEQ ID NO: 548

TA[CG[AGGGGCAGGGG[CG[TGGCAGGAGCCCTGCCTGGC[CG[CCCCTGGTGGGAAAAGCCCCTAGGGGT[CG[[A

GGGG[G[CAGAGGATCAAGAGCC[G[[G[[CG[G[CG]AGGAG[CG[[CG[CTCAGC[CG[GGCTTGGGAGC[CG[C[

CG[[CG[G[CG[CCAACTTTTCCCAT[CG[[CG[GGAG[CG[AAGAGCAG[CG[GAGAGAGGGGTCCCAGAA[CG[AAGGT

GG[CG[GCA[CG[AGCTCTG[CG[CTGG[CG[GCTGTGGGGGGC[CG[[G[CG[[CTCAGGACCCCAACTCCATCCAAGTT

[[[[G[GGGGGG[G[[G[GAGG[CG[G[CG[C[CG[GGCAGGTGG[CG[GC[CG[CTTGCC[CG[GGCTGG

AGTCACTGG[G[GAG[G[GG[G[[G[GG[G[CTGG[G[GG[CG[A[CG[[[CG[GGAGGGAGGGCAGG[CG[CTG

[G[GGACT[G[[G[[G[[G[TC[G[[G[GC[CG[AGCTG[CG[CTG[CG[CAC[CG[GGTCTC[CG[GG[CG[CT

GGAGG[G[[CG[C[CG[G[CG[ACCTC

SEQ ID NO: 549

CTGGC[CG[CCCCTGGTGGGAAAAGCCCCTAGGGGT[CG[AGGC[CG[AG[CG[TGGAG[CG[GAGCTGGGGTG[CG[G[

CGAGGGGGGGG[G[[G[[CG[CAGA[CG[CC[CG[GGG[CG[CAGAGGATCAAGAGCCC[CG[[CG[C[CG[

G[G[AGGAG[C[[G[CTCAG[G[GGCTTGGGG[G[[CG[C[CG[G[CG[CCAACTTTTCCCAT[CG[[CG[GGAG[C

G]AAGAGCAG[CG[GAGAGAGGGGTCCCAGAA[CG[AAGGTGG[CG[GCA[CG]AGCTCTG[CG[CTGG[CG[GCTGTGG

T[CG[CAGG[CG[CTGC[CG[C[CG[CCTCT

SEQ ID NO: 550

CCCAGG[CG[CCCCCCT[CG[TCCTCCTCAAGTGCCCT[CG[GAAAG[CG[[GACCAGACTCACCTACTGCCAGGCAGA

TGGGCAGCAGCAGCCTGAAGATGAGCC[CG[CACACCACTTCTGAGGCCAT[G[[CG[T[CG[GTC[CG[G[CG[AGT[C

G[GAGCAGAGGGG[CG]AGGCT[CG[AGGGTCCCTAGGGGTGGTGGGA[CG[CAAGGCCCATGCC[CG[TCTATGGCCT

]CCC[CG[AGGGCA[CG[CTCC[CG[GGGCTCTTGGC[CG[CCCCT[CG[CCCAC[CG[GGCTCTGGGTAGCCCCTCAC

CAGGCTCTTGG[G[GCCACCTAG[G[G[CG[CC[CG[GCCCCCTG[CG[GC[CG[GCCCATTTAGTGTGAATCCTGG

ATC[CG[GCAG[CG[G[CG[G[CG[GCTTCTTCAGGGGTAGCTGATGC[[CG[GGGCCTTGGAGAGGGA[CG[CTTTGGGA

GGGTCCTGGGGG[G[G[CG[[CG[G[CG[AGCAAAGGGGGCAAGAAGGG[CG[TGCTGTGCTCC[CG[CCTGGCTCC[C

G[GGG[CG[T[CG[TTTGGGGG[CG[GC[CG[GGGAGTTTTCTACTTGGAAGCCCCTCTGAAGCCAC[CG[[

SEQ ID NO: 551

TACAACCTGGTCC[CG[TTTTATTCTGC[CG[TACCCAGTTTTTGGATTTTTGTCTTCCCCTTCTTCTCTTTGCTAAA[C

G]ACCCCTCCAAGATAATTTTTAAAAAACCTTCTCCTTTGCTCACCTTTGCTTCCCAGCCTTCCCATCCCCCCAC[CG[

AAAGCAAATCATTCAA[CG[ACCCC[CG[ACCCTC[CG[A[CG[GCAGGAGCCCCC[CG[ACCTCCCAGG[CG[GAC[CG[C

CCTCCCCCC[G[[G[[G[[G[GGTTC[G[GGCC[G[G[CG[AGAGGG[CG[[CG]AGCACAGC[CG[AGGCCATGGAG

GTGA[CG[G[CG[GACCAGC[CG[[CG[CTGGGTGAGCCACCACCACCC[CG[C[CG[TGCTCAA[CG[GGCAGCACC[[CG

[[GACA[CG[CACCACC[CG[GGCCTCAGCCACTCCTACATGGA[CG[[CG[G[CG[CAGTACC[CG[CTGC[CG[GAGGAGG

TGGATGTGCTTTTTAACAT[CG[A[CG[GTCAAGGCAACCA[CG[TCC[CG[CCCTACTA[CG[GAAACT[CG[GTCAGGGC

CA[CG[GTGCAGAGGTACCCTC[CG[ACCCACCA[CG[GTGAGTG[CG[CC[CG[GGGTGC[CG[GGGCTCC[CG[C[CG[GC

[CG[CTTCAGC[CG[TCC[CG[GCT[CG[GGGAGGT[CG[GGAGGGACCTGAGGGC

SEQ ID NO: 552

CAAGCAATTCTCCTGCCTCAGCCTCCCAAGTAGCTGGGACTACAGG[CG[CACACCACCATGCC[CG[GCTAATTTTT

GTATTTTTAGTAGAGA[CG[GGGGTTTCACCATATTGGTCAGGC[CG[GTCT[CG[AGCTCCTGACCTCAGGTGATCCA

CC[CG[CCT[CG[GCCTCCCAAAGTGCTGGGATTACAGG[CG[TGGGCCAC[CG[CTCC[CG[G[CG[GGGCC[CG[AGTTT

CTTGAATGAAGTCCCCCCAGCATGGC[CG[TTGCCATG[CG[GGTCCTGGGTTGTGGAGAGATG[CG[G[CG[GTACTT

GC[G[ACAG[CG[G[CG[G[CG[CTTGGGGTCCTGGGCTCC[CG[GCCA[CG[CTACAT[CG[C[CG[GTCTGGGAG[CG[C[

CG[GAGA[G[[G[TCTGATCC[CG[CC[CG[C[CG[GGCAGAGTTG[CG[GGCTT[CG[CT[CG[GCT[CG[GGGTTCCCCA[C

G]ATCTCTCACCCTGTGTTT[CG[G[CG[GAGTTG[CG[GGGGTTCCCTCTGCTCC[[CG[GGTCCCTGAGATCCCTGATC

C[CG[CTCTCAGGGCAGGGAATTC[CG[GGGTT[CG[CCCCTCTGGGCTTCCC[CG[[CG[ATCCCAGAGCC[CG[[CG[TTC

CAACAGAATTGGGAGGGTTTATTG[CG[CTAGAGGAGTCTTCAGG

SEQ ID NO: 553

GC[CG[TACCTGCTGCTC[CG[TCCC[CG[GCTC[CG[TCC[CG[GGCTCCTGG[CG[GCTGT[CG[CTG[CG[GTTCCTTCC[C

G][CG[GGC[CG[GGCCCCTTCCCTG[CG[CCTT[CG[C[CG[CCTCCT[CG[[CG[CCTGCC[CG[GGGCC[CG[CAGCCTC[CG[

CAC[G[GGAACC[G[GAGGACC[G[AGG[CG[GG[CG[CAGGGG[CG[AAGC[CG[GGGC[CG[GGGAGGGGC[CG[CCT

[G[CT[G[GGTT[G[AGA[G[GAAGAAACA[G[[CG[G[CG[CAGGCTC[CG[GAG[CG[A[CG[GCTC[CG[A[CG[G

GGACC[CG[TTAAATAATTTATTGATGATACAAAG[G[ACT[G[[CG[CCCACC[CG[GGGC[CG[CCCC[CG[GATTC

]GGCTGACCAG[CG[CCAAGTT[CG[AGGGTTTGTGCTTCTTGAGCAGC[CG[[CG[TGATCTTCT[CG[T[CG[TC[CG]AG

TTGGGGTCCAGGGGC[G[GTTGTATT[G[[CG[T[CG[TCCTC[CG[[CG[TC[CG]AGC[CG[CCCACCTTCAGCTTCT[C

G]G[CG[TC[CG[AGTCCTGCTTCTTCTTGGC[CG[A[CG[CCATCTCCAC[CG[[CG[TGC[CG[CTTG[CG[CCACTTGGTC[C

G[GC

SEQ ID NO: 554

CCCCCAAG[G[[G[TC[G[AATC[CG[CCC[CG]AGG[CG[AGG[CG[GGC[CG[GGC[CG[TACCTGCTGCTC[CG[TCCC[

CG[GCTC[CG[TCC[CG[GGCTCCTGG[CG[GCTGT[CG[CTG[CG[GTTCCTTCC[CG[[CG[GGC[CG[GGCCCCTTCCCTG[

CGCCTT[G[[CG[CCTCCT[CG[[CG[CCTGCC[CG[GGGCC[CG[CAGCCTC[CG[CAC[CG[GGAACC[CG[GAGGACC[

CG]AGG[CG[GG[CG[CAGGGG[CG[AAGC[CG[GGGC[CG[GGGAGGGGC[CG[CCT[CG[CTC[CG[GGTT[CG[AGA[CG[G

AAGAAACA[G[[G[[CG[CAGGCTC[CG[GAG[CG[A[CG[GCTC[CG[A[CG[[GGGACC[CG[TTAAATAATTTATTGA

TGATACAAAG[G[ACT[G[[CG[CCCACC[CG[GGGC[CG[CCCC[CG[GATTCTGCAAAAATAGATT[CG[CCCCCA

CC[G[[G[GGTCCTCACAAGG[G[TCCCC[G[[G[[G[[CG[C[CG[CA[CG[GGCTGACCAG[CG[CCAAGTT[CG

]AGGGTTTGTGCTTCTTGAGCAGC[[CG[[CG[TGATCTTCT[CG[T[CG[TC[CG[AGTTGGGGTCCAGGGGC[CG[GTTGT

ATT[G[[G[[G[TCCTC[CG[[CG[TC[CG[AGC[CG[CCCACCTTCAGCTTCT[CG[G[CG[TC[CG]AGTCCTGCTTCTT

CTTGGCC

SEQ ID NO: 555

AATCAGTGTTTTACTGTCAGTGCAGTGTTAAATGTCAATGCAACACTTAAGTTGCATTGACATTCATGTGTTGAT[C

G[GATTGTACAATGTGA[CG[TGTGAGATTTCT[CG[GGAC[CG[T[CG[AAGCTCAGACAACTCCAGGGCTGCAATTT

ACT[CG[TCTGGCTGCCCT[CG[AACCAGGCTCCCTTGG[CG[[CG[TGGGGCTCTCC[CG[G[CG[CTTGGTCC[CG[ACC[C

G][CG[C[CG[CAGTCAGGATACCA[CG[GCAATCTGGGGT[CG[CTTTGTAAGGAGCTC[CG[ACCTC[CG[GGCAGT

GCAGGGATACT[G[A[G[[CG[[CG[[G[ATGTCC[G[[G[GCT[CG[[CG[AGCCTGG[CG[[CG[CTGAGAGC

[G[[G[GC[CG[TGA[CG[TCA[CG[CC[CG[GGACTGGC[CG[TTGCAGCAAGA[CG[GC[CG[[CG[TTC[CG[GTTC[CG[

GTAGGTTGCC[CG[GGAGA[CG[[CG[GGTACACAGAGAAG[CG[GCTCC[CG[T[CG[GAGGC[CG]AGT[CG[T[CG[CC

A[CG[AT[CG[CCCCCTTGGTGGACT[CG[CAGGC[CG]AG[CG[GCTTCCC[CG[CAGAGCT[CG]AGGAGGGCAGAC

SEQ ID NO: 556

AGGGG[CG[AGGCT[CG[AGGGTCCCTAGGGGGGGGGA[G[CAAGGCCCATGCC[G[TCTATGGCCTCT[G[[C

GGGCA[CG[CTCC[CG[GGGCTCTTGGC[CG[CCCCT[CG[CCCAC[CG[GGCTCTGGGTAGCCCCTCACCAGGCTCT

TGG[G[GCCACCTAG[G[G[CG[CC[CG[GCCCCCTG[CG[GC[CG[GCCCATTTAGTGTGAATCCTGGATC[CG[GC

AG[CG[G[CG[G[CG[GCTTCTTCAGGGGTAGCTGATGC[[CG[[GGGCCTTGGAGAGGGA[CG[CTTTGGGAGGGTCCTG

GGAGG[G[[CG[[CG[G[CG[AGCAAAGGGGGCAAGAAGGG[CG[TGCTGTGCTCC[CG[CCTGGCTCC[CG[GGG[CG[

T[CG[TTTGGGGG[CG[GC[CG[GGGAGTTTTCTACTTGGAAGCCCCTCTGAAGCCAC[CG[[CG[TCTCCTTTGCC[CG[

GCCT[CG[TCTC[CG[CTGCCCA[CG[CAGGCTGC[CG[[CG[CTCTGGCCT[CG[GCCC[CG[GCTCT[CG[GAGCTGCC[CG[

SEQ ID NO: 557

GGGCTTTTCCTCCCAGCCTTCCTTTTGGGAAA[[CG[[CAGTGTGCTAAAAAAGTGCATGCAGCCCAGGCTGTGGCCT

AGGC[CG[T[CG[GTTCC[CG[GCCATGCCTAGCTCCTCTGAGGT[CG[CCCTTAGTGAGGACA[CG[AGGTGCCCTCACC

CG[CC[CG[[CG[GAGCCAGACCTCCCAGCTCTG[CG[CCCCAGGAC[CG[[CG[[CG[GTGCAACCTG[CG[CATG[CG[CA

CC[CG[[CG[TCC[CG[CTGCTGTTTAGC[CG[TTTCCAAGGCTA[CG]AAGCCCAT[CG[GC[CG[GGGATAAGAGAGCA

AGAAAATGAAGCTCAAGAGCCTCCTGCTC[CG[GTATTACC[CG[CCAGGTA[CG[CACCAGCC[CG[GCCC[CG[TC

ATCCCCA[CG[TGGGACCCTGGGCTCCCAGACTGGGAGGGTTTGGGG[CG[GAGGAGGG[CG[CAGCCACTGAAAGG[

CG[G[CG[GGGTCCCCAGGTGGGGCAGGAAGT[CG[GGCACTTCCCAACCTGTGCCCCTCATTCCTTCAGATGCTGGA

CTCTTCCTCAAAACATTAACAATTACTCTTTTAGGAATTTAAAG

SEQ ID NO: 558

GCAAAGGGGC[CG[[CG[CATTGGA[CG[GGGCTCCCAAGCCACAGCCCTGGGGGCCTTGAGGAGT[CG[[TGGTA[CG[

GTCCAGGGCAGT[CG[GGGCTG[CG[GGGCC[CG[TGAAGCCAGA[[CG[[AGGCTA[CG[GACTTAGGGTCCCTGCAACC

AAGAC[CG[[CG[AG[CG[ACTGTGGACT[CG[GGA[CG[GAT[CG[CACAAAGGAGGAAGGGGGAATCAGAGGGG[CG[T

C[CG[GTCCAGGA[CG[TGTCAGGCCTGGG[CG[GGG[CG[GAAAACTGACACCAGGG[CG[AGGACAAGGATTT[CG[[

CTCCTCCAGGGCTGCCAGGGGAGGGGCT[[CG[CCAC[CG[TCACTCTCCATGGGCTCTGGCCC[CG[A[CG[GTGTTTA

AAGGG[CG[GAGGGCTGGGC[CG[GGCTGGT[CG[CACC[CG[GG[CG[CTGCTGG[CG[GCCAAGCTGGATGGGT[CG[C

CAGTGAGTTT[CG[GTG[CG[GCAC[CG[CTGGCCCAGGCC[CG[GG[CG[[CG[GCTGGACATGGCCACCTACTG[CG[A[C

G]ACCTGGGCCCCTCCT[CG[GCCC[CG[CC[CG[GCCAGGCCCAGGCCAC[CG[[CG[CACCCCC[CG[GGCTATGAGCCA

GGGGATCTGGG[CG[[CG[GTGGG[CG[GGGGCCCCCTCCTGTGGGTGAA[CG[[CG[CCAGC

SEQ ID NO: 559

AGGGC[CG[CTGTCCAGGCCCAGCCC[CG[[CG[TTCTCCACCT[CG[CCACCT[CG[CTCTG[CG[GCTCCAGCCTGGAGA

TCTA[CG[GACTTCATTG[CG[ATCTCTTG[CG[CAGTGTAGT[CG[CCCTCTATCCCTAGCCC[CG]AGTCC[CG[GGTAA

ATTGGA[CG[GGGCTCCCAAGCCACAGCCCTGGGGGCCTTGAGGAGT[CG[TGGTA[CG[GTCCAGGGCAGT[CG[GG

GCTG[CG[GGGCC[CG[TGAAGCCAGA[[CG[AGGCTA[CG[GACTTAGGGTCCCTGCAACCAAGAC[CG[[CG[AG[CG[

ACTGTGGACT[CG[GGA[CG[GAT[CG[CACAAAGGAGGAAGGGGGAATCAGAGGGG[CG[TC[CG[GTCCAGGA[CG[T

GTCAGGCCTGGG[CG[GGG[CG[GAAAACTGACACCAGGG[CG[AGGACAAGGATTT[CG[[CTCCTCCAGGGCTGCC

AGGGGAGGGGCT[[CG[CCAC[CG[TCACTCTCCATGGGCTCTGGCCC[CG[A[CG[GTGTTTAAAGGG[CG[GAGGGCT

GGGC[CG[GGCTGGT[CG[CACC[CG[GG[CG[CTGCTGG[CG[GCCAAGCTGGATGGGTC

SEQ ID NO: 560

GTCTTCCCCTTCTTCTCTTTGCTAAA[CG[ACCCCTCCAAGATAATTTTTAAAAAACCTTCTCCTTTGCTCACCTTTGC

TTCCCAGCCTTCCCATCCCCCCAC[CG[AAAGCAAATCATTCAA[CG[ACCCC[CG[ACCCTC[CG[A[CG[GCAGGAGCC

[[CG[AGCACAGC[CG]AGGCCATGGAGGTGA[CG[G[CG[GACCAGC[CG[[[CG[CTGGGTGAGCCACCACCACCC[CG[

C[CG[TGCTCAA[CG[GGCAGCACC[CG[GACA[CG[CACCACC[CG[GGCCTCAGCCACTCCTACATGGA[G[[CG[G[C

G[CAGTACC[CG[CTGC[CG[GAGGAGGTGGATGTGCTTTTTAACAT[CG[A[CG[GTCAAGGCAACCA[CG[TCC[CG[CC

CTACTA[CG[GAAACT[CG[GTCAGGGCCA[CG[GTGCAGAGGTACCCTC[CG[ACCCACCA[CG[GTGAGTG[CG[CC[C

G[GGGTGC[CG[GGGCTCC[CG[C[CG[GC[CG[CTTCAGC[CG[TCC[CG[GCT[CG[GGGAGGT[CG[GGAGGGACCTGAG

GG[CG[GGGAGAGGTCAAG[CG[AAAGCCCCCATCTGC[CG[TTCCTGGTTCATTTA

SEQ ID NO: 561

GTTTTGCCAGATACCAGGTGGACTAGGGTGAG[CG[CC[CG[AGGGC[CG[GGA[CG[CA[CG[CA[CG[GGC[CG[GGTA

GGATGG[CG[CTGG[CG[T[CG[ATGCC[CG[[CG[[CG[CTTCAGGGCCTGGTCTGGC[CG[CCCCTCCATCCTTGT[CG[GT

TTCT[G[GGT[G[[G[A[G[[G[[G[[G[[CG[GG[CG[ATGCTGGCCTGCC[CG[TGGCCACCACCT[C

G[CTTCATTCC[CG[TCTCTTTGGGC[CG[C[CG[CATT[CG[TCCA[CG[TGCC[CG[TCTCTCCCTG[CG[CAAAATTCCAA

GATGAGAAATACTGGGCTCA[G[GTGGAG[G[[CG[[CG[GGGGCCCCCCTGAGC[CG[GGG[CG[GGT[CG[G

GGG[G[GGACCAGGGTC[G[GC[CG[GGG[CG[TGCC[CG[AGGGGAGGGACTCCC[CG[GCTTG[CG[ACC[CG[G[CG[

TTGT[G[[G[GTGTCAG[G[[G[CC[CG[GG[CG[[CG[CCATGGGGAAC[CG[CAGCAC[CG[[CG[GA[CG[[CG[G

A[G[GGCTGCTGGCTGGG[G[[CG[GGC[CG[GC[CG[[CG[GGGGCATCTG[CG[GGGGCATCTG[CG[GGGCTGGCTGG

GCAGGG[CG[[CG[G[CG[G[CG[CTGGTGGGGGG[CG[TGCTGCTCAT[CG[G[CG[[CG[GTGCT[CG[[CG[GGGAACT[CG[

CT[CG[TGTG[CG[T

SEQ ID NO: 562

AGGTTTTGCCAGATACCAGGTGGACTAGGGTGAG[CG[CC[CG[AGGGC[CG[GGA[CG[CA[CG[CA[CG[GGC[CG[GG

TAGGATGG[CG[CTGG[CG[T[CG[ATGCC[CG[[CG[[CG[CTTCAGGGCCTGGTCTGGC[CG[CCCCTCCATCCTTGT[CG[

GTTTCT[G[GGT[CG[[G[GAC[G[[G[[CG[[G[[CG[GG[CG[ATGCTGGCCTGCC[CG[TGGCCACCACCT

[CG[CTTCATTCC[CG[TCTCTTTGGGC[CG[C[CG[CATT[CG[TCCA[CG[TGCC[CG[TCTCTCCCTG[CG[CAAAATTCCA

AGATGAGAAATACTGGGCTCA[G[GTGGAG[G[[CG[[[[CG[[GGGGCCCCCCTGAGC[CG[GGG[CG[GGT[CG[

TTGTC[C[[G[GTGTCAG[G[[G[[G[GG[CG[[CG[CCATGGGGAAC[CG[CAGCAC[CG[[CG[GA[CG[[CG[

GA[G[GGCTGCTGGCTGGG[CG[[CG[GGC[CG[GC[CG[[CG[GGGGCATCTG[CG[GGGGCATCTG[CG[GGGCTGGCTG

GGCAGGG[G[[G[G[CG[G[CG[CTGGTGGGGGG[CG[TGCTGCTCAT[CG[G[CG[[CG[GTGCT[CG[[CG[GGGAACT[C

G[CT[CG[TGTGC

SEQ ID NO: 563

TCCCTTTGCCCCCTACA[CG[[CG[TGTTCT[CG[TCAACAGATCTCCAGAGGTGGTGCAGAAA[CG[ACCC[CG[[CG[C[

CG[[G[CCCCATCCTG[G[GCCAGTGCCT[G[[CG[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCCCAG

ATTTC[CG[GAGGAGCAGG[CG[GG[CG[GGGTCC[CG[[CG[GGGC[CG[GCTGC[CG[TCAG[CG[CCCCTTCC[CG[G[CG[

GC[G[[G[ACCCCCCC[G[CTGACCTCACT[G[AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCA

TCTGAAGAGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[[GA

TCC[CG]AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCTCTCC

TTC[CG[CAGA[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCACCTT[CG[GTTCTCTGA

GAGCTTCCTGGAGAACAGGGC[CG[GTGCACAGG[CG[[GG[CG[CTGTGCT[CG[CACCCC[CG[GGTCCTCCC[CG]AG[

CG[CAGGC[G[GGGACC[CG[A[CG[GGAGGCA[CG[G[CG[[CG[GGCACAT[CG[GAGGCTCT[CG[CTGCTG

SEQ ID NO: 564

AAAGTTTTGTGGTGCTTGAGACTGTTGACTTATGCAACTGGGGAGAGGGTTTTTTTAAC[CG[CTTTGAGATATTGG

TCCATCCCTTTTCTCTCAGAA[CG[TCCTCAAGGGCA[CG[TAAGAGTTGGAGGTGACCTC[CG[GGAG[CG[CCTAATT

TTGAGC[CG[[CG[GAACTT[CG[GCCCACTTCTC[CG[AGGGGACCAGG[CG[[CG[[CG[CCAATA[CG[CATGTG[CG[G

GCTCTGAG[CG[CTCAGAG[CG[[CG[CCTCTTCCTTCC[CG[GCTCCC[CG[[CG[GTG[CG[CACC[CG[CTGGCCACTCTG[

G[A[G[[CG[[CG[C[CG[GGTGCCC[[CG[GCCTAAGGC[CG[TTGACCT[CG[GGTTCTCCC[CG[GCACAGT[CG[AA

TCCA[CG[CCAGGGCCCTCAGGC[CG[GTAGCTGTCCTGCAGTC[CG[AG[CG[GAGCTG[CG[ACCT[CG[GGCAGCTGG

AAGCCTGTGGGCTGCTGCTTCTCCAGGCAGG[CG[G[CG[[GAGGGATGCAGGCAGGATGAG[CG[G[CG[GTCCCTT[

CG[C[CG[CCACC[CG[GAGAAC[CG[[CG[GCTGGTGCCCTTGAAGGCCCTGGGATGCCTGGGTTGGGTGGGTGAGTG

AA[CG[AGAACCCTGAGTGAGTGAGGGGAGGG[CG[GGTCCCCTCCTGGCTT

SEQ ID NO: 565

ACTGTTGACTTATGCAACTGGGGAGAGGGTTTTTTTAAC[CG[CTTTGAGATATTGGTCCATCCCTTTTCTCTCAGAA

[CG[TCCTCAAGGGCA[CG[TAAGAGTTGGAGGTGACCTC[CG[GGAG[CG[CCTAATTTTGAGC[CG[[CG[GAACTT[C

G[[GCCCACTTCT[G[AGGGGACCAGG[CG[[CG[[CG[CCAATA[CG[CATGTG[CG[GGCTCTGAG[CG[CTCAGAG[C

TGCCC[CG[[GCCTAAGGC[CG[TTGACCT[CG[[GGTTCTCCC[CG[GCACAGT[CG[AATCCA[CG[CCAGGGCCCTCAG

GC[CG[GTAGCTGTCCTGCAGTC[CG[AG[CG[GAGCTG[CG[ACCT[CG[GGCAGCTGGAAGCCTGTGGGCTGCTGCTT

CTCCAGGCAGG[CG[G[CG[[GAGGGATGCAGGCAGGATGAG[CG[G[CG[GTCCCTT[CG[C[CG[CCACC[CG[GAGAA

C[CG[[CG[GCTGGTGCCCTTGAAGGCCCTGGGATGCCTGGGTTGGGTGGGTGAGTGAA[CG[AGAACCCTGAGTGAG

TGAGGGGAGGG[CG[GGTCCCCTCCTGGCTTCAAATTCAACCCAATCAGCT

SEQ ID NO: 566

CTC[G[[CG[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCCCAGATTTC[CG[GAGGAGCAGG[CG[GG[CG[GG

ACT[CG[AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCATCTGAAGAGGGCT[CG[GCAGG[CG[CC[CG[

GGGTCCTCAG[CG[[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[[GATCC[CG]AGTCCC[CG[GATCC[CG[GACCCAT

CCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCTCTCCTTC[CG[CAGA[CG[GTGTC[CG[GGAGCACTG

GAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCACCTT[CG[GTTCTCTGAGAGCTTCCTGGAGAACAGGGC[CG[GTGCA

CAGG[G[GG[CG[CTGTGCT[CG[CACCCC[CG[GGTCCTCCC[CG[AG[CG[CAGGC[CG[GGGACC[CG[A[CG[GGAGG

CA[G[G[CG[[CG[GGCACAT[CG[GAGGCTCT[CG[CTGCTGGGCACTCAGGT[CG[CCAGAGTC[CG[CAGC

SEQ ID NO: 567

GCT[G[[G[CCCCCCCC[G[CCCCT[G[[CG[GCTCCCCCACCCT[CG[[CG[TT[CG[GCAG[CG[CCAGGCTG[CG[C

TCTCCC[G[GTGCACACC[G[GC[CG[[CG[C[CG[AGAACTAAATC[CG[[CG[GGCTGAAATTA[CG[TTTTAAAAATTA

ACATGTTGAAG[CG[[TGTGCCATTTAGTGAGAGGTGTTTTGGGCAAAGAATCAATTTAACTGTGACTGAC[CG[A[C

G[GGCTTGACTGTATTAATTCTGCTAC[CG[[AAAAAAAAAAAAAAAAAAAAGCAATGAGC[CG[CAAGCCTTGGAC

T[G[CAGAGCTG[G[GTGCC[G[TC[CG[[AGAGCCCCACCAG[CG[[CG[GCTCA[CG[CCTCAGTCT[CG[C[CG[CCC

CAAGGTGGGATC[CG[A[CG[CCCAAAGGAGGG[CG[CCCCAAGGTGGGATC[CG]AG[CG[GGC[CG[CCCTAGGAGGA

GTGAACCC[CG[CC[CG[GG[CG[CACAGCTC[CG[TG[CG[CCTGTCCTCCCTCCTCCAG[CG[AAATCACACC[CG[CTTT

GCCTCCTCTTGCAGCAC[CG[[CG[[CG[TGCCTAGGTTCT[CG[GTCTG[CG[CAGCTGGGAGTCTCCCCCACCAG[CG[C[

CG[[CG[GAGC[CG[CC[CG[CTTC[CG[CTCCCTCTTTC[CG[[CG[GGTTTGAGCCTCC

SEQ ID NO: 568

CACACACATGCACACATTTTCT[CG[[CG[CTCTCTC[CG[GCTCTCCTTTGTTTATTTTCTAATCTATATTTTTACTGGA

AGATTTCCTCTTTATTCTCTCC[[CG[CCCTCCTACAAG[CG[CTCTTGCTGGC[CG[TCTGGGTGCACACAC[CG[CTCC

CT[CG[ATCACCCCAGCCCCCTTCCTGGTCTCC[CG[AG[CG[[CG[GGGTTTGAAGGTCACCTCCTTTCCAGTCCC[CG[T

G[CG[AGC[CG[[CG[CTGC[CG[C[CG[CCTCCTCCAGCCAGAGT[CG[GTGGGACTGGCTG[CG[CTGCCCTGAAGTGGT

TCTCCAAGCA[G[[G[GGGGGG[CG[GA[CG[G[CG[GA[CG[GAGCCCAGGGGC[CG[[CG[T[CG[GGTGGGG

AAACC[CG[AACT[CG[[CG[GAGGGGAATCCCTCCCCCTC[CG[CCCCAGCCCCCCAGCAGCACC[CG[[CG[GTGGGG[

TC[CG[GGGCTGAAGAAGGAAGGAGTGAGC[CG[AGC[CG[AGCACCCCACATCTGGAGGGGACAGCCAGC[CG[TGG

GCC[G[CCC[G[G[CG[TC[CG[GAGCAGGAGAACTC[CG[AGCTTCTTGCCCA

SEQ ID NO: 569

GGGGGCTG[G[GCC[CG[GCC[CG[CAGCTCCT[CG[[CG[GC[CG[GCTGGGAAGTGG[CG[GGTC[CG[GCTAGTC[C

G[[G[GG[G[GG[G[GAG[CG[[CG[C[CG[T[CG[CTGCCAGTGTCCCCCTTTAACATTCCTTCCC[CG[AGCCTTTCCCT

GCTCCTC[G[CTCT[G[AGCC[G[GGG[CG[GCCC[CG[CAGACACCAG[CG[CCTCTATCCTG[CG[CTCCTTGG[CG[

TA[G[CAG[G[[G[AGGT[G[[G[[CG[GGAATGGG[CG[C[CG[AGGCCCTGCC[CG[CCAGGGC[CG[CATCT

G[CG[GCC[CG[AGACTTACTTCTGCTTTGCTTTCCTGCACCTGGCC[CG[GGGCAGGCTTTCTAGTTTCTGCCT[CG[[G

CCAGAGGAGC[CG[ACTTC[CG[CAGGA[CG[GGCTTGGGGCAGGGGGTGC[CG[GTGGGGGCAG[CG[GGG[CG[AGG[

CG]AGGT[CG[CAGGGAGA[CG[ACCAGGCCTGCTTGGGCCTGGGC[CG[CTCCAGC[CG[CCT[CG[CCTCTTCAGGGAC

CT[CG[CCC[CG[GGACCACC[CG]AG[CG[GACCCACAGCTTCTGAGGAAACAGCTGCCT[CG[GGCCT

SEQ ID NO: 570

TCC[G[[G[GACCC[G[[G[CCCT[CG[[CG[CTCCC[CG[GCCCTGGC[CG[GGGTCTCCTCCC[CG[CTG[CG[C

CC[CG[C[CG[ATGC[CG[GCCCCCTGGTGGCCTCTGGCCCTCTGGGACCCAG[CG[CAC[CG[[CG[AGGGAGGCTC[CG

GGCT[G[CACCAAGGGAAG[G[GAAG[G[AGGGG[G[G[CG[C[CG[GAGCCAGGCATGTCC[CG[CTGCC

CAG[G[[G[GGGCTGAGGG[G[CAGA[G[GGGAC[CG[[CG[[CG[AGC[CG[CTCTCTACCTGGCCTCCT[CG[GAGTC

G[CG[GATTTCTGTTGCACAAATGGGCCAAACAGGTT[CG[TAAGGCCCC[CG[[CG[GGTCCCCTGGCC[CG[GAAGTT

GAGC[CG[[CG[GGTGCCTGGTCTGAAGTTC[CG[[CG[CCCCACAGTGGCC[CG[[CG[GGCCT[CG[G[CG[GCTCCTGCC

CTA[[CG[[C

SEQ ID NO: 571

TGCTGAGGATGACAGGGAGC[CG[GGAGC[CG[GAGGATGGAGGATGGTGCAGGCTGGGGAGATGC[CG[GTACCTT

TCCCTGGGTCATGGTGC[[CG[[TCTCT[CG[GGGAAGGGGTCCCTGAGGCC[CG[GGTGGC[CG[CTTGGGTAAC[CG[

CAGCCTGCCTG[CG[TCTCTTCCTTCCTC[CG[[CG[TGGGTTCTAGCAACATCCACTGCAGC[CG[GGCCAGG[CG]AGC[

CG[[G[[CG[TACCAT[CG[G[CG[[CG[GGGGGAGGAGAGGGC[CG[GGCCTGGGAAGATGCTG[CG[GAGGA[CG[CT

[G[GATT[G[[G[AGCC[G[GGGTAGG[G[[G[G[CG[CAC[CG[CCCCCTCC[CG[C[CG[CTTCCCCCCCAC

CC[CG[CCCCCCAC[CG[C[CG[CCCTTAGCCCTCCCC[CG[GGATGAGAGAGAGT[CG[[CG[CTG[CG[GAGCAACCCCA

GTGGATGGGTC[CG[[CG[GGGGCTGAG[CG[GG[CG[GAGGA[CG[[CG[GGAACTC[CG[[TGACAC[CG[ACCAGCTGA[

CG]CTGCC[CG[[CG[TGAAACCAGAGC[CG[GGCATCAGGGCCTCATCTCCACTGTCTCTGCACCTCTCTGCAGCTCC

AGCTG[CG[CCTCTGCCTTTTCCTCCTCCCTCTTTGGATG[CG[GCCCTGATTTCTGTCTC

SEQ ID NO: 572

TTCCTCCTTCAAAACCAAACCAAACCACCACCAACAAAAACTTCTGTGCTACTCTGGCTTCTCTGGTTTTGTTTGGG

AACAGTGGAACCAAGTTAGCC[CG[GGCCAGGG[CG[CAGATGATGGACTCAGAG[CG[CCCAGGGACCCTAGAGAG

AGGAGCACTCCTCAAGAGCCCCCTGGCCATCACC[CG[AG[CG[CCCTGGAG[CG[CCATCACC[CG[AA[CG[[CG[[CG[

CTCCAGGCCCT[CG[AACAAGGCCTCTGGCTGCCAGAG[CG[AGTGAGGGG[CG[[CAGAGG[CG[GCAGAGAG[CG[G

A[G[GCA[G[GCCAG[CG[CAGACA[CG[C[CG[[CG[GGGTCT[CG[GGC[CG[GAGC[CG[TGCAGC[CG[GGCC[CG[CTG

CCTCTTTGCCCCTCATGGCTC[CG[[CG[[CG[GGAGGAAAC[CG[GGCCTTCTC[CG[CC[CG[CCCTCCTCT[CG[CTG[CG

GTGTCCCCAGCACCCC[G[[G[[G[[G[[G[GTCCCCAC[CG[T[CG[[CG[CTCCCCTCCCTCCT[CG[CC

CT[CG[CTC[CG[[CG[CCTCCTGTTGGCAGAGATGGCCT[CG[AAGGCCTCTTCCAATTTGAA

SEQ ID NO: 573

GGGG[CG[CAGAGCTCTTGAGGT[CG[TGGG[CG[GG[CG[CAGGGCCC[CG[G[CG[GATACTTGGCAGAGGCTTGGGGT

CTGGGC[CG[GG[CG[GAGGAGACCCCCAGCCTGGGTTGAG[CG[GGG[CG[GATCTGGGACTC[CG]AGGCTTCCTA[C

G[TGGGG[CG[GGTTCCCAG[CG[GA[CG[CCTCTGC[CG[CACCCCTGG[CG[GGGACCCAGCTG[CG[CCCCTTCC[CG[[

CG[GCCCTCCTAGGGCCTGGGTGCTTGGAGGCT[[CG[AGGCCCCAAGATCCATGT[CG[CC[CG[GAATCC[CG[GTG

CCTAGGCCTTGT[CG[[CG[GGCCCTGGGACCAACT[CG[[CG[GGGGTCAGGAGCTGGGGGTTGAGAGAAAGATGATC

AGGTGGGTTGGAGAAAGGAGA[CG[CTTCC[CG[CTGGG[CG]AGTGAGCCCAGGA[CG[[CG[GCAGAAGAGGGCAGA

CG[CCTCAGTCTCCC[CG[CCTC[CG[CCTCCCCACCCATAGTGTCACTC[CG[ACCCTAGCCCT

SEQ ID NO: 574

GGGGATCCAGGAGGGAAAGCC[CG[CAGG[CG[CAGAGGGGACAATC[CG[GGAAGTGGTAAAGGGGACACC[CG[G

GCACAGGGCCTGTGCTTT[CG[TTGCAGG[CG]AGGAAGTGGAG[CG[[CG[[CG[CTGCAGATTCAG[CG[[CG[GGGCT

AGAGGAGGGGACCTGGATCCCTGAACCC[CG[GGG[CG[GAAAGGGAGCCTC[CG[GG[CG[GCTGTGGGTGC[CG[[CG

[CTCCT[CG[GAGCCAGCAGCTGCTGGGG[CG[G[CG[TC[CG[AACTCCCCAGGTCTG[CG[CA[CG[GCAATGGGGGCA

C[CG[GGCCTTCTGTCTGTCCTCAGAATA[CG[[TAGGATACC[CG[[CG[GG[CG[ACAAGC[CG[GGCCAGGCTAGGAG

CCTCCTTCCCTGCCCCTCCCCAT[CG[GC[CG[[CG[GGAGGCTTTCTTGGGG[CG[TCCCCA[CG[ACCACCCCCTTCTCA

CC[CG[GTCCCCAGTTTGGAAAAAGG[CG[CAAGAAG[CG[GGCTTTTCAGGGACCC[CG[GGGAGAACA[CG[AGGGC

TC[CG[A[CG[[CG[GGAGAAGGATTGAAG[CG[TGCAGAGG[CG[[CCCCAAATTG[CG[ACAATTTACTGGGATCCTT

TTGTGGGGAAAGGAGGCTTAGAGGCTCAAGCTATAGGCTGTCCTAGAGCAA

SEQ ID NO: 575

GACCCT[[CG[[TAGTGTGGGGAATTTCCTGGGAGGAAGATACTA[CG[[CG[GGGC[CG[GGAGCAGAATTTGCTCCA

GGCACTGGGCCAGTCCATGAGGGCTCCAGGATCCAGGGGCCCCACTCCCTTCT[CG[C[CG[GGCTC[CG[GGCCAA

GGAAG[CG[[CG[GC[CG[GAGTCC[CG[GGAAGCCCCT[CG[GCAGCCAGCCAAGGGCCCTG[CG]AGGATGTGGATGG[

G]AGC[CG[GGATAAGGGGCCCCTT[CG[GCT[CG[[GTTGACCCAGGTCAGATCCTCC[CG[C[CG[ACCTT[CG[GCC[C

G[CCCTCTACAGG[CG[GCCCAGTTCTTCCCCTGCT[CG[GCTGCCCCTGCC[CG[CCCCT[CG[AGGGAG[CG[CC[CG[[T

AGCCAG[CG[CCCC[CG[TAAAGAAATAAGGAGG[CG[CC[CG[GCTTCC[CG[CCCAGGTA[CG[TGT[CG[GGACAG[CG[

TCCTTGGACCC[CG[GGGCTTGCAGGG[CG[GGCC[CG[GGGCTCTCTGAG[CG[[CG[AGGCTGC[CG[

SEQ ID NO: 576

AGGT[CG[AATGAAGAGGGTTGTGTGAGTTTTG[CG[[CG[GGCAGG[CG[GGATAA[CG[GAGGAGGGAGGCC[CG[[CG

GCCC[CG[CCCCCT[CG[GC[CG[GCTGTG[CG[[CG[CTGATTGGCCCCTGC[CG[GCCT[CG[[CG[CTCCCT[CG[CTC[CG[

GGTTGG[CG[GGAGACCTTAGAG[CG[GGTAC[CG[CTGCTGGCTAG[CG[AC[CG[A[CG[AGCAAC[CG[TCTGAGGCC

AGGAG[CG[CTG[CG[A[CG[GAGCCTTGAC[CG[C[CG[TTGCC[CG[GCCCTCTCC[CG[[CG[CAGCCC[CG[GGCTTC[C

G[CAGGTACCTGTGCT[CG[CCCC[CG[GGAAGGGGCCT[CG[CAGG[CG[AATCTCCAGTTT[CG[AGTGTGCC[CG[GTC

CCTGGGTT[G[CT[G[[G[[CG[ACCCCAC[CG[CC[CG[CCTTAGATGAGAAGGCAG[CG[CTCCAGCCT[CG[TCC

TCA[G[[G[CT[G[GGG[G[CCCTAGCTGCTT[G[[CG[G[CG[A[CG[ACACA[CG[[CG[CTCCC[CG[CAG[

CG[GGCTCTGGGCTGAGGGACCTGG[CG[AGGGAGGCAGTGGC[CG[[[CG[CAGGTTGGGGCTTTGGC[CG[CCCTC

SEQ ID NO: 577

ACCTCCTCTCCCTCCCAGC[CG[[CG[A[CG[[CG[CAGGGGG[CG[GGCTCTACCTCCCCCT[CG[CCCC[CG[CTT[CG[GT

TTTAAGC[CG[[CG[GAGG[CG[CC[CG[GTGGGACCT[CG[CTGCTGTCCAATCAGGGGGGAC[CG[GGTGAGCTCCTCT

TCCTGGAGC[CG[GGCTCCACCAG[CG[C[CG[CAGGCTCACAGGC[CG[GGGGTGGGGGCTCTGGAC[CG[AGGGG[

TCC[G[[G[[G[CTC[G[GC[CG[CCC[CG[GGGATTC[CG[CCACCAAA[CG[CA[CG[[CG[TCCCAGGTGG

GCACC[CG[CCT[CG[GTC[CG[TCTTTGAGTCTGACCCTAG[CG[CAAGAGTCCCTGG[CG[ACA[CG[CAGGGGCCAGA

G[G[GGGGGG[CG[[CG[C[CG[CAATAGCAGCAG[CG[CCAG[CG[CCAACACCCTGTCC[CG[CTGAGGGGC[CG[CTT[

CG[GGT[G[GGGTAGGGT[G[TGGG[CG[CTCTGGTGCAGC[CG[[CG[G[CG[CAG[CG[TGTACC[CG[GAGCC[CG[C

ACACTCCCTGCT[CG[GGG[CG[CCCTGTGGCCAGGCTTGAGGGGCAGAGTGAGAGGGAGTTTCTAGAACCTGTTG

SEQ ID NO: 578

CC[CG[GGCCCACCC[CG[CACAGG[CG[CTCAGAATGTT[CG[ATA[CG[TG[CG[CCTCCTTACACCCCTGCCTCACCAG

GC[CG[AGCTCATGGAAATC[CG[TGGGCTT[CG[ACCCTC[CG[C[CG[CA[CG[TTGTCCCTTCACACTGGTCCTATAGA

GC[CG[[ATCCTAATTCCCATGGCCTGACAGTACAAC[CG[CATGGAGATGCA[[CG[[TCTCTAAGA[CG[CCTCACCAC

TGCCTAAGAAGCAATCAAGGTGA[CG[[CG[[CCCAC[CG[GAAA[CG[[GAAGTAGT[CG[ACT[CG]AGGTGTGGGACT

ACCTTTCCCAGAACCCTC[CG[CAG[CG[CAGTC[CG[ATCCTAGGGG[CG[ATGGTGT[CG[TAAATG[CG[[CG[TCC

ACCT[G[AGTCA[G[CCCACT[G[AGG[CG[[G[CG[[GGAGG[CG[[GCATGCAAGGTGTTTCTGAGTTGAAAAGA

ATGTCTTTACTCAGTACTAACATATT[CG[[CG[TTGTAGCAAACCTGACTATATTCTCAAACAAGCCCATCATCCCA

TCACCAGGGATATAAAGCATTATTGATTTTCTGGTGTAAAAGCCAACTAAATATTTATTTCAAAAGTAGTTCATAT

TACATGTAAAGAATGGTTTAAAAAAAATTCTTACTTAATCC

SEQ ID NO: 579

ATGACTGTTCTCCCACACCC[CG[TTGAGGGGACTGGT[CG[AGATCTACCTTGGGAGAAGCAAAAACCTCAACAAA

ATCTGCAGAGCAGGAACTAAGTTGTAATACAACCATAAAAGGCAACAAAAAG[CG[GAAGA[CG[GGAGAACCCA[

CG[CAGGAA[CG[GCTCCAGGCAACCC[CG[GCTCACTGCCCATTCATTTTGGC[CG[ACTTTGGAGGTGCCTTCA[CG[

TCTCCTGCCAATTTGCAGCACACTGGCCCAGTCAGTCAGGTTTGGGGGTTCACAAGCCCCCATTGC[CG[G[CG[AGG

GGTGA[G[GATG[CG[CA[CG[AT[CG[G[CG[TTCCCCCCACCAACAGGAAAG[CG[AACTGCATGTGTGAGC[CG]AG

TCCTGGGTGCA[G[TCCCACAGCTCAGGGAAT[G[[G[[G[[CG[[CG[[CG[GGGACT[CG[CTC[CG[TTCCTCTTCC

TG[CG[GCCTGAAAGGCCTGAACCT[CG[CCCT[CG[CCCC[CG[AGAGACC[CG[[CG[GCTGACAGAGCCCAACTCTT[C

G][CG[GTGGCAGTGGGTGCCTC[CG[GAGAAGCCC[CG[GGC[CG[AC[CG[[CG[GCCTCCAGG[CG[GGGTT[CG[GGGG

CTGGGCAGG[CG[ACC[CG[C[CG[CAGGTCCC[CG[GGAGGGG[CG[AA

SEQ ID NO: 580

GG[G[TACT[G[[G[CCTTGTA[G[GCCACTG[G[AG[CG[[CG[TCCCAC[CG[T[CG[GAGCTGCCTGGACTCAGG

GACTTGGAAGC[CG[AGTCTTCCCCTCCCCTCAGGCAGAAGC[CG[A[CG[CCAACCC[CG[AAACCCAGCAGTGCA[C

G][CG[AGCTAG[CG[GTGA[CG[ACCACCC[CG]AGCAACTGG[CG[ACCCC[CG[GGGCCCTGGGACCAGCTA[CG[CCT

GC[CG[CCCTGGCT[CG[TGC[CG[CTGCACTA[CG[ATCTGGAGCTGTGGC[CG[CAGCTGAGGCC[CG[A[CG[AGCTTC[

CG[GC[CG[GGTCTTTGCCCTTCACTGGC[CG[[CG[[TGAACATCA[CG[GTG[CG[CTGCA[CG[GTGGCCACCTCT[CG

]ACTGCTGCTGCATAGCCTCTTCCAGGACTG[CG[AG[CG[[CG[C[CG[AGGTG[CG[GGGACCCCTTTCCC[CG[GGCAC

TGGGAA[CG[CCACAGTGGGC[CG[[CG[TGCC[CG[TGGA[CG[A[CG[TGTGGTT[CG[[CG[CTGGACA[CG[GAATACAT

GGTGCTGGAGCTCAGTGAGCCCCTGAAACCTGGTAGCAGCTA[[CG[]AGCTGCAGCTTAGCTTCT[CG[GGCCTGGT

GAAGGAAGACCTCAGGGAGGGACTCTTCCTCAA[CG[TCTACAC[CG[ACCAGGG[CG[A

SEQ ID NO: 581

CCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTCCTCCTTTAGGC

CAACTACAG[CG[CAGAGGAG[CG[[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCTGCAGC[CG[GTCCT

CTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGTGCTGCTGG[CG[[GTG[[

CG[[CG[[ACC[CG[[CG[[CCTGCACA[[CG[[CCCATGTACTACTTCCTCTGCCACCTGGCCTTGGTAGA[CG[[CG[GGC

TTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCTGGCTGC[CG[[CG[[

CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCTCCTGG[CG[GT

GATGGTCTGGAC[G[[G[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[

CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GTTG[CG[CAAAC[CG

[G[CTCCTGGCTGAG[G[GC[G[CTGTG[G[[CG[[CCC[CG[CCTGCTGGACCACTTCATCT

SEQ ID NO: 582

AAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTCCTC

CTTTAGGCCAACTACAG[CG[[CAGAGGAG[CG[[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCTGCAGC[

CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGTGCTGCTGG[

[G[GTG[G[[CG[[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGCCTTGGTAGA[C

G][CG[GGCTTCACTACTAG[CG[[TGGTGC[CG[[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCTGGCTG

C[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCTCC

TGG[G[GTGATGGCTCTGGA[G[[G[[G[GC[G[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG]GGGCT[CG[TC

TCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTCACCAACT[CG[GTTG[CG[

SEQ ID NO: 583

CCAAACATTCTGGGAGTTTTCCTCCTTTAGGCCAACTACAG[[CG[[CAGAGGAG[[CG[[CTTTCTCCTGCTGGGTTTC

TC[CG[ACTGGCCTTCCCTGCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGC

AACT[G[[G[CTGGTGTGTGG[G[GTG[G[[CG[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTC

CTCTGCCACCTGGCCTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[[TGGTGC[[CG[[C[CG[CTGCTGGCCAACCTG

[CG[[CG[GACCAG[CG[CTCTGGCTGC[CG[[CG[[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTG

G[CTG[CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[[CCTCCTGGCTAA

G[[CCTGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[[GA

SEQ ID NO: 584

GTTCCTCCAAAG[CG[[GTATCATTACAGATTAACTGTAATGTGTAGGATTAGAATAAAAGCATAAGGGATTAGGT

AAAAGGG[CG[A[CG[CTCCAGACATAA[CG[CC[CG[AG[CG[CATCT[CG[ACTGAGTCAGCCTAGGGAGACTG[CG[A

AGG[CG[CAGGGTGT[CG[GGG[CG[CCA[CG[GGGC[CG[CAAAGC[CG[GACT[CG[GTTCCTC[CG[CTCC[CG[GCCCTG

GCC[G[GCCCCAGAG[G[GT[G[GGACAG[G[G[CG[C[CG[GAAGGCCAA[CG[[CG[GC[CG[AAGGTTT[CG[GAG

CCAGGCTTCC[CG[GG[CG[TCAGGGGCTAGGGA[CG[[GGTCCC[CG[GAGCTGGGGAAGATGAGGGGC[CG[AGAGG

G[GGA[G[[G[GTCTC[G[[G[GGG[CG[AAG[CG[CAGGGAAGG[CG[G[CG[AGGGGGTCCCCACACC[CG[CA[C

G]GGGCAC[CG[GGTTTGTCCATGTGGGTGACACTGCCTTCAAGGCCCAGGCC[[CG[[ATGGGGCCCTTCCTGG[CG[T

CCTCCTCACCCCCACTC[CG[C[CG[[CG[CCTCCCCTGTCCAGCTGGGGCTGGGGACAG[CG[GCAGGGG

SEQ ID NO: 585

GT[G[TCTGCAT[G[[G[[G[AAG[G[[G[[G[TC[G[[CG[C[CG[GTGCC[CG[CAG[CG[[CG[CA

G[GGCAGGA[CG[GG[CG[[CG[G[CG[GGTGGGGCCTGGC[CG[TCTCCCCCTGCCCT[CG[GGGC[CG[AACA[CG[CACA

G[CG[AGAGTCTAG[CG[T[CG[G[CG[TGGCTG[CG[GCCAGC[CG[GGTCCCCCTGGAGGCCTC[CG[GA[CG[AT[CG[GA

AGTGACTGAG[CG[TC[CG[GGTC[CG[TGAGGC[CG[GGGGT[CG[[GCC[CG[CCCTAAGACTCCCACCTGGTCC[CG[

GTTCTC[CG[TC[CG[CTAGGCTGGC[CG[[CG[GGGCCCCTGGGGCC[CG[ACCTTCC[CG[GGGTGCCCCAACCTG[CG[G

CAAGGC[CG]AGGTCC[CG[CTGAGGCATGAGTCC[CG[GGT[CG[GGGAC[CG[CTCTGGGC[CG[ACCCC[CG[GAGGA[

CG[GACTAGGC[CG[ATCCCCAGAGGGAAGGGGGCCAGGC[CG]AGGCCATGGCAG[CG[[CG[TTCCCTGATCC[CG[T

GTTCT[CG[GCTCCT[CG[[CG[TCCCACTAT[CG[GCTGTCCCTTT[CG[TG[CG[GGACTGA[CG[GCTCACAGAACAGTT

SEQ ID NO: 586

[[CG[CAGCAACTTGGC[CG[C[CG[GGTCC[CG[GC[CG[CCC[CG[GTAGAGGCTGGGTACAG[CG[AGGGGGC[CG[GG[C

GCC[G[GGCAGGA[CG[GG[CG[[CG[G[CG[GGTGGGGCCTGGC[CG[TCTCCCCCTGCCCT[CG[GGGC[CG[AACA[CG

[CACAG[CG[AGAGTCTAG[CG[T[CG[G[CG[TGGCTG[CG[GCCAGC[CG[GGTCCCCCTGGAGGCCTC[CG[GA[CG[AT[

G[GAAGTACTGAG[G[TC[G[GGT[G[TGAGGC[G[GGGGT[CG[GCC[CG[CCCTAAGACTCCCACCTGGTC

C[CG[GTTCTC[CG[TC[CG[CTAGGCTGGC[CG[[CG[GGGCCCCTGGGGCC[CG[ACCTTCC[CG[GGGTGCCCCAACCTG

[CG[GCAAGGC[CG[AGGTCC[CG[CTGAGGCATGAGTCC[CG[GGT[CG[GGGAC[CG[CTCTGGGC[CG]ACCCC[CG[GA

GGA[CG[GACTAGGC[CG[ATCCCCAGAGGGAAGGGGGCCAGGC[CG]AGGCCATGGCAG[CG[[CG[TTCCCTGATCC[

CG|TGTTCT[CG[GCTCCT[CG[[CG[TCCCACTAT[CG[GCTGTCCCTTT[CG[TG[CG[GGACTGA[CG[GCTCACAGAA

SEQ ID NO: 587

A[CG[GCCT[CG[CACAGCCAGGGGTG[CG[CACTCACCTT[CG[TACT[CG[GGGG[CG[GG[CG[C[CG[GGGCTGG[CG[G

[G[GGGGGGCT[G[GAGCCTTCCT[G[GG[G[CTTGGGGCAGG[G[GGC[CG[[CG[[CG[CCCAGCCTCCTATCC[

CG[CTCCTT[G[[G[CCC[G[GG[CG[CCC[CG[CTC[CG[C[CG[GGAAGGTGC[CG[AGGATCC[CG[T[CG[TCCTTGGT

AAACCCCAGGATGGCCT[CG[[ATGCTGTGAAGT[CG[[CG]AGGTGCTCC[CG[CC[CG[GGCTG[CG[GAGCAGGTGGC

[CG[GCAAG[CG]AGAAGCTCC[CG[T[CG[GCCATGGCTGG[CG[[CG[CAGCC[CG[GCAGGTGCATGGGGAG[CG[C[C

G[GGAGG[CG[GGAGGG[CG[CTTTGGAGA[CG[GAGAGGAGAGGCT[CG[AAGC[CG[GGTCTTCC[CG[AGTG[CG[G[

CG[GTGCAACC[G[A[G[GGTCC[CG[ACCCTAGGTCAAGCTC[G[[CG[GG[CG[AAGCC[CG[CC[CG[GGCTG[CG[C

A[CG[CTGGGGGTGGC[CG[AG[CG[CTCAGCC[CG[CTGC[CG[CCTTAGTCCCAGAAGT[CG[GAAGTT[CG[GGCT[CG[

GGGTAGCTGGGGCTCT[CG[G[[CG[[CTAAAGG[CG[GGGAGCCAACTGGCCCT[CG[GCTCCTCCCCTCT[CG[CCCT

GGAC

SEQ ID NO: 588

GA[CG[AGAAAGTCTCAACAGTCTGCTAAACTAACA[CG[GCCTT[CG[AATCCCAATCTGAACACAGTAGCTGAAA

CAAGCTGTCCACAAAGAGGAAAGCCAGAGGGGGCCAATTAGGAAGGAAGAAATTAAAGAAAAGAGAAAAGCCA

AGATGAAAGGTCCAG[CG[CAAAGTGAATGACT[CG[ACTGGAGAATGGCAGCCCTGGCAGGGTCTG[CG[GC[CG[G

CTG[G[GAGGGGGGA[G[[G[GC[G[[CG[[CG[GA[CG]AGTGACAGGTTGGTC[CG[G[CG[CAGCAAAGGGAG[

GGGG[G[[G[GTAGGGCCTCT[G[GGGGCAG[CG[[CG[AGGGCCTCCCC[CG[GGGCAG[CG[[CG[GGC

CAAGG[CG[GGGCCTCCAGAG[CG[GGGGCAGCAGAGGAGGGAG[CG[GAA[CG[GGAGC[CG[GG[CG[GAGG[CG[GC

[CG[GC[CG[[CG[CTC[CG[GGCTTCTCTTTTCCCTC[CG[A[CG[[CG[CCA[CG[GCTGCCCAGACATTC[CG[GCTGC[CG[

GGTCTGGAGAGCTCCC[CG[AACCCCTC[CG[[CG[GAGAGGAG[CG[AGG[CG[G[CG[CCAGGGTGGCCCC

SEQ ID NO: 589

TCTCCTTCAACATTTTGAGCATACTGGAATGCCAACCCCCTAGGTAGGTGCCAGGGCCACCACAGGAACCTGACT[[

CG[[CAGGAGT[CG[TCCTC[CG[TCTCTA[CG[[CG]AAG[CG[CCCCCT[CG[AGGTGGGCAGGGGGTGG[CG[G[CG[G[

CG[A[G[GTGG[CG[GAGC[CG[CAGAG[CG]AGCTAGAGAG[CG[AGAG[CG[[GTGAGACTCTG[CG[GA[CG[[TCTTC

ATG[G[CCTCAAGAACCAGGTAGAAG[G[CCT[G[G[CG[CAGGCCC[CG[CACCCC[CG[ACTCTGCC[CG[CCCTC

TGTTA[CG[GACACC[CG[CTGGGCCA[CG[TGGT[CG[[CG[ACTGGCTTCTCCCAG[CG[GCCAGCCTGGCCACCC[CG[

ACTCCCAGGGAGGGGGAGAGGGCCCTTGCAAGAGGATCCTGCCCC[CG[[CG[CTGCCCAGACCTGAGGGCTCCTGG

[CG[ACCCCACC[CG[CAGCCCATCTGG[CG[GCTCTGGCCC[CG[CAGGTCAGGGTCACACCCCTGC[CG[GCCTCCTGA

GACTTCC[CG[GCCCCAGGGGAGAGAGCTGAAACTTGGGTTGA[CG[[CG[[CG[CCCCCTC

SEQ ID NO: 590

AGGGTCC[CG[ACTTCTAGCCCCCAATTTCTTGCCCACATCAC[CG[CCCCCTGC[CG[[CG[TTTAG[CG[GCTG[CG[TA

GGCCTGCTCAC[CG[G[CG[[TGCCTCAGCCCTCTCAG[CG[TACAGCATGAGCTGGCTGAAGCAGCCCCAAAAGGGG

CAG[CG[[TGTGAGCAGCAC[CG[AACCCAACTGCATGATCAGCTGCAACATCCAC[CG[TCT[CG[AACCTATCTT[CG[

A[[CG[CCATCTTGGGAAAGGGCAGTC[CG[CTG[CG[GCCTCACCCCAGTCAGAGAAGCAGG[CG[[[CG[GGGATGG

GACA[CG[CAGCTTC[CG[GGTCAAG[CG[[CTTTTTCTTTTTCCTCC[CG[GAAACAA[[CG[[GTGTCATTCTCTAGTTC[[

CG[[GATCTAAGGTGACCCAGTTG[CG[AAGTCCAGCCTTCT[[CG[[TCTGCTCATGGAGCCTTCAGGGCCATATTTG

TCCCTG[CG[AATTTGAAAACTAGACTAGAGGAAGGAACAGTGGGTTCAGGATAGCAGAAGTCTTGGAC[CG[[TAG

TATGATGTATTGAAGCAAACTGGTCTTTGAATGCAGCC[CG[[ATCAGGGCCCTAATCCTGATTCCAACCCTGTGTG

ATTCTGGGCACATCACCTAAACTTTATGAGACTCAT

SEQ ID NO: 591

CCTCCCAGGGAGGTCCCAATTCCTCCCAGTTCAAGGGTCC[CG[ACTTCTAGCCCCCAATTTCTTGCCCACATCAC[C

G]CCCCCTGC[CG[[CG[TTTAG[CG[GCTG[CG[TAGGCCTGCTCAC[CG[G[[CG[TGCCTCAGCCCTCTCAG[CG[TACA

GCATGAGCTGGCTGAAGCAGCCCCAAAAGGGGCAG[CG[TGTGAGCAGCAC[CG[AACCCAACTGCATGATCAGC

TGCAACATCCAC[CG[TCT[CG[AACCTATCTT[CG[A[CG[CCATCTTGGGAAAGGGCAGTC[CG[CTG[CG[GCCTCAC

CCCAGTCAGAGAAGCAGG[CG[[[CG[GGGATGGGACA[CG[CAGCTTC[CG[GGTCAAG[[CG[CTTTTTCTTTTTCCTC

C[CG[GAAACAA[[CG[[GTGTCATTCTCTAGTTC[CG[[GATCTAAGGTGACCCAGTTG[CG[[AAGTCCAGCCTTCT[C

G[[TCTGCTCATGGAGCCTTCAGGGCCATATTTGTCCCTG[CG[AATTTGAAAACTAGACTAGAGGAAGGAACAGTG

GGTTCAGGATAGCAGAAGTCTTGGAC[CG[[TAGTATGATGTATTGAAGCAAACTGGTCTTTGAATGCAGCC[[CG[[

ATCAGGGCCCTAATCCTGATTCCAACCCTGTGTGATT

SEQ ID NO: 592

GTCTGGCATTTTGCTGATGGTATCTGGGTGAGGGAGAAAGG[CG[TGTTGTTGG[CG[T[CG[GGGAAGGGGCCTCCC

CAATTGCCAAGGGGGTCCCTGGGGG[CG[G[CG[GGAAGGGGGGTAG[CG[GCCTCAGGGTCTTGGGGGTGCTGAGG

GGCAGAAAGGGGCAAAGGAG[CG[TGGAGGAG[CG[GAAGT[CG[AGAGTGGGACAGAAGTGGAG[CG[CTGGG[CG[

GCAA[CG[AGGAAACTAAAGCCACAGAAGCC[CG[G[CG[CAGGG[CG[GGAAG[CG[TGGGAAGGCCCCTTCCTT[CG

[G[[G[AGGTGCCCCCCT[G[CC[CG[AAA[CG[C[CG[GCCCAGGCC[CG[CCTC[CG[GCTCCCAGGC[CG[TCAC

CTCCTCCCCCC[G[C[CG[[CG[GGTCATCCACTGG[CG[TC[CG[CT[CG[GTGGGCCT[CG[[CG[GCCTGG[CG[GCCTG

GAG[G[TACCA[G[[G[[G[GAG[G[G[CG[GGTTGGGG[CG[T[CG[CA[CG[GTGAGAAAGGC[CG[GGGCCTGA

GAAAAA[G[[G[[G[GT[CG[C[CG[GGGCAA[CG[GGA[CG[GGGCA[CG[TGCCCCCCC[CG[CCAGAGC[CG[

GAAG[CG[GCAGGCT[CG[TG[CG[TCCCTCCTGAGCT[CG[AAGCCAACCAGGCCT[CG[AG[CG[GCT[CG[CTGC

SEQ ID NO: 593

GGGCACACTCTCCTTGA[CG[TCTGGCATTTTGCTGATGGTATCTGGGTGAGGGAGAAAGG[CG[TGTTGTTGG[CG[T

[CG[GGGAAGGGGCCTCCCCAATTGCCAAGGGGGTCCCTGGGGG[CG[G[CG[GGAAGGGGGGTAG[CG[GCCTCAGG

GTCTTGGGGGTGCTGAGGGGCAGAAAGGGGCAAAGGAG[CG[TGGAGGAG[CG[GAAGT[CG[AGAGTGGGACAGA

AGTGGAG[CG[CTGGG[CG[GCAA[CG[AGGAAACTAAAGCCACAGAAGCC[CG[G[CG[[CAGGG[CG[GGAAG[CG[TG

GGAAGGCCCCTTCCTT[G[[G[[G[AGGTGCCCCCCT[G[CC[CG[AAA[CG[C[CG[GCCCAGGCC[CG[CCTC[C

G[GCTCCCAGGC[CG[TCACCTCCTCCTCCCC[CG[C[CG[[CG[GGTCATCCACTGG[CG[TC[CG[CT[CG[GTGGGCCT[C

G[[G[GCCTGG[G[GCCTGGAG[G[TACCAC[CG[[CG[G[CG[GAG[CG[G[CG[GGTTGGGG[CG[T[CG[CA[CG[GTGA

GAAAGGC[G[GGGCCTGAGAACAA[G[[G[[G[GT[CG[C[CG[GGGCAA[CG[GGA[CG[GGGCA[CG[TGCC

CCCCC[CG[CCAGAGC[CG[GAAG[CG[GCAGGCT[CG[TG[CG[TCCCTCCTGAGCT[CG[AAGCCAACCAGG

SEQ ID NO: 594

[G[GTGTTTCAGGCAGCTCTTGGG[G[[G[[CG[GGCT[CG[GGG[CG[GG[CG[C[CG[TGGAGGGCT[CG[GTCCC

AATTCTCT[CG[GGCT[CG[GTCCC[CG[CTCCTCTCT[CG[GGCTC[CG[TCTC[CG[CTTCTCTCT[CG[GGCTCAGG[CG[C[

CG[GCCCTGGGGGCCCCTTCTCCTCATC[CG[GGAGCA[CG[GG[CG[G[CG[T[CG[GCTC[CG[CTTCCTT[CG[GGACAC

TG[G[TTCTGGCC[CG[T[CG[[CG]AGCAGAGGG[CG[CCTCTGAGGTGG[CG[G[CG[GGGTCAGTCT[CG[GGGGGAGT

[CG[TGTCCCCCTCAGGGATGG[CG[GTGGGAAA[CG[GGCT[CG[[CG[A[CG[TCTT[CG[GGAGCACAGACCACCTCC

TC[CG[CCTTGTC[CG[TGGC[CG[GGGCACA[CG[GGCCTG[CG[GGGGG[CG[CCTCCCCATCCTGCTTTC[CG[C[CG[T[C

G[GGAC[CG[GGATT[CG[GGGGGCCCTC[CG[G[CG[GGGA[CG[GGGGCTCCA[CG[[CG[GAGAGTGGGGGC[CG[ACT[

CG[GGCT[CG[G[CG[AGCTC[CG[GGGTGGC[CG[GG[CG[GCTTGAGGGGTCCTCCC[CG[GGGA[CG[CCCCCCTCCTCC

A[CG[CTGGC[CG[TGAG[CG[[CG[GAGGAGTGCTGCAGG[CG[GG[CG[[CG[TCTGGCA[CG[GGCCCCTC[CG[GG

SEQ ID NO: 595

[CG[GTCTCCAGGG[CG[GAAAGGGGTGGAAGCTGACCCT[CG[CCCTTCCCTCCAG[CG[CTGGCTTCAGGTGTGCCTT

CTGCTACCTCCTGTACTG[CG[AACAGGGGCC[CG[C[CG[AGCTC[CG[[GGAGCCCCTAGAAGAGGAAGACTCCTCT

GGCCCCACTAGGTATCATC[CG[[CG[CTCTCC[CG[CTTTCCACCTG[CG[CCCT[CG[CTTGGGCCAATCTCTGC[CG[CA

[CG[TGTCCATCCCTGAACTGCA[CG[CTATCCTCCACCCC[CG[GGGGGTTCCTG[CG[CACTGAAAGAC[CG[TTCTC[C

GGCAGGTTTTGGGATC[G[[G[A[G[GCTGAC[G[[G[[CG[C[CG[CCCCCA[CG[CC[CG[GTTCCA[CG[ATGCT

G[CAGAGGCTTTTCCTG[CG[[CG[TT[CG[GCCC[CG[GGAAAGGGG[CG[GGAGGGCTGGCTC[CG[GGAG[CG[CA[CG[

GG[CG[[CG[G[CG[GGGAGGGTACTCACTGTGAAGCA[CG[CTG[CG[CCCATGGATCATGTCTGTG[CG[[TTACACCA

GAGGCTC[CG[GGCTCCACTAATTCCATTTAGAGA[CG[GGAAGACTTCCAGTGG[CG[G

SEQ ID NO: 596

[CG[GAGCAACCA[CG[AGGAGGAGGTGGC[CG[ACCTTCTGGCCCAGATCCAGGCAT[CG[CACATCA[CG[GTGGAG[

CG[CAAAGACTACCTGAAGACAGACATCT[CG[A[CG[G[CG[CTGAAGGAAATC[CG[CTCCCAGCT[CG[[AAAGCCA

CTCAGACCAGAATATGCACCAGGC[CG[AAGAGTGGTTCAAATGC[CG[CTA[CG[CCAAGCTCAC[CG[AGG[CG[GC[

CG]AGCAGAACAAGGAGGCCATC[CG[CTC[CG[CCAAGGAAGAGAT[CG[C[CG[AGTAC[CG[G[CG[CCAGCTGCAG

TCCAAGAGCAT[CG]AGCTAGAGT[CG[GTG[CG[[CG[GCACCAAGGAGTCCCTGGAG[CG[GCAGCTCAG[CG[AC

AT[CG[AGGAG[CG[CCACAACCA[CG[ACCTCAGCAGCTACCAGGTAGGAAC[CG[[CG[GCTG[CG[[CG[GCCAGCCT

[G[CCAG[G[CCAG[G[[G[[G[[CG[CCCC[CG[ACACTTGGGCT[CG[TGCCCAGG[CG[CCCTCTC[CG[C[CG[[

CG[CTCCCTGGGGC[G[CT[G[CTAGAGA[G[[CG[[CG[C[CG[CAGACCTAGGGTATTTG[CG[GATCAG[CG[TC

CT[CG[CCCATCTCATCCTCCACACTC[CG[CCCCCACCCACCTGCCCCAGCTGCTAAGGGTCTTGACC

SEQ ID NO: 597

[CG[TCTGTGGGGAGTAGCTAGGGGCCTGCC[CG[G[CG[GGGG[CG[CAGGAACC[CG[GTTG[CG[[GTGC[CG[GGAG

GAGGGT[CG[GGAGGGTCTCAGCCCCCTCCTTGCTCCCAGGCTTCCACTCCTTGAGGTATTTCCACACCACCATGTC

[G[[G[[G[[G[[G[GATCCC[G[CTTCCTCTC[G[TGGG[CG[A[CG[TGGA[CG[ACA[CG[CAGTG[CG[T

G[G[GCT[CG[ACAG[CG[A[CG[CCA[CG]AGTCCCAGGATGGAGC[CG[[CG[GG[CG[C[CG[TGGATGGAGCAGGAGG

GGC[CG[GAATATTGGGAAGAGGAGACAGGGAC[CG[[CCAAGGCCAAAGCACAGTTTTAC[CG[AGTGAACCTG[[

CG[[GACCCTGAG[CG[GCTACTACAACCAGAGTGAGGCCTGTGAGTGACAC[CG[[GC[CG[GGGG[CG[CAGGTCAC

TACCCCTCCACATCCCCCA[CG[GAC[CG[CC[CG[GGTCTCCC[CG[AGTCTCTGGGTC[CG]AGATCCA[CG[C[CG]AGG

CAG[CG[GGACCTGGAGACCCTTGACC[CG[[GGAGAGGCCCAGGAGC[CG[TTACC[CG[GTTTCATTTTCAGCCAAA

SEQ ID NO: 598

CCCTGTAGCAAAGCAGGGAACTGGACCTCAAAGGGCTGCTGGGGAAGA[CG[GGATCTGAATAGAGGTCTGAAGG

AAAGAAGCCAGG[CG[GGGGACCC[CG[GGAGGGC[CG[GA[CG[GGGCTGGGGGTGCTGTTGACACTGGAGC[CG[GA

CTGGAGACCTGGGAACCTGGGGCAGAGT[CG[GCAG[CG[GGGAGGGGG[CG[AC[CG]AGGTGGGAAAA[CG[GGG[C

G[GGGC[CG[GAGA[CG[ACTCCAGGGCTGGGTGAGG[CG[CTGACCCCCAGGAGCTGGGGTGC[[CG[AGGGG[CG[[[[

CCAGCCCC[G[CTGGGCC[G[[CG[CC[CG]AGCTCTCTGG[CG[CAG[CG[CTAGCTC[CG[C[CG[[CG[CTCAGCT

GCCCTG[CG[C[CG[GCACCCCTGGTCATGAG[CG[CCCCCT[CG[A[CG[CTGCCCCC[CG[GGGG[CG[AGGAAGGGCTG

GGGA[CG[GCCTGGCCCTCTGCAGCCAATGCCAGTAG[CG[CTC[CG[G[CG[GAGG[CG[GAGGAGG[CG[GTGG

SEQ ID NO: 599

GTAGCAAAGCAGGGAACTGGACCTCAAAGGGCTGCTGGGGAAGA[CG[GGATCTGAATAGAGGTCTGAAGGAAAG

AAGCCAGG[CG[GGGGACCC[CG[GGAGGGC[CG[GA[CG[GGGCTGGGGGTGCTGTTGACACTGGAGC[CG[GACTGG

AGACCTGGGAACCTGGGGCAGAGT[CG[GCAG[CG[GGGAGGGGG[CG[AC[CG]AGGTGGGAAAA[CG[GGG[CG[GG

GC[CG[GAGA[CG[ACTCCAGGGCTGGGTGAGG[CG[CTGACCCCCAGGAGCTGGGGTGC[CG[AGGGG[CG[[[[CG[[

AGCCCC[G[CCCTGGGCC[CG[C[CG[CC[CG]AGCTCTCTGG[CG[CAG[CG[CTAGCTC[CG[C[CG[[CG[CTCAGCTGCC

CTG[CG[C[CG[GCACCCCTGGTCATGAG[CG[CCCCCT[CG[A[CG[CTGCCCCC[CG[GGGG[CG[AGGAAGGGCTGGGG

A[CG[GCCTGGCCCTCTGCAGCCAATGCCAGTAG[G[CTC[CG[G[CG[GAGG[CG[GAGGAGG[CG[GTGG[CG[GGGC

SEQ ID NO: 600

[CG[GGGCT[CG[GGGCTTTGGTACAGAGGAGCAGCAGAAG[G[C[CG[C[CG[CAGA[CG[CC[CG[GATG[CG[GAGG

ACCCAGAG[CG[CTG[CG[CAGCTGAGGAGCACCTGGGGAGCCAC[CG[C[CG[G[CG[CCAACTTTTGCCATCC[CG[GG

AGCCATAG[CG[GCAGAGAGGGGGTCC[CG[GACC[CG[AGGTGGCAG[CG[AGGGGCTCTGCTTTGGCAGCTGT[CG[

GGGCTGGAGCTCAGGACCCCAACTCCAGCCAAGT[CG[GGC[CG[[CG[G[CG[GGGCAGG[CG[TAGGCTG[CG[CAGG

CAGGGGGG[G[[G[GGTGTGAGCCAGT[G[[G[[CG[[CG[CAGG[CG[GG[CG[CTGGAGTCTCAGCTACCT

GG[CG[[CG[AC[CG[CCAGCAGCACCCAG[CG[[CG[GGGC[CG[GGAGCTGCTGGGGGCCCAGGCTC[CG[CTCTCCCC

AC[CG[CTCTGCAC[CG[CTGC[CG[GCTG[CG[GACAGACC[CG[ATG[CG[CCACCACCAC[CG[CAGTTGCCA[CG[ACC

CCCATGGAAT[CG[CTGG[CG[CCTC[CG[CTC[CG[GTTCTCTAACC[CG[G[CG[CACTCTGGGATCCCAAAGCTTGC[C

G]TGGGTTGGAGGCTTCCTACTCTTTGTG[[CG[[TTGAGGCTTTGACCTGACCCAGAG[CG[CAG

SEQ ID NO: 601

GCTGGGG[CG[CCCCT[CG[GACCTG[CG[GGAT[CG[CCCCTACACTCTGG[CG[[CG[CTGAGGG[CG[GTGAG[CG]AGG

G[G[CCAAGGCACAGGGGGG[G[GGAGT[G[A[G[[CG[GAGGCT[CG[GGGGG[CG[GGA[CG[[CG[GGGC

CTGGGAG[G[GCCAGGGAC[CG[[CG[GCAG[CG[CCTCAGTGCCAGCCTGG[CG[CC[CG[[CG[ACTGCCTGCCCCAG

G[[CG[[CTACAGACTCC[CG[AGAACAGCCCTGGCTGTCAG[CG[AGCACCAGC[CG[CTTCCTGTCCCCAT[CG[[CG[

G[CTC[CG[CAGCC[CG[G[CG[CAGCTCATGGTGAG[CG[CCCTCTGGGGCT[CG]AGGGTCCCTTGGCTGAGGGGG[CG[

CATCCT[CG[GGGTGCC[CG[ATGGGGCTGCCTGGGGGT[CG[CAGGGCTGAAGTTGGGAC[CG[[CG[[CACAGAC[CG[

CCCCTGCAGTCCAGCC[CG[AAATGCTGC[CG[CCAGGCAGCAA[CG[GCAC[CG[[CG[TACC[CG[GGGCAGTT

SEQ ID NO: 602

GGGATTACAATCCACAAACTGACCTTGTATATGATTCCATTCCTTCTCCCAGCCCAGCCCCACACTCCAAGGTTTT

CCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTCCTCCTTTAGGC

CAACTACAG[CG[[CAGAGGAG[[CG[[CTTTCTCCTGCTGGGTTTCTC[[CG[ACTGGCCTTCCCTGCAGC[CG[GTCCT

CTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGTGCTGCTGG[CG[GTG[[

G[[CG[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGCCTTGGTAGA[CG[[CG[GGC

TTCACTACTAG[CG[[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCAG[CG[CTCTGGCTGC[CG[[CG[[

CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[CG[AATG[CG[TCCTCCTGG[CG[GT

GATGGCTCTGGAC[G[[G[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[CTATG[CG[GGGCT[CG[TCTCCC[CG[[

CG[CCTATGT[CG[CA[CG[[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GCCTC

SEQ ID NO: 603

TC[CG[GAGACCC[CG[GGGCCACTTAC[CG[ATCTTGGCCAAGCTGGCCA[CG[AGGATCCAGAG[CG[[CG[ATGA[[CG

CG[[G[GGCTCCACCT[G[A[G[[G[[G[[CG[CCAGCC[CG[CCCAG[CG[CCAG[CG[CCAGCAGCAGCC

CC[CG[GT[CG[GGGCCC[CG[GGCCC[CG]AGTCCCCACATTGC[CG[CCTGCTCAG[CG[CAGGGCTGGGA[CG[[CG[CA

TGT[G[[G[GGGGGTCC[G[GCTGGGGGG[G[A[CG[[CG[[CG[GGGCTGGGACC[CG[G[CG]AGGACC[CG[G[

CG[[G[CTC[G[GTG[G[GTA[G[GCTACAGTC[G[ATCCC[CG[CC[CG[C[CG[GGGTGGCCTTTAATCC[CG[[CG

GCCCCCTCC[G[[G[GGG[G[GAGCCTGCC[G[CCCC[G[[G[[CG[CACT[CG[[CG]AG[CG[CAGACAC[CG[

[G[CAGCT[G[[[[G[[G[[G[[CG[CA[CG[CCCACCC[CG[[CG[CTCCCTGGTGCCCACCC

TCCCC[CG[GAGCC[CG[[CG[GCCTGGAGGTC[CG[GGAGGT[CG[[CG[GCAAGAG[CG[AGCC[CG[GGACTG[CG[[CG[

GC[CG[CCTTCCT

SEQ ID NO: 604

TCTTCATGCCTCAGAAA[CG[TGGCCTACTCTGCATT[CG[GTGTGTG[CG[GAAGCAGCAATCACAGAGGCAGCCCT

AATAC[CG[GAGG[CG[G[CG[G[CG[GCAGCAGCAGGGCCAGGTGGTAGCT[CG[GGGCTGAGGAT[CG[[CG[G[CG[GG

AC[CG[C[CG[C[CG]AGGAGGCCACCTGGGACTTGTGGC[CG[CAGTC[CG[A[CG[AGGG[CG]ACA[CG]AGGGCAGA[C

GGTGTAG[G[AAT[G[TAGCCAGAGCTGGG[G[G[CG[G[CG]AG[CG[CC[CG[TGCACCTTCATGTGCTTA[CG[C

AG[CG[AGCTGGGGTG[CG[TGTAGCACTTGT[CG[CAGCCC[[CG[[CACCTTGCA[CG[TGTATGGCTTGT[CG[CTAGTG

TGCA[CG[TG[CG[AATGCTTCTTA[CG[GT[CG[CTGCTGTTGG[CG[AAG[CG[C[CG[CT[CG[CAGCCCT[CG[AACT[CG[

CATCTGAAGGGCTTCT[CG[CCTGG[CG[GAGGCAA[CG[CAGAGACATTAGTGCTTGTGGGT[CG[TGTTCC[CG[TCAG

GTGCTTGCCACCCTCCCCCATT[CG[TCTCTCATTTTCTGGAAAAGAACTACAAAATAT

SEQ ID NO: 605

GGGGGGTCACCAATTTGCAGAGCTGAGGGAGAAGAGAGGAGGGAGGAAGGAGAGCAGGAGGGAGGGGAAGCTG

TCCCCAGCTGCCAGATGGGAAGTGTCAGCTTGGCCTTGGCCACCT[CG[[GGTCAC[CG[CTCCTCCCTTTCAGG[CG[

CC[CG[GGTTTGCCCAC[CG[[CG]AAGAGCAGTGG[CG[GAGACAT[CG[CAGCAA[CG[CTAA[CG[GGGCAGAC[CG[C

ATAGGGGCCCTGAGAGGCACACA[CG[[CG[CCTTCTGCTCACACCTCAGGCAGT[CG[GAGGGGCC[CG[G[CG[GAGC

TGTGTT[CG[TGTTGTCATGG[CG[A[CG[GAAGCAGACCATTAGAGCATTA[CG[AGGAAATGAGAAGACTTGGGGT

TAATGGGGTCTCTGCTGGGCTAGTGTCC[CG[CATCAG[CG[GTAATGGGGC[CG[GCCCACC[CG[GAGGCAGCC[CG

]GAGCAG[CG[T[CG[CCCCAGCAGGCTTATG[CG[GACCTGGCTAACTCCAGAGGC[CG[G[CG[GCTCCTTG[CG[GTGG

GGAGAGGAGGACAGAGGGGCCAGGTGGAG[CG[GGGTCTGCAAACAGC

SEQ ID NO: 606

GGAGAGGCAGGACTTTAGAAGGGCTCAAAGTAGATGAACAAAA[CG[GAGGTCTCCTGGAAGCAGGTGACTGAGT

TAGGCAAC[CG[AGATGCCCACATATCTGTG[CG[G[CG[TT[CG[[CCCCAAGAGGCCAGC[CG[GCTC[CG[CTCAGC

TCC[G[[G[[G[TGGC[G[CATCCC[CG[C[CG[CC[CG[ACTCCCAGCC[CG[CTTCCTCTCTC[CG[[CG[AG[CG[GG

GGGGGGAGCTGCAGG[G[GGGCC[CG[AAG[CG[CCC[CG[GGGGCA[[CG[[TGGAG[CG[GCCTCTGGCTCACCTG[CG

GCTCATTGGCTGC[CG[CT[CG[GAGGGGAGGGGAAGGGG[CG[GCTG[CG[GGGGTCTCATTAG[CG[ATG[CG[GACTC

T[G[CCT[G[CT[G[TAGTT[G[GGGCC[G[GCAG[CG[G[CG[[CG[AGGGCTGGGAACTG[CG[[CG[G[CG[GGGA

[CG[[CG[CCCTTTCT[CG[GGGTGCCCATTCAG[CG[G[CG[GCT[CG[GAGCTCCCTGCCC[CG[CTGCTTTAGGAAG[[C

G]]

SEQ ID NO: 607

CTGGGGAGCCAC[CG[C[CG[G[CG[CCAACTTTTGCCATCC[CG[GGAGCCATAG[CG[GCAGAGAGGGGGTCC[CG[GA

CC[CG[AGGTGGCAG[CG[AGGGGCTCTGCTTTGGCAGCTGT[CG[GGGCTGGAGCTCAGGACCCCAACTCCAGCCA

AGT[G[GGC[CG[[CG[G[CG[GGGCAGG[CG[TAGGCTG[CG[CAGGCAGGGGTGGC[CG[[CG[GGTGCTGAGCCAGT[[

G[[[G[[G[[CG[CAGG[CG[GG[CG[CTGGAGTCTCAGCTACCTGG[CG[[CG[AC[CG[CCAGCAGCACCCAG[CG[[

CG[GGGC[CG[GGAGCTGCTGGGGGCCCAGGCTC[[CG[CTCTCCCCAC[CG[CTCTGCAC[CG[CTGC[CG[GCTG[CG[G

ACAGACC[CG[ATG[CG[CCACCACCAC[CG[CAGTTGCCA[CG[ACCCCCATGGAAT[CG[CTGG[CG[CCTC[CG[CTC[C

G[GTTCTCTAACC[CG[G[CG[CACTCTGGGATCCCAAAGCTTGC[CG[TGGGTTGGAGGCTTCCTACTCTTTGTG[[CG[[

TTGAGGCTTTGACCTGACCCAGAG[CG[CAGCTTATGCCCTGGCTTGGGCAGAAAATAATATTAATTACTGATCCTT

TGTGCTCC[[CG[[GTCCTGGCTTCCTAAAGCACTCCTCTCTCATTCAGCACC

SEQ ID NO: 608

GGATTGGGACT[CG[GGTCTGTGGGTAATCCAAGGCTGCCC[[CG[[CTTACCCTTCAAATGCTCTTTCCCCCTC[CG[G

AAGCCCT[CG[[CG[TCCTCATCCTTACCCCACCTCTTGTTCCCCAAG[CG[TGGCCAGGGCTAAGGCTCCAGGGATG[

CG[CCAAGCACCCTT[CG[GTTTTCC[CG[GGGAGAATTTTCCC[CG[GCC[CG[GGGACTAGGGTCTGG[CG[CTGGGG[

CG[CCCCT[CG[GACCTG[CG[GGAT[CG[CCCCTACACTCTGG[CG[[CG[CTGAGGG[CG[GTGAG[CG]AGGG[CG[CCA

AGGCACAGGGGGG[G[GGAGT[G[AG[G[[CG[GAGGCT[CG[GGGGG[CG[GGA[CG[[CG[GGGCCTGGGAG

[CG[GCCAGGGAC[CG[[CG[GCAG[CG[CCTCAGTGCCAGCCTGG[CG[CC[CG[[CG[ACTGCCTGCCCCAGCCCCTCA

TACAGACTCC[CG[AGAACAGCCCTGGCTGTCAG[CG[AGCACCAGC[CG[CTTCCTGTCCCCAT[CG[[CG[GAGACT

GGAGGGG[CG[CACCA[CG[GCCATGGAGCCAGAGG[CG[CTTCAGGAGGCAAGAGAAGTCCC

SEQ ID NO: 609

GGACT[CG[GGTCTGTGGGTAATCCAAGGCTGCCC[[CG[[CTTACCCTTCAAATGCTCTTTCCCCCTC[CG[GAAGCCC

T[CG[[CG[TCCTCATCCTTACCCCACCTCTTGTTCCCCAAG[CG[TGGCCAGGGCTAAGGCTCCAGGGATG[CG[CCAA

GCACCCTT[CG[GTTTTCC[CG[[GGGAGAATTTTCCC[CG[GCC[CG[GGGACTAGGGTCTGG[CG[CTGGGG[CG[CCCC

T[CG[GACCTG[CG[GGAT[CG[CCCCTACACTCTGG[CG[[CG[CTGAGGG[CG[GTGAG[CG]AGGG[CG[CCAAGGCACA

GGGGGG[G[GGAGT[G[AG[CG[[[CG[[GAGGCT[CG[GGGGG[CG[GGA[CG[[CG[GGGCCTGGGAG[CG[GCCA

GGGAC[CG[[CG[[GCAG[CG[CCTCAGTGCCAGCCTGG[CG[CC[CG[[CG[ACTGCCTGCCCCAGCCCCTCAGTGG[CG[

TCC[CG[AGAACAGCCCTGGCTGTCAG[CG[[AGCACCAGC[CG[CTTCCTGTCCCCAT[CG[[CG[GAGACTGGAGGGG[

CG[CACCA[CG[GCCATGGAGCCAGAGG[CG[CTTCAGGAGGCAAGAGAAGTCCC[CG[[CG[

SEQ ID NO: 610

GTCTGTGGGTAATCCAAGGCTGCCC[[CG[[CTTACCCTTCAAATGCTCTTTCCCCCTC[CG[GAAGCCCT[CG[[CG[TCC

TCATCCTTACCCCACCTCTTGTTCCCCAAG[CG[TGGCCAGGGCTAAGGCTCCAGGGATG[CG[CCAAGCACCCTT[C

G]GTTTTCC[CG[GGGAGAATTTTCCC[CG[GCC[CG[GGGACTAGGGTCTGG[CG[CTGGGG[CG[CCCCT[CG[GACCT

G[CG[GGAT[CG[CCCCTACACTCTGG[CG[[CG[CTGAGGG[CG[GTGAG[CG[AGGG[CG[CCAAGGCACAGGTGGGG[C

GGGAGT[G[A[G[[G[GAGGCT[G[GGGGG[CG[GGA[CG[[CG[GGGCCTGGGAG[CG[GCCAGGGAC[CG[[

[CG[[GCAG[CG[CCTCAGTGCCAGCCTGG[CG[CC[CG[[CG[ACTGCCTGCCCCAGCCCCTCAGTGG[CG[GCTTGCTCT

CTTCTCT[CG[CTC[CG[AACCAGACACAGC[CG[CTGC[CG[CTGC[CG[TC[CG[G[CG[[CG[[CTACAGACTCC[CG[AGA

ACAGCCCTGGCTGTCAG[CG[AGCACCAGC[CG[CTTCCTGTCCCCAT[CG[[CG[GAGACTGGAGGGG[CG[CACCA[C

G[GCCATGGAGCCAGAGG[CG[CTTCAGGAGGCAAGAGAAGTCCC[CG[[CG[[CG[CTC[CG[CAG

SEQ ID NO: 611

TGGGACT[CG[GGTCTGTGGGTAATCCAAGGCTGCCC[[CG[CTTACCCTTCAAATGCTCTTTCCCCCTC[CG[GAAGC

CCT[CG[[CG[TCCTCATCCTTACCCCACCTCTTGTTCCCCAAG[CG[TGGCCAGGGCTAAGGCTCCAGGGATG[CG[CC

AAGCACCCTT[CG[GTTTTCC[CG[GGGAGAATTTTCCC[CG[GCC[CG[GGGACTAGGGTCTGG[CG[CTGGGG[CG[CC

CCT[CG[GACCTG[CG[GGAT[CG[CCCCTACACTCTGG[CG[[CG[CTGAGGG[CG[GTGAG[CG[AGGG[CG[CCAAGGCA

CAGGGGGG[G[GGAGT[G[A[G[[[G[GAGGCT[CG[GGGGG[CG[GGA[CG[[CG[GGGCCTGGGAG[CG[GC

CAGGGAC[CG[[CG[GCAG[CG[CCTCAGTGCCAGCCTGG[CG[CC[CG[[CG[ACTGCCTGCCCCAGCCCCTCAGTGG[C

GGCTTGCTCTCTTCTCT[G[CT[G[AACCAGACACAG[G[CTGC[G[CTGC[CG[TC[CG[G[CG[[CG[[CTACAGA

CTCC[CG[AGAACAGCCCTGGCTGTCAG[CG[[AGCACCAGC[CG[CTTCCTGTCCCCAT[CG[[CG[GAGACTGGAGGG

G[CG[CACCA[CG[GCCATGGAGCCAGAGG[CG[CTTCAGGAGGCAAGAGAAGTCCC[CG[

SEQ ID NO: 612

GCCAGCAAGGAGC[CG[G[CG[[CG[GGGGGCATGTCC[CG[CAGGCTCACAGC[CG[[CG[[CG[[CG[TCCCACTGCAG[C

CG[G[CG[GCAGCAGCAGCAGCAGCAG[CG[GGGAGG[CG[GGGGG[CG[GGGAGGCTGGGGGGGGCCCCCTC[CG[CT

CG]ACACCCTG[CG[CCAGACC[CG[GC[CG[AAGCAGCC[CG[CCCCACTG[CG[CAGGGCCATGCAGGG[CG[GCCC[CG

A[G[GGAA[G[GAGCCAGAAG[G[[G[GAGGG[CG[GC[CG[[[CG[GGGCC[CG[GTACCCCTGTGGGTCCAG

CT[CG[[CG[GGTGG[CG[GTGCCCAGCAAGGAGCCTGCAGGTC[CG[[CG[[CG[CCCAG[CG[GAACCTGCTTCCCCTT

TTACCCCTC

SEQ ID NO: 613

[G[CCCTGGAATTGC[CG[[CG[G[CG[G[CG[GATGCAGAGGCCAACCCAGAGTGCAACCATGGAGA[CG[[CG[A[CG[

TGTGTCCCATAGTAACCTGTTACAACATTATTTATAAGCTGCCATCCCTAGCCTTCCCC[CG[CTTCCCCTC[CG[CTC

CCT[CG[CCAGACTTG[CG[GG[CG[A[CG[GGCACAGC[CG[[CG[TCTGGCTCTTCC[CG[GCCTCTCCCTTCTCT[CG[[CG

]GG[CG[CAGC[CG[ATCAATAGTTAACACC[CG[GCTG[CG[GA[CG[G[CG[GCTCCATC[CG[[CG[GCAATCAC[CG[TAG

TGCTTGTTTGTGGAAGC[G[AG[G[TG[G[TG[G[[G[[CG[[CG[[CG[CACCCAGTCCAG[CG[[CG[GAGTGGG[

CG[TCTACC[CG]AGGAGGGGTGTCTGGGGAGGGGCTGCCCT[CG[[TTACCCAAACAGTTTG[CG[CT[CG[[CTTAA

CCTTGATGCAGCT[CG[AGGCTTCCCAGTCCAGCTCAGTTCAGACAGAAAACCTGG[G[[G[[G[[CG[[CG[[CG[CA

CACACACA[G[CCCCCCTGG[G[T[CG[C[CG[CC[CG[GC[CG[GGTCCCTGCCCTTAGGGACCAGAG[CG[G[CG]AC[

CG[CTGCACCC[CG[CAC[CG[CCTGCTGGAGGAGCCCC[CG[GAGC[CG[GGGC[CG[AGC[CG[C[CG[G

SEQ ID NO: 614

TCTG[G[CCCTGGAATTGC[CG[[CG[G[CG[G[CG[GATGCAGAGGCCAACCCAGAGTGCAACCATGGAGA[CG[[CG[A

[CG[TGTGTCCCATAGTAACCTGTTACAACATTATTTATAAGCTGCCATCCCTAGCCTTCCCC[CG[CTTCCCCTC[CG[

CTCCCT[CG[CCAGACTTG[CG[GG[CG[A[CG[GGCACAGC[CG[[CG[TCTGGCTCTTCC[CG[GCCTCTCCCTTCTCT[CG

[CG[GG[CG[CAGC[CG[ATCAATAGTTAACACC[CG[GCTG[CG[GA[CG[G[CG[GCTCCATC[CG[[CG[GCAATCAC[CG[

TAGTGCTTGTTTGTGGAAGC[CG[A[CG[TG[CG[TG[CG[[CG[[CG[[CG[[CG[CACCCAGTCCAG[CG[[CG[GAGT

TTAACCTTGATGCAGCT[CG[AGGCTTCCCAGTCCAGCTCAGTTCAGACAGAAAACCTGG[CG[[CG[[CG[[CG[[CG[[C

G[CACACACACA[G[CCCCCCTGG[G[[G[C[CG[CC[CG[GC[CG[GGTCCCTGCCCTTAGGGACCAGAG[CG[G[C

G|AC[CG[CTGCACCC[CG[CAC[CG[CCTGCTGGAGGAGCCCC[CG[GAGC[CG[GGGC[CG[AGC[CG[CC

SEQ ID NO: 615

CCCACCTGCCCCTCTCTGCCTGCCTCCCAC[CG[G[CG[CCTGGGCATCCTG[CG[C[CG[GCTACAGGTCCTTGCTCACT

GAAG[CG[TCACCTCTCACTCCCCAGTAAGCCTC[CG[CAGCCCACT[CG[GACTGCAGCCTGTTTGC[CG[CC[CG[T

CCTCCCATTGAGACT[G[GGG[G[ACAGAGAGGGGGAGG[G[[CG[[CG[GGGA[CG[GGGA[CG[CCCAGGAGG

ACCCACT[CG[[CG[GGTCC[CG[CTC[CG[CTC[CG[GCAGCAGCATGGGGAAAGGA[CG[[CG[[CG[GGC[CG[AGTTGGC

GGCA[CG[CAACTC[CG[CCTCCAGGGCTCTCTCCCT[CG[[CG[[CTCTCTCCCAGC[CG[CTTGCT[CG[CAGCCCCAGC

AGC[CG[C[CG[CAGCATCACTTCACACAAAGGACTGTCACC[CG[[CG[GAGCAGCTCCTCCACCTCCA[CG[TCCTCC

TC[G[GTGAAGCAGCC[G[ACAGCAGGGCT[G[GG[G[[G[G[CG[G[CG[G[CG[[CG[GGGGGTGGGGGGACCT

GTCACTCCCTGTAACTGAGG[CG[G[CG[GCAG[CG[GTTTTTTTGCCTTTTCTATTTTGC

SEQ ID NO: 616

GGTGGGGTGGGGTGGGCAATGGGCAATGAGA[CG[GAGGG[CG[GGGC[CG[GGACCTAATATGG[CG[GGTCAGGAG

GGTCTGGAAGA[[CG[[AAGAAGAGGGACAGGCAATGCCAGGTCTAGGACTAGGAGGGAGG[CG[[CG[GG[CG[GTAT

TAG[G[GCTGGGGGGCTT[G[GGGG[G[[CG[A[CG[GC[CG[C[CG[CCTGGTGCTACCCACCCAGGGG[C

G][CG[[CG[ACCCTCCCTT[CG[GTCTGGCTCCAAAGACCTAGCAGCACTGACTTCACCCAGCTGTGGTTCCAA[CG[

[[G[GGTCCAG[G[GCT[G[[G[G[CG[C[CG[TCCTCCTGCTGGCCCAACAGGCC[CG[CCAGCC[CG[CCCC

TGTA[CG[TCTGTGATTGGA[CG[G[CG[G[CG[GCCACTGATGTTCAAG[CG[ACAGGTCCTGGCC[[CG[[GGAGCCAAT

CTGCAGGTGTTGAGGCCCAGGCTC[CG[AGAG[CG[GGC[CG[AGGAGG[CG[TGGATACCCTGATTCCTAGGGGGCAG

GCCTGGTTCCCC[CG[AGGAGGACC[CG[GCCTATGAATGACTGGAGTTCTGGGGTTCTGGC[CG]AAAGAGGAAGTG

GGACAGGGC[CG[GGTGTGATGGGGCCTAGAGTCACAGAGCCTTG[CG[GC

SEQ ID NO: 617

AAAGACCTGGCCCA[CG[CCTCCCAGAGGCTTTACCTGGTGAAGAGGAGGAGCAGCCACTGCAG[CG[[CG[GTGGA

G[CCACCAC[CG[TG[CG]AGTCCC[CG[GC[CG[CCTTCTTTTC[CG[CAGAGAGGATAAAGG[CG[TCCATCATGT[CG[[C

GGGGGG[CG[GCCC[CG[GGC[CG[AAGGCTTT[CG[CAGTGCCTCAAGAACTTGTCCAGGATGAAGTTGCTGAAGTT

G[CG[GTTGAGCTGCT[CG[AATT[CG[[CG[[GAAAA[CG[GTG[CG[CAC[CG[GGTTGGGGAAGTACTGCAGCCAGGGC

ATCA[CG[TCCACCAGGCTGCC[CG[[CG[CCCAC[CG[TG[CG[CC[CG[AACTCTT[CG[TTGTGGCTGAGCAGCTCA[CG[

GAACT[CG[GGGT[CG[T[CG[TGGCTGTAG[CG[GCAGC[CG[AAACACA[CG[GCACTCATGA[CG[TTGGCCA[CG[GCC

SEQ ID NO: 618

G[G[[G[ATG[CG[CAG[CG[[CG[TTGGCA[CG[CTCCAGC[CG[GGTG[CG[GCCCTTCCCAG[CG[[CG[CCCAG[CG[GG

TGCCAGCTCC[CG[CAGCTCAATGAGCTCAGGCTCCCC[CG[ACATGGCC[CG[GTTGGGCC[CG[TGCTT[CG[CTGGCT

TTGGG[CG[CTAGCAAG[CG[[CG[GGC[CG[GG[CG[GGGCCACAGGG[CG[GGCCC[CG[ACTTCAG[CG[CCTCCCCCAG

GATCCAGACTGGG[CG[G[CG[GGAAGGAGCTGAGGAGAGC[CG[[CG[CAATGGAAACCTGGGTGCAGGGACTGTGG

GGC[G[AAGG[G[GGGGGG[CG[[CG[CTCT[CG[CAGAGCCCCCCC[CG[CCTTGCCCTTCCTTCCCTCCT

AGATACC[CG[TGTTTCTGGAGGCCAGCTTTACTGTGCTAGAGGAAGAGGGTCCCCACATC[CG[GCCCTGGCCCTCC

TGGTC[[CG[GTTTGCTGAAGCAACACACTTGGCCTACCCACTGGGTGGGGCAGGAAGTCT[CG[[AGCCTTCACTTG

GGGTGAGGAGGAGGGAGAT[CG[GTCAGCAGCTTTAC[CG[CC[CG[CTCTGCTCTCCA

SEQ ID NO: 619

GTCTGGAAGGGGA[CG[G[CG[GTAGA[CG[AGAGGGG[CG[GATGGAGGCTTTTAA[CG[CTGTCCCCTCCT[CG[GGAC

TCAGGTGATTATG[CG[GGCCTTCAGC[CG[[CG[AGGCACT[CG[AATGCTA[CG[TGC[CG[GTGATCAC[CG]AGGA

AGTGGGCAGCAGCCTGGAGCAGTGGCTGAGCTG[CG[G[CG]AG[CG[[CG[GCCTCCTGGTCTACCC[CG[AGGTGAAG

[CG[CCTCATGTTC[CG[AAT[CG[CCATG[CG[CATCCTACTGGGCTG[CG[AACCCCAACTGG[CG[GG[CG[A[CG[GGG

ACTC[CG]AGCAGCAGCTTGTGGAGGCCTT[CG[AGGAAATGACC[CG[CAATCTCTTCT[CG[CTGCCCAT[CG[A[CG[

TGCCCTTCAG[CG[GGCTGTAC[CG[GGTAAGGG[CG[GCAAA[CG[GGCTG[CG[GACTAGGGG[CG[[CG[GGACCTGG

G[G[TCTGCTCAC[G[[CG[[CG[[CG[CTCTCTG[CG[CTCAGGGCATGAAGG[CG[[CG[GAACCTCATTCA[CG[[CG[[

CG[CAT[CG[AGCAGAACATT[CG[[CG[CCAAGATCTG[CG[GGCTG[CG[GGCATC[CG]AGG[CG[GGCCAGGGCTGCA

AAGA[CG[[CG[CTGCAGCTGTTGAT[CG[AGCACT[CG[TGGGAGAGGGGAGAG[CG[GCTGGACATGC

SEQ ID NO: 620

GGCTAGGAGGC[CG[GG[CG[GGGGG[CG[AGGACTTGGGAAGAG[CG[GGGTGA[CG[GGGGTGGGGGCTGGG[CG[TC

CCCCAAACCTATTGCTTTGTTTCCTTTAGTTTAGAAGTGAACA[CG[[GC[CG[TGG[CG[TT[CG[TAAGAAGCAAAAC

CTTCCAGAGAGGAGAGGAAAGGA[CG[[CG[GACAGAGA[CG[GATGGACAGGGG[CG[[CG[AGGGGGCCAGGC[CG[

GGGGG[G[GAGAG[G[[G[[G[TG[CG[GA[CG[CAAATACTCA[CG[G[CG[GAG[CG[ATC[CG[AACCC[CG[GAG

TC[G[[G[TGCAGGGGGGGGACCAGG[G[[G[CCCT[CG[CCC[CG[CC[CG[CAGCCCCC[CG[TCTGCTAT

G][CG[GGGCTGCCCTT[CG[G[CG[GCCCTGGCCT[CG[GG[CG[CTGCTGGGTGGG[CG[GTAAACAGCAAGAGAAAGG

GG[CG[TCCCAGG[CG[ATGGGGCTCCAGCCACC[CG[[CG[GGCAGAGGAGCA[CG[GGG[CG[GACTGGGGGGGTCCT

GGGGG[G[[G[[G[CCCCTTG[G[GGGGGGGG[G[G[CG[GG[CG[[CG[GGCAGGG[CG[GGCCTGGGGCTA

SEQ ID NO: 621

G[CG[GGGTGA[CG[AGCTGGGGGGG[CG[GGGGG[CG[GTGT[CG[GAGCAAATA[CG[G[CG[GCCAGGCCCAGCCTCT[

CG[[G[CTTTCCAGAA[G[[G[[G[GC[CG[C[CG[CCAGCTGCTTGG[CG[CTGACCC[CG[TTGGC[CG[GGCTG

[G[TCACCCTGGG[G[A[G[[G[[CG[[CG[GAAAA[CG[GGGAGGGA[CG[AGACAGACACAGGC[CG[GTCT

GGCT[G[GAATCTCCTGCTCCTCTGCCCAATCCCCCACCCC[G[CCC[G[[CG[GGA[CG[C[CG[GTGCC[CG[GTCT[C

GCTCCC[CG[CCCC[CG[CCCCCAATCAGGAC[CG[GTCCAGACCTCCAGGCC[CG[G[CG[CTTAGCTC[CG[TTTCC[CG[

TCCCTCC[CG[TCTCCCTCTCCCCTTTGCTGGGGCCTAGC[CG[GGGATTTAGGAGCCACACACCCTCCACCTCA[CG[[

[CG[[CTACCCTCCA[CG[GGGCTTCC[CG[CAGCCAGGGCC[CG[CCCCTTCC[CG[GCTCCC[CG[GGAGACCCTGGCAA

GTTCCCTCCCTC[CG[CCC[CG[CAACCTGGCACCCTC[CG[[CG[GCCCTTGCCTACCCA[CG[CAC

SEQ ID NO: 622

CACC[CG[CCCACCCACATTCCC[CG[[GTTCAGCAATTTTCAGCCCAGA[CG[CAGAAGCATCTGTTTCCCTGGCCAG

GG[CG[CCTTAA[CG[ATCCCC[CG[AATTC[CG[[CG[TCTCC[CG[GAGGCCAGAGGTTTGGGTACCCAGGAAGGT[CG

][CG[CCTCCT[CG[TGCCC[CG[ATACT[CG[GGTTGTAAAGGGAGGAGACAT[CG[CCT[CG[G[CG[CATCCCTGGC[CG[

CTGAACAA[CG[[CAACCCCTA[CG[TCCC[CG[CA[CG[GGAATC[CG[GCTGATAATCTCCTCTTGCCTGAGAAT[CG[G

CAGGTGTG[G[TCCCCAG[G[CT[G[CCTCCTC[G[GC[CG[[CG[CACTGAGCATG[CG[[CG[GGCTC[CG[GGCCTC

CG]AG[G[TCTCCCC[G[CCC[G[[CG[GCTAAGGAGC[CG[GCAGCC[CG[AACTC[CG[G[CG[[CG[CCAGGTTTTTCC

AGC[G[[G[[G[A[G[[G[GGGGGGGGCAG[G[[CG[[CG[CCAGA[CG[GAGCC[CG[GGGTT[CG[A

SEQ ID NO: 623

ATC[CG[GAGGGAAATGGCCTCTG[[CG[[GGGAGGAGGTAGGGGCC[CG[[CG[CACTGGGG[CG[CAGGACC[CG[GGG

AGCAG[CG[CAAGGAGGAGGGT[CG[GA[CG[GGTCTCAGCCCCTCCT[CG[CCCCCAGGTACCCACTCCATAAGGTAT

TTCAGCAC[G[[G[TTC[G[GC[CG[GGT[CG[[CG[GGGAGCCC[CG[GTACAT[CG[CAGTGGGCTA[CG[TGGA[C

GACA[G[CAGTT[G[TG[G[GTT[G[ACAG[G[A[CG[[CG[G[CG[ACTC[CG[AGGATGTAGC[CG[CAGT[CG[C[CG[

TGGTTGGAGCAGGAGGGAC[CG[GAGTATTGGGAC[[CG[GAGCACA[CG[GAACATCAGGCC[CG[[CG[CACAGACT

GACAAGAGTGAACCTGCCCATGC[G[[CG[[C[CG[CTACTACCACCAGAGCTAGGC[CG[GTGAATGACCC[CG[GCC

TGGGG[CG[AAGGTCA[CG[ACCCCTCCTCATCCCCCA[CG[GA[CG[TCC[CG[GGTCCCCCC[CG[[CG]AGTCTC[CG[G

CTCCAAGATCCACCC[CG[AGGCTG[CG[GGACC[CG[CCAGATCCT[CG[ACC[CG[GGAGAGGCCCAGG[CG[CCTT

TACCAGGTTTCATTTTC[CG[TTTAGGCCAAAATCCC[CG[[CG[GGTTGGT[CG[GGG[CG[GGGG[CG[GGG

SEQ ID NO: 624

[CG[CTGCAGATCAA[CG[C[CG[GTGGCAAGAAGGGGC[CG[CAAGGGTTTC[CG[CAGACACCCACACATGCAGG[[C

G[[TTCCCACAGAGGGTACCAGGGATTTCCCAGACCCCCACCAGCCCTCAGGAATAG[CG[TAGAGAGAGGAA[CG[T

[CG[CCTGGCTGAGAAAGGTGGATGGGCATACCCATGTACCTTTGTGTATTAAGTACCCACAACCTC[CG[AACTTAG

C[CG[TCCCTGTCC[CG[GCC[CG[CCCAACTGCTGC[CG[C[CG[CATCTGCAGAAACCACT[CG[TGTTGAGGCCT[CG[

GAGCAGC[CG[GGAGCACCA[CG[[CTGGAGCAAAAAAGC[CG[GAGGG[CG[CAGGGCTCCAGCC[CG[GCTGACCAT

G[CT[CG[[CG[GACTAGTTCCTCAGACTGTGGGACTCCCTAGTGC[CG[GCTTTGCCCAGGGCTTTCCAAGGCTGTCTC

ATGCCCTAGATCTGCCCCAGCAGCTCAGGCCTTGGACTG[CG[AACCCAGTATCC[CG[AGACAC[CG[ATTCCATCA

GTCCCCATCC[CG[ACCCCTCTCCAGC[CG[GGTTCATC[CG[CCT

SEQ ID NO: 625

CCTGAA[G[G[CG[GAA[CG[[CG[[CG[GCT[CG[GGGGATCCCCTCTCCCTGGGAC[CG[GCCCTGTCC[CG[GGT[CG[C

CCCACCTCC[G[CAG[G[[G[[G[[G[GCT[G[[CG[[CG[CTCC[CG[C[CG[GCACCATGGAGGAATTCCT

GGGACAAC[CG[CCTGCAGC[CG[G[CG[ACTTTTCCCCAGGAATCTCTGGCCTGG[CG[CCCTTTGGGTGAGATGA[

CG[GGGTGCTGGCATCCCTGT[CG[GTCCCAGATTACC[CG[GAAAAGCCCTGGCAGGTAAAGAGAGGACC[CG[[CG

TCTGTTTATATAG[CG[TCTGGAGGC[CG[GGAGGCATTGCCCACCCC[CG[CCAGG[CG[[GCC[CG[CCCTCCCCTCC

TGGGCTC[CG[GGCTGC[CG[CA[CG[TGGCAGACACCAG[CG[A[CG[TCTC[CG[[CG[GAAGGCAGG[CG[C[CG[GGGA

GTGGGG[G[[CG[GG[CG[AC[CG[TGTGCAGC[CG[[CG[G[CG[CATCTC[CG[CCTTC[CG[CTCCTCCT[CG[CAG[CG[CC

CT[CG[TC[CG[CTTCCAAGCCCAGCACAGACTT[CG[GTTTCTC[CG[CCTCCATCCCCTTTA[CG[[AGAAGA

SEQ ID NO: 626

CATTCAAGCTTTCCTAA[CG[CAG[CG[CCTTCCTCTC[CG[CTCAGCTCC[CG[CCAGGCTTGGCCCCCTC[CG[CAGCCT

CCTGCTCCCCCCT[CG[CC[CG[CCTCCCTCCCTCTCTCATTCTA[CG[TCATGAGATGA[CG[T[CG[GAAGC[CG[GG[CG

]GGAGGAGGAGCCCCCCTCCCCAGTCAG[CG[GCTCC[CG[CTGCAGCTTGCTTAGCCCAGCCTCC[CG[CTCTCC[CG[

]CCCCCC[CG[[GCTCTAAAA[CG[AGCCCCCCA[CG[CCTGGCAGGAGCTATATAAGG[CG[G[CG[TGAGGCAGG[CG[

AGGGGGGCAG[CG[CAGC[CG[AG[CG[GAGCCCAGGAGAGCAGAGAG[CG]AGCCTGAG[CG[AGAGA[CG[GGGAA

GCA[G[GAGGAGGAAG[G[[G[GTG[CG[T[CG[GGA[CG[GGAG[CG[CAGGTGCT[CG[GGCACC[CG]AGCTGGA

GCT[G[CAG[G[[G[GTCATGTAC[G[CTCCACCAAGGG[G[CCTCCAAGG[CG[[CG[C[CG[GGACCAGATCA

A[CG[C[CG[AGATC[CG[GAACCTCAAGGAGCTGCTGC[CG[CTGGC[CG[AAG[CG[GACAAGGTC[CG[GCTGTCCTA

CCTGCACATCATGAGCCT[CG[CCTGCATCTACACT[CG[CAAGGG[CG[TCTTCTT[CG[CT

SEQ ID NO: 627

AGCATCCTTCCCTCAGCCCTGGGGACCAG[CG[GGGACTACAGAACCCAGAAGGTTTTGTCTCCAGC[[CG[[CAGGG

ATGCTGAGCCAATC[CG[[[CG[CTGAGAAAAGGGT[CG[TTTC[[CG[CTTTGGGACCAATGGGT[CG[GGGAGGGACT

TC[CG[GTATCACTTCAGTGG[[CG[GTCATTTTTGCAG[CG[CTTGGGTGCATCCAGAC[CG[TCAGAGCTTTGGGAG[C

G[CTTTGTTTGG[CG[[ACAGT[CG[[GAAGG[CG[[CG]AGGGGAGGGGTCCTCC[CG[CTGAACAGTGGGGGTTCTAA

GGGT[G[G[CG[G[CG[G[CG[GGGTTGA[CG[GCTTTGCCTAGGTCCCTC[CG[CC[CG[TAGCTGT[CG[GGTCC[CG[GC

CC[CG[CTCTGCCCACAGACTC[CG[ATGGCTG[CG[GC[CG[[CG[CTGAGGGCCC[CG[ACTCAGGTGAG[CG[CTGCCT

CTACTGGGCCTCACCCTCCATCCCCAAATTAGTGCCTTCTTGGGTCACTA[CG[GT[CG]AGATCCTCATGTCCAGTA

CAGTGGGGGCT[CG[TGGGTGGGGTCCCTATTTCCAGAACTTGGGTGATGGGGCA[CG[GAAGAGGGTTACAGGCAA

AGGGACCAG[CG[TTTCTAAACTCTTGGAGACACAGTGAAGAA

SEQ ID NO: 628

ATAAATATTAATGTCAGCAAGAGTGTGCTGTTGGCAGGA[CG[TAT[CG[[CG[AGCCTGGAGATTTTGGTGGC[CG[C

AGTTGGTAAGTGGCTACAATCCAGAAAGTAGGAT[CG[AGTTGCTCCCCTTGTCTTATCAGTGTAT[CG[TTTCT[CG[

GG[CG[[[CG[GGTCTAACACCTTACAAGTGGTAATTTC[CG[CTCA[CG[GCAGCTTTGTCTCTCTTCTACCATCCCCA

GACCCAGCCTTGCACTCCAAGGCTG[CG[CAC[CG[CCAGCCACTATCATGTCCACTCC[CG[GGGTCAATT[CG[TC[C

G[CCTCCTTGAGCCC[CG[AC[CG[GCTGAACAGCCCAGTGACCATCC[CG[G[CG[GTGATGTTCATCTT[CG[GGGTG

GTGGGCAACCTGGTGGCCAT[CG[TGGTGCTGTGCAAGT[CG[[CG[CAAGGAGCAGAAGGAGA[CG[ACCTTCTACA[

CG[CTGGTATGTGGGCTGGCTGTCAC[CG[ACCTGTTGGGCACTTTGTTGGTGAGCC[CG[GTGACCAT[CG[CCA[CG[

TACATGAAGGGCCAATGGCC[CG[GGGGCCAGC[CG[CTGTG[CG[AGTACAGCACCTTCATTCTGCTCTTCTTCAGCC

TGTC[CG[GCCTCAGCATCATCTG[CG[CCATGAG

SEQ ID NO: 629

GGGAAGTAAA[CG[GCCCCAA[CG[CAAGCCTGACTG[CG[AGA[CG[TGCCCAAGGGAGGTAGGT[CG[AATGAAGAG

GGTTGTGTGAGTTTTG[CG[[CG[GGCAGG[CG[GGATAA[CG[GAGGAGGGAGGCC[CG[[CG[GC[CG[AGGCT[CG[GG[

CG[GG[G[GGGGGGGGGGGG[G[GGGTT[G[[CG[G[CG[[CG[CACTCCCAGGCAGGCCC[CG[CCCCCT[CG[G

C[CG[GCTGTG[CG[[CG[CTGATTGGCCCCTGC[CG[GCCT[CG[[CG[CTCCCT[CG[CTC[CG[GGTTGG[CG[GGAGACCT

TAGAG[CG[GGTAC[CG[CTGCTGGCTAG[CG[AC[CG[A[CG[AGCAAC[CG[TCTGAGGCCAGGAG[CG[CTG[CG[A[C

G[GAGCCTTGAC[CG[C[CG[TTGCC[CG[GCCCTCTCC[CG[[CG[CAGCCC[CG[GGCTTC[CG[CAGGTACCTGTGCT[C

G[CCCC[CG[GGAAGGGGCCT[CG[CAGG[CG[AATCTCCAGTTT[CG[AGTGTGCC[CG[GTCCCTGGGTT[CG[CT[CG[C[

CG[[CG[ACCCCAC[CG[CC[CG[CCTTAGATGAGAAGGCAG[CG[CTCCAGCCT[CG[TCCTCA[CG[C[CG[CCTCC[CG

GGG[G[CCCTAGCTGCTT[G[[G[[G[A[CG[ACACA[CG[[CG[CTCCC[CG[CAG[CG[GGCTCTGGGCTGAG

SEQ ID NO: 630

ACCTCCCAGC[CG[TCTC[CG[C[CG[CC[CG]AGCATCCTTGAGGTGGGA[CG[AGCAGGGGCTTGGATCCCTGC[CG[G

[G[TCTGGTGTGTGAGGCTTGCA[G[GCCCCTGGCTGCCC[G[[CG[CCT[CG[C[CG[GAGCC[CG[AGGGGG[CG[

CAGGTC[CG[GGG[CG[AGGGC[CG[[GC[[CG[GGCTGTTTGATGGCTTCACTGAGAAGAGTCAAAGTGCTGTTGGTG

TTGAACTTGAT[CG[[CG[GTAGC[CG[GCTT[CG[TGCTCTTCCTGGCCAAGTGC[CG[GCCCAT[CG[[CG[GTG[CG[CAG

[G[GAGA[G[CCTTCCA[G[AGATC[G[[G[[G[[CG[C[CG[AGGTGGCCAACCTCAG[CG[[CG[CACAG[CG[C

CAGCCCCATCCAGGATG[CG[GTCCTGAAG[CG[CCTGT[CG[CTGCTGGAGGACAT[CG[TGTAC[CG[GCAGCTGAAT

GGTAAGGA[G[A[G[[G[[G[CCT[G[GGGCT[G[A[CG[[CG[GG[CG[GGC[CG[GGCACAGGGTGAGCCCC

AGGGTCCTTG[CG[[CG[CTG[CG[CCCTGTGCCTGGGAGC[CG[GCACACCCTGGCTCC[CG[[CG[[CG[CTCCTTCTTAC

CCTTCCTGCCC[CG[TTT[CG[GGCAGATGGC[CG[GGGCTGCTGGAAAGAACAACTTGCCTGATTCT

SEQ ID NO: 631

TATTC[CG[CTCCCCCCTAGACCTCTATTCCTCCCACTTCTTGTTGCCAAACTT[CG[C[CG[ATTCTCACCAC[CG[CTC

CG[G[CG[[GCTCCAGGGCCCCCC[CG[GAAGAGTTGTCCATGTTCCAGCTGCCCACCCTCAACTTCT[CG[C[CG[GAG

CAGGTGGCCAG[CG[TCTGTGAGA[CG[CTGGAGGAGA[CG[GG[CG[ACAT[CG[AG[CG[[GCTGGGC[CG[CTTCCTC

[CG[[CG[C[CG[TGGT[CG[CCTTCCACA[CG[GGCAACTTC[CG[[CG[ACCTCTACCACATCCTTGAGAACCACAAGTT

CACCAAGGAGTCTCA[CG[GCAAGCTGCAGGCCATGTGGCT[CG]AGG[CG[CACTACCAGGAGGC[CG[AGAAGCTG[

CG[[G[GC[G[CCCACT[CG[GCC[CG[GTGGACAAGTAC[CG[[CG[TG[CG[CAAGAAGTTCC[CG[CTGCCA[CG[CA

SEQ ID NO: 632

[G[[G[GGG[G[[G[[G[[CG[C[CG[CAAG[CG[CCCCCTGCAG[CG[[CG[GGAAGC[CG[CCCTACAGCTAC

AT[G[[G[CTCAT[G[CCATGGCCAT[G[[G[CA[G[[G[CC[CG[AG[CG[C[CG[CCTCA[CG[CTGGG[CG[GCATCT

ACAAGTTCATCAC[CG[AG[CG[CTTCCCCTTCTAC[CG[[CG[[ACAACCCCAAAAAGTGGCAGAACAGCATC[CG[CC

TACTGGG[CG[CTTGACCCCAA[CG[[CG[GAGGACATGTT[CG[AGAG[CG[GCAGCTTCCTG[CG[C[CG[C[CG[CAAG[

CG[CTTCAAG[G[CT[G[GACCTCTCCACCTACC[G[GCTTACATGCA[G[A[CG[[CG[G[CG[GCTGC[CG[CAGC[CG

TACTAC[G[[G[G[CG[T[CG[CC[CG[GCCCTTGC[CG[[CG[TCTT[CG[GCCTGGTTCCTGAG[CG[GC[CG[CTCAGC

CCAGAGCTGGG

SEQ ID NO: 633

TCAGCAGCCTGCTGAGGAGTGGGGA[CG[[AAGAGCAGCCTAAACTTAGGGCT[CG[GGATATTT[CG[ATGCCACCC

TTA[CG[T[CG[CAG[CG[AGATCTGTGCTGGGATAATTAGAGAGGAGTTGGGCTGAGC[CG[AGTCCTCTTTCAGCAG

CAGCAG[G[GAG[G[[CG[C[CG[CAGCC[CG[GTGGGGCAACCCTGACT[CG[GAC[CG[CT[CG[GGAGAGCCC

CAGGAGAGGCCAG[G[[G[[CG[CAGCAGC[CG[CCC[CG[CTG[CG[CCCACCTCCC[CG[GCTGCTCC[CG[GAGGG

CTCACAAAGG[CG[GTGGC[CG[CC[CG]AGTGGCCTTCTCCATCCAGG[CG[TT[CG[[CG[TCCTCCTCCCCACCTTCT

CTCC[CG[AAGG[CG[AAAATGGCAGGGCCAGG[CG[AGAACCTGGGACAG[CG[[GTGGCCCTAGCCCTG[CG[ATC

CTCACCCCTCCTGCTAGGAGAGGCTG[CG[GGCTGCC[CG[[CG[GA[CG[ATGTGGC[CG[[CG[[GCTGCTCC[CG[AG[C

G|CATCTT[CG[GCC[CG[GGTCCC[CG[C[CG[CCACCCCTCTTCTCTGCTCCTTCCATCC[CG[CCC

SEQ ID NO: 634

GGTGTCTTCCC[CG[AGACTCTGGTACTGTGAAGGGTC[G[GGT[CG[[CG[[CG[GGG[CG[T[CG[TC[CG[GAGCAGGG[

CG[GACT[CG[GGCTTTGG[CG[[CG[GCCTTTGCCC[CG[GTTTTTGG[CG[[CG[GGAGGACTTT[CG[ACCC[CG[ACTT[C

G[GC[CG[CTCATGGTGG[CG[G[CG[GAGGCAGCTTCAAAGACA[CG[CTGTGACCCTG[CG[GCTCCTGA[CG[CCAGCT

CT[G[GT[CG[GGAC[CG]AG[CG[GGTCTCTCCA[CG[GCAAC[CG[C[CG[A[CG[TCA[CG[AA[CG[TACAACTGTAC[C

GT[G[[G[AGAGGA[G[TAG[G[[G[GTGATTGG[G[[CG[C[CG[CTG[CG[GCTG[CG[CAGGAGA[CG[A

CCCC[CG[[CG[GG[CG[CTCCCACCCCCATCT[CG[[CG[[CG[GACT[CG[CTTTAGGTCT[CG[G[CG[]AGTTTCTCTGAT

ATG[CG[CT[CG[[CG[GGGGTGCTGCCATTTCATCTCTTC[CG[[CG[[CG[GGCTCAT[CG[TGCTCTCAGGGTCT[CG[TTG

AACAAGGCAA[CG[CTAAGAGCCATCACCACCTGTCCCCCATCACCTGTTTTCTAAACTAAACATCTTCAGCTCCTC

CAGTTATCTCTTGTGGCATCTGTCATGAAGAAAGTGCT[CG[GG[CG[TGTGTGTCTCTCTTTGA

SEQ ID NO: 635

TCTCTGACACCTTGGGGATCTTCTGCAGCCCCACCTTGT[CG[CAGATGA[CG[TGCTGCAGGT[CG[CTGTGGCAGTG

GCAGTTCTGGGGGCAGG[CG[GCCAG[CG[C[CG[GCAGCAGACCAGCCAGGAGGC[CG[AGGCTGAGCAAGAGCAT

CAG[CG[G[CG]AGTCCTAGG[CG[CT[CG[GGTCTGC[CG[CCCTCTTTATA[CG[GTGGCCCTGAC[CG[CAGC[CG[[GCA

GC[CG[AGCCAGCTCCTA[CG[TGGAGCAT[CG[]AGGCCACTGGGCTTAACT[CG[CT[CG[[CG[CCCAGAGATG[CG

[CCCC[CG[CCCTCCA[CG[GGGAAGGGGG[CG[GGGC[CG[TTCCCCCAGC[CG[GCTAC[CG[TGCATGAGGGGGTGGG

AC[CG[[TGGCCCC[CG]AGCCC[CG[AGCCCTGAGCCC[CG[GCTGTAGCCCCC[CG[CTCTCCTATGGTGCTCCTCTGC

CTAC[CG[[CCTTTCC[CG[GGGCTTTTCTGGGAAGGGGGAATAGTTATGTCTGGAGCCC[CG[AGTTTACAT[CG[GA

GAGAGGGAGG[CG[TTCCCTCAACTTATTTGTTTGCTCAGGTTTGAGCCTCCA[CG[[

SEQ ID NO: 636

CCACACAGGGTG[CG[GG[CG[GGG[CG[GG[CG[GGGCTGGGGTGT[CG[GGGGCT[CG[GATT[CG[GAGCCAGCTCTG

C[CG[TGGGG[CG[GGCTGGGGCAGGCTTCC[CG[CTCTGGGAAATTTGCCCCTGCTCTCCCTGCCAGTTG[CG[GT[CG[

TGGG[CG[GCCT[CG[CCTTGGAGCCCTGGCCA[CG[GAGC[CG[CA[CG[GGG[CG[GTAGAGAGGCTGGTGGGGAGGG

ACCAG[CG[GG[CG[GTGGAGGGG[CG[GCCCTGCAGG[CG[A[CG[[CG[GGGACTGGAAAGGG[CG[CCTGGGTGGGAA

GAGG[CG[CTGG[CG[GGTGAT[CG[TCCCCAC[CG[GGCCAGTCCC[CG[GGATCTGCTGC[CG[CCCCTCTC[CG[AAAT

TCACAGCCAGAG[CG[GG[CG[CACTGGTGTGTGTGG[CG[CCTGGAG[CG[CTAGGGTCCCCACCCAAGTG[CG]AGGC

CCC[CG[[CG[GGGAGCCCAGCCCAGGGG[CG[TCCACAGTCCAGGCCCCAGACCCCAGGTCCTGGCTAGATT[CG[CC

AAAGTCAGAGGCTGGAATCTGGAGGG[CG[GATGTGAGGGTGCCAGCTAAGCCCAGCCCCTGCC[CG[G[CG[GTGG

CCAGCATAA[CG[[CG[GTGACACTCTCTGGAGCCCCCACTGCCACCACTC

SEQ ID NO: 637

ACCAGAG[CG[CCCAGCTAAG[CG]AGCTGCCTCCACCCCCACTGTGT[CG[GG[CG[G[CG[CAAACTG[CG[GG[CG[CA

GGCAGAGGAG[G[[G[GCTCTG[CG[C[CG[GG[CG[GGAGC[CG[AAGCCCAGAGCCT[CG[CCAGGGCCTCCC[CG[

C[G[AG[CG[CACTTAC[CG[T[CG[CTGAGGCAGAG[CG[[CG[GTCAGCA[CG]AGGACCAGCA[CG[ACCA[CG[ACCTT

GG[G[TTCATGG[G[[G[[G[[G[[G[[G[[G[GA[G[AG[CG[[CG[GGT[CG[GGGGC[CG[GA[CG

G]AGTGCTGGC[G[TGGC[G[GGGTCTCTGA[G[[CG[[CG[ACTCCCT[CG[G[CG[GCACCCCCCACCCATCCCCTT[C

G[CCCCTCCTC[CG[CTCCCTCTGTGCTCC[CG]AGG[CG[CAGTG[CG[CTC[CG[GCCTTTGACCTTCTCAGGCTC[CG

]CTGGGCCC[CG[CAC[CG[CTGGCC[CG[GTCTGCAGTGAGGTC[CG[CAGCCTGAG[CG[A[CG[C[CG[GCTGGAGGG

C[CG[CTTATTGTC

SEQ ID NO: 638

G[CG[[CG[GTCAGCA[CG[AGGACCAGCA[CG[ACCA[CG[ACCTTGG[CG[TTCATGG[CG[[CG[GG[CG[GG[CG[GG[CG[

GG[G[GG[G[A[G[A[G[[G[GGT[G[GGGGC[CG[GA[CG[C[CG]AG[CG[GGCAATG[CG[GCTGA[CG[GAGAG

TGAAAGT[G[[G[GGGGGG[G[[G[[G[[CG[GG[CG[CTTTAGAGGGGAGAGCCAGG[CG[GGG[CG[

GGG[G[GGG[CG[[CG[[CG[GTGAGGGG[CG[GGCC[CG[GAGC[CG[AGTGCTGGC[CG[TGGC[CG[GGGTCTCTGA[CG

][CG[[CG[ACTCCCT[CG[G[CG[GCACCCCCCACCCATCCCCTT[CG[CCCCTCCTC[[CG[CTCCCTCTGTGCTCC[CG[A

GG[CG[[CAGTG[CG[CTC[CG[GCCTTTGACCTTCTCAGGCTC[CG[CTGGGCCC[CG[CAC[CG[CTGGCC[CG[GTCTGC

AGTGAGGTC[CG[CAGCCTGAG[CG[A[CG[C[CG[GCTGGAGGGC[CG[CTTATTGTCCCTGTGACAGGGCCCCACTG

GAGAGACTGAGGACCTTAGG[G[TAAAGTGGGG[CG[[CG[[CG[TGGAAAGCTG[CG[GGA[CG[GGGCCTTT[CG[AT

GG[CG[GGAACTGAATGAGAACCAATGAAAAGCAAACAAGTTAGTCC[CG[GG[CG[GAGGGCCTGCTGG[CG[GTGG

[CG[GCCC

SEQ ID NO: 639

TCCCCACCC[CG[CAAGAACCAGACCCTCTTCAGGACTGGGGGGGTTAC[CG[CTT[CG[CCTCCTCTACC[CG[GACTC

AGAAGCCCCAACCCAAGACC[CG[CCTAG[CG[T[CG[CTTGTCAGAACCCCTCTGTGGCA[CG[ACTTTGAGCAGAGG

G[CG[AGGGAAAGGAGGGTCAG[CG[TT[CG[GCCC[CG[TCCCCTGCCTGGGCTTTCTCCCC[CG[CTTCCC[CG[TCCCT

CCCCCCT[CG[C[CG[GTTCAC[CG[CATCCCCACAGGAGTCATAAAGATCAGGCCCCAG[CG[C[CG[GACACAAAGGC

CAAGGGTTCC[CG[GGAGC[CG[[CG[GGTATTCAGAGCCAGGAGAGGGGTCC[CG[G[CG[[CG[GAGGGTGCTG[CG[

GCCCAGCCTCCTGGCCACAGAG[G[[G[[G[GC[CG[[CG]AGGGAGGACCAAGGTCCCCAACCA[CG[CC[CG[[CG[

TGGAG[CG[CAGAGGGGTGTGCTTGGGAGGGGG[CG[GGAGGGCACTTTCCTCTGTGT[CG[GTGAAAGGAAGAGCTT

CCAGCTCCCTCCTC[CG[CACAAACCTTCACTTCCTCTCTTGTT[CG[ATC

SEQ ID NO: 640

GT[G[GGGG[G[GA[CG[C[CG[AG[CG[GGCAATG[CG[GCTGA[CG[GAGAGTGAAAGTG[CG[G[CG[GTGGGAG

GG[CG[GGCC[CG[GAGC[CG]AGTGCTGGC[CG[TGGC[CG[GGGTCTCTGA[CG[[CG[[CG[ACTCCCT[CG[G[CG[GCAC

CCCCCACCCATCCCCTT[CG[CCCCTCCTC[[CG[CTCCCTCTGTGCTCC[CG[AGG[CG[CAGTG[CG[CTC[CG[GCCTT

TGACCTTCTCAGGCTC[CG[CTGGGCCC[CG[CAC[CG[CTGGCC[CG[GTCTGCAGTGAGGTC[CG[CAGCCTGAG[CG[A

[CG[C[CG[GCTGGAGGGC[CG[CTTATTGTCCCTGTGACAGGGCCCCACTGGAGAGACTGAGGACCTTAGG[CG[TA

AAGTGGGG[CG[[CG[[CG[TGGAAAGCTG[CG[GGA[CG[GGGCCTTT[CG[ATGG[CG[GGAACTGAATGAGAACCAAT

GAAAAGCAAACAAGTTAGTCC[CG[GG[CG[GAGGGCCTGCTGG[CG[GTGG[CG[GCCCAAGGCAGC[CG[AGGGGGT

CCTGC

SEQ ID NO: 641

CC[CG[GGGAGCAG[CG[CAAGGAGGAGGGT[CG[GA[CG[GGTCTCAGCCCCTCCT[CG[CCCCCAGGTACCCACTCCA

TAAGGTATTTAGCAC[G[[G[TGTCC[CG[GC[CG[GGT[CG[[CG[GGGAGCCC[CG[GTACAT[CG[CAGTGGGCTA[

CGTGGA[G[ACA[G[CAGTT[G[TG[G[GTT[G[ACAG[G[A[G[[CG[G[CG[ACTC[CG[AGGATGTAGC[CG[CA

GT[CG[C[CG[TGGTTGGAGCAGGAGGGAC[CG[GAGTATTGGGAC[CG[[GAGCACA[CG[GAACATCAGGCC[CG[[CG

]CACAGACTGACAAGAGTGAACCTGCCCATGC[CG[[CG[[C[CG[CTACTACCACCAGAGCTAGGC[CG[GTGAATGA

CCC[CG[GCCTGGGG[CG[AAGGTCA[CG[ACCCCTCCTCATCCCCCA[CG[GA[CG[TCC[CG[GGTCCCCCC[CG[[CG[A

GTCTC[CG[GCTCCAAGATCCACCC[CG]AGGCTG[CG[GGACC[CG[CCAGATCCT[CG[ACC[CG[[GGAGAGGCCCA

GG[CG[CCTTTACCAGGTTTCATTTTC[CG[TTTAGGCCAAAATCCC[CG[[CG[GGTTGGT[CG[GGG[CG[GGGG[CG[GG

GCT[CG[GTGGG[CG[GGGCTGAC[CG[[[CG[[GGGG[CG[GGGCCAGGGTCTAACACCCTCCAGATAATGT

SEQ ID NO: 642

CCTCCAGCCCCCAGG[G[GCC[CG[[CG[G[CG[GATCCC[CG]AGAGGCAG[CG[CAGCTCAGCCCCTG[CG[CCCCCCA

GCTT[CG[GGC[CG[GAGAGAC[CG[GGGTGGGAGCTGCCAGG[CG[[CG[CAGAACCATCCC[CG[CCACCA[CG[GGGC

]AG[CG[TGGGGAGAAATGGAGACCAGAG[CG[CATAT[CG[GGTGAGTGGGTCTCCCACTCCCTCCTCCAC[CG[CCT

TGCAGCCT[G[CCCT[G[[G[[G[CAG[G[GGGCTCCC[G[G[CG[G[CG[[CG[[CG[CTTCTCCACCTTCAATGAA

ACTTT[CG[AAGCCCTCACT[CG[GGGA[CG[GG[CG[TGTCCCC[CG[GCCAATGGGATGG[CG[GCTC[CG[GGGCCTG[C

G][G[[CG[[CG[GAGCC[CG[CCCCTGAG[CG[GCTGGGGAAGTGAGAGCCTTGCAC[CG[G[CG[[CG[GAGGGCAAGCC

CCCACC[CG[[CG[GCTCC[CG[[CG[CCTGGGAGAGACC[CG[GCCTGGCCTGCCAGTGGGCTG[CG[[[CG[[CCTTG

SEQ ID NO: 643

CCCCATCTC[CG[CAGTTTCTCTTCTCCCTCTCCCAACTTATGTAGGGTCCTTCTTCCTGGACACTCAGGATGTGGAC

TCAGTTCTCACCCCCATTTGGTGT[CG[GGTTTCTAG[CG[AAGCCAAT[CG[G[CG[T[CG[CTGGGGTCCCTGTTCCAG

AAGTCCC[CG[[CG[AACCCATTGGGACTCAGATTCTCCCCAGA[CG[C[CG[AGGATGGGGTCATGG[CG[TCC[CG[A

ACCCTCCTCCTGCTGCTCTTGGGGGCCCTGGCCCTGAC[CG[AGACCTGGG[CG[GGTGAGTG[CG[GGATC[CG[GAG

GGAAATGGCCTCTG[CG[[GGGAGGAGGTAGGGGCC[CG[[CG[CACTGGGG[CG[CAGGACC[CG[GGGAGCAG[CG[C

AAGGAGGAGGGT[CG[GA[CG[GGTCTCAGCCCCTCCT[CG[CCCCCAGGTACCCACTCCATAAGGTATTTCAGCAC[C

GC[G[TGTCC[G[GC[CG[GGT[CG[[CG[GGGAGCCC[CG[GTACAT[CG[CAGTGGGCTA[CG[TGGA[CG[ACA[CG[C

AGTT[G[[G[GTT[G[ACAG[G[A[CG[[CG[G[CG[ACTC[CG[AGGATGTAGC[CG[CAGT[CG[C[CG[TGGTTGGA

GCAGGAGGGAC[CG[GAGTATTGGGAC[CG[[GAGCACA[CG[GAACATCAGGC

SEQ ID NO: 644

TCTGTGCTGGGATAATTAGAGAGGAGTTGGGCTGAGC[CG[AGTCCTCTTTCAGCAGCAGCAGC[CG[GAGC[CG[[C[

[G[[C[CG[CAGCC[CG[GTGGGGCAACCCTGACT[CG[GAC[CG[CT[CG[GGAGAGCCCCAGGAGAGGCCAG[CG[C[C

G[[G[CAGCAG[CG[CCC[CG[CTG[CG[CCCACCTCCC[CG[GCTGCTCC[CG[GAGGGCTCACAAAGG[CG[GTGGC[

CG[CC[CG[AGTGGCCTTCTCCATCCAGG[CG[TT[CG[[CG[TCCTCCTCCCCACCTTCTCTCC[CG[AAGG[CG[AAAAT

GGCAGGGCCAGG[CG[AGAACCTGGGACAG[[CG[[GTGGCCCTAGCCCTG[CG[[ATCCTCACCCCTCCTGCTAGGAG

AGGCTG[CG[GGCTGCC[CG[[CG[GA[CG[ATGTGGC[CG[[CG[GCTGCTCC[CG]AG[CG[CATCTT[CG[GCC[CG[GGT

[CG[C[CG[CTGCTGAAGC[CG[[CG[GCTGATGGATGCCAGGGAGTGC[CG[CATTGCTTAG[CG[ACCC[CG[CCTCTG

GGTTTGCTGGTAGGAG[CG[GCTGCTCTTTCTTCTTTCTTGCTTTGGGGTTTTATAGAA

SEQ ID NO: 645

GCCCCTT[CG[GAAGGTCCCAGTCCCTGTCCATTCTTCTGTCC[CG[CAGCTCTCTC[CG[[CG[CAGG[CG[GGGCAGAG

C[CG[GGGAAGAAGA[CG[CTGGA[CG[AGGGGTCTTGGGGC[CG[CCT[CG[CTGGCTG[CG[GTTGGAAGCACC[[CG[[T

TTTCC[G[CC[CG[CC[CG[[CG[CAGG[CG[CTGCTCTGTGGCCACCAGCAGAGGTTTCC[CG[GC[CG[CTGTGAGT[CG[

CCC[G[[G[AG[CG[A[CG[TGGGGATA[CG[GGG[CG[CA[CG[GAGTCTCAGCTGC[CG[CCA[CG[CAG[CG[CTTGCC

CTGCC[CG[AGCTT[CG[GCTCACTGGCAG[CG[G[CG[AGGCCAC[CG[ACCACCCTC[CG[CCTTCCAGTCCTAAACT[

CG[GGGCTGGAGAC[CG[CAGGAGCTAAACCAGGAAGAAGAAAGAGGGCAGGGCCTGAGGC[CG[GGAAGAG[CG[

GCC[CG[GGGGTCAA[CG[GTGAG[CG[GGTGCATA[CG[AGGCAAGAGCCAGAGTGACATTAAGTGGGGC[CG[CC[CG

]GGCAAACCTTG[CG[[CG[TGCACCC[CG[GCCCACCTGCAGGGCATTCTCCCCTGCCTTTTCTCCTTGGCTTGAGTG[

CG[GG[CG[GCTGACTCCTGTGGG[CG[GGGAGGAGAGGGTGGTCTTCCCAGGGCT

SEQ ID NO: 646

T[CG[GTTTCTC[CG[GG[CG[CAACCAGCAG[CG[CCACAAGC[CG[GTTGGGTCCCCTGGCTCCCTCTCCAAGGCCAG[

CG[[CG[GTCATG[CG[GG[CG[GG[CG[GG[CG[GTGTTCCCCAGAGAC[CG[CCCATCC[CG[[CG[GTGGGGGTGGTGGA

AC[CG[[CAGAGGCCAC[CG[GATACAG[CG[ACCTCAGGCCTGGCAG[CG[CCCATGG[CG[GGCCCTGTGGCC[CG[GG

TACTG[CG[AAT[CG[C[CG[GGGCTTGG[CG[GCCTCTGGAACAGGGGCCTC[CG[CCT[CG[AGGAGG[CG[G[CG[GGAC

CTGAGGGGC[CG[TGGT[CG[CTGCACTTTGTC[[CG[AGACCCCTAGATTGGCCAATAGGAGAC[CG[GAAAGGTGCA

GGGAGGGCCAGTGGGGC[CG[ATGGGC[CG[GGGCCC[CG[GACAGGCTGG[CG[[CG[GGGTT[CG[GGGGTTCTCTCCT

GTCTCTGA[CG[CCTGCCCC[CG]AGGAGGCAGAGCTGGGCAGCCCTGGGCCTC[CG[C[CG[AGCCCAGCTTTCCTAA

GC[CG[GGAAGT[CG[GGGGTTCCTGGGC[CG[GGTGGGAACTGT[CG[TCCCTGGAGGACCC[CG[CCCCTGAGATCCC[

CG[CCCCACATC[CG[GGTAG[CG[TGGGGGCACCTGGGGTTCC[CG[AGATGAGA

SEQ ID NO: 647

CAGCTC[CG[[CG]AATGCCCCTCC[CG[[CG[A[CG[GGGCCT[CG[CTCTGGGCTCCC[CG[CCTAGATCTGGGC[CG[CTG

GGGCCAGGGGTG[CG[GTGGGG[CG[ATGGTCTGTGACCCCTG[CG[[CG[GCTCAGAGCCTAGGGGACAGGGGCAG

GAG[CG[GAAAG[CG[[CG[GGCCTGATTAC[CG[GA[CG[TGGAGA[CG[CTGT[CG[CTG[CG[CTTCTGG[CG[GC[CG]AG

[CG[CAGG[CG[G[CG[GA[CG[GCTGGGAGCCAG[CG[GGGCAG[CG[GGCT[CG[GGGCCCCTGGG[CG[GCAGGAA[CG[

GA[G[TC[G[CTAGGGGGGGGTGCT[G[A[G[GC[CG[[CG[G[CG[GCTG[CG[TGC[CG[AAGCCACAG

AGGAGGC[CG[AGTCCCAG[CG[GTAGGGCCCCA[CG[[CG[CCAGGCTGGAGC[CG[TCAAGCCC[CG[GGCC[CG[GGC

A[CG[G[CG[[CG[ACTGC[CG[GACCCT[CG[CAGCCAGATCCCTGTCCTGGGCCAG[CG[GG[CG[C[CG[GCAGCT[CG[G

CCTCCAAGCCCAGCAGGTC[CG[TGATGG[CG[AAGCCC[CG[GGGG[CG[[CG[AGCCCCTAGGGGAAC[CG[CCAGGC

ACCAG[CG[CCCTGCTGCTAGTG[G[CC[CG[T[CG[GAAAG[CG[AGTCC[CG[GC[CG[GTCATGGTTCCTTAGCAAG

SEQ ID NO: 648

TTTGCAAGGTTGTTGTAAGGGCTGAATGAAGTAA[CG[GGAAATCTGGGGTA[CG[[TGGGAGATAGTAAATGGCAG

C[CG[TCCCTGTG[CG[CCCCCTGACACCTCC[CG[CC[CG[GTCCTAGCCCTGTACTGGGTCAGTGTCAGCATCCTTCC

A[CG[[CG[TGCTCTCTCTCTGCCAC[CG[[CACACCCAAAGAC[CG[[CG[CCTCT[CG[CTGCTCTCACCTG[CG[GGGCA

G[CG[GAGGG[CG[CAGAGGTCAGGCAGCTG[CG[GGAGGGCT[CG[TGAGAGCCAATGAGAG[CG[[CG[GAAGG[CG[G

[CG]AG[CG]AGCCAATGGA[CG[[CG[G[CG[[GTGGGGCAGGGGG[CG[GGGCCTGGG[CG]AGGC[CG[GGGG[CG[GAA

TGGGCTGAGTGCCCTGTCTGAATG[CG[GGGAA[CG[TCTGGGCCTCCC[CG[CCTGGCC[CG[CTCTTTTAC[CG[T[CG[[

CG[CAGGCCC[CG[CTCCAGGCCAGCCACTGGCCCCACCAAGCCC[CG[CTT[CG[CAGCC[CG]AGAGAG[CG[GGAAT

AAATTAAGCTATTCTTAGTAGGGCCTGAAAAGGAGCCCTTTCTGACTACTAAGAAAACAAAGTTG[CG[TC[CG[TCT

CTAGTTCTCAAACCCAAGCACAGTGATGTGGGT[CG[CC[[CG[[GTGCT

SEQ ID NO: 649

CTTGGAAGAGGAGAGAAAGAGAGT[CG[AAGA[CG[CCCTGTCAAGATGCCACTCACCTAAA[CG[CCAGGAACATC

TCCC[CG[[ACTAAGGACAGGC[CG[ACCCCCAGCAGGACCAG[CG[CCA[CG]AGCTTCCCCATGGTCT[CG[GGGTGC

CCAG[G[[G[ACTG[G[[G[[G[[G[AGAGCTCT[G[GGGG[CG[[CG[G[CG[GG[CG[GTTCCTGCCT[CG[[CG[

TA[G[GATTGGGGCC[G[CT[CG[GCCC[CG[CC[CG[CACA[CG[CCTCCTACTTACCTGAG[CG[GCC[CG[GGTGC[CG

CAGCAGGG[G[CTGA[G[AGTCC[G[[G[AGCCC[G[C[CG[CC[CG[GGTTCAAGGC[CG[CCTTCA[CG[CCCA

[CG[ATTCCTTGTTTTTTGGGCAGAGGTCAAGGCTCAA[[CG[[GAGAGGGAGCC[CG[GGAC[[CG[[AGTTGTGGTGGG

AGTTTGCTCCTAACACC[CG[[[CG[AAATCCTACCTCAATTCCTCAGATGGCCTGAGGGAGAAAC[CG[GAGGGCC[C

G[GGAATGG[CG[GGGAGCTCCAGTTCAGAGC[CG[GAACTC[CG[GACTTCTGCAAGGCCAGA[[CG[[TGAGG[[CG[[A

CACTAATTGCTCC[G[AGA[G[[G[GGAAGGG[CG[AAGGCAAT[CG[AAG[CG[[AAGAGCTTTAACT

SEQ ID NO: 650

GGG[CG[G[CG[GTAGGAAGCCACCACCA[CG[GCCAGCTTGCCAAGG[CG[[CG[TGTG[CG[GGAAGCAGGACAG[CG[

CCTGCTG[CG]AGAGCA[CG[AAG[CG[GCTGC[CG[CCCA[CG[TTGAC[CG[TGAAGCAGTCCC[CG[AG[CG[CCAAGGG

CTCCCCTTCACCCT[CG[CTGCAGAAGACACTAGAGTCCAGGGAGGTCAGGGAGC[CG[CTGTCCAG[CG[G[CG[AGT

CCAGCAG[CG[CTCTGC[CG[CTGGAAGGCATCTCTAACCCAGT[CG[C[CG[[CG[GCCTGAGGG[CG[CCACAAAGTTG

GGGACA[CG[C[CG[GAAGCTTTGGTCC[CG[[CG[AGGG[CG[GTGGCA[CG[GCCCCTGGTGG[CG[GC[CG[GGATTCC

C[CG[GGCTCC[CG[AAGGGGTTACCTCTCCTTGG[CG[CACCCTCTCCACC[CG[CTGTG[CG[CCTTCCTCCTCCTGC[C

G[CTAGGGAGC[CG[GGAGTG[CG[[CG[GAAGCAG[CG[CACAAGTGGCAGAAAGAGGAGACAGGGAGCAGAGGAA

GGGT[CG[[CG[[CTAAGAGAGAGGATCAGGTGAGGTCCAAGCC[CG[ACACAGTCCCTGTGCACACTGC[CG[GT[CG[

CCCTGGCCCTTCCCAAA[CG[TTGTCACCC[CG[CCTCCCAACTT[CG[CAATTG[CG[[A

SEQ ID NO: 651

AGAAGTTTCAGACCCAGGCATATTTGGGAAGG[CG]AGTGCTTTACATGATTCCCCATTTCCCAAT[CG[GACCAGCT

TAGCCTGGGCAGGCAGCCT[CG[TGCTGAGGTGCCTGGAGAC[[CG[[CCCACCCCCTAGGTGCT[CG[CTTCCCCC[CG[

GGTCTGACCTGAT[CG[AAGTAAATGATG[CG[[CG[TCTTGTTGCTCATCT[CG[GATGGCT[CG[TGGTTGGTGCTC[CG

[CAC[CG[C[CG[AGAAGG[CG[ACCTTGGAGTTGGC[CG[CC[CG[GAC[CG[ATATCCCCAG[CG[GGGAGGAAGAGGAG

CCCTTGGAGTC[CG[TGGC[CG[[GGTT[CG[AGT[CG[CACACCACCAGACACTTGCCCTCCAGCA[CG[ATGGGCTC[C

G[TGT[CG[TTCTGTGCCCAGA[CG[GGCAGCCC[CG[GCAG[CG[TGAGGACCAGCAGCA[CG[GC[CG[GCAC[CG[[CG[

GACAG[CG[CC[CG[G[CG[CC[CG[GAGCCCATGGTGAGC[CG[TGTGGGCAGC[CG[CAGC[CG[GCTGG[CG[CTGGTGC

T[G[CC[G[[CG[T[CG[CCTCCTACCC[CG[GGATCC[CG[GTGCT[CG[GGAAGATGCTAG[CG[GCTAGGT[CG]ACAG[

CG[CTGCAGGAG[G[A[G[[G[[CG[G[CG[G[CG[[CG[CACACTTCCACCAATTCTG

SEQ ID NO: 652

TGAGATT[CG[CTTTCCTCC[CG[TGTAGAA[CG[ATAATAAAAAGTGGTACTAATTTCA[CG[AGCTTTAATAGGATTG

AATGTGAGCCCAG[CG[CTTGGCACAGGGCAAG[CG[[CCCCATAAAATGGCAGTTAGGATTAAAAT[CG]AGGTTGC

GCTTTGACTTCTGATCCCC[CG[AAG[CG[CTCTGGGGTCCTTTGGGCCCCACCCCCACCCACCCCAC[CG[G[CG[GGT

CTTGGGCTC[G[AACCCAGGG[G[CCC[CG[[CG[CAC[CG[AGC[CG[TTG[CG[TTTGAAACCCACAGAAAGAATT

G[G[CG[[CG[GCTGGGGCAGGGGTCTGCTGGGGGC[CG[GGGACTAAGGGCTGTGGGCCCATCCACACA[[CG[[CCTC

ATCCCTTCTTTC[CG[GGGGCAGCAGAGCAGCAG[CG[GGAGAC[CG[GGAGCAGGA

SEQ ID NO: 653

TCATCTG[CG[CCATGAGTGT[CG]AG[CG[[CTACCTGGCCATCAACCATGCCTATTTCTACAGCCACTA[CG[TGGAC

AAG[CG[ATTGG[CG[GGCCTCA[CG[CTCTTTGCAGTCTATG[CG[TCCAA[CG[TGCTCTTTTG[CG[[CG[CTGCCCAAC

ATGGGTCT[CG[GTAGCT[CG[[CG[GCTGCAGTACCCAGACACCTGGTGCTTCAT[CG[ACTGGACCACCAA[CG[TGA[

CG[G[CG[CA[CG[C[CG[CCTACTCCTACATGTA[CG[[CG[GGCTTCAGCTCCTTCCTCATTCT[CG[CCAC[CG[TCCTCT

GCAA[G[TGCTTGTGTG[CG[G[CG[[CG[CTGCTC[CG[CATGCAC[CG[CCAGTTCATG[CG[C[CG[CACCT[CG[CTGG

GAC[G[AGCAGCACCA[G[[G[[G[[CG[GC[CG[CCT[CG[GTTGCCTCC[CG[GGGCCACCC[CG[CTGCCTCCC

]]AGATCCAGATGGTCATCTTACTCATTGCCACCTCCCTGGTGGTGCTCATCTGCTCCATCC[CG[CT[CG[TGGTGAGT

GAC[CG[GGGCTGGGGCCCTACT[CG[GCCTTTTTCT[CG[CATCCACCTCC[CG[[CG[TC

SEQ ID NO: 654

GCAATCCCTAGATTCCCTGGGGACCA[CG[AAACTCCCATTC[CG]AGGAAACCTCCCCCCATTCCCCAGC[CG[CCCA

CC[CG[TTTCCCCCCCTTACCTCAGCA[CG[CAGCCCCTCCCTG[CG[TGATGATGCAAACCAGTGGGGAGGGCTGG[[C

G[[CTGGGAAGGGTGGGGAGAGAAGGAGAGCCAG[CG[AGGGAGGGAGGGAGTGGGAGGAGGAGGAGAGGGAGC[

CG]AA[CG[ACCATTTAAAG[CG[ATAGCAGTCCCTGCCCTCTCCCCAGTGCTGGGCTGTTGGAGAGAG[CG[[AGCAG

CAGGCTGGCAGG[CG[C[CG[[CG[GGACCCCTCACCCTCTCTGGT[CG[CCCCTCCC[CG[GATTCCCCCACCCTC[CG[T

GCCTGCAGGAGCCCCTGGGCTTTCC[CG[GAGGAGCT[CG[CCCTGAAGGGCC[CG[GACCT[CG[G[CG[AGCCCAC

CAC[G[TTCCCTCCAG[G[[G[[CG[C[CG[CCAC[CG[CAGCAGC[CG[[GAGCAGCATGGTCCAGCTGAGGAAGC

TGCTC[CG[[CG[TCCTGACTTTGATGAAGTTCCCCTGCTG[CG[TGCTGGAGGTG

SEQ ID NO: 655

TAAGAGAGAAGGAG[CG[AAGGAG[CG[GGG[CG[[CG[ACTCTTACCCCCCAGCCAGTTGT[CG[GAAATGTTCTGGA

GCATGGTGA[CG[GGAATGCAGAAGAAGGTGATGAGCAGGTCACTGAG[CG[CCAAGGAGCAGATAAAGATGTTGG

TGA[CG[GTG[CG[[CATGGCCTTGCTG[CG[GGTCACCA[CG[TAGAACACCAGAGCATTGCCAAAGAG[CG[CCAGGG

[CG[AAGATGAGCA[CG[C[CG[GTGAGCA[CG]AGGGCCAGCTTGG[CG[[CG[TCC[CG[GCAGCTCTGGGGTGTAGA[C

G]AG[CG[GT[CG[CAGC[CG[GTACAGAG[CG[ATGAACTGCTCC[CG[[CG[[TCAGGTTGTGGTCC[CG[CAGCAGC[C

G]AGAGAACTGCTC[CG[GGGTAATGTTAAG[CG[CCTGCATTGCTGTG[CG[CTCC[CG[GGA[CG[[CG[GGGCCAC[C

G[CC[CG[CTACTGGCTGGCCATC[CG[CATCTG[CG[GGGCAG[CG[AGGGCTT[CG[GGGGACCAGC[CG[GAGGC[CG[

CCTCCCTTCCTCTACTCTGGAGTCAGC[CG[[CG[[CG[GGAGGGCTCTAGGCTGCACCC[CG[GGAGGTT[CG[GGAA

AGGAGAGCAGCTCAGGGATCAAACCCA[CG[ATAAAGAGG[CG[GGAAGCCAAAGCACT

SEQ ID NO: 656

CTTACAGGACCTGCCCTCTGAGT[CG[[CCAGGATATTT[CG[GGGGCACACTCTCCTTGA[CG[TCTGGCATTTTGCT

GATGGTATCTGGGTGAGGGAGAAAGG[CG[TGTTGTTGG[CG[T[CG[GGGAAGGGGCCTCCCCAATTGCCAAGGGG

GTCCCTGGGGG[CG[G[CG[GGAAGGGGGGTAG[CG[GCCTCAGGGTCTTGGGGGTGCTGAGGGGCAGAAAGGGGCA

AAGGAG[CG[TGGAGGAG[CG[GAAGT[CG]AGAGTGGGACAGAAGTGGAG[CG[CTGGG[CG[GCAA[CG]AGGAAAC

TAAAGCCACAGAAGCC[G[G[CG[CAGGG[CG[GGAAG[CG[TGGGAAGGCCCCTTCCTT[G[[CG[G[CG[AGGTG

CCCCCCT[G[[CG[AAA[CG[C[CG[GCCCAGGCC[CG[CCTC[CG[GCTCCCAGGC[CG[TCACCTCCTCCTCCCC[CG

]C[CG[[CG[GGTCATCCACTGG[CG[TC[CG[CT[CG[GTGGGCCT[CG[[CG[GCCTGG[CG[GCCTGGAG[CG[TACCAC[C

G[[G[G[CG[GAG[CG[G[CG[GGTTGGGG[CG[T[CG[CA[CG[GTGAGAAAGGC[CG[GGGCCTGAGAACAAAC[CG[[C[[

CG[[G[GT[CG[C[CG[GGGCAA[CG[GGA[CG[GGGCA[CG[TGCCCCCCC[CG[CCAGAGC[CG[GAAG[CG[G

SEQ ID NO: 657

GGCTCACAGGCAGTCACACACCTATA[CG[[GGCTGACAC[CG[CTAAGTGAACAGGTGCAGACACAATGGCACT[C

G[GGGA[CG[GGCTCACA[CG[[CG[GTCACACACCTGCAGGAACA[CG[[CG[CACACTACACAC[CG[TTGCTCT[CG[CC

TCC[CG[GTATCACCTT[CG[AA[CG[[CG[CTGGC[CG[GCCCCCTCCTAGCCTGGTGCAGT[CG[GCTC[CG[CTTCTAC

TCAGTCT[CG[GGTCCTCCTGGGCCAA[CG[CAGACCCTGGTGCCTCCTTCCTTAGA[CG]AGCTAAGGTCAAGACTTC

TGCTGCTG[CG[GAGGAGCC[CG[[[CG[CACCAGGC[CG[GGGTGGACTG[CG[CCTG[CG[CAT[CG[GGCC[CG[CCTGG

TTCTTAGGAACTA[G[ACTCCCAGGGGG[G[CTG[G[[G[CT[G[C[CG[GCAC[CG[[CG[[ACTAAAGCTTGCA

AAGCCTGGGTCAT[CG[[AAACTACAACTCCCAGAAGGCTAAG[CG[TCTGCACA[CG[CTAGGTC[CG[CAGGG[CG[

CTGACCCCTGGGGGCC[CG]AGGAG[CG[C[CG[GGCTGCTGCCC[CG]AGCCC[[CG[[CCCACTACAGCCTCAGTGCAT

GG[CG[GTGGG[CG[CTTCCAGTAACTCAGGGGTGGGACTTTTTTCTTGCTCAGGGG

SEQ ID NO: 658

C[CG[[CG[GCTTGGGGTGCAC[CG[CTGCCCACC[CG[GCTCTTGGT[CG[[CG[GGGTCCTGGGGAGC[CG[[CG[G[CG[G

C[CG[CCAC[CG[CAGGAGCCTGCTGGAGGGTGGTGGTGATGATGGTGGCCT[CG[CC[CG[CCT[CG[CTCATGCCTCCT

GGGGGGT[G[[[CG[CAG[CG[GAGGCAGCT[CG[AGCTT[CG[[GGATG[CG[[CG[CT[CG[CTTCTTGGGCTCCT[CG[C

T[CG[ATCTTACTGCCCCCTTTTTTCTCTCCCTCCCTCCCTTCCTTCCTCCCTCCCTCCCTCCCTCCCTCCCTCCCTTCC

TTCCTTTCCTTTCTTTT[CG[TCTTTTTTTTCTTTCCTTTTCTTTCAGAGTCT[[CG[CTCTGTCACCCAGGCTGGAGTGC

AGTGGCA[CG[ATCT[CG[GCTCACTGCAGCCTCCATCTCCTGGGTTCCAG[CG[ATTCTCCTGCCTCAGCCTCTTGGGT

AGCTGAGATTACAGGCATG[CG[CCACCACACCAAGGCTAAT

SEQ ID NO: 659

GCCCCACCATC[CG[CTGACCTT[CG[CC[CG[GTC[CG[GCCTGGAGCC[CG[GC[CG[[CG[GCCTCCCTAGGCCTCTCTA

G[GG[CG[CCAGGC[CG[GGGG[CG[GGCTGGGGA[CG[CCCTGGGAGTGCCC[CG[GGGGC[CG[CCTTCTTCCC[CG[CA

]TGGGTAGAACAGACC[CG[[AGCTGGGAGCCAGGCCTG[CG[GCCCCT[CG[AACACTAGCCACATCTGGCC[CG[C[

CG[GGCCTAGCA[CG[GAGAGAGGCCCTGGGGCTTGG[CG[GC[CG[GGGC[CG[GGAGAGGT[CG[[CG[[CG[GCCAAG

GACACC[CG[AGGGCCTGGGCTGCCTCCC[CG[CCCTTCCC[CG[CCCCTCCCCT[CG[GCCCTGGAATCAATAGTGGC[

CG[CTGACTTTTCA[CG[ACAATTGCAGCTGTCTAATTCATCAG[CG[AATAATTAAATCAGAGGC[CG[C[CG[GGCCT

GCCTGGAGT[CG[GAGA[CG[AGGGGT[CG[CTCCTCTCAAATCCTGTCAAATTGGGGAGCCAGT

SEQ ID NO: 660

TTCCCAGTC[CG[[CG[GAAGCCAGGTC[CG[GGAGA[CG[G[CG[GGGCTCACTGTGCCTT[CG[GACCTACACTCTGCT[

CG[GGGGC[CG[GATTTCTGCAAAG[CG[TCCACTTGGAAAGAAGTTTCACTTGCAGGGAAGG[CG[GGTGTA[CG[CA

ATGATGGTC[CG[TGTGTC[CG[GGATGTGAATGCCAACCAAGACTG[CG[TC[CG[TTGGTGGAGTGTG[CG[[CG[GGT

CCTC[CG[TGAGGGTGCTTCTGGCAGTCACAGTTCA[CG[AGTTAG[CG[AGAAGATGGCTGGGAGG[CG[G[CG[AGCC

CC[G[CTCC[G[GGG[CG[[CG[CATTT[CG[AACTCCATAGGTATGGGTGAGTTGGTTAGCATTGGATT[CG[AGTGC

TTGTTCTTATCTGAGTACAGACACCTGGTAACCTT[CG[GGCCTGCAGAGGCCCCTGTGCTCCTTTGGAGGG[CG[CT

GCAGGA[CG[GGCTGGGTTGCATC[CG[GGCCTTTACCCCAGGTAGC[CG[GCAGCAAGTGAACTGGCCTGGATTGGC

[CG[GCCCAGGGCACCTCCACACACAGAGCCC[CG[[CG[GCACAAGGCAGCTGTGCAAAA[CG[GTCTCTAGAGGGG

CTGCCCT[CG[CCCTGGTGAATGGGCAGGAAGG[CG[TGTG

SEQ ID NO: 661

C[CG[TGCTAAGCCCCTGAGT[CG[CCTGTAGATCC[CG[TCTATTC[CG[TTCTTCAATTCTTCCCTTT[CG[ACCTCTAA

GGCAACCCAAAACTCCTTGCCCTC[CG[[CG[[CG[CCCCCAACCCCACTTCCCAAGCAGGCCCAGGCTGGGCTCCAA

GC[CG[GGCACTCACCAGCTGCAGCAAGCCAGGGACCACCA[CG[AGGGGCAG[CG[GC[CG[CAGG[CG[CATGGTGC[

CGGCTG[G[[G[GCTTTTCA[G[AGCTG[G[[CG[CCCT[CG[CCTGCCTCT[CG[[CG[CATCTCCACTT[CG[[C

G[TGC[CG[[CG[CAGCTCTGGC[CG[GGTGGG[CG[GGCAGGGAAGGGGGAGGGTGGG[CG[GAC[CG[GAGGTGCCTCT

[G[GCCCCC[G[[CG[[CG[CCCCTCCT[CG[GAGGGGGC[CG[GCAAAGAGCCTG[CG[GGGCAGCT[CG]AGCTC[C

G[GCA[CG[[CG[G[CG[GGGGGCTTCAGT[CG[[CG[CCTTGGACTCTCC[CG[CTTGGC[CG[GGCTTGGGGTGAG

SEQ ID NO: 662

CCCCTCATCTGGGG[G[[G[GTGGAGAAGGG[G[CACCC[CG[CC[CG[[CG[GAGACCCA[CG[[CG[CTCACCTT

TAGAAG[CG[GC[CG[C[CG[CTCTTGTGCCCTC[CG[GGTGGGACCA[CG[TGGGGAGGCAG[CG[GTGACCC[CG[GAGG

GTA[G[[G[[G[GGGT[G[GATTGG[G[[G[[CG[CC[CG[CCCCCTCCC[CG[CCCAGC[CG[ACCCTCCC

[CG[GCAGGAG[CG[[CG[GGC[CG[TGCAGGGTCT[CG[GGGGT[CG[[AAC[CG[TCCTGGAGGTCACA[CG[GCCCCAGA

GTTGCCTGTCCCAGGGGT[CG[CCCAGTC[CG[GAGGGT[CG[CTCCATCCC[CG[GGTCACA[CG[TCCCC[CG[ATTGCC

[CG[GCCCAGGGCTGCAGCATCCCAGCCTTGCAGAGG[CG[AT[CG[[CG[CCACCCACCCCAGA[CG[GGC[CG[CTCCC

TG[CG[[CG[GA[CG[CAC[CG[GGTT[CG[G[CG[CCTTGCAGGCTGCTGG[CG]ACCC[CG[CTGC[CG[GGTTTCTCCC[CG[

GACCTCA[CG[GCCTGGACAGCACACT[CG[GAA[CG[G[CG[GCATGCATTTGAAGCCAT[CG[CTGCCTG

SEQ ID NO: 663

TTTTG[CG[GCTTTTTGC[CG[C[CG[[CG[GCTTTTGGCCCC[CG[C[CG[C[CG[[CG[ACTTTTTTCCCCTGT[CG[C[CG[CA

GGTTTCTCCTGCCC[CG[GCTTCTTGCCCCCAC[CG[CC[CG[AGCTTTTTGCCCCCAC[CG[C[CG[[CG[GCTATTTG[CG[

GCTATTTGCACCTGCCA[G[[G[GAGTTTTGCCC[G[TAG[G[GCTTC[CG[GCCCC[CG[C[CG[CCA[CG[GCTTTT

TATCACCCC[G[[G[TTTTTGCCCC[G[C[CG[C[CG[[CG[GGTTTTTGCCCC[CG[CCCC[CG[TTGCTTTTTACCCC[

CG]C[CG[C[CG[[CG[GCTTTCTGCCCCTGC[[CG[[A[CG[AGGGTTTTTG[CG[GCTTTATATCCC[CG[CTGTCATGGCTT

TTTG[CG[GC[CG[TGGCTTTTTGCCCCCTCAGC[CG[TGGTTTTTTTG[CG[GCTTTTGGCACC[CG[T[CG[C[CG[CAGCT

[G[[G[[CG[GCTTTTTGCCCC[CG[C[CG[T[CG[[CG[GCTTTTTGCCCCCAATGC

SEQ ID NO: 664

CAGGAGATTTG[CG[GGGG[CG[GGCTG[CG[TCTCCAAGAGAG[CG]AG[CG[TCTCCAAGAGAG[CG]AGCTCCCTGTC

ATGGG[CG[GTGTCCACAAAATG[CG[CCTCTGTGGG[CG]ACAGAGGGGTG[CG[GTGGGGCCTAGGAGGCT[CG[TGG

G[CG[ATTC[CG]AGCAC[CG[[GGT[CG[GTCC[CG]AGTGAGGGGCCAGCCCTGGGGCTGGGAGGAAGG[CG[AGAGG

CAG[CG[CCACTGCTCCTGACTCCC[CG[GG[CG[ACTCCA[CG[AAGGAAGGCAGAGGGCTGAGCCCCAG[CG[[CG[GA

TCAGCCAAACT[CG[A[CG[GGCCCTTGC[[CG[[GTCACC[CG[TCCCTAACCCTGGTTGGGCTGGGAGGGGTCTTCT[C

G[CAAGTCTTCT[CG[CC[CG[G[CG[GAGGCTTCTCCTTCCCAACCCC[CG[[CG[A[CG[GG[CG[CATGCCTTAAGCTGCT

CT[CG[CC[CG[C[CG[GGCTCCTCTCT[CG[CTCCCAGGGCCTGGTGGCC[CG[[CG[GTGGCC[CG[[CG[TCCAT[CG[TGT[

G]TT[CG[GGGTCCTC[CG[GGAGCAGGTG[CG[AAGGA[[CG[[TGTCTGGAGTCTGT[CG[TCTGG

SEQ ID NO: 665

CG[[CG[G[ CG[[T[CG[GGAATGAGCTCCTC[CG[GCTTGTCC[CG[ACCACA[CG[CATCTTCCAGGGAAGCC[CG[GGA

AAATCAGCCAGAGGAGAAATGAGGCAGCAGTTTTGTTTTGCTTTTCCTTGAAGGGGGTTTAAAATAAAATCAAAT

CCTATCTGCTCCC[CG[CA[CG[AGC[CG[GCAGCAGGCACCAGAGA[CG[CAGGGACCTG[CG[[CG[T[CG[CATCCAG

[G[CCCCCCCCTTC[G[TC[G[[G[[CG[G[CG[GTGTG[CG[GCAGGCAGGAGCCCCCACAATCATCTGA[

CG]AGCCCACAGT[G[[G[[G[GCTGCCTGGG[G[TCATCC[CG[[CG[[CG]AGCATC[CG[CAGGCTGGGCTG

GGAGAGGG[CG[GGGAGGGGGAG[CG[GCTGGGGCTCTCTCTGCATCCCCCCCTCCAG[CG[TCCCCC[CG[GTCCCTT

GCAGCCTTGGAAGGTGGC[CG[GTGGC[CG[GT[CG[GGGAGGGGTGGGGGCTCCCTGGCAGAGGACTCAGGACATT

T[[CG[GTGTTAAAGCCCCTGAGGACACCAGCCCCCTCTGGGGATGATGAATTCA

SEQ ID NO: 666

CTTGGAGATTAGCCACCC[CG[TG[CG[CCCAGGTGAAAGATATCATTCTTC[CG[TG[CG[ATC[CG[AAGTGC[CG[TGG

AAGTTAGTGCCCTAGCCCAGTCCAGGAGGAAGGGG[CG[T[CG[TGC[CG[G[CG[GTTTTAAGCT[CG[GAAGGGGCAG

GGGAATGAGCCCAGGGACCCCAG[CG[GGG[CG[CAGGTAGGAGGCTGTG[CG[CT[CG[C[CG[GGTG[CG[CTC[CG[

GCCC[CG[ATTCCCAG[CG[CAGCCAGTAAGTGG[CG[CTGGGCCT[CG[GGTTTGG[CG[GCC[CG[GAGGAG[CG[GGCT

G[G[GATTACCTGCAGCAG[G[GGGAGC[CG[C[CG]AGCTCCTCCC[CG[CC[CG[CCCCCACACCCCACCCCCAC[

[CG[CTGCACTAACCC[CG[GCTCAGCTGGCTC[CG[[CG[CACTTGCT[CG[GAGGAGC[CG[GGGC[CG]AG[CG[GAC[C

G[C[CG[GCTGCAGGCAG[CG]AG[CG[[CG[GCTGGGCTG[CG[GGGCTGCTTCCC[CG[[CG[TCCTC[CG[GGCC[CG[GGC

SEQ ID NO: 667

CCCCAGGAAAGTGGGATTTGGGTGTT[CG[GGTCA[[CG[AGTGGGCTGAAGG[CG[[CCTCTACTCACCTGCA[CG[T

AGTCCAC[CG[AATCTC[CG]AG[CG[CCTTGAAGGCTGTGTACATGACCT[CG[[CG[CTTGC[CG[CCCCAG[CG[CTG[C

G[CCA[CG[CACA[CG[CACCTG[CG]AGTCCTCACCAG[CG[CCTCCACTGCCAGC[CG[CCCAGGATCCTC[CG[CCTCC

ACCTCC[G[ATAGGCT[G[[G[CCA[G[[G[[G[C[CG[C[CG[[CG[GGTTCCCAGGGCTGGTGGTAGTTGC

[CG[TCCCACA[CG[TA[CG[TGG[CG[GGGTCCT[CG[TCAG[CG]AAGACCT[CG[[CG[GAACATGT[CG[ACCATGTAG

AGGTCCT[G[[G[[G[GTTGCCATCCACCACATGAGGA[G[[G[CAGC[G[[CG[[CG[[CG[[CG[GGTACAGCAG

GG[G[[G[GG[CG[GA[CG[CCAGGCACTGG[CG[CAGGTA[CG[[CG[GGGTCCTCCTGGTAGG[CG[GAGATGGTCAGI

TCCAGGTA[CG[[CG[AAGAGGCTCTG[CG[CCACCAGGTG[CG[CTGAAAGGAAGGCCC[CG[TAGAGGC[CG[AAGG

SEQ ID NO: 668

TTA[CG[CCCTGGCACAGGTTCC[CG[G[CG[ACTGGTGTTCCCAAGGGAGCCCCCTGAGCCTAC[CG[CCCTTGCAGGG

GGT[CG[TGCTG[CG[GCTTCTGGGTCATAAA[CG[C[CG[AGGT[CG[GGGGTGG[CG[GAGCTGTAGAGGCTGCC[CG[[

CG[CAGAAAGCTCCAGGATCCCAATATGTGCTTG[CG[TGGAGCAGGGAG[CG[GAAGAGGCAGC[CG[GTCCTCACC

CTCCTCTCC[CG[CCA[CG[CACATATCCTTCTTGACTT[CG]AAGTGGTTTGCAATC[CG]AAAGTGAGACCTTGAGT

CCTCAGATGGC[G[GCAA[G[[CG[C[CG[AGGTCA[CG[CTCCCCAGAAACACCCCTCTCCCCTCCCCTACCCCAGC

TCCCCCTGGGG[CG[GGTGGTAATTGGGGGAGGAGAGGC[CG[CAGGCAGGGAAGGGGTGGGAAAGCCAGAGAGG

GAGGCACAAAGTGATGGCAGCC[CG[GCAAACACTGGGGCTT[CG[GGCTGGGC[CG[[CG[CT[CG[TTTAATCCCACA

AAAATCCCATTTTGGAGGTGAGAAATAGAGGTTAGAGGT[CG[GGCCCTTCTGGAGATCAGAC[CG[AGGAGA[CG[

GGCCCAGCTGG[CG[TCTTAAAGCAAGGAGGGGGAGT[CG[[

SEQ ID NO: 669

[CG[AGG[CG[CTCATGAACAAGTT[CG[GCTTCCAGTGGCC[CG[AG[CG[GCTG[CG[CTG[CG[AGAACTTCC[CG[GTG

CA[CG[GTG[CG[GG[CG[AGATCTG[CG[TGGGCCAGAACA[CG[T[CG[GA[CG[GCTC[CG[GGGGCCCAGG[CG[G[CG

]GCCCCACTGCCTACCCTAC[CG[[CG[CCCTACCTGC[CG[GACCTGCCCTTCAC[CG[[CG[CTGCCCC[CG[GGGGCCTC

AGATGGCAGGGGG[CG[TCC[CG[CCTTCCCCTTCTCATGCCCC[CG[TCAGCTCAAGGTGCCCC[CG[TACCTGGGCTA

[G[CTTCCTGGGTAG[G[[G[ATTGTGG[G[CCC[CG[TG[CG[AAC[CG[GGC[CG[TGCCAA[CG[GCCTGATGT

ACTTTAAGGAGGAGGAGAGG[CG[CTT[CG[CC[CG[CCTCTGGGTGGG[CG[TGTGGTC[CG[TGCTGTGCTG[CG[CCT[

CG]A[CG[CTCTTTAC[CG[TTCTCACCTACCTGGTGGACATG[CG[G[CG[CTTCAGCTACCCAGAG[CG[GCCCATCATC

GTGTG[CG[TGGAG[CG[CTTCT[CG[GA[CG[ATGGCTAC[CG[CA[CG[GTGG[CG[CAGGGCAC

SEQ ID NO: 670

[CG[[CG[G[CG[G[CG[TTTCCTGGGGCAACAGCAATGG[CG[GCCT[CG[CTGTC[CG[AG[CG[GCTCTTCT[CG[CTGGAG

CTGCTGGTGGACTGGGTG[[CG[[TTTGGAAGCC[CG[GCTGCTGC[CG[TCCCC[CG[CTGC[CG[CAGTGGAGCAGGAG

GAGGAAGAGGGGAAAAGGGGGGGGAGGCT[G[[G[[CG[[CG[[CG[GTCTGTGCCC[CG[C[CG[TGGCCT

C[CG[TGGCC[CG[GTGTCATC[CG[CTT[CG[GT[CG[[[CG[GCAAGTCCTGCCTCTTC[CG[CCTGCAGCCTGCTACCCT

GCACTGC[CG[GCTCCTG[CG[GACCC[[CG[CTTGCCACCTTGCTGCTGCAGCTGCCCCCTGGG[CG[CC[CG[A[CG[CC

CACCCCACAGCTCCTGGGGGCCTG[CG[ACATTT[CG[CTGGCCAC[CG[CAG[CG[CACAGGGT[CG[TGGGGC[CG[GC[

CG[CCTC[CG[GATGCTCCCAC[CG[TCAC[CG[GGGA[CG[TTTCCCCCTGCATAAT[CG]AGTGGG[CG]AG[[CG[[GACT

GGGGACATTGCACTGGCCTAC[CG[CCTGACTGACCTGGGAAGC[CG[CCTGCTGAGCCA

SEQ ID NO: 671

GGAGAGGCAAGTTG[CG[AGTT[CG[CAGGGCTTGGGAGTTTTTTG[CG[G[CG[GAAGAAGCTGAATCTAGGGGCTGA

GTCCC[CG[GGAAGGGATGGC[CG[CCTCTTAGCTTT[CG[CCAGGAGATTATCTTGGAGCCCAG[CG[GC[CG[AGAT

TGAGAGCTCTTTCTG[CG[[GAACCTGCCTC[CG[GAGTCAGATGAGCAAGGGGAC[CG[CCA[CG[[TCCTCAC[CG[A

GCTCCCAG[CG[GCCTTTGGGG[CG[GGTC[CG[GGGACAAGC[CG[GAGGACTAGGCTTCTCCCAGAG[CG[[CG[GCTG

TCTTTCC[CG[GAAAGACCCAAGTG[CG[[CG[ATGTCAGCC[CG[CCTGCACTTCATCTGAGTTGTCCTTATGTGGCC

ATTTCTGTTTCAAATTTCAGATTTTTCTACTAAAAAAGGATGGGTTAAAACAGCTGAGAG[CG[[CG[CCTGCTCTTT

CC[CG[CCCTGGGTTCTACATCTCTCTAGC[CG[CCCACCAGACTGCATCTCCAATCTGGGAGCTATCCTCACCTTG

GGAGGGTGGGGCAACAATGTTATTCT[CG[TTTCC[CG[ATAAGGAAACCAA[CG[TCCCTACAACTTGA[CG[TTAA

ATGGTCCCAGGTTCCTGAGCCTCAAATCTAGGACT

SEQ ID NO: 672

CACC[CG[GCCTCACCTG[CG[CTTCCCCACCAGGCCCTGTAGCAGC[CG[CTGGAGC[CG[[CG[[CG[CCCTCC[CG[CAG

G[CG[GCTGAGCT[CG[CTGGTGAA[CG[TCC[CG[TCTGAGTGT[CG[C[CG[GGCCCTG[CG[GG[CG[GT[CG[GGGGT[CG

]GGGTCAGGG[CG[CACTGGGGG[CG[GGTGGGGCC[CG[GGGGG[CG[GG[CG[GGCCTGG[CG[GG[CG[GCTCACCTGG

GGGG[G[[G[GGG[G[[CG[[CG[G[CG[GAGCCCC[CG[AGGAGCAGCAGCAGCAGCAGGAGGGGC[CG[GGGGGCC

ATGG[CG[GGGT[CG[GGG[CG[CAGGAGCTGAG[CG[CTG[CG[[GCCA[CG[GCCC[CG[GGCCCC[CG[CAAGGCCCCT

TTATGG[G[[G[[G[GAAGGGGA[G[GCC[G[GC[CG[[CG[CCCAG[CG]ATCC[CG[GGAAGGTCAGGGC[CG

TGGGGGGGGGGA[G[TC[G[GCCTGGGGGG[CG[AA[CG[GAG[CG[[CG[GGCCTGGGACC[CG[CAGAGGGAAC[

CG[CAC[CG[[CG[AAGCCT[CG[GAGCCTG[CG[GGGG[CG[GAGGGGC[CG[GAGGGCTTGGGGGAGGGTTTGGGGGG

GGAC

SEQ ID NO: 673

CACCCCACC[CG[GCCTCACCTG[CG[CTTCCCCACCAGGCCCTGTAGCAGC[CG[CTGGAGC[CG[[CG[[CG[CCCTCC[

GGT[CG[GGGTCAGGG[CG[CACTGGGGG[CG[GGTGGGGCC[CG[GGGGG[CG[GG[CG[GGCCTGG[CG[GG[CG[GCTC

ACCTGGGGGG[G[[G[GGG[G[[CG[[CG[G[CG[GAGCCCC[CG[AGGAGCAGCAGCAGCAGCAGGAGGGGC[CG[G

GGGGCCATGG[G[GGGT[G[GGG[G[CAGGAGCTGAG[CG[CTG[CG[[GCCA[CG[GCCC[CG[GGCCCC[CG[CAA

GC[CG[GCTGGGGGAGGGGGA[CG[TCC[CG[GCCTGGGGGG[CG[AA[CG[GAG[CG[[CG[GGCCTGGGACC[CG[CAGA

GGGAAC[G[CAC[CG[[CG[AAGCCT[CG[GAGCCTG[CG[GGGG[CG[GAGGGGC[CG[GAGGGCTTGGGGGAGGGTTT

GGGGG

SEQ ID NO: 674

TTC[CG[TTTTAAGTAAGAAGAAAATA[CG[TAATTA[CG[AAGGAGGCTTTACCTTTGGGAAAACAAAAAGCCACTT

TTGACCAATTATTCCCACAGATACACACC[CG[GGTCCCCAACCACC[CG[CCAGGAGGGCCCATCCTGGTGCCTGG

AAGG[CG[GGGGTTCCTG[CG[ATCTGGGGTTGGGATTT[CG[GCTCAGGC[CG[TG[CG[[CG[GTGGCCTTGGGT[CG[[C

G[CC[CG[CCCTGCCTGGGCCCCCAGCCCAAGGGAC[CG[AG[CG[GGTG[CG[GG[G[GGGGGGGGGGGGG

[CG[GGG[CG[GGGGTGT[CG[GGGGCT[CG[GACT[CG[GAGC[CG[TCCCTGCCAGTGGCTTT[CG[TGGG[CG[GCCC[C

GCCTTGGAGCCCAGGCCAA[G[AGC[CG[[CG[[CG[GGA[CG[GAAGAGCTG[CG[GGTGGGGAGGGACAAG[CG[GG[

CG[GAGAAGGGG[[CG[[GCCCTGCTGGAGGCCCAG[CG[AGTCTGAGTGATTGACAAGTGAATGAGCTGGGAATGAA

GACTCCTGGGGC[CG[GGAGGGAGAGAGGGGGTTGGAGGGTGGTGAATGCCTGGGCCTCTGGGGCTCCAGGCTGC

CAGTGGCC[CG[ACCAGGCTCT[CG[GTGTCCTCCTCCAACCTCAGTTTC

SEQ ID NO: 675

GG[CG[[CATGTTAGAGGCACAAAGATGAGAATGTTAAAAGACATAAAATACAGGTCTGCTCTGGGAATGCAAAA

ACTGGTAAAAGGAGAGATAAAAGAGCAGGTGCAGTCTAGTGAAGTACC[CG[[CTACCTCCTATCAGCAAATATCT

GTCCACCTAGGGTGCAG[CG]AGCTGGAGAGGAAGGGGTGGCCTAGAG[CG[CAGGGGAAGGATTCCTCCCCAGC[C

G[CCTGCACCCCTACCC[CG[GTAG[CG[GTCCCTGGGAT[CG[TC[CG[TGTCTCCAGGAGAAC[CG[GAC[CG[CTCTC

CCCCCCTCCC[G[AG[CG[AGAAAGGAGGACCACAGAGATG[CG[G[CG[CCCTC[CG[C[CG[TCCTAGAGCAAC[C

G[GAG[CG[GCC[CG]AGCCC[CG[GCCTCC[CG[GATGCTGGGGCCTGG[CG[GGTGTGGAGCA[CG[GGGAGT[CG[GG[

CG[TGGGG[CG[[GGCAGGGAGTGGAGT[CG[GGGTCTTACTC[CG[GTGGCTGCAGGG[CG[CAGGGTAGC[CG[TGTC

AGGCTGCCAGGTGCAGAG[G[CTCTTC[G[[G[ACCCCAACAGCCTCTGGTC[G[GTCTGG[CG[[CG[CCCT[C

G[CTTTCCCAGAGGG[CG[ACCTGGGCTATGG[CG[GC[CG[TGG[CG[CTGG

SEQ ID NO: 676

G[CG]AGGCAGAGAG[CG[[CG[ATT[CG[GCTCCAAACTC[CG[G[CG[CTGCAGC[CG[AT[CG[GACTCTGGGC[CG[[CG[

GTGGGCAC[C[[G[[G[CAGCTAGGGGC[G[AGAAC[G[[G[G[CG[AGCCC[CG[AGGA[CG[CCCAGAG[CG[[CG

]AGGGT[G[CTG[G[CCT[G[CAGAG[G[GAG[G[AGT[CG[AGC[CG[GG[CG[CC[CG[GGCTGCCTGGC[CG[[CG

[[G[CATGGGGG[G[CCCC[G[[CG[GCTCTC[CG[[CG[CTGCC[CG[CCAC[CG[CCT[CG[GCCAGTGGC[CG[GAGG

CCAC[G[[G[CCAGCTCC[G[GGCACCATG[CG[AAC[CG[CCC[CG[AGCCTC[CG[C[CG[CTG[CG[TCTGCCTGCTG

CT[G[[G[[G[ATCCTGGACCTGG[G[[G[[G[GTGAGTG[CG[[CG[GG[CG[CCTGG[CG[GGAGC[CG[AG[CG[GT

GAA[CG[TG[CG[[CG[GGGA[CG[GGGTGC[CG[GGGGAGGG[CG[CTGGC[CG[GGGT[CG[CTC[CG]AGAGGCT[CG[G

GCTA[CG[AGCAC[CG[GTCCTGCC[CG[GGGTCTGTGGAGCTGGTTGGCT[CG[ATGAGGGAGGGAGGA[CG[CCTCTT

GGAGAG[CG[CTCATGG

SEQ ID NO: 677

G[CG[[CG[CT[CG[CTCCTGGTTTCCTTCCAATTTAGGCAAAGGCCCTGGC[CG[CC[CG[TCTTCCTGCTTCTGCTGTGC

CCTGCCACAGCACTCCTAAGA[CG[G[CG[AATT[CG[TTTCTG[CG[CCAATTTTGTTTTGAATATCTACAAACCACTTT

TCCTTGCATGAAGAAAACAAGGCAGGGCCCCCTGGCC[[CG[[TCCCACACCTG[CG]AGAGGCAGAGATACAGAGG

CCT[CG[GGCCTCAGCCTTCATTTCCC[CG[CCCTAGCTT[CG[[CG[CCAAGCTGCAGTGTCCC[CG[ACACACTGTCAG

GACA[CG[[CG[CTTTT[CG[CCCCTACTTTGTTCTTG[CG[CAGTCTTCCCAGCTG[CG[GAGAGGAGGGAG[CG[AAAG

CAAAA[CG[AAAGCACC[CG[GGG[CG[CATCAGTTGCAATAGCTTCCCTGAG[CG[[CG[GC[CG[TGGGAGGCCAAGAT

CTGAGGT[CG[[CG[AGG[CG[A[CG[GTGGGGGCC[CG]AGCTG[CG[CAGAAACTGGGTGGGGG[CG[GTCCCTGGAGG

G[CG[CC[CG[GGAGCTGCTAGAAGTTGTC[CG[GAGCCCCTCAACCCCCTTGGAAAAG[CG[AA[CG[[CG[GATGTTAA

TATACCAACTC[CG[CAGGGAACTTTTGGCC[CG[GGTCTTGA

SEQ ID NO: 678

T[[CG[GTC[CG[CAGGTTT[CG[CAGGCTCAGGGG[CG[TGCCT[CG[TTCTCACCCCCACTC[CG[GACCC[CG[GTCCTC

G[G[CG[[CCTCTAGGGCCCCCCAGAT[CG[[CG[CAGACCCTGACATCCC[CG[CCTGGCCCTGGGTTCTGGGAGCTGA

GAG[G[GCCAGGGTCCTGCT[G[TACCT[G[GG[CG[CCCAGCCT[CG[GGTCTGCTCCC[CG[[CG[GA[CG[CCCC

AACCTCCC[G[[G[AATGGATGGTGGTG[G[[CG[[CG[[CG[TCCTACTC[CG[G[CG[GTGC[CG]]GCCTTTTCT

GTTGCCAAAACTAGACCCAAACCTCTGCATGGGATT[CG[TCTTTGGGTCCCCACCC[CG[TG[CG[CCCAGCAAACAG

AGAGAACCCAGTCTG[G[CCAGCC[CG[GCT[CG[CT[CG[[CG[AAGCCA[CG[GGCTTCACTGA[CG[C

SEQ ID NO: 679

GAGTGAGGCCTGTGAGTGACAC[CG[GC[CG[GGGG[CG[CAGGTCACTACCCCTCCACATCCCCCA[CG[GAC[CG[

CC[CG[GGTCTCCC[CG]AGTCTCTGGGTC[CG]AGATCCA[CG[C[CG[AGGCAG[CG[GGACCTGGAGACCCTTGACC[[

CG[[GGAGAGGCCCAGGAGC[CG[TTACC[CG[GTTTCATTTTCAGCCAAAATCCC[CG[CAGGTTGGTCCTGG[CG[[A

GGG[G[GGGCT[CG[GTGGG[CG[[GGGCTGGC[CG[[CG[GGGG[CG[GGGCCAGGGTCTCACACCCATCTAGAGGA

TGTCTGTCTG[G[A[CG[TGGGGT[CG[GA[CG[GG[CG[CCTACTC[CG[[CG[GGTATCACCAGCTTGCTTA[CG[AT

GGCAAGGATTACAT[CG[TCCTGAA[CG[[AGGACCTGTGCTCCTTGACAGC[CG[CAGACA[CG[[G[CG[GCTCAGAT

CACCCAGCTCAAGTGGGAGG[CG[GCC[CG[GGGGG[[CG[[GAGGTTCATCCTCACAGGGATAGGCACCTATTAGATG

TGGTGTGGTTTTCCTCTCTACTCTTAGACCCTCAGCCAGTATCACTATTGGCATTCCTGAGCCACTGGCTCAGAATT

TCAGTACATTATCTGCC[CG[[[[CG[[GGACACACCTCAGAGGAAAGGGGATGA

SEQ ID NO: 680

AATACCAGGTGTTG[CG[[TAATCTCTACTTGGAGATTAGCCACCC[CG[TG[CG[CCCAGGTGAAAGATATCATTCTT

C[CG[TG[CG[ATC[CG]AAGTGC[CG[TGGAAGTTAGTGCCCTAGCCCAGTCCAGGAGGAAGGGG[CG[T[CG[TGC[CG[

G[CG[GTTTTAAGCT[CG[GAAGGGGCAGGGGAATGAGCCCAGGGACCCCAG[CG[GGG[CG[CAGGTAGGAGGCTGT

[G[CT[G[[CG[GGTG[CG[CTC[CG[GCCC[CG[ATTCCCAG[CG[CAGCCAGTAAGTGG[CG[CTGGGCCT[CG[GG

TTTGG[CG[GCC[CG[GAGGAG[CG[GGCTG[CG[GATTACCTGCAGCAG[CG[GGGAGC[CG[C[CG]AGCTCCTCCC[C

G[CC[CG[CCCCCACACCCCACCCCCAC[CG[[CTGCACTAACCC[CG[GCTCAGCTGGCTC[CG[[CG[CACTTGCT[CG[

GAGGAG[G[GGGC[CG]AG[CG[GAC[CG[C[CG[GCTGCAGGCAG[CG[AG[CG[[CG[GCTGGGCTG[CG[GGGCTGCT

T[G[ACCACC[G[[G[[G[AG[CG[TC[CG[[CG[CCTCCTCCTC[CG[CTCTGCAGG[CG[GGGAC[CG[CCC

SEQ ID NO: 681

TTACAAGGAC[CG[GGCACTGTTGGACCA[CG[TGGCTCCATCATGATGACTCCAGTTAGATGTCACCC[CG[CCCCT

GAGCTCAGGTCTTGCTGAATAAGGTCAC[CG[CCCAGGGGGCAGT[CG]ATGAACA[CG[[CG[[CG[[CG[AGGGCTCT

G[CG[AGTGGCCT[CG[TGACTTTGTCCCTAACTC[CG[GGTGTCCCCTCCTTCCCATCAG[CG[TC[CG[G[CG[CCTGGTC

CTGGTCC[CG[GTCCC[CG]AGGCCCC[CG[GGATTCTTCC[CG[AG[CG[TTTTC[CG]AGTTGG[CG[[CG[GGGGGTGGAG

G[G[GGGCCATAG[G[[G[TCC[CG[GGGAC[CG[TTGCATC[CG[GAGG[CG[GC[CG[T[CG[TG[CG[GCTCCTT

CC[CG[CCT[CG]AGAGTGAGGTGGC[CG[GGCCTTGA[CG[AGAAGGCCCA[CG[CCTGC[CG[[CG[GGGGTGGCT[CG[[

CG]ATGGCAGT[CG[GGGTT[CG]AGTCC[CG[CCTGGGGGGCTGCTCCTGCTGGAGAAAA[CG[CCTCCCTGAGGG[CG[

G[G[GCAAA[CG[[CG[CAG[CG[AGGCCC[CG[TGC[CG[[CG[CCAGAAGCCACCCTGAGAAAGGGGCAC[CG[GGACA

C[CG[AGGGGTTCCCACTTTCTCCTCAGCCTGTGA[CG[CC[CG[[CG[TCCT[CG[GGTGGGTTC

SEQ ID NO: 682

[CG[TCTGGACATCACCCTGAACC[CG[AG[CG[G[CG[AGGGAG[CG[TTCCTGCATCTGGTGTCCAAGGG[CG[GACTG

GAC[CG[TGAGGTCACTC[CG[CAGTACCAGCTCCTGGTTGAGGTGGAGGACAAGGGTGAGCCTAAG[CG[G[CG[[GG

GCTACCTTCAGGTAAA[CG[TGACTGTGCAAGACATTAATGACAACCCCC[CG[GTTTTTGGCAGTTCTCACTACCAG

G[CG[GGGGTGCCTGAGGA[CG[[CG[GTTGTGGGTTCCAG[CG[TCCTCCAGGTGG[CG[G[CG[G[CG[GA[CG[[CG[GA[

CG]AGGGCACCAA[CG[[CG[GACATC[CG[CTAT[CG[CCTGCAGGA[CG[AGGGGACCCCCTTCCAAATGGACCCTG

AGA[CG[GGACTTATCA[CG[GTG[CG[GGAGCCCCTGGACTT[CG]AAGCT[CG[G[CG[CCAATACT[CG[CTTA[CG[GT

GCAGG[G[ATGGACAGAGG[G[TGCCTTCCCTCATGGG[CG[[CG[C[CG]AGG[CG[CTGATTCAGCTGCTGGA[CG[

TGAATGACAATGACC[CG[GTAGTGAAGTTC[CG[CTACTTCC[CG[GCCACCT[CG[[CG[CTA[CG[CCT[CG[GTAGATG

AGAATGCTCAAGTGGGCAC[CG[TGGTGGCTCTGCTCAC[CG[[TGA[CG[GA[CG[CA

SEQ ID NO: 683

CAAGAATCTCCCTCCTCCCA[CG[CCCAAAAGGAATAAGCTG[CG[GGGCACAC[CG[CC[CG[CCTCCAGATCCCCCA

TTCA[G[TTGAGC[G[GGG[CG[[CG[CT[CG[GGG[CG[GT[CG[CCTGCAGTATCAGTATCAGCATCAGCATCAGCA

TCAGCATCTGCATGAGCATCAGCTCAGCTCAGCTCAGCTCAGCATCAGCTCAGCTGTCCTGAGGCAGC[CG[G[CG[

]GCTGTGAAGGAGCTCCAGGCTGCCCCCATCCCCA[CG[CCCTTCT[CG[GCTCAGGG[CG[TGCATGAACCTG[CG[GA

[G[[G[CCCCCC[G[[G[GTCTGCTG[G[[G[[CG[G[CG[GC[CG[CTGCTGCTGCTGCTTCTGC[CG[C[C

G[CTGC[CG[C[CG[C[CG[CTGCCTGGATATAGTG[CG[GCAAGAG[CG[GAGCTTGCAGTCACTTTG[CG[[AGG

SEQ ID NO: 684

ACATGCCCTTTCCAGGAAAT[CG[CCCCTTTCACCACCCC[CG[CCCCCATTTCCAGATACCTTAA[CG[AGAC[CG[AG

AGAAAAGTGGTTCTGCTTTGGTTTC[CG]AGTGGA[CG[AGGTTCTCTGGGCAG[CG[GGACTGAGTCTTGG[CG[[CCC

AGGTGAGC[CG[CCCTTCTC[CG[A[CG]AGAAACTACTTGTTGG[CG[TTTTC[CG[GATTCAGGTGGTTGAGC[CG[CTT

GTGATCTG[CG[GATTTGCCAGT[CG[[CCAACCTC[CG[[CG[CCCAGAGTCACCAT[CG[[CG[CAGGGTTGGGCAAAC

CATGGAGCT[CG[GGG[CG[GGTCCAGC[CG[GCACTGCC[CG[ACCCCTC[CG[GGAG[CG[GGCAGAT[CG[GCTGGC[[C

G[[TGAATGGAGTGGAGACTGGC[CG[CAGGTCAGGAGAGCTCACCACTTGAAGGTGAAGT[CG[CCCTGCT[CG[[G

ATTCCATCTGCAGATTTTGTTTCTCCCCCAAATCAGCCACTGCTGGAGCTGTCCCTTCAGCACCACT[CG[[CCATCA

ACCTCC[CG[C[CG[CCATC[CG[AAGCACAGGGCTCAGGAAAGAGTG

SEQ ID NO: 685

TGTCTGT[CG[[CACATATATTATAT[CG[TGTATGTAATGTATAAGTATTTATTT[CG[[TTTGCTTGGGGTTTTGTTTG

CTTTTGCTGAGTC[CG[ACCCCTCTACCTGC[CG[CCTGGCCCTTGCCTCA[CG[CTCCAGTGCCACTGAGATCAAGGA

GAGA[G[AATTTGC[G[CTGACTGGGCAGAG[G[AG[CG[[CG[TGGAT[CG[[CG[[GCCAC[CG[CC[CG[TTCATCA

CC[G[[CG[[CG[CATCTGGGCTGGCAC[CG[GG[CG[AAGAAT[CG[TG[CG[GGTCTGGGACCTGGGGGCCCAGAGGG

AG[G[AGCTCCTG[G[[CG[GG[CG[CT[CG[GTC[CG[CAGGTTT[CG[CAGGCTCAGGGG[CG[TGCCT[CG[TTCTCA

CCCCCACTC[CG[GACCC[CG[GTCCTCTTCCCTAGACAG[CG[GCCCCCTCCACCCCTGGCTCC[CG[CAGGC[CG[CTA

GTAGTC[G[[G[CCAGGCCC[CG[C[CG[G[CG[CCTCTAGGGCCCCCCAGAT[CG[[CG[CAGACCCTGACATCCC[CG

]CCTGGCCCTGGGTTCTGGGAGCTGAGAGC[CG[GCCAGGGTCCTGCT[CG[TACCTC[CG[GG[CG[CCCAGCCT[CG[

GGTCTGCTCCC[CG[[CG[GA[CG[CCCCAACCTCCC[CG[GC[CG[AATGGATGGTGGT

SEQ ID NO: 686

GGGAGA[CG[[CG[GGAGGTTTGCAAACAGACCTTGGCCTGGGCTG[CG[CAGGGACAAAGTGTTCAAGGGCAGCAG

GGGAGGCTGAGGGAGTACA[CG[GCTGGGAACAAGGGACACTGC[CG[CCCCCAGCCA[CG[CAGGAG[CG[GTGTCT

GCACCACTGAAAGTCCCC[CG[GGGCCCACAGCTCTATCCAGG[CG[GAAGGGAAGCAGCCAGGC[CG[C[CG[[CG[G

[G[AGAACCTGAGATTCAGGGCT[G[[G[[CG[GTC[CG[G[CG[CT[CG[GTTCAGGA[CG[TC[CG[GGAACCC[

CG[CAG[CG[CTTACCCTCTGCAGCAGG[CG[T[CG[CTGG[CG[CCTCCAAGGGCAGGGG[CG[GGTC[CG[G[CG[GGTA

CAAGT[CG[[CG[ATTGA[CG[[CG[A[CG[GCCCAGGCAGGCACTGTGGGCTTCAC[CG[CC[CG[CAACTTTTGACCCT

AGAGGCCCTG[[CG[[CTGCAGCCTGTGGCC[CG[GAGGGACAGAAGTGGGAG[CG[TGTTTGGGCCACTCTGCAG[CG[

AAAA[CG[ACCTTCCCTCATGGAACTTTCAGTAACTAACTCCTGAGAGCTG[CG[AGAG

SEQ ID NO: 687

TATTTAATGAAAGTCT[CG[AGAGATTTTTACCTCTGTATAAAAATTCTAA[[CG[[TTGGACCAATTGTGTGAAGCCA

GAGCATTTTGCCTCCAGACAAGGAAATTAAATGAGAATAGAATTTTGCTTTTTGGAAACAAAAGCAAAG[CG[ACC

CAACTATATTCTGAAGTGCCTCTGCTGCAAGACCCAAGCACCCAGT[CG[GG[CG[[[CG[[CCTTGCATTTGTCTCCAT

GT[CG[TAGGAATGTCAAGAAAGTTAC[CG[CCAAGTGGTTTACCAAAA[CG[[CG[G[CG[GAAGGAATCAGGACAGTT

TGCC[G[A[CG[GG[CG[GGT[CG[G[CG[GCTTTCAGG[CG[GGAGAGATCTTGCCAGGGGCAGAGAGAGATCC[CG[

AAAAT[CG[CCCCCAGCCTTG[CG[TCCAGCCCTTTCT[CG[C[CG[A[CG[TTTTTTCTTGATCCTC[CG[AAGGCCCAGG

G[G[A[CG[TTTGCCAT[CG[[CG[GCTTCC[CG[AAAGGA[CG[G[CG[C[CG[GGTTTGCTGGAAGACAGCTCAGTTTTA

GGCATGGCC[[CG[[GTGGGGGTGGGGGTGCTCATTTTCTTGGGTT[CG[GATTCCCTCTCTTTGAC[CG[CACTTATCTT

AGCTTTAGGAGATTCTGGCATCTCATAGGAAAAGG

SEQ ID NO: 688

TC[CG[GAG[CG[GCTGGAGGAG[CG[CAGTGGGAACTGGGAAGAGCTAGCC[CG[GCTGGAGGG[CG[GACCTCTG[C

G[[TC[CG[GGAGC[CG[GGTCTCAGGCAC[CG[CTGGGGG[CG[AAGCCA[CG[[CG[TCTTTT[CG[GGCAGCCAATTTCA

CA[CG[[CG[CCTGTGTG[CG[GTTC[CG[GGCATCCCAGTAAGCTCTAGCACC[CG[GG[CG[[CG[GGTAA[CG[GGAAG[C

G[CAGAACCAAATCCCCAG[CG[CCCAGGTCACCTCCCCAGACCCAGCCTTGCAGGGACCAGGGCTTTAGGGCTC

A[CG[GACCCAA[CG[GCCAGGTCAGAC[CG[[CG[[AAC[CG[GGAGGAG[CG[[CG[GGCCCCACCCTAAAGAGGG[CG[

CAGC[CG[GGAGCTGGGGAG[CG[GGTGC[CG[[CG[CTCCAGAGATTGTGT[CG[TGGG[CG[C[CG[TCCTAGTGG[CG[

GGGAG[CG[CACCTC[CG[AGGGGGCATGAGAT[CG[GAGAAATCCCTTA[CG[CTGG[CG[G[CG[C[CG[GGGGAGGT

C[CG[TGGGC[CG[GAGGGAGAGCAACAGGATG[CG[GGAGACTTCC[CG[GAGGC[CG[G[CG[GGGG[CG[GGGGCTGC

TGTAGTAG[CG[AG[CG[GCTGGTGATCAATATCTC[CG[GGCTG[CG[CTTTGAGACACAATTG[CG[CAC

SEQ ID NO: 689

[CG[GACCTCTG[CG[TC[CG[GGAGC[CG[GGTCTCAGGCAC[CG[CTGGGGG[CG[AAGCCA[CG[[CG[TCTTTT[CG[G

GCAGCCAATTTCACA[CG[[CG[CCTGTGTG[CG[GTTC[CG[GGCATCCCAGTAAGCTCTAGCACC[CG[GG[CG[[CG[G

GTAA[CG[GGAAG[CG[CAGAACCAAATCCCCAG[CG[[CCCAGGTCACCTCCCCAGACCCAGCCTTGCAGGGACCAG

GGCTTTAGGGCTCA[G[GACCCAA[G[GCCAGGTCAGAC[G[[CG[AAC[CG[GGAGGAG[CG[[CG[GGCCCCACC

G]TCCTAGTGG[CG[GGGAG[CG[CACCTC[CG[AGGGGGCATGAGAT[CG[GAGAAATCCCTTA[CG[CTGG[CG[G[CG

]C[CG[GGGGAGGTC[CG[TGGGC[CG[GAGGGAGAGCAACAGGATG[CG[GGAGACTTCC[CG[GAGGC[CG[G[CG[GG

GG[CG[GGGGCTGCTGTAGTAG[CG[AG[CG[GCTGGTGATCAATATCTC[CG[GGCTG[CG[CTTTGAGACACAATTG[C

G[CACCCTGT[CG[CTGTTTC[CG[GACA[CG[CTGCT[CG[GAGACCCTGGC[CG[G[CG[AGTC[CG[CTTCTT

SEQ ID NO: 690

TGGAGCTGCTGGTGGACTGGGTG[CG[TTTGGAAGCC[CG[GCTGCTGC[CG[TCCCC[CG[CTGC[CG[CAGTGGAGC

AGGAGGAGGAAGAGGAGGAAAAGGAGAGGGGGAGGCT[G[[G[[CG[[CG[[CG[GTCTGTGCCC[CG[C[CG[T

CG]AAC[CG[TGGCC[CG[GTGTCATC[CG[CTT[CG[GT[CG[[[CG[[GCAAGTCCTGCCTCTTC[CG[CCTGCAGCCTGCTA

CCCTGCACTGC[CG[GCTCCTG[CG[GACCC[CG[CTTGCCACCTTGCTGCTGCAGCTGCCCCCTGGG[CG[CC[CG[A[C

G[CCCACCCCACAGCTCCTGGGGGCCTG[CG[ACATTT[CG[CTGGCCAC[CG[CAG[CG[CACAGGGT[CG[TGGGGC[C

G[GC[CG[CCTC[CG[GATGCTCCCAC[CG[TCAC[CG[GGGA[CG[TTTCCCCCTGCATAAT[CG]AGTGGG[CG[AG[CG[

GACTGGGGACATTGCACTGGCCTAC[CG[CCTGACTGACCTGGGAAGC[CG[CCTGCTGAGCCAACTTGAG[CG[[GC

CCCTCACCTTCACC[CG[CACAGGAGGAGGAG[CG[GAGGTCAGTCCCCAAACCC

SEQ ID NO: 691

CCT[CG[[GTGCCCCTGACCTGCAGT[CG[TCACCTGCACTCCAGG[CG[GGCAACAACAG[CG]AGGACACCCTGCC[C

G[GCCAGGCTCCCAGCATCAGAGA[CG[CTGGGTGGACAA[CG[TGGTGG[CG[GCCAATCCAGGTGGTC[CG[CCAGA

C[CG[[CG[GCAGAGACAA[CG[CAGAGGCTG[CG[GGTTAGGACTGCCCAG[CG[CTAG[CG[GCCCCCAGCTCTGTG[C

G[CC[CG[CTGAGGAGGAGACAGCCAGCAG[CG[TGGTCAGGCAGGCTCT[CG[[CG[CTGAGGAGGCAGTGCACTCAG

GATACTGAGGC[CG[CCCAGAGCA[CG[CCC[CG[CCAACCCACCTAGG[CG[CCTGAGCTGCAGCCTCTG[CG[C[CG[

TCTCTGC[CG[[CG[GTC[CG[GCAGGC[CG[CCTGGATTGGC[CG[C[CG[C[CG[CTGCTGCCACCA[CG[GTGTCCACCCA

A[CG[ACTCTAATGTGGGAAGTCTGG[CG[GTGGAGGGTGT[CG[[CG[GGCTCTC[CG[GCAGACC[CG[TAGCTGGTGG

TGGAGCTGAGGGCCCTGGGGCATGG[CG[GGCAGGGACTTGAGGCC[[CG[[CAGGAGGAGGGGGC[CG[TGC[CG[AT

GCTGGCTGTGC[CG[GGGCTGCCTGAGAACC[CG[[CG[GAGGCTGGGGGG[CG[A

SEQ ID NO: 692

TTTGGGTGCCTGTTTTTGGTTCTGGGTGAGATGCACTCACCAGGGTGATAAAGACCCTGCCTGGCTTGTTCATGG[C

G[TCTCCAGGACCTAGTATGGTGCCTGAC[[CG[[TGGCACTCATAGGGTGTTTGTTGAGTGAATGAATGATGCCTTTT

CAGCTGAACT[CG[[AGCTAGAAGACTCCAGGGCTCACTCCACTGTGCCCATTCCACAGATC[CG[GCCC[CG]AGGT

GTGCC[CG[TTCACCAGGCAGAGGTGTCATC[CG[AATTCAGGCTCCTGGGGCC[CG[GGAGGGTC[[CG[ACTCTA[C

G[[GACCCAGGT[[CG[CTGTGGCCCAT[CG[CTTT[CG[ATTTGACTTGGTTTCTGT[CG[CCACT[CG[[CG[GAAGG[CG

[G[CCCCC[G[[G[[G[[G[GCC[CG[CCC[CG[CCC[CG[CCCCTGCTCTTCCTC[CG[GGGC[CG[CTGGCA

CTG[G[[G[CTC[G[CAGGCAGAGAAG[G[GGAG[CG[GG[CG]AGG[CG[G[CG[G[CG[GCAGCAG[CG[ATGGT

GAGGGCCCAGG[CG[GGGC[CG[GCCAGCCCTG[CG[A[CG[GGCAGAGGG[CG[AGTGG[CG[AGGGTGGGAGAGAG

GAGTCCAAAGTC[CG[[CG[GGCTGGGGCCTCCCCTGGGGCCCA[CG[AGGGC

SEQ ID NO: 693

TCTCC[CG[CAGGG[CG[AACAAAGGCCCAG[CG[GGTCCC[CG[[CG[CCCAGGTCCCCCCA[CG[TCCCCCTT[CG[GAG

GTTCCCTTCT[G[TCCCAAGTCCCCAGGCCCCC[G[[G[[CG[CC[CG[ATGCCCCCTCCACCCTC[CG[[CG[CCCCC

[CG[[CG[GCACTCACAGGATGGAGGTCTG[CG[G[CG[CCA[CG[G[CG[GGCA[CG[GCCTCCAGCAGCAGATGCATGCA

G[CG[CA[CG[GTGGTG[CG[GAAGCACAGGCAG[CG[GCT[CG[GACACCCTG[CG[CC[[CG[GCTTCTGGGCCACCA[

CG[GCCAG[CG[TCCCCCAGG[CG[CAGAACAGCA[CG]AG[CG[CCAACAGGCAG[CG[G[CG[CC[CG[GGGCCCCTGGA

G[G[CTTGGCATGGC[G[A[G[[G[[CG[GA[CG[GA[CG[CT[CG[GA[CG[CA[CG[GAGCCACCA[CG[GC[CG[GCT

[G[ACT[G[CC[CG[CC[CG[GC[CG[[CG[GCCCA[CG[TCCCAGCTGTG[CG[[CG[GGGGG[CG[GGGGG[CG[CCA

GCTGTGCACATG[CG[[CG[AGGCTCCTCC[CG[GCCCCTCTGAATCCC[CG[AGGG[CG[GGG[CG[GGG[CG[AGAACC[

CG[G

SEQ ID NO: 694

ACCAGCTTCCTCCTG[CG[TGTCTATTTCCAGCCAGGAC[CG[C[CG[GCCAC[CG[C[CG[CAC[CG[GTGCCCTCAC[CG[

ACCCTCAACT[CG[GGGGAGAATGGCAC[CG[G[CG[ACTGGGCTC[CG[[CG[GCT[CG[TGTTCAT[CG[AGGAGCCCC[C

GGG[G[GTGG[CG[G[CG[TGGCCCCCAG[CG[[CG[GTCCCCACT[CG[CCCCC[CG[GGAC[CG[CAG[CG[CTGCAGGG

AGCAGAG[CG[ACTGGGCAT[CG[GA[CG[TGGAAGTCCTGGGGCCCTTG[CG[TCC[CG[GGGG[CG[TGGCAGGCT[C

CG[[G[GCTTCCTGCTG[G[[CG[TT[CG[CC[CG[[CG[GTTGTA[CG[GCCCAGG[CG[GGGACCTGCTGCCCCCTG[CG

]TGGCTG[CG[GG[CG[CT[CG[GGG[CG[CTCCTGCTGCTAGCCTTGT[CG[GCCCTGTTCAG[CG[GCCTG[CG[CCTGAG

CCTGCTGT[CG[CTGGACC[CG[GTGGAGTTA[CG[GGTGCTG[CG[GAACAG[CG[GCT[CG[GC[CG[C[CG[AGCAGGAG

SEQ ID NO: 695

GGCCCAG[CG[GGTCCC[CG[[CG[CCCAGGTCCCCCCA[CG[TCCCCCTT[CG[GAGGTTCCCTTCTG[CG[TCCCAAGTC

CCCAGGCCCCC[G[[CG[[CG[CC[CG[ATGCCCCCTCCACCCTC[CG[[CG[CCCCCCACCTC[CG[ATCACCCCTG[CG[C

GGTCTG[CG[G[CG[CCA[CG[G[CG[GGCA[CG[GCCTCCAGCAGCAGATGCATGCAG[CG[CA[CG[GTGGTG[CG[GAA

GCACAGGCAG[CG[[GCT[CG[GACACCCTG[CG[CC[CG[GCTTCTGGGCCACCA[CG[GCCAG[CG[TCCCCCAGG[CG

[CAGAACAGCA[CG]AG[CG[CCAACAGGCAG[CG[G[CG[CC[CG[GGGCCCCTGGAG[CG[CTTGGCCATGGC[CG[A[C

]GC[CG[[CG[GCCCA[CG[TCCCAGCTGTG[CG[[CG[GGGGG[CG[GGGGG[CG[[CCAGCTGTGCACATG[CG[[CG]AGG

CTCCTCC[CG[GCCCCTCTGAATCCC[CG[AGGG[CG[GGG[CG[GGG[CG]AGAACC[CG[GGGCCCCAG[CG[TC[CG[GC

CTGA

SEQ ID NO: 696

GGCAGTTGG[G[[G[GTCTAGAGAGAGGGCA[G[AACCT[CG[GG[CG[C[CG[TC[CG[GGGTT[CG[GGTCTGGATCC

CCAGGAGAAGTCTCAG[CG[C[CG[CTCTC[CG[C[CG[CAGGTTGGGGGCCAGGGGAGGGTC[CG[AACAC[CG[GCTCT

GTTCCTGCTACTTAG[G[GGCACCTGG[G[CTC[G[G[CG[[CG[GCAGCCTG[CG]AGGCCAGGGC[CG[AG[CG[[CG

[G[GAG[G[ATGTGGGCT[G[GGGAT[G[[CG[GC[CG[C[CG[CCTCTAATC[CG[CCCTTAAGTAGTCTC[

CG[CCTG[CG[TCA[CG[CCAGGT[CG[G[CG[GAGGGGAGCAGAG[CG[[CG[C[CG[TG[CG[GCTGT[CG[CTG[CG[[CG[T[

CG[GAGCC[G[AGGGG[G[GGGA[G[[CG[[CG[[CG[GGGGGAGAGGGGCAAGAGTCCTGGAGGCC[CG[G[CG[GG

GAG[CG[GGG[CG[ATTT[CG[AAAGGAAGGACTGCAG[CG[CCCCT[CG[GGGCTTCT[CG[GGGAGCCCAGGTAAC

CTCACCTGAC[CG[CCAGACCCAAGCAGG[CG[GAGGGGGAGC[CG[GGAG[CG[GA[CG[[CG[TGGGTGAGTGGGGAG

GGGAGTG

SEQ ID NO: 697

TTCTTTTTCCTCTTC[CG[CTAGTTGTGAAAGACAGGGGAAGGGTGTTCTTTCTCTCTGCCCTCCCTTTCCATCTCCA

GCTCCCCATTTCCTTTCTCACCTCCTCCTCCACTCCCTGCCTCTTCTCCCCACCCATCCTGG[CG[GG[CG[GGCTG[CG

][CG[GAGGCT[CG[GGAGCTGGC[CG[GGGAGGGG[CG[[GATGGAGGGGCCTGGGTTGCCAGCTCCCTTGGT[CG[GG

GTCCTGCT[G[CTGGGGCTTGTGTGTTCTCTG[G[G[CG[GGC[CG[[CG[TCCC[CG[CTGAGCCT[CG[[CG[GTGACA

GC[CG[CCTTTGGCAG[CG[AG[CG[CT[CG[GGGCACTTCTATCCC[CG[[CCTCTCAAAGGGTGGGGACAGC[CG[TTT

CCAGATTTGAATTTTTTCTGTTCTTTATTTTTAA[CG[CTGCATCTT[CG[[CG[TGTGCTCAGAGGTGGTTGTTGG[CG[

GAGAA[CG[C[CG[[C[CG[CAGTGTTTGACCTCTAG[CG[GTGAAGGGGGAAGGGGAAGAGGAAAGGAGAGAAGTGG

T[CG[GTGTCTGTTTCCTTCTGTCCCC[CG[GGGC[CG[TGGAGCTGT[CG[GAGGGAAGGAGGA[CG[GTG[CG[GGGC[C

G[CAGGGGG[CG[[CG[GGG[CG[[CG[G[CG[GGACCCAGGCTAC

SEQ ID NO: 698

GOTTCCC[G[CCCC[CG[GCTCAGAGGTCTTGGGG[G[GG[G[CCC[G[T[CG[GC[CG[C[CG[GCTTCCTCCTTG

AAA[G[[G[[G[CACATGAGGC[G[CTGCCCC[CG[C[CG[CAGG[CG[CTGG[CG[GCCCCCT[CG[[CG[GTGCC[

CGTGGTGATGCCATGCC[G[CACCA[G[[G[GGAGGAGAGGAGGG[G[G[CG[C[CG[C[CG[GGCTCTGGGTGA

AGAG[G[[G[A[G[[G[[CG[G[CG[G[CG[GG[CG[GGGGG[CG[CTTGGGCAG[CG[GCATGAAGGATGTGGA

GTC[CG[GC[CG[GGGCAGGGTGCTGCTGAACT[CG[GCAGC[[CG[CCAGGGG[CG[A[CG[GCCTGCTACTGCTGGGCA

[G[[G[[G[GCCA[G[CT[G[GTGG[CG[G[CG[G[CG[GTGGCCTGAGGGAGAGC[CG[C[CG[GGGCAAGCAGGG

GGCC[CG[GATGAGCCTGCTGGGGAAGC[CG[CTCTCTTACA[CG]AGTAGCCAGAGCTGC[CG[G[CG[CAA[CG[TCAA

GTAC[CG[G[CG[GGTGCAGAACTACCTGTACAA[CG[TGCTGGAGAGACCC[CG[[CG[GCTGGG[CG[TTCATCTACCA[

CG[CTTT[CG[TGTGAGTACC[CG[[CG[CCCCCTGCTATGCC[CG[CTGCAGGGGACCACTGTCCCTGGCCCCC

SEQ ID NO: 699

GAGG[CG[G[CG[TGGA[CG[CTGG[CG[C[CG[TTGCTGTAGGGGAAATGGTCCT[CG[T[CG[TCCT[CG[TCCT[CG[TCCT

CCT[CG[GGGTCACTGTCCCTCAAGTCC[CG[CAGG[CG[G[CG[TC[CG[CTGCCCTTGTCTC[CG[GG[CG[CTGG[CG[GC

GTTTCTC[CG[CTTCCTG[CG[C[CG[CCTGCTCTTTGGCCTTTTTGCTG[CG[TTTCCATTTCATC[CG[C[CG[GTTCTGGA

ACCAAATCTTCACCTG[CG[GGCACAAG[CG[[GG[CG[TGAGAAAC[CG[GCCAC[CG[CCACCCCAGGGCTTCCTGTC

CC[G[GAGTCCCC[G[GC[CG[[CG[TG[CG[CCTGGGCCCCATTGGGT[CG[GCCCTGGAATGGCCTCAGGGTGAGA[C

G[ACTTAGAAGCAGAATGGGGAGGGGGCT[CG[TAGCTTCCTCCTCCC[CG[CAACCCCCCACTCAGCAGCAAACCCC

AGAGCTGGGCTGGAGCTC[CG[TGGGAGCTAGGACTATGTCCCCAA[[CG[ACCCAGGC[CG[GGGACTTTTCTACC[C

G[[CG[CCCTC[CG[TCTG[CG[GAGGAAGGGTCAGGGCAGCTGGCTA[CG[T

SEQ ID NO: 700

GGG[CG[GG[CG[GGTCACT[CG[GTGC[CG[GTTCC[CG[GTGCAAACCCCC[CG[G[CG[[CG[CCTCTGGCTTTGTGCAGC

C[CG[AGATGGTTGAGTTTGGCTC[CG[GAGC[CG[GGAGTGGGG[CG[CAGATTGATTTTTAAATATGGAGAAGGAG

A[CG[CATCTGC[CG[CTGG[CG[[CG[TT[CG[GTC[CG[AGCCCCCCAC[CG[GTCCCCAC[CG[GCAC[CG[CCTC[CG[CCA

GCCCCAGG[G[CAGCCCCCAGG[G[CC[CG[[CG[GAGGGGAGGGAG[CG[ACAGGGGC[CG[[CG[GCTGCTCCCTG

TTTCACAGATGGGGCAGCTC[G[GACTG[G[[G[CCC[CG[C[CG[[CG[GTCACCCTGAGGCCAGGGGCC[CG

]GGAG[CG[[CG[ACCTCCTGGC[CG[C[CG[TCTGGGACTTTGACCTTCCAGAGGCCATGGAGGCTGG[CG[GGGAGC

AGGG[CG[CCACCTGAT[CG[CCTCCCCCTGGA[CG[CCTCCTCCAG[CG[G[CG[CTCA[CG[CTTC[CG[CAACTTTGCAG

[CG[CTCATGGTGAGTA[CG[GGGGTCC[CG[GGGGTCCTGCAGCTGGGGGCTAGGC[[CG[CTG[CG[G

SEQ ID NO: 701

G[CG[TGTTAGGGAGGGAT[CG[CCCCA[CG[GGGCAGGAGAGC[CG[GGCAGT[CG[GCTTG[CG[GGGGAG[CG[GAC[C

G[T[CG[GT[CG[GGGAACTCAC[CG[TTAGCTGTCTC[CG[C[CG[G[CG[GCTGTGC[CG[GGCTGCTATGCAGGGC[CG[G

GGT[CG[AGCCTGGGACCTTGGTGGTCC[[CG[[GGCTG[CG[[CG]AGGCCCAGCAC[CG]AGTTCCTGGG[CG[CCCCCA

GAG[G[GG[G[A[G[[G[[CG[[CG[AAGG[CG[GCCAGGG[CG[AGCAGGAGCCCCCACATGG[CG[GGGATT

GAGTGCCAGGGG[G[[CG[[CG[GGCTA[CG[G[CG[GGTGG[CG[GGT[CG[GTCTCTTCCTGC[CG[AGTG[CG[C[CG[

AGCCCCC[CG[CCCCTTCCTGCCCCC[CG[CCCCTC[CG[CAGCCTCCTGCC[CG[CCCACAGCC[CG[CTGCC[CG[CC

T[CG[GACCT[CG[GAGAGGAGGAGAGGGC[CG[GGAGGAG[CG[AG[CG[GGGCTGACCTCCAAGGGGC[CG[CCCCA

G[CTG[CG[CCTTTATAGTCTGCAAAGCCACACTGAAGAGACCAGAGATCACCTGGTGGCCATCAAGT[CG[ACC

SEQ ID NO: 702

CAAGCTAATTGGCTGAGGCCCT[CG[GCTGGGGACCAATCAC[CG[GCTCTGAGAAAGTT[CG[GCAGTGGCCACCA

CATCTGGTTCT[CG[TTAACTTTTCTAAGGCAG[CG[[GC[CG[CTGGAGCAG[CG[[GGGCTGG[CG[GGGTAAAAGC

TCCTGGCCAGGGCTGCCTGGAGCTGCCCCTTCCACTC[CG[CCCCCAGGGAGCTCC[CG[GGTCATCCTCTCATC[CG

]GGCTGCCC[CG[[CG[GCCCCCAAGGAGCCCCACCCC[CG[GGACCAAATGGCC[CG[CAAGGTTTGGGGCAG[CG[G[

G[CTGTGGCCCCAACAGGCTGGCAGGG[CG[[CG[GG[CG[GGTGG[CG[GGGTTG[CG[GTATGAGCTTTGCTCCCTGCC

CTGGGGTCC[CG[GG[CG[CTCCTGGCTCTGGAGGCCTGGCCAT[CG[GTC[CG[AAAAGCAAAGGGACATTGT[CG[TG

GTCCCCT[CG[GC[CG[CTT[CG[CTCCACCCAGAGA[CG[CCCTGAGGAGAAG[CG]AGCCTTTGTA[CG[AAGGCAGAG

GGCTGACTCCTAAGTTCTGTCCCCCTCC[CG]AAGGC[CG[GC[CG[CTAGG

SEQ ID NO: 703

CCCCCCATTCTCTCTCTCTCTCTCTTTCTCTCTCTCTCTCTCTTGCTCTACTCT[CG[CC[CG[TCTG[CG[[TTCTACA

TTGGTTCTG[CG[GC[CG[TGTCCCTTT[CG[TGTGTGTCTGCCCTGTGTTTCTC[CG[T[CG[TCTC[CG[TGTGGATCT[CG

]]GTCTTTGTCT[CG[CCCTCTAGCTCTCT[CG[TG[CG[CCTGTGTTTAAT[CG[TG[CG[CTTCTCTCAATCTCTCTGTCCC

TCCCTTTGCCCCCTACA[CG[[CG[TGTTCT[CG[TCAACAGATCTCCAGAGGTGGTGCAGAAA[G[ACCC[CG[[CG[C[

CG[[G[CCCCATCCTG[G[GCCAGTGCT[G[[CG[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCCCAG

ATTTC[CG[GAGGAGCAGG[CG[GG[CG[GGGTCC[CG[[CG[GGGC[CG[GCTGC[CG[TCAG[CG[CCCCTTCC[CG[G[CG[

GC[G[[CG[ACCCCTCCC[CG[CTGACCTCACT[CG]AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCA

TCTGAAGAGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[[CTGCAGACTCCTGACCTGC[CG[ACTG[[CG[[GA

TCC[CG]AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTA

SEQ ID NO: 704

GGGACCAATCAC[CG[[GCTCTGAGAAAGTT[CG[GCAGTGGCCACCACATCTGGTTCT[CG[TTAACTTTTCTAAGGC

AG[CG[GC[CG[[CTGGAGCAG[CG[[GGGCTGG[CG[GGGTAAAAGCTCCTGGCCAGGGCTGCCTGGAGCTGCCCCT

TCCACTC[CG[CCCCCAGGGAGCTCC[CG[GGTCATCCTCTCATC[CG[GGCTGCCC[CG[[CG[GCCCCCAAGGAGCC

CCACCCC[CG[GGACCAAATGGCC[CG[CAAGGTTTGGGGCAG[CG[G[CG[TTGCAGGAGATGAGCTCAG[[CG[[CAA

AGGGAACCC[CG[CAG[CG[G[CG[AGTG[CG[GCTGCTGGCCTG[CG[[CG[CTGTGGCCCCAACAGGCTGGCAGGG[C

G][CG[GG[CG[GGTGG[CG[GGGTTG[CG[GTATGAGCTTTGCTCCCTGCCCTGGGGTCC[CG[GG[CG[CTCCTGGCTCT

GGAGGCCTGGCCAT[CG[GTC[CG[AAAAGCAAAGGGACATTGT[CG[TGGTCCCCT[CG[GC[CG[CTT[CG[CTCCACC

CAGAGA[CG[CCCTGAGGAGAAG[CG[AGCCTTTGTA[CG[AAGGCAGAGGGCTGACTCCTAAGTTCTGTCCCCCTCC[

CG]AAGGC[[CG[GC[CG[CTAGGGAAGACTTGGCCACCCTCTGGAAGTACC

SEQ ID NO: 705

GCA[[CG[[ACCAAAGTTTTTGGCTTGGTCTCTTGCTTTCCACAA[CG[AGATAAAGTCTGAAGCCTGTAACTCTCCCT

GTCC[CG[[CG[GGAG[CG[TGCAAAGGGAGGGAAGATAAG[CG[G[CG[TGGGTGAGGGGTGG[CG[G[CG[CAGAACC

CAGGAAGGGAGCAGAGG[CG[AGAGCCAGCCTC[CG[GCAGGAGGG[CG[[TAGACCC[CG[GTGCCAGCCAGAA[CG[

GCTCCAGCCTTCC[CG[[CG[GCCAGAGAGCCAG[CG[G[CG[GGAGGGGA[CG[GG[CG[GGACCTC[CG[[CG[GACAGC

CC[G[GGTG[G[GACCAG[G[GGCAG[G[GC[CG[G[CG[[AGACCCTCCCTGGATC[CG[CCCAGAGCTTAC[CG[

GACCTG[G[[G[[G[TC[G[GCTCC[G[GC[CG[GCT[CG[GGGGAGAAGG[CG[CC[CG[AGGGGAGG[CG[C

[CG[GACAGAT[CG[[CG[TTT[CG[GAGG[CG[G[CG[CAGGTGTGTCAGGGGTGGGGGTC[CG[CTGGCATCTCT[CG[TG

C[CG[G[CG[CTGGGGGGGTCTCC[CG[TGGAGGAAGGGCTGAAGGTGCTC[CG[GGAGGGGTCCACT[CG[TTATGGAA

AGGAAG[CG[GGG[CG[[CG[GTCAGGGTCCCT[CG[TC[CG[CAGTGGGGGTGGTC[CG[GGCCCCTCAGCC

SEQ ID NO: 706

CTCTCTCTCTTTCTCTCTCTCTCTCTCTTGCTCTACTCT[CG[[CC[CG[TCTG[CG[TTCTACATTGGTTCTG[CG[GC[

CG[TGTCCCTTT[CG[TGTGTGTCTGCCCTGTGTTTCTC[CG[T[CG[TCTC[CG[TGTGGATCT[[CG[GTCTTTGTCT[CG[

CCCTCTAGCTCTCT[CG[TG[CG[CCTGTGTTTAAT[CG[TG[CG[CTTCTCTCAATCTCTCTGTCCCTCCCTTTGCCCCCT

ACA[CG[[CG[TGTTCT[CG[TCAACAGATCTCCAGAGGTGGTGCAGAAA[G[ACCC[CG[[CG[C[CG[G[CG[CCCCATC

CT[G[GCCAGTGCCTC[G[[CG[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCCCAGATTTC[CG[GAGGAG

TCC[G[CTGACCTCACT[G[AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCATCTGAAGAGGGCT[C

G[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[GATCC[CG]AGTCCC[CG[

GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCT

SEQ ID NO: 707

[CG[TCCC[CG[GGAACTCCCT[CG[GCTTTT[CG[[CG[CATCCAGGTCCCCAGCCCCAGCTACTGGTG[CG[CCC[CG[AG

CCCCTAGGTGCCAGAG[CG[GTGGT[CG[GC[CG[GGCTCCTGCCCAGTCT[CG[GCTCCTCCCTCCTCCCCACCAGAAG

GAAAAACTTGGGCCCTT[CG[AGAACCCTGTGGAATGTTCTTTGTAATCAACTGTACATC[CG[CTTCCA[CG[GCA[C

G[GCCT[CG[TGCAAAAT[CG[[CG[GGTTT[CG[GGGCCTTGGAGCAAATTG[CG[CTTGTCAG[CG[G[CG[A[CG[TCAGG

AGGACAAGGGGAGGGGTT[CG[[[CG[[GCTGAAACTGCAGCTT[CG[CAGCACAGAGCCATTTTAGGCTGCTCCCCAC

CT[G[[G[GGGCCCATGGGAAG[G[GCC[G[GGAGGG[CG[[CG[CCCAAA[CG[CAGGCTGGAGGAGCCA[CG[

GA[G[[CG[TCCTGGC[CG[G[CG[TGT[CG[CCAT[CG[TTCAGCCT[CG[CTGCCCAGGTGGGAGGGGTCACCTGC[CG[[

CG[GGGTCTCCAAGCCAGTGC[CG[CTTGCTCC[CG[GCCCCCACCCACTGACAGCA[CG[G[CG[TC[CG[[AGTGACCC

TGTCTAGCCT[CG[TTCTG[CG[CTCCTGCAAACCA[CG[TTGCTG[CG[CTAAC

SEQ ID NO: 708

CAGGTGAGA[G[CAGCCCCTC[G[GGAGCCAGGGAAAA[G[C[CG[G[CG[AAGATCTGGAG[CG[GTAAGG[[C

G[CAG[G[GG[CG[GAGG[CG[CC[CG[GGAAGGGGACCCCAGTGCTCT[CG]AGATCAC[CG[TCCCTTCC[CG[AGAA

GGTCCAGCTC[CG[GGCTCC[CG[AACCCACCCTCTCTCAGAAGGTCC[CG[G[CG[CAAAGA[CG[GTGCCACCAGGCA[

G[GCCAC[G[GATCCC[G[CTCC[CG[CTGGCT[CG[[CG[CCT[CG[GGGGAAGCTCAGACTCCTAAACT[CG[CA

G[[G[[G[CT[CG[C[CG[GGACAGCCC[CG[[CG[GGCCATGGAGCTGG[CG[GT[CG[GGAACCTCAG[CG]AGG

GCAA[G[[G[AGCTGGC[G[GAGCCCCC[CG[CCC[CG[GAGCC[CG[GGC[CG[CTGTT[CG[GCAT[CG[G[CG[TGGAG

AACTT[CG[TCA[CG[CTGGTGGTGTT[CG[GCCTGATCTT[CG[[CG[CTGGGTGTGCTGGGCAACAGCCTAGTG

SEQ ID NO: 709

C[CG[AGCAACAGGTGCAGCA[CG[CAGCCCCTC[CG[GGAGCCAGGGAAAAC[CG[C[CG[G[CG[AAGATCTGGAG[CG

[GTAAGG[CG[GAGAGAAGGGTCTTTCCACCTG[CG[[CG[GCTGCAGC[CG[G[CG[GATCCCTCTTCCCAGGCTC[CG[

TGGT[G[[CG[CAG[CG[GG[CG[GAGG[CG[CC[CG[GGAAGGGGACCCCAGTGCTCT[CG[AGATCAC[CG[TCCCTTC

C[CG[AGAAGGTCCAGCTC[CG[GGCTCC[CG[AACCCACCCTCTCTCAGAAGGTCC[CG[G[CG[CAAAGA[CG[GTGCC

ACCAGGCA[G[GCCAC[CG[GATCCC[CG[CTCC[CG[CTGGCT[CG[[CG[CCT[CG[GGGGAAGCTCAGACTCCTA

AACT[CG[CACTCTC[CG[TGCTTTG[CG[C[CG[GGACCCCTGGCCACCCC[CG[G[CG[CCTACTATCC[CG[CCCTCCCT

[G[[G[[G[[G[[G[CT[CG[C[CG[GGACAGCCC[CG[[CG[GGCCATGGAGCTGG[CG[GT[CG[GGAACCT

CAG[G[AGGGCAA[G[[G[AGCTGGC[CG[GAGCCCCC[CG[CCC[CG[GAGCC[CG[GGC[CG[CTGTT[CG[GCAT[CG[

G[CG[TGGAGAACTT[CG[TCA[CG[CTGGTGGTGTT[CG[GCCTGATCTT[CG[[CG[CTGGGTGTGCTGGGCAACA

SEQ ID NO: 710

GGTGCAGCA[CG[CAGCCCCTC[CG[GGAGCCAGGGAAAAC[CG[C[CG[G[CG]AAGATCTGGAG[CG[GTAAGG[CG[[

AG[CG[GG[CG[GAGG[CG[CC[CG[GGAAGGGGACCCCAGTGCTCT[CG]AGATCAC[CG[TCCCTTCC[CG]AGAAGGT

CCAGCTC[CG[GGCTCC[CG[AACCCACCCTCTCTCAGAAGGTCC[CG[G[CG[CAAAGA[CG[GTGCCACCAGGCA[CG[

GCCAC[G[GATCCC[CG[CTCC[CG[CTGGCT[CG[[CG[[CCT[CG[GGGGAAGCTCAGACTCCTAAACT[CG[CACTC

TC[CG[TGCTTTG[CG[C[CG[GGACCCCTGGCCACCCC[CG[G[CG[CCTACTATCC[CG[CCCTCCCTCCC[CG[[CG[[CG[

CCC[G[[G[CT[CG[C[CG[GGACAGCCC[CG[[CG[GGCCATGGAGCTGG[CG[GT[CG[GGAACCTCAG[CG[AGGGCA

A[CG[[CG[AGCTGGC[CG[GAGCCCCC[CG[CCC[CG[GAGCC[CG[GGC[CG[CTGTT[CG[GCAT[CG[G[CG[TGGAGAAC

TT[CG[TCA[CG[CTGGTGGTGTT[CG[GCCTGATCTT[CG[[CG[CTGGGTGTGCTGGGCAACAGCCTAGTGAT

SEQ ID NO: 711

ACAC[CG[CCAGGAGCACAATCCCTGAGGCCAATAAAGACCCCAGCTTTGCAAGTCAGGGG[CG[[CG[AGCACTCTT

GCCCCTCAGGTTCCCAGAAGAAAC[CG[CCA[CG[AGGGTGGGGTG[CG[GGGTCAGTGTGCTCCACAGGACTTC[CG[

AGGA[CG[TGCCCCCCAAGCTGCTC[CG[TTCCTCCACCCCCTGGGATGCCACAGAACACC[CG[CCAG[CG[AGTTTCT

TCCCCAG[CG[CCCATGAGAGGAGGCTG[CG[GG[CG[GCAGC[CG[CAAG[CG]AGGAATCCAG[CG[CAGGGAAAGTA

GCCCCAGGGGGCC[G[G[CG[[CG[TCAGCCCCACT[CG[[CG[TGGCAAAACTTG[CG[GGGGCCCC[CG[[CG[TGC[C

CTCACCT[CG[GAA[CG[CTGGGTGGACTT[CG[CAGTAAACCTTAACTTOCCATOCAGG[G[GCAG[G[G[CG[[CG[G

TGCCT[CG[GCTT[CG[CTCCTGGCAC[CG[CAGGT[CG[CC[CG[TTC[CG[[CG[TTCCCAAAAGCATCAGGCTCACTTAG

AAGCTCAGGCAGCCT[CG[[CG[ACCCTCACCTACCCCTCCCAGCAC[CG[C

SEQ ID NO: 712

AGTGATTTAAATCCAGCTTATTT[CG[G[CG[[GCAGCTGGACTATTCCTTTGCTTATTTGGGGATGGGTGAGGGGCA

TACCCTTTAGGAAAA[CG[TTTCCAAATGATGTAATAATTTCTCTCTCATCTCTGGTCTTGCTCCAGACTTGGCCTCT

TCCT[G[CCACTCTGTCC[G[GCCTCC[CG[CCCC[CG[CAGGCTCC[CG[TG[CG[GACTTAGCAGTT[CG[[CG[C[CG[T

AGCCCTCCTGGTTTTTTAC[C[[G[CCTTGGT[G[[CG[[CG[GCCCC[CG[GTG[CG[GGCCT[CG[T[CG[CTC[CG[ACA

GCCCTACAGCTGTCCCTA[CG[GCC[CG[CAC[CG[ACAGCT[CG[TCCC[CG[CCACCTCCCTC[CG[GGCTGTAGGGA[

CG[T[CG[AGATC[CG[AATCCTCACAG[CG[CCTGACC[CG[GGGC[CG[TGTTGGGTA[CG[GGTA[CG[G[CG[AGAGCCT

TC[CG[AGC[CG[CCTCCAAAACTCTCCC[CG[[CG[GACCTCAGCAGTCCCTCCA[CG[[CG[T[CG[GGGCCCTGCTGGC[

CG[GCCATGCCCTCTGAGGAGA[CG[[CG[GAAAAGAG[CG[AGGCATATAGGAAGGTGGGG[CG[TTTTATC[CG[CCT[

[CG[[GTTTTGACCCATCTGCCATGTAGTCTCCCCAGGCAC[CG]AGGGAA

SEQ ID NO: 713

AGAAACAGATTAGACAGAGATAGATGGATCCAT[CG[[ATTGATTAGATAGGTTAAGATAGTCCTTGCATTCAGGC

AAGCCACAGCAGGTGC[CG[[CCTAGGGCAG[CG[GCCTCTGCCCAGACACTCAGTGCTGCAGAACAGGAGGGAGG

C[CG[GGGCCTGTGG[CG[GG[CG]AGGGAAATG[CG[GGGCC[CG]AGGACTGGGGTGAGGGAGAGAGG[CG[G[CG[GC

CCAGAGGAGCAGCAGG[CG[[CG[CCTCTGG[CG[GTTTCCTGTC[CG[GGCTGG[CG[GGGC[CG[CCAGT[CG[G[CG[TG

GGGTG[CG[GCAAGGGGAG[[CG[GGG[CG[CTGGGTCAGC[CG[AGGGC[CG[GGCCT[CG[GGGG[CG[CAGC[CG[GA

CTGGA[CG[G[CG[GCTCCTGTGGGCACTTGGC[CG[GGTTTGCTGGTTTTT[CG[GGAAATAAGGCCACTGGGGACAG

TCACTA[CG[TTTTCAGGAAC[CG[[CTCAGCCCCTCTGAGTGCCC[CG[CAGATGGACCTGG[CG[G[CG[TTCCTGGC

TA[CG[GCTGACTGGGCTCC[CG[GAG[CG[AGGAG[CG[CCCCTG[CG[GGCCCAGCCTGGGCCCTGGG[CG[GTGGGAG

GGCCTC[G[CCCCCTTCC[G[CTTC[CG[CCC[CG[CTGG[CG[C[CG[GACCCC[CG[CC

SEQ ID NO: 714

GGC[G[AGAGGAAGGAGCCAGCCC[G[C[CG[GGC[CG[C[CG[CCTG[CG[ACTTCCCCTCTGATCCACAGGTGC[CG[

GTAAACAAAAGTGC[CG[CAGCTACCCCCC[CG[CCCCCACCC[CG[[CG[GAGTT[CG[GCCCAAGGTTA[CG[C[CG[GG

GTT[G[GG[CG[G[CG[CC[CG[C[CG[GGGGCCCCCAAACCCAGCTTCTGGACTCTCCC[CG[GCTTCTCAAGCCCAC[C

G[GGC[CG[GGAGCCTTCCTCTGGCTC[CG[AGCTGCTCCCCT[CG[CTCCAGGCTGGATTCCCCCCTGAAATGTTGGTC

[CG[GGAAAACCAGCCTGGGTCCT[G[[CG[[CG[CCCTTCTGCA[CG[GGGACCCCAGCCCACCCC[CG[TA[CG[GA

CA[CG[CCTTCCACCATCT[CG[[CCTAGAAGGCTGCTGGGACCCCAGACCCAGAGCCC[CG[GTCACACTCC[CG[TCC

CATGCTGTCCCCCTCC[CG[CAAAGCCCA[CG[GTGGGAACAGAGGGCAC[CG[[CG[[CG[AGC[CG[ATGCCACCCTCA

CTGC[CG[GCCCCACCCAGACCTGC[CG[GTGCTGCAGTGCCC[CG[TATGTGCAGCCTGCAGCATCCCAG[CG[GCTG

GGGCAGGCC[CG[GGGG[CG[GCT[[CG[[CACAA[CG[CAGCTGGGGAC[CG[GGT

SEQ ID NO: 715

[CG[GGAAGGCCATGCTG[CG[GGG[CG[[CG[CCAGGACTAGGCCTCA[CG[G[CG[[CG[GAAGGGGGC[CG[AGGACTC

TG[CG[GAGGACTTGGGGGGCCCCTGCCC[CG[AGCC[CG[GGGG[CG[ATT[CG[GGGGTGCTGGGGG[CG[AA[CG[G[C

TCCAAGG[G[[G[[G[CATGGC[CG[CCAA[CG[TG[CG[GGAG[CG[CAAG[CG[CATCCTAGACTACAA[CG]AGGCC

TTCAA[G[[G[CTG[G[[CG[GG[CG[CTG[CG[GCA[CG[ACCTGGG[CG[[GCAAGAGGCTCTCCAAGAT[CG[CCA[C

GTC[G[[G[CCC[G[CTG[G[CCT[G[TGCCCCC[CG[CA[CG[[CG[CCCCTGGCA[CG[GCCCAGTG[CG[GTGGC[CG

]AGGGGC[CG[GGCCT

SEQ ID NO: 716

GGGGAAGCCATACTGTGGC[[CG[TGGCAACTGAAGACATCC[CG[[TCCCAAACTCTGGAAAGGATGAGGGAGGG

GGCTGATGCCTAGGCCTC[CG[TGGGGAGGAGGTCTGGG[CG[GTAGG[CG[GTGGGGTGGGTGGAACCTAG[CG[TCC

AGCTAGG[CG[[GAAGGG[CG[[GAGCTTCAGGTCTCCATGGAGG[CG[GCTTCTCCTAGCAACT[CG[A[CG[GG[CG[T

TGAG[CG[GAGC[CG[CTGACCTGATGGA[CG[C[CG[ACAGCCTCCTGCTGTCTCTGGAGCTGG[CG[TC[CG[GCAGTG

GGCAGGGCCTCAGCC[CG[GAC[CG[T[CG[[GGCCT[CG[CTGCTCA[CG[TCTCTTATGCTGGTTAAG[CG[[CG[ACTAC

[CG[CTATGAT[CG[GGTTCTCTTCTGGGGC[CG[CATCCTTGGCCT[CG[T[CG[C[CG[ATTACTACAT[CG[[CG[CAGGG

CCTGAGTGAGGACCAGCT[CG[CAC[CG[[CG[CAAGA[CG[CTCTATAGGTGAGGAGGCCCC[CG[GGA[CG[GGCTCCC

CAGAGGGTGGCTACCTGGAGGCAGGG[CG[GGGTGGG[CG[GGT[CG[CAGCAATTGAAAGGGG[CG[GGGCCCATGG

GGCCAAGGGAGGTGTGGG[CG[GGATCTGAGATGAGTGGAATGGGGGAGA

SEQ ID NO: 717

CTGATTTC[CG[A[CG[AAATGTCTGAATGCCTACAGTTATTTGGCCATCCTGAAAAGTGCAACTTATCCTGA[CG[[T

CT[CG[[AGGGA[CG[GAAAAGTTAC[CG[AAGTCCAAGGAATGAGTCACTTTGCTCAAATTTGATGAGTAATATCAG

GTGTCATGAAACCCAGTTT[CG[[AAGGAGAGGGGAGGGGG[CG[TCAGATCTGCAGA[CG[[GAAGCAGGC[CG[CT

C[CG[GATTGGATGG[CG[AGACCT[CG[ATTTTCCTAAAATTG[CG[TCATTTAGAACCCAATTGGGTCCAGATGTTAT

GGGCAT[CG[A[CG[[AGTTAC[CG[[TCT[CG[GAAACTCTCAATCA[CG[CAAG[CG[AAAGGAGAGGAGG[CG[GCTA

ATTAAATATTGAGCAGAAAGT[CG[[CG[TGGGGAGAATGTCA[CG[TGGGTCTGGAGGCTCAAGGAGGCTGGGATA

AATAC[CG[CAAGGCACTGAGCAGG[CG[AAAGAG[CG[[CG[CT[CG[GACCTCCTTCC[CG[G[CG[GCAGCTAC[CG[A

GAGTG[G[GAG[CG[ACCAG[CG[TG[CG[CT[CG[GAGGAACCAGAGAAACTCAGCACCC[CG[[CG[GGACTGTC[CG[

T[CG[CAGTAAGTGCC[CG[[CG[[CG[GTGCTGGC[CG[[CG[GCTGCC[CG[GGTCACCCC

SEQ ID NO: 718

ATAAAACTGACACATGGGCAGTGAGGGGAATTTGCTCTCCTGCCTCCCTCCCTAAGTTCATCTGCTGAGAAAAATG

CTTTGAGATAAACCTGGAGCCACAGCTCTCTGCACAGTCAGAT[CG[[CAGGAA[CG[[[CG[[GCCTAGCTGCTTCAG

CCA[CG[TTCT[CG[[CG[G[CG[CCACCTGGTGGCCATGGAC[CG[CCAT[CG[C[CG[CTGGA[CG[TCAGGGC[CG[CCAG

GCCCAG[CG[AGATGTCACCTCCTCTGAGGAGCCTTCCAGGAT[CG[CACC[CG[GCA[CG[[CG[CTCCA[CG[CCT[CG[T

TGTCTGTTCTT[CG[GAGCAC[[CG[[ACCATGATCACAAATCAGCT[CG[CT[CG[CTGTGTTTCCTGC[CG[GGT[CG[CT

AC[CG[CCATGATC[CG[CA[CG[TAGTGGTCAAGGCTGAGGTTGTATGAATGTGGA[CG[[TTATAACCCTGGCTCCCT

CTCCCTCCCTATGCTGGGCTCCCCT[CG[ATCCCCAGG[CG[GTGGGGTGCCCCTGGTTTTTCCTTTTTAAAATTATAA

GTCTGGC[CG[GA[CG[[CG[GTGGCTCAGGAC[CG[TAATCCCAGCACTTTGGGAAGT[CG[AGGGAGGGTGTATCACT

TGAGGCCAGGAGTTCAAGACCAGCCTGGCCAACA

SEQ ID NO: 719

GCACCAGCCTTCTAGTGTGCCCCTGCCCAA[CG[GGAGGGAGGAGGGAG[CG[GGGAGCCC[CG[G[CG[AGGGAGGA

GAGGG[CG[GGCCCTGAGAGGAGTTTGAAAAGAGGAAGGAAGTGGGGCCCTG[CG[G[CG[CCCAGCCACCCCCTGA

[CG[GCTTCCCCA[CG[GGAGGA[CG[[[CG[AGGCCC[CG[GCCCAGCCATGGCCCCCTGG[CG[CAAAGCTGACAAGGA

G[CG[GCA[CG[G[CG[TGGGTAGGTG[CG[GGCCCCAGGG[CG[[CG[GCAGGGAG[CG[GGACAGGTGG[CG[GGAGAGC

[G[[G[AGCAGGAGGATGTG[G[GGG[G[[CG[G[CG[[CG[GGGTGGGCAGGG[CG[[CG[CTGCCTGCAGGTC

AGAGGG[CG[CAGCCTG[CG[G[CG[GGGCCT[CG[GGG[CG[GGAAAGC[CG[AGGCT[CG[GGGAGAGGA[CG[G[CG[G

GACCCCACCC[CG[CAGGCTAAGCACAGCCCT[CG[CCCTCT[CG[CCTGCTGAGGGAACCTTAGACATTTC[CG[AGAT

AGGGTCAAGACCTG[CG[CTTGACAACTCAGTTCTT[CG[[CG[CCAAACT[CG[G[CG[TCCCCAGGAGTGCCCCAGCT

[CG[C[CG[[CG[TGGGAGACTTGGCCTTGTAGAGGGAGCTCCACTCTCCCCTGGCTCAGC

SEQ ID NO: 720

CCTCCAGCCTTTCTCTCTGGGCCTAG[CG[GGACTCTCCCAGGCAGGCCCCTCCCTGCC[CG[[CG[GG[CG[CACTTTC

CC[CG[CCTGCATCTGAGG[CG[TGG[CG[CAGCTGGGAGCAAAGCACAGGTGGGCTGGG[CG[[[CG[GTTTGGGGTT[

CG[GG[CG[TGGCAGAGTGG[CG[G[CG[GGGTCTGGGGAAGAGTTGTCTTGGGGGCAG[CG[CCAGCCACCAGAGCC

[CG]AGTCAG[CG[[CG[GCCAGGACTCTGCAGGGGCAGGTAG[CG[ACCCTTAGAGA[CG[CAA[CG[TGG[CG[CAG[CG

]GACT[CG[GCTG[CG[TGGGGCAAGGGC[CG[GGGC[CG[GACACAGGAGCAG[CG[GGGATGC[CG[GGTG[CG[CTC[

CG]AGGGTGTGGCCCC[CG[GGCTGTG[CG[GGGCTCAGAGCTGCTTGCTGGG[CG[[[CG[[GTGCC[CG[ACAAAGGTA

AGGCAGGAGTGGG[CG[TCTTTCT[CG[[CG[GGA[CG[CTGGGT[CG[GAGGGAGCTTGAACTTGAGGTTGTTGGGGAG

AGCCAGAAAGGA[CG[CCAGTGCCACAAGGAG[CG[CCTGCCTTGGGG[CG[TGGAGC[CG[CTCCTCCCCTCACTGGG

CAGACC[CG[GCCAGCAACCAGGTAGGAGAGTGGGGGCAAATGTGGCCATTC

SEQ ID NO: 721

CAGAGAAAGT[CG[CTCTTTGGCCACCTGAAG[CG[T[CG[GATCCCTACAGTGCCTCCCAGCCTGGG[CG[GGAG[CG[

G[CG[GCTG[CG[T[CG[CTGAAGGTTGGGGTCCTTGGTG[CG[AAAGGGAGGCAGCTGCAGCCTCAGCCCCACCCCAG

AAG[G[GCT[G[CAT[G[CTG[G[GTGGG[G[TTCT[G[GGCTT[G[ACTT[CG[CCAG[CG[C[CG[[CG[GGGCAG

AGGCACCTGGAGCT[CG[CAGGGCCCAGACCTGGGTTGGAAAAGCTT[CG[CTGACTGCAGGCAAG[CG[TC[CG[GG

AGGGG[CG[GCCAGG[CG[AAGCCC[CG[G[CG[CTTTACCACACACTTC[CG[GGTCCCATGCCAGTTGCATC[CG[[CG

]GTATTGGGCAGGAAATGGCAGGGCTGAGGC[CG[ACCCTAGGAGTATAAGGGAGCCCTCCATTTCCTGCCCACATT

TGTCACCTCCAGTTTTGCAACCTATCCCAGACACACAGAAAGCAAGCAGGACTGGTGGGGAGA[CG[GAGCTTAAC

AGGAATATTTTCCAGCAGTGAGCAGGGGCTGTATGGGA[CG[[CG[[GGAGGAGCTCAGAGGAGG[CG[[CG[GAGAG

TGCC[CG[AGGTTGGGTGAGTGCCTAGAGGGGAGATAGTTG

SEQ ID NO: 722

GAATC[CG[GGGT[CG[CAGGGTGGTAGAGC[CG[GAAGATTGGATTCCATCTC[CG[[CAAGGATTGAGAAAAA[CG[

GACTCAC[CG[ACTGAACTATTCCATCTCCAAGTTGTTTTTATTTTCCACTTTAAGCATAAGAA[CG[ATGAGAACCA

GGAGCCAGG[CG[GCCC[CG[[CG[TAG[CG[GTGGGAG[CG[CAGGTACC[CG[AGAGTACCCTCTGGGGGC[CG[GCC[

CG[[CG[[CG[CT[CG[CTCCTCCT[CG[CCTTTC[CG[GGAAC[CG[TG[CG[CAGGAGCTCACA[CG[GCA[CG[CCTG[CG[

GCCAGGGGCAAT[CG[GGTTCT[CG[GTTCC[[CG[GAGTCCCAGTTCC[CG[GTTTCCAGTTTCCTTAT[CG[A[CG[[CG[

ATTGTTC[CG[T[CG[GGGTCTTCCAAGGGGATC[CG[AATGGTGGCCAAGTCC[CG[CTGGGGAAATC[CG[CAGGGGT

G[CG[GCCTG[CG[GGGCCTTTGGGGG[CG[CACCTA[CG[CCA[CG[GGCTCTGCCATTCCTATC[CG[[GAAAATTCAA

GCTGTTTGGGCACCAGGAGGGACTCTGAGACAGAGGG[[CG[T[CG[GAGAAGG[CG[[CG[TCTCTGCTTGTCCTCTT

GGGCTGACTGAGGGTCTCA[CG[CTAGGCCAG[CG[CTGGCTT[CG[GGACAGCTCC

SEQ ID NO: 723

AG[G[CA[G[[CG[[CG[AGGGC[CG[G[CG[GGAAATGTAGTCTCA[CG[C[CG[GTAAAGCCACAGAG[CG[A[CG[AT

GAGG[CG[AGA[CG[TCTG[CG[TTCTTCTCAGGCCTGAGACCCAAC[CG[GCC[CG[[GGCACCAGCTCCTGCTGGACC

CCAGAG[CG[CCTGGAAAGCTC[CG[GAACCTCTCACCTGC[CG[CCTCCT[CG[GGTCCAAGTGCCAC[CG[[CG[GC[CG

AGATGG[G[CAGA[G[CACAAAGCACA[G[ATGTG[G[CCATGATAGGG[CG[G[CG[C[CG[CAGTGTCTTC

[CG[[GGAAACATAGTCTTTAGG[CG[[TAAAGGCAGCAGCC[CG[[GCCTTGAAGC[CG[GATCT[CG[[[CG[ATGTTT

CAGGGTGAGC[CG[GA[CG[CAGG[CG[TGCCTG[CG[CAGTG[CG[[CG[GAGGAGTGCTGTT[[CG[[TGTGTT[CG]AGTC

CCTGGGTTGCTTCCTGGGGTCTGTGGTGCTGGGTGTGCTATCTG[CG[[TGTGATTCTCTAG[CG]AGAGATTGTGGG[

CG]AGTGAC[CG[AGTGGGCAAGGGGC[CG[TCACTGTGTGTG[CG[TGATTTTGACAGTGTGTGGTGGTA

SEQ ID NO: 724

TCATAGAGCATCCAGCAGC[G[CTGTCCA[G[[CG[[CG[C[CG[AGTTGCAG[CG[GCTCAAGTAGGGCTGCAGGTTG

GGGTGGT[CG[CTGCTGCATTCATAGTGG[CG[GCCCTGGAAGCCC[CG[GTCCT[CG[TAGAGGGTGATCTGCAAGGC

AAGG[CG[GGACAAGG[CG[AGGTCTCACAGGCCTGCTCCTGCCCCAGTCTCTGGCCCC[CG[[CG[ATGGAGGAAGCT

C[CG[GGGTCC[CG[GGG[CG[CAGGCTGGGCTCACCTTCCCCATGGCTGGCTGGG[CG[CA[CG[G[CG[GTGCTGAGCT

GGGGGG[G[[G[[G[CTGAG[G[GGGGGGCTG[CG[G[CG[[CG[G[CG[GGCTATATAGCAGGAGGGCTGCT

G[CG[TTGGCAAGAAC[CG[CACAAAAGGGGCCCC[CG[GAGGGGAGCAAGGGCATTTT[CG[TGTTCTCTTTTTTTCTC

TTTGCTGTGCTAGACCA[[CG[[GGGCTTGTTGTGGGTTTTGGT[CG[[CATTCTCTCTGGAGTATT[CG[GATTGCTAT

CACTGGCTGATGCTATTGAGAATGTTTGTAAAA[CG[[GCAATTTGGGACATTGTCTATTTATAATGGAAGTGGAGC

TTCAGCTATTTCACATATAGTTCA[CG[CTTTTATT[CG[TA

SEQ ID NO: 725

GGCTGCCC[[CG[[TGCTCTGTGAC[CG[G[CG[CATATTCACCA[CG[GGTGAGCCCCT[CG]AGCTGGGCCCTGGGGAG

AGAGAGGG[CG[GTGCCCAAGCCAGGACCCTG[CG[GGC[CG[GGGCTGGAGGAGG[[CG[CAGGTCC[CG[G[CG[TCC

ATGTGCAGCCCTG[G[[G[GGG[CG[[CG]AGATCTCCC[CG[CAGG[CG[GC[CG[CTCCC[CG[CCAGGGGCTTC[CG

]GGAGAGC[G[AAGCCTGAACCTGGA[G[AGC[G[[CG[AC[CG[CAGC[CG[G[CG[GGGGGTGC[CG[TCCTCCT[CG

]CCCTCCCTGGAGCC[CG[GCCCTGGGCCCA[CG[C[CG[TGCCC[CG]AGCCTCCTCTG[CG[GCC[CG[CCCCCAGTTCC

G[CTTGTCCCCAG[CG[CAGGAGGAGC[CG[GGACC[CG[A[CG[[CG[CACCCTC[CG[GCCTGCTGGAGGCTGAGC[CG[

C[CG[CAGGGAAAGCA[CG[TGGGTGAAGGGCCCAG[CG[[CG[G[CG[GTTCCTTGAAAAAG[CG[GGAGCCTGGTCTC

AGCTGGGGCCTGGGGCCTGCCC[CG[CCCATGCAGGGGT[CG[[CG[GGAGCAGGGGCT[CG[GCCTCC

SEQ ID NO: 726

TGACTCC[CG[CCCCCAGGAGGTGGAGCAGGTGA[CG[TTCAGTAC[CG[CCCTGGAGGGGCTCA[CG[GACCAC[CG[G

GCAGTG[CG[CCTGCAGCTC[CG[AGTCTCAGTGTCCTCCTAAGGCAAGCACAGATGAGGGG[CG[[CG[[CG[GCTGG[

CG[[CG[CACAGACA[CG[ACT[CG[GAGCA[CG[AACTAGG[CG[C[CG[TAGCTG[CG[TCCCCAGAAC[CG[GGAGACTT

AAGGCATCTTTATTG[CG[GGATCCTCACA[CG[GCCTCCTGGGCC[[CG[[G[CG[ATACTCATAGA[CG[CTGC[CG[TGC

T[G[GGAAAGGCCAGTGTTG[G[GGGG[CG[[ACCC[CG[G[CG[GTGGGG[CG[GGGTCCTC[CG[GGTCCCCATAGC

CAC[CG[C[CG[C[CG[GG[CG[TGTGGAGACAGAACACATCCTGTTGG[CG[[CG[GGGGGGGG[CG[GGGAGG[CG[GGC

TCAGTGCAGG[CG[TGGCCCCTCCCTGTCACCTG[[CG[CAGTCCCCTCCCCAC[CG[GGCAG[CG[TCCATCACC[CG[C

CCCCATGGACCA[CG[GAGGCC[CG[GTA[CG[[CG[CCCCCTTTCCTTC[CG[GGGCCAAATTAAACT[CG[GCCTCTGGT

CAGGTCTGCAACTGTTCCCCCTCTGTGGGATGGGGC[[CG[[GGAGGGGAGGGGAGG

SEQ ID NO: 727

CT[CG[GTCTGGGTTCCCC[CG]AGGAAAAATACCCACC[CG[[CG[AGGGCT[CG[G[CG[[GCTTTT[CG[ACT[CG[G[CG[

GGGATGAACTGTGGCAACTT[CG[[GCAGCCCCCAC[CG[[CG[GTG[CG[GAAGTAAAGAGGGCAACATTGG[CG[ACT

G[G[GCT[G[GAGGGGCTGGAG[G[[G[TGAAGC[G[TGGGGG[CG[[C[CG[TG[CG[CCTCC[CG[CTCTCT[CG[TT

T[CG[GC[CG[CAGGTCCTGGGACTC[CG[ACTT[CG[GTGCTC[CG[GGTGATAG[CG[GCTG[CG[G[CG[CCTGCAGTCCA

GATCCT[G[CAGTTCT[G[GG[CG]AAGGAGG[CG[[AA[CG[GAAT[CG[[GCCCCCAGTGGGGAG[CG[[CAACA

AGCCACAGTAGCCAAACCC[CG[[CG[CTCCTGCC[CG[GGCTCCCAGA[CG]AA[CG[CAGC[CG[CAG[CG[GGGGGC[C

GGG[CG[AGA[[CG]][[G[[CG[[CG[CCAG[CG[GTGGGGGG[CG[GGCTGGGGG[CG[GGG[CG[

GC[G[GGGCTGCCTTCC[G[GG[G[CATATG[CG]AG[CG[CAGCACC[CG[G[CG[CTGC[CG]AGCCACCTCCCC[CG

C[CG[CC[CG[CTAGCAAGTTTGG[CG[[GCTCCAAGCCAGG[CG[[CG[CCTCAGGATCCAGGCTCATTTGCTTCCAC

CTAGCT

SEQ ID NO: 728

[CG[GTGCTC[CG[GGTGATAG[CG[GCTG[CG[G[CG[CCTGCAGTCCAGATCCT[CG[CAGTTCTG[CG[GG[CG[AAGGA

GG[CG[[AA[CG[GAAT[CG[GCCCCCAGTGGGGAG[CG[[CAACAAGCCACAGTAGCCAAACCC[CG[[CG[CTCCTG

C[CG[[CG[CCAG[CG[GTGGGGGG[CG[GGCTGGGGG[CG[GGG[CG[GC[CG[GGGCTGCCTTCC[CG[GG[CG[CATATG[

CG]AG[G[CAGCACC[G[[G[CTG[G[AGCCACCTCCCC[G[[CG[CC[CG[CTAGCAAGTTTGG[CG[GCTC

CAAGCCAGG[CG[[CG[CCTCAGGATCCAGGCTCATTTGCTTCCACCTAGCTT[CG[GTGCCCCCTGCTAGG[CG[GGGA

CCCT[CG[AGAG[CG[ATGC[CG[ATGGATTTGATTTTAGTTGTGTGGTTCTGTGTGTGCACTGCCAGGACAGGTAAGC

ATGACTGTGG[CG[GTTAGAGGGATC[CG[GGAAATGGGGGTGCCCACAGACCA[CG[G[CG[G[CG[TGGGGAGACC

TGGAGC[CG[AGCTTTG[CG[CTGGTCTGGGGAA[[CG[G[CG[GTAG[CG[TGGAC[CG[GTTCCTGGGATCTC

SEQ ID NO: 729

[CG[GGTCCCTCAGAGTCTC[CG[GATC[CG[AAATCTACCC[CG]AGGCAG[CG[GGACC[[CG[[CCCAGACCCTCCACC[

[CG[[GGAGAGTCCCAGG[CG[CCTTTACCCAGGTTCATTTTCAGTTTAGGCCAAAATCCC[CG[[CG[GGTTGGG[CG[[

GGGAGGGGG[CG[GGGCTAGCTGGG[CG[GGGCTGACTG[CG[GGGAC[CG[GCTAGGGTCTCACACCCTCCAGGGAA

TGAATGGCTG[CG[ACATGGGGCC[CG[A[CG[GA[CG[CCTCCTC[CG[[CG[GGTATCACCAGCA[CG[[CG[TA[C

TCAGATCACCCAG[CG[[CTTCTATGAGGCAGAGGAATATGCAGAGGAGTTCAGGACCTACCTGGAGGG[CG[AGTG

CCTGGAGTTGCTC[CG[[CAGATACTTGGAGAATGGGAAGGAGA[CG[CTACAG[CG[[CG[CAGGTACCAGGGGCCAT

GGG[CG[CCTTCCCTATCTCCTGTAGATCTCTTGGGATGGCCT[[CG[[CACAAGGTTGGGAGGAA

SEQ ID NO: 730

TCT[CG[TTT[CG[GC[CG[CAGGTCCTGGGACTC[CG[ACTT[CG[GTGCTC[CG[GGTGATAG[CG[GCTG[CG[G[CG[CCT

GCAGTCCAGATCCT[G[CAGTTCT[G[GG[CG[AAGGAGG[CG[AA[CG[GAAT[CG[GCCCCCAGTGGGGAG[C

G[[CAACAAGCCACAGTAGCCAAACCC[CG[[CG[CTCCTGCC[CG[GGCTCCCAGA[CG[AA[CG[CAGC[CG[CAG[CG[G

GGGG[G[GGCCC[G[AGCCCC[G[[G[[G[[G[[CG[[CG[CCAG[CG[GTGGGGGG[CG[GGCTGGGGG[CG

GGG[G[GC[G[GGGCTGCCTTC[G[GG[CG[CATATG[CG[AG[CG[CAGCACC[CG[G[CG[CTGC[CG]AGCCACCT

CCCC[G[[CG[CC[CG[CTAGCAAGTTTGG[CG[GCTCCAAGCCAGG[CG[[CG[CCTCAGGATCCAGGCTCATTTGC

TTCCACCTAGCTT[CG[GTGCCCCCTGCTAGG[CG[GGGACCCT[CG[AGAG[CG[ATGC[CG[ATGGATTTGATTTTAGT

TGTGTGGTTCTGTGTGTGCACTGCCAGGACAGGTAAGCATGACTGTGG[CG[[GTTAGAGGGATC[CG[GGAAATGG

GGGTGCCCACAGACCA[CG[G[CG[G[CG[TGGGGAGACCTGGAGC[CG[AGCTTTG[CG[CTGGTCTGGG

SEQ ID NO: 731

GTCTTTTGCTAAAAAC[CG[GCAGTG[CG[CTT[CG[CCTCCCTGCCCAGC[CG[CAGCCTGC[CG[TCCCCTAGACAAAA

ATGGTGCCAGCA[G[GGG[G[[G[[G[AGGG[CG[GGGG[CG[GGAGGC[CG[[CG[AAGAGGGT[CG[GG[CG[GG

AGGGGAGGAGA[G[[G[GAGCAGCCAATC[G[[CG[[CG[[CG[[GCCCATCAGCTGAC[CG[CCTTTGCTTACAC

GTAA[G[AGG[G[AGG[G[TG[G[CC[CG[[CG[GCTGCAAG[CG[CC[CG[CCTGG[CG[GGGAGAGGGGC[CG[A

[G[[G[TCAGCC[G[GG[CG[G[CG[GCATCCCTAGG[CG[[CCTGGGG[CG[CCTTCCTC[CG[GACCTGGC[CG[CT[C

G[CTGCCC[CG[CCCTCTGCACCCCACTTCTC[CG[ACCCTCCTTCCCAGTCCTGCCTCCCCCTGCCCTGGCCTCTGAG

AGC[CG[ACTGAGCCCAGCCC[CG[TGCAGCAG[CG[GTTGCCTGTGT[CG[C[CG[CCTAGTCTC[CG[GTCTTGGTGCTC

SEQ ID NO: 732

AGCCAGCCACAGTGTTCA[CG[C[CG[[CG[GGTCCTCAGCC[CG[GGAGGCCACTCCCTTCCCT[CG[TGACAGGGGG

GTCCTGGACTGGTTTTGGGCTGACCC[CG[GG[CG[CCCAGGACAG[CG[CTGTCCTC[CG[TGGTTCTGTCCCTGGTGA

CAG[CG[ACTCC[CG[CTAGCTAGGCC[CG[GGAGCACCAGGGGGAGGGAGGCAGGAGGGCCAC[CG[TGGGTG[CG[G

GCCTGG[G[[G[GGCTCAGCC[G[[G[GGGGC[CG[[CG[TGGG[CG[GGGA[CG[GGG[CG[TCTTGT[CG[[CG[GGCA

CCTGTG[G[[G[TGGG[G[GG[CG[[CG[CACT[CG[[CCAG[CG[CTTTGTT[CG[TGAC[CG[GCCTTTTAAGGGCTGTC

TCACCCATCTTGTCTGGCTCTGCCTCCCTGTTTCCTTTC[CG[TCCTCTCTCCCACCACAGCCAGCTCCCCACTTTTTT[

CG[[CG[GGGGCCCCCTCCAGCCTGTC[CG[GGGCCTCCC[CG[TTCCCAGGCCAGGGCTTCCCCCTCCTCCCAGACCT[

CG[TTGCTCTGCC[CG[GTGAGGCCC[CG[GGCTCCCAGCAGGGGG[CG[CCTGCT[CG[[CG[ATCAGGTGG[CG[GCCTG

GGGG[G[GCCTGG[CG[GTCC[CG[G[CG[GACCCTGA[CG[[CG[G[CG[GGGC

SEQ ID NO: 733

AAATGT[CG[ATGGGCA[CG[TTGAC[CG[GC[CG[G[CG[GATG[CG[GCCCC[CG[GACTGATAGTAGTAGAGGATGG[C

G[T[CG[AAGCTGGGC[CG[GTTG[CG[GT[CG[AAGAAGTACT[CG[TTG[CG[GAG[CG[GGT[CG[AAGTACCTCATG[CG[

C[CG[CTTGGGGT[CG[CCCAGCAG[CG[TCT[CG[GGGAACTGGCAAAGGGTCTTCAGCTG[CG[TCT[CG]AAG[CG[CA

CGGCAG[G[GCT[G[TAG[G[GT[G[CAG[G[[CG[[CG[CCACAGC[CG[CCTTGAGG[CG[GGGCCCCTCCAC

CAT[CG[GCCACCTC[CG[GCTCCAGCAGGTGGTCCC[CG[GGCACCA[CG[GTCATGT[CG[GG[CG[GCAGCT[CG[[CG[

GCCTG[CG[G[CG[GGCTC[CG[[CG[TAGC[CG[TGGTTCACCAG[CG[TGTGGGCAC[CG[C[CG[CTGCT[CG[CTGGG[CG

CT[CG[TCCATG[CG[G[CG[GGGAAGAGG[CG[GCAG[CG[GTGAGGCCAGGT[CG[CTCCTCCT[CG[[CG[CTCCC[CG[C

CCTTT

SEQ ID NO: 734

CACAGGCACACTCATG[CG[CTTGCCACCCCATCCCCCCACCCAGACACAGACACACAACACAACACACA[CG[[CA

CACACTGCACACACCTGGCAC[CG[TGTGCACCACCTCATGCCACAAGCAGCCACACACCCCACA[G[[CG[CC[CG

]AACAACACCCTTCACCCACACTGCACA[CG[CTGCAGCCCTGTACA[CG[CCACATAACACA[CG[CACCCCACACAC

CCACT[G[GGACCC[CG[A[CG[[CG[GGTGAACAAG[CG[ATGGGAACAGGCCCT[CG[GGGTGGGC[CG[TAG[CG[GG

TAGGG[G[GG[G[[G[GGGGT[G[CACC[G[GGT[G[G[CG[CA[CG[[CG[CAGCAGGCTAGTGC[CG[CCCCCTC

CCCCT[CG[C[CG[GCTGCCA[CG[TCTTTGCCCTCTC[CG[[CG[GC[CG[GGCCCTG[CG[GGGCACCCTGGGTGCC[CG[A

[G[GCCTC[G[GGAG[CG[[CG[GTGGGCTCCAGCCC[CG[CACCC[CG[[CG[AAGGAA[CG[GTCAG[CG[CAGTCCCC[

CCCAGGG[G[[G[G[CG[CAGCCAA[CG[[CG[CAACC[CG[CCCAGGTCAGGGGTGCC[CG[[CG[CCTG

SEQ ID NO: 735

TCCCCCTA[CG[C[CG[CTGGGGGCTGCTGAAATTAGAAGAGGGAGT[CG[GGAAGTCATACCCCTCCCTGTGGG[CG[

T[CG[GGTTGCACTGTTGACTAACTTAGAAAG[CG]AGATTTCTAAAAATGATGCTGGGGCTGCAGGCTG[CG[GGCT

G[G[GGCTG[G[GGCTG[G[GGCTGCTGC[CG[[CG[G[CG[GGGGCTTC[CG[G[CG[G[CG[CTCTCTTCTGGGTCCCCC

ACCCCTGGACCAG[CG[AC[CG[A[CG[[ACCAGCCAGACAGCCCTTTCCTG[CG[AATGGACAATGGGAGAGGCTGG[

CG[CAAC[CG[AGAATAGCCAG[CG[[CG[GAGGAAGGGCTC[CG[GA[CG[GAGCTAGGAGGGTGGGGCT[CG[GAGG

G[CG[CAGGAAGAG[CG[GCTCTG[CG]AGGAAAGGGAAAGGAGAGGC[CG[CTTCTGGGAAGGGACC[CG[CA[CG[A[

CG[A[G[CC[CG[AAGGG[CG[T[CG[GGGGAAGTGGTAGGCCC[CG[GAGACTG[CG[[CG]AGGCTCCTCAGCAAAGGA

G[CG[CCTCTCAGCACCTGTACCT[CG[CCAGA[CG[[CG[GCCTCA[CG[GAGA[CG[GGGATCTGCAG

SEQ ID NO: 736

GAGCCCATGGA[CG]AGGCCTTGTC[CG[[TTCCTAGAGCTCTGCTCTCACTTGGTCCTTCTCTCCACTTCTCTCT[CG[

CTTCTTTTTTACTCT[CG[TTTCTCTCTGCTTCCA[CG[TCTCTCACAAATCTGG[CG[TTTCTCTCTTCCATCTCTTCCTC

TCTAGGTCTCCTTGTT[CG[CATTCTTGCCTCTCCCTCCT[CG[TCTCCTCATGCCCTCTCCCCTCTGTCCTCTG[CG[CT

CTTCT[CG[CCTCTCCTCTCCCTCCC[CG[TCTGGTTCTGTTAGTGTAAAGCCACCAGACTGACCAGGC[CG[A[CG[G[C

GGGG[G[[G[GAAGGGGTG[CG[AAGGCAGCCAG[CG[GC[CG[GC[CG[ACCAGGGCTCTCCCCAC[CG[ACTGC

CTGCTTTGGCACC[CG[GCTACCCCCCTTGGCCTGGCTTTCCTGGGGCCTTT[CG[[CG[TT[CG[CT[CG[CTTTCTACTG

T[CG[GTATTTGCAGCAG[CG[CTCCCTCAGGTCC[CG[[AGCAGAGCTAAGCCAGCCAGCACCCAGGGGAAGGGGAC

CCACAGCCC[CG[TGGAAAGAGGTCTAT[CG[AGATGCTTTGCAGCAAAGTGCTCTGCA[CG[TGGCCCTGGCCAAAA

TGTGCACCACCCCCTTTCAGAAAG

SEQ ID NO: 737

[CG[GCAG[CG[[[[CG[TGACCCACTGTGCACCTG[CG[CCTTGATGTAGGGGGGAGACCCTGCAGAGAG[CG[CTTCC

TTC[CG[CCCTGTCCAGTGCCCTCCCTGCCTCACCCCTCTTCC[CG[CAGGCC[CG[CTCAGGG[CG[CTGAAGGGCTCC

TGAC[G[TGGGT[G[TCCTT[G[CTG[G[TCTGGGGGG[CG[TCCCC[CG[[CG[CTGCCTCTGACC[CG[CC[CG[GCC

CTG[CG[TTTGTCTGAAGCCCCT[CG[TTC[CG[CATCTC[CG[GACCAGGGTC[CG[GGGG[CG[TGGTCTGCTGGGGG[C

G[GGCC[CG[GGTTGTGGTTTGAGAGC[[CG[CT[CG[GCCTGTCTGGGCCTC[CG[CCTC[CG[GGT[CG[CCCTCCAGCCT

TCCTGC[CG[C[CG[CTTTTCCAGTCTTGCCCAACC[CG[GTATTTCTG[CG[CTTGCCTCAGCCACC[CG[CAGGAG[CG[C

AGGC[CG[CCCTT[CG[TCCTCC[CG[TCCTCTG[CG[CCCACAGGACCC[CG[GGCCC[CG[CCCAGTC[CG[CAGGTCC[C

G[CAGGTCCCCC[CG[GG[CG[TGTCTTCCTGGCCCTG[CG[ACCCC[CG[GGACAG[CG[CTGAGAACA[CG[[CG[GAAG

GTGGGGAGA[G[[CG[[CG[G[CG[CTGGC[CG[GGTCCCTGG[CG[C[CG[TTCT[CG[[CG[GT

SEQ ID NO: 738

CC[CG[AGCACCCA[CG[TGCAGCTTC[CG[ATCACAGCCCTGG[CG[TGGCTTCTCTGTCCC[CG[GCTAAGGCC[CG[

[CG[GT[CG[CTGCAGGGTGCCT[CG[C[CG[AGGGTG[CG[GGCT[CG[GGGCTCACAGTGCTCCCAGCCTCTCCCAC

CCCAACCC[CG[CCATTAAGGGGAGCCCCAG[CG[A[CG[CCCTGAACCCTGAAAGTCACACTGGGGC[CG[GGGCT

GCACTTGG[CG[TC[CG[CTTCCCCTCC[CG[TCACAGTGACCAGGGCTAGGGC[CG[[CG[GT[CG[GGGC[CG[T[CG[

GGGAGAG[G[GAGGG[G[[G[GGGAATGGGGCT[G[CTG[CG[CCA[CG[GAAATCC[CG[[CG[C[CG[CCCTT[

CG]AGTCCTCCCAGCTGCTC[CG[CAGAGC[CG[GGGC[CG[CTGCCAT[CG[[CG[TCTGCCC[CG]AGGGTG[CG[CAG

G[CG[GGTACCTGTCC[CG[ACT[CG[GGGAACAG[CG[GGAGCC[CG[GAGA[CG[CC[CG[T[CG[GGCTTCCCAGCCC

CACCTGGGA[CG[TCTCTAGGGG[CG[GGAGGCCAGGAGAGAAGAGGGTGGGAGAGATGAGCTGCAGGGGGAT

A[CG[GGACCCAGGGACC[CG[GGATCTTATAACA[CG[CTTTCCACC[CG[TAGGATTGGGGCCCACAAATGACCA

SEQ ID NO: 739

CC[CG[AGCACCCA[CG[TGCAGCTTC[CG[ATCACAGCCCTGG[CG[TGGCTTCTCTGTCCC[CG[GCTAAGGCC[CG[

[CG[GT[CG[CTGCAGGGTGCCT[CG[C[CG[AGGGTG[CG[GGCT[CG[GGGCTCACAGTGCTCCCAGCCTCTCCCAC

CCCAACCC[CG[CCATTAAGGGGAGCCCCAG[CG[A[CG[CCCTGAACCCTGAAAGTCACACTGGGGC[CG[GGGCT

GCACTTGG[CG[TC[CG[CTTCCCCTCC[CG[TCACAGTGACCAGGGCTAGGGC[CG[[CG[GT[CG[GGGC[CG[T[CG[

GGGAGAG[G[GAGGG[G[[G[TGGGAATGGGGCT[G[CTG[CG[CCA[CG[GAAATCC[CG[[CG[C[CG[CCCTT[

CG]AGTCCTCCCAGCTGCTC[CG[CAGAGC[CG[GGGC[CG[CTGCCAT[CG[[CG[TCTGCCC[CG]AGGGTG[CG[CAG

G[CG[GGTACCTGTCC[CG[ACT[CG[GGGAACAG[CG[GGAGCC[CG[GAGA[CG[CC[CG[T[CG[GGCTTCCCAGCCC

CACCTGGGA[CG[TCTCTAGGGG[CG[GGAGGCCAGGAGAGAAGAGGGTGGGAGAGATGAGCTGCAGGGGGAT

A[CG[GGACCCAGGGACC[CG[GGATCTTATAACA[CG[CTTTCCACC[CG[TAGGATTGGGGCCCACAAATGACCA

SEQ ID NO: 740

CCAAGTCTGCAGAAAAAAAATAAATGAAGTCTGCCTATCTC[CG[GGCCAGAGCCCCTCCCCT[CG[GCC[CG[[CG

][CG[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[CG[C[CG[C[CG]AGGGTCAGGAGCC[CG[GGAG[CG[[CG[

ACCCTCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGCCAGTCCC[CG[[CG[GTCTCTGCC[CG[GGCTGA[CG[CCC

AGGAATGTGGT[CG[A[CG]AGAAGCCCCAACAGCA[CG[G[CG[TGGCCTCTCAGCCT[CG[GTGAGTACC[CG[C[C

G[TGGGGAAGGGTCCTGGGGACCCACTGGAGGC[CG[[[CG[[GCC[CG[CAGCAGCCAGGGGC[CG[AGCCA[CG[G

CCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG[GGCCTCCAGG[CG[GAGGAGG[CG[TC[CG[CTGGGCTC

G[GACCCCTA[G[[CG[CAGCCTCCA[CG[[CG[CTC[CG[AGCTGGAGAAGC[CG[CCAGCC[CG[CCCTCCCAGGG[

CG[TGT[CG[CC[CG[CTTTCTGTTTCTTTGTG[CG[GGGCATGTGAAATGTGTGGGGCCAGAATTGTCTCCCTAAAG

AACA

SEQ ID NO: 741

GGTTAGAAAAG[CG[TGGTTCTTG[CG[CAGGAAAGTTGGAGCAAAGAAGAGTTCAGAAGTGGG[CG[GGTGTGT

GTTTAAAAAAAAAAAAGGGGGTGGAAACCCCACCAGCCAAGTCTGCAGAAAAAAAATAAATGAAGTCTGCCT

ATCT[G[GGCCAGAGCCCCCCCCT[G[GCC[G[[CG[[CG[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[

CG[[G[C[CG[AGGGTCAGGAGCC[CG[GGAG[CG[[CG[ACCCTCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGC

CAGTCCC[CG[[CG[GTCTCTGCC[CG[GGCTGA[CG[CCCAGGAATGTGGT[CG[A[CG[AGAAGCCCCAACAGCA[

CG[G[CG[TGGCCTCTCAGCCT[CG[GTGAGTACC[CG[C[CG[TGGGGAAGGGTCCTGGGGACCCACTGGAGGC[CG

][CG[GCC[CG[CAGCAGCCAGGGGC[CG]AGCCA[CG[GCCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG

]GGCCTCCAGG[CG[GAGGAGG[CG[TC[CG[CTGGGCTCAGATCCC[CG[ACTCCAGCCC[CG[GTTCCC[CG[G[CG[C

CTGGGCTG[G[[G[GAGTCCCTGTCC[G[[CG[TCC[CG[GACCCCTA[CG[[CG[CAGCCTCCA[CG[[CG[CTC[CG[

AGC

SEQ ID NO: 742

CTCTA[G[GAGA[G[[G[AGAAG[G[[G[GAGAG[CG[G[CG[GGAGCCAACC[G[[CG[GGC[CG[C[CG[

CC[CG[GAAGGC[CG[CCTG[[CG[CCTG[CG[ACCAGAAGCCCTGCAGCTGCTCCAAAGTGGATGTCAACTA[CG[[

CG[TTTCTCCATGCAACAGGTAAAGACTCAG[CG[GGGAGCCC[CG[GGG[CG[CCCCTGCCCCTCTCTCTGCCC[C

GCCCA[G[[G[GC[CG[GTG[CG[GGTC[CG[G[CG[CTGAGAGC[CG[GACAGGGG[CG[T[CG]AGGTGGCAG[CG[

GAGG[CG[[GGACCTGCCAGAATCTTCAGATAAAAG[CG[AGAAATG[CG[GGACCTGCC[CG[CTGGGTCCAAG

CCCC[CG[AACCTGGCCT[CG[GAGCTCCAAGAGGGCTCTGAGGC[CG[TGG[CG[CTCTTCCCCCAG[CG[[CG[GCC

CTTGGGATGG[CG[GGTGGC[CG[A[CG[ATCCAGG[CG[CT[CG[TG[CG[CTCACTGAAT[CG[ATGA[CG[GCTGGCT

TCCCTAGGC[CG[CTGGGGCCT[CG[GGTGGGACTCAGTTTCCAAATAC[CG[TGCC[CG[AGAATTCAGAATTGCA

TTTTTTTTAGGTCTTTAGATCA[CG[AGAGTGATTTGTAGCTGCAATTGCACAAGAGAA[CG[ATTCCATTCACA

TGAA

SEQ ID NO: 743

CCAAGTCTGCAGAAAAAAAATAAATGAAGTCTGCCTATCT[G[GGCCAGAGCCCCTCCCCT[G[GCC[CG[[CG

][CG[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[CG[C[CG[C[CG[AGGGTCAGGAGCC[CG[GGAG[CG[[CG[

ACCCTCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGCCAGTCCC[CG[[CG[GTCTCTGCC[CG[GGCTGA[CG[[CCC

AGGAATGTGGT[CG[A[CG[AGAAGCCCCAACAGCA[CG[G[CG[TGGCCTCTCAGCCT[CG[GTGAGTACC[CG[C[C

G]TGGGGAAGGGTCCTGGGGACCCACTGGAGGC[CG[[CG[[GCC[CG[CAGCAGCCAGGGGC[CG]AGCCA[CG[G

CCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG[GGCCTCCAGG[CG[GAGGAGG[CG[TC[CG[CTGGGCTC

G[GACCCCTA[CG[[CG[CAGCCTCCA[CG[[CG[CTC[CG]AGCTGGAGAAGC[CG[CCAGCC[CG[CCCTCCCAGGG[

CG[TGT[CG[CC[CG[CTTTCTGTTTCTTTGTG[CG[GGGCATGTGAAATGTGTGGGGCCAGAATTGTCTCCCTAAAG

AACA

SEQ ID NO: 744

GGTTAGAAAAG[CG[TGGTTCTTG[CG[CAGGAAAGTTGGAGCAAAGAAGAGTTCAGAAGTGGG[CG[GGTGTGT

GTTTAAAAAAAAAAAAGGGGGTGGAAACCCCACCAGCCAAGTCTGCAGAAAAAAAATAAATGAAGTCTGCCT

ATCTC[G[GGCCAGAGCCCCTCCCCT[G[GCC[CG[[CG[[CG[GGAGGAGTGTGACCCAGGTGC[CG[CTTCCTCT[

G[[G[[G[AGGGTAGGAGCC[G[GGAG[CG[[CG[ACCCTCCCC[CG[GCC[CG[GCCTGGCC[CG[GCCTGGC

CAGTCCC[CG[[CG[GTCTCTGCC[CG[GGCTGA[CG[CCCAGGAATGTGGT[CG[A[CG[AGAAGCCCCAACAGCA[

CG[G[CG[TGGCCTCTCAGCCT[CG[GTGAGTACC[CG[C[CG[TGGGGAAGGGTCCTGGGGACCCACTGGAGGC[CG

[[CG[GCC[CG[CAGCAGCCAGGGGC[CG[AGCCA[CG[GCCA[CG[GA[CG[CCCTGGTGTCC[CG[GTC[CG[TGC[CG

CTGGGCTG[G[[G[GAGTCCCTGTCC[G[[CG[TCC[CG[GACCCCTA[CG[[CG[CAGCCTCCA[CG[[CG[CTC[CG[

AGC

SEQ ID NO: 745

CC[CG[GAAGGC[CG[CCTG[CG[CCTG[CG[ACCAGAAGCCCTGCAGCTGCTCCAAAGTGGATGTCAACTA[CG[[

CG[TTTCTCCATGCAACAGGTAAAGACTCAG[CG[GGGAGCCC[CG[GGG[CG[CCCCTGCCCCTCTCTCTGCCC[C

GCCCAC[G[[G[GC[CG[GTG[CG[GGTC[CG[G[CG[CTGAGAGC[CG[GACAGGGG[CG[T[CG]AGGTGGCAG[CG[

GAGG[CG[GGACCTGCCAGAATCTTCAGATAAAAG[CG[AGAAATG[CG[[GGACCTGCC[CG[CTGGGTCCAAG

CCCC[CG[AACCTGGCCT[CG[GAGCTCCAAGAGGGCTCTGAGGC[CG[TGG[CG[CTCTTCCCCCAG[CG[[CG[GCC

CTTGGGATGG[CG[GGTGGC[CG[A[CG[ATCCAGG[CG[CT[CG[TG[CG[CTCACTGAAT[CG[ATGA[CG[GCTGGCT

TCCCTAGGC[CG[CTGGGGCCT[CG[GGTGGGACTCAGTTTCCAAATAC[CG[TGCC[CG[AGAATTCAGAATTGCA

TTTTTTTTAGGTCTTTAGATCA[[CG[[AGAGTGATTTGTAGCTGCAATTGCACAAGAGAA[CG[ATTCCATTCACA

TGAA

SEQ ID NO: 746

CTACAAGTAGCCTGGGACTGAAAGGGGACCTGGGGGAGGGGCTGGGCCCAGGGCAGAAAAGTCCAGGTTCCC

ATG[G[GCCTGGGCCCA[G[TGGAG[CG[GG[CG[CTGAATCAC[CG[TTCAGC[CG[CCCCCCTCCCCTCCTCCC

[G[[G[GTGCC[G[CAGTCCC[G[CCTCCT[G[GC[CG[C[CG[CCTCCA[CG[GGG[CG[GGGCCCTGGCC[CG[

GGACCAG[G[[G[[G[GCTATAAATGGGCTG[CG[G[CG[[AGGC[CG[[GCAGAA[[CG[[CTGTGACAGCCAC

A[CG[CCCCAAGGCCTCCAAGATGAGCTACA[CG[TTGGACT[CG[CTGGGCAACC[CG[TC[CG[CCTAC[CG[G[CG

]GGTAAC[CG[AGACC[CG[CT[CG[AGCTTCAGC[CG[[CG[TCAG[CG[GCTCCC[CG[TCCAGTGGCTTC[CG[CT[CG[

CAGT[G[TGGTCC[CG[[CG[GCT[CG[CCCAGCAC[CG[TGTCCTCCTCCTATAAG[CG[CAGCATGCT[CG[CCC[C

G[[CG[CCT[CG[CTTACAGCT[CG[GCCATGCTCAGCTC[CG[C[CG[AGAGCAGCCTTGACTTCAGCCAGTCCT[CG[

TCCCTGCTCAA[G[G[CG[GCTC[CG[GACC[CG[G[CG[G[CG[ACTACAAGCTGTCC[CG[CTCCAA[CG[AGAAGGA

GCAGCTGCAGG

SEQ ID NO: 747

CTACAAGTAGCCTGGGACTGAAAGGGGACCTGGGGGAGGGGCTGGGCCCAGGGCAGAAAAGTCCAGGTTCCC

ATG[CG[GCCTGGGCCCA[CG[TGGAG[CG[GG[CG[[CTGAATCAC[CG[TTCAGC[CG[CCCCCCTCCCCTCCTCCC

[G[A[G[GTG[G[CAGTCCC[G[CCTCT[G[GC[CG[C[CG[CCTCCA[CG[GGG[CG[GGGCCCTGGCC[CG[

GGACCAG[G[[G[[G[GCTATAAATGGGCTG[G[G[CG[[AGGC[CG[GCAGAA[CG[CTGTGACAGCCAC

A[CG[CCCCAAGGCCTCCAAGATGAGCTACA[CG[TTGGACT[CG[CTGGGCAACC[CG[TC[CG[CCTAC[CG[G[CG

]GGTAAC[CG]AGACC[CG[CT[CG]AGCTTCAGC[CG[[CG[TCAG[CG[GCTCCC[CG[TCCAGTGGCTTC[CG[CT[CG[

CAGT[CG[TGGTCC[CG[[CG[GCT[CG[CCCAGCAC[CG[TGTCCTCCTCCTATAAG[CG[CAGCATGCT[CG[CCC[C

G][CG[CCT[CG[CTTACAGCT[CG[GCCATGCTCAGCTC[CG[C[CG[AGAGCAGCCTTGACTTCAGCCAGTCCT[CG[

TCCCTGCTCAA[CG[G[CG[GCTC[CG[GACC[CG[G[CG[G[CG[ACTACAAGCTGTCC[CG[CTCCAA[CG[AGAAGGA

GCAGCTGCAGG

SEQ ID NO: 748

GGCCCCACTCCCTTCT[CG[C[CG[GGCTC[CG[GGCCAAGGAAG[CG[[CG[GC[CG[GAGTCC[CG[GGAAGCCCCT[

CG[GCAGCCAGCCAAGGGCCCTG[CG[AGGATGTGGATGG[CG[[[CG[GATGG[CG[[CG[GCCTCCACCTG[CG[GG

CAGTGGAGAGAG[CG[G[CG[AGAGGAAGAATATTCCC[CG[[CG[AGC[CG[GGATAAGGGGCCCCTT[CG[GCT[[C

G[[GTTGACCCAGGTCAGATCCTCC[CG[C[CG[ACCTT[CG[GCC[CG[CCCTCTACAGG[CG[GCCCAGTTCTTCCCC

TGCT[CG[GCTGCCCCTGCC[CG[CCCCT[CG[AGGGAG[CG[CC[CG[TAGCCAG[CG[CCCC[CG[TAAAGAAATAA

GGAGG[CG[CC[CG[GCTTCC[CG[CCCAGGTA[CG[TGT[CG[GGACAG[CG[CAGGGGACTGGCTTGGGG[CG[G[CG[

GGGGTAG[G[[G[[G[[G[[CG[G[CG[CTGGAAA[CG[GCCC[CG[CTTCCTTGGACCC[CG[GGGCTTGCA

CG[GAGGACCTGTGTGTTTGT[CG[GGGCCTGGGGTGAGAGAGGGGACT[CG[AGGGGAGAAGTAGAG[CG[GGA

AACCAAGAGGGGG

SEQ ID NO: 749

GGCCCCACTCCCTTCT[CG[C[CG[GGCTC[CG[GGCCAAGGAAG[CG[[CG[GC[CG[GAGTCC[CG[GGAAGCCCCT[

CG]GCAGCCAGCCAAGGGCCCTG[CG[AGGATGTGGATGG[CG[[[CG[GATGG[CG[[CG[GCCTCCACCTG[CG[GG

CAGTGGAGAGAG[CG[G[CG[AGAGGAAGAATATTCCC[CG[[CG]AGC[CG[GGATAAGGGGCCCCTT[CG[GCT[[C

G[[GTTGACCCAGGTCAGATCCTCC[CG[C[CG[ACCTT[CG[GCC[CG[CCCTCTACAGG[CG[GCCCAGTTCTTCCCC

TGCT[CG[GCTGCCCCTGCC[CG[CCCCT[CG[AGGGAG[CG[CC[CG[TAGCCAG[CG[CCCC[CG[TAAAGAAATAA

GGAGG[CG[CC[CG[GCTTCC[CG[CCCAGGTA[CG[TGT[CG[GGACAG[CG[CAGGGGACTGGCTTGGGG[CG[G[CG[

GTGGGTAG[G[[G[[G[[CG[[CG[G[CG[CTGGAAA[CG[GCCC[CG[CTTCCTTGGACCC[CG[GGGCTTGCA

CG[GAGGACCTGTGTGTTTGT[CG[GGGCCTGGGGTGAGAGAGGGGACT[CG[AGGGGAGAAGTAGAG[CG[GGA

AACCAAGAGGGGG

SEQ ID NO: 750

[G[G[CG[CC[CG[GCAGAGCCC[CG[GGACTCCTAGTTTTTGC[CG[C[CG[CTGAGGA[CG[[CG[G[CG[[CG[GGCT

GCTGGC[G[[CG[T[CG[C[CG[AGGGAGGGCC[CG[GACAGCCCTGCAG[CG[[[CG[TCTCAG[CG[GAGCCCTGGGG

GC[CG[[CG[C[CG[CTCCTCCAAACATGATTCAGAAC[CG[CC[CG[TCAGCCTTGGCTCCAG[CG[CCTGG[CG[[CG[

GGCCTTA[CG[CCCA[CG[GTCCA[CG[CTTGCAACACCAGGGCTGTA[CG[G[CG[GGTC[CG[CAGCTGGGTCTG[CG

]CCTGGGACT[CG[GGGCTCCCTG[CG[CTCCT[CG[TGC[CG[CACCCCTTGCCTTAACCCCAAG[CG[GA[CG[GGTC

CTGGGGCTTCAC[CG[GCCAGGC[CG[GAGCCCCAGCCCCACAACTCCCCCCCTCCCAC[CG[CACTGCCCCCTCTG

[CG[CTGTGG[CG[GGAGTTGGGGACTGGGGC[CG[GAGAAAGGAGA[CG[[CG[C[CG[GTCCTCAAGTCTCTTGAGC

CATTT[CG[GTTC

SEQ ID NO: 751

[G[G[CG[CC[CG[GCAGAGCCC[CG[GGACTCCTAGTTTTTGC[CG[C[CG[CTGAGGA[CG[[CG[G[CG[[CG[GGCT

GCTGGC[G[[CG[T[CG[C[CG[AGGGAGGGCC[CG[GACAGCCCTGCAG[CG[[CG[TCTCAG[CG[GAGCCCTGGGG

GC[CG[[CG[C[CG[CTCCTCCAAACATGATTCAGAAC[CG[CC[CG[TCAGCCTTGGCTCCAG[CG[CCTGG[CG[[CG[

GGCCTTA[CG[CCCA[CG[GTCCA[CG[CTTGCAACACCAGGGCTGTA[CG[G[CG[GGTC[CG[CAGCTGGGTCTG[CG

[CCTGGGACT[CG[GGGCTCCCTG[CG[CTCCT[CG[TGC[CG[CACCCCTTGCCTTAACCCCAAG[CG[GA[CG[GGTC

CTGGGGCTTCAC[CG[GCCAGGC[CG[GAGCCCCAGCCCCACAACTCCCCCCCTCCCAC[CG[CACTGCCCCCTCTG

[CG[CTGTGG[CG[GGAGTTGGGGACTGGGGC[CG[GAGAAAGGAGA[CG[[CG[C[CG[GTCCTCAAGTCTCTTGAGC

CATTT[CG[GTTC

SEQ ID NO: 752

TTTCTGTACCCA[CG[CTCCATACC[CG]AGGCTGGG[CG]AG[CG[GTGAACCCTAGCAGT[CG[[CG[G[CG[ACTGG

ACA[CG[GGGGTTCTACTCTTTCTGAAC[CG]AGACAAGCCCCTGGGCCC[CG[TGCCCCAGAGCTA[CG[ATCCTG

CTGCCCCTACCTG[CG[GCCTGGC[CG[[CG[CTCTCACCTGAGCCCCCTG[CG[CCAGCTGCTC[CG[CCTC[CG[GTC

[G[[G[GG[G[CT[G[CTCCAGGTCCCC[G[[G[[G[G[CG[G[CG[CACACTGAAC[CG[AAGACCT[CG

]TAGG[CG[GGCCT[CG[GGGGGATGATGC[CG[TTGG[CG[G[CG[[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[

TAGAGCAGCTGCAGCT[CG[[CG[[CG[CCT[CG[TTCTCCTCCTG[CG[CCTGCTGCCTG[CG[CAG[CG[CCACCTG[C

G[[G[CCATACA[G[CTGG[CG[CTC[CG[[CG[ATGAG[CG[TGCACTTGG[CG[CACAGGCAGTCCTTCCAG[C

GGGGGTC[CG[[CG[GGTACTTCT[CG[GCTGCC[CG[CAGCAACAGTGG[CG[GCCCC[CG[CAGCAAGC[CG[CCTGC

CA[CG[CTCAC

SEQ ID NO: 753

CCTGAGCCCCCTG[CG[CCAGCTGCTC[CG[CCTC[CG[GTCCC[CG[[CG[GG[CG[CTCC[CG[CTCCAGGTCCCC[CG[

[G[[CG[G[CG[G[CG[CACACTGAAC[CG]AAGACCT[CG[TAGG[CG[GGCCT[CG[GGGGGATGATGC[CG[TTGG

[CG[G[CG[[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[TAGAGCAGCTGCAGCT[CG[[CG[[CG[CCT[CG[TTCT

CCTCCTG[CG[CCTGCTGCCTG[CG[CAG[CG[CCACCTG[CG[C[CG[CCATGACA[CG[CTGG[CG[CTC[CG[[CG[ATG

AG[CG[TGCACTTGG[CG[[CACAGGCAGTCCTTCCAG[CG[ACAGTAG[CG[TTTGTGGCCCTTGAGGGC[CG[A

CACCA[G[CATGGTTG[G[ACAG[CG[[CG[[CG[CACTTGGGGGTC[CG[[CG[GGTACTTCT[CG[GCTGCC[CG[C

AGCAACAGTGG[CG[GCCCC[CG[CAGCAAGC[CG[CCTGCCA[CG[CTCAC[CG[GTAG[CG[ATGCAG[CG[GC[CG[C

[G[[G[[CG[[CG[C[CG[GGCA[CG[CTGGGCAGCTC[CG]AG[CG[CAGCTCCATGACAGGACCTGA[CG[GG

AAAGAAGGTGGGAGAGGGGAGAGA

SEQ ID NO: 754

TTTCTGTACCCA[CG[CTCCATACC[CG[AGGCTGGG[CG[AG[CG[GTGAACCCTAGCAGT[CG[[CG[G[CG[ACTGG

ACA[CG[GGGGTTCTACTCTTTCTGAAC[CG]AGACAAGCCCCTGGGCCC[CG[TGCCCCAGAGCTA[CG[ATCCTG

CTGCCCCTACCTG[CG[GCCTGGC[CG[[CG[CTCTCACCTGAGCCCCCTG[CG[CCAGCTGCTC[CG[CCTC[CG[GTC

[G[[G[[G[CTC[G[CTCCAGGTCCCC[G[[G[T[CG[G[CG[G[CG[CACACTGAAC[CG[AAGACCT[CG

TAGG[G[GGCCT[G[GGGGGATGATGC[G[TTGG[CG[G[CG[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[

TAGAGCAGCTGCAGCT[CG[[CG[[CG[CCT[CG[TTCTCCTCCTG[CG[CCTGCTGCCTG[CG[CAG[CG[CCACCTG[C

G[[G[CCATACA[G[CTGG[G[CTC[CG[[CG[ATGAG[CG[TGCACTTGG[CG[CACAGGCAGTCCTTCCAG[C

G]ACAGTAG[G[TTTGTGGCCCTTGAGGGC[G[ACACCA[G[CCATGGTTG[G[ACAG[CG[[CG[[CG[CACTT

GGGGGTC[CG[[CG[GGTACTTCT[CG[GCTGCC[CG[CAGCAACAGTGG[CG[GCCCC[CG[CAGCAAGC[CG[CCTGC

CA[CG[CTCAC

SEQ ID NO: 755

CCTGAGCCCCCTG[CG[CCAGCTGCTC[CG[CCTC[CG[GTCCC[CG[[CG[GG[CG[CTCC[CG[CTCCAGGTCCCC[CG[

[G[[G[G[CG[G[CG[CACACTGAAC[CG[AAGACCT[CG[TAGG[CG[GGCCT[CG[GGGGGATGATGC[CG[TTGG

[CG[G[CG[[GCCAG[CG[CCAGCCCCT[CG[GCAGTGC[CG[TAGAGCAGCTGCAGCT[CG[[CG[[CG[CCT[CG[TTCT

CCTCCTG[CG[CCTGCTGCCTG[CG[CAG[CG[CCACCTG[CG[C[CG[CCATGACA[CG[CTGG[CG[CTC[CG[[CG[ATG

AG[CG[TGCACTTGG[CG[CACAGGCAGTCCTTCCAG[CG[ACAGTAG[CG[[TTTGTGGCCCTTGAGGGC[[CG[[A

CACCA[G[CCATGGTTG[G[ACAG[CG[[CG[[CG[CACTTGGGGGTC[CG[[CG[GGTACTTCT[CG[GCTGCC[CG[C

AGCAACAGTGG[CG[GCCCC[CG[CAGCAAGC[CG[CCTGCCA[CG[CTCAC[CG[GTAG[CG[ATGCAG[CG[GC[CG[C

[G[[[[G[[G[C[CG[GGCA[CG[CTGGGCAGCTC[CG]AG[CG[CAGCTCCATGACAGGACCTGA[CG[GG

AAAGAAGGTGGGAGAGGGGAGAGA

SEQ ID NO: 756

TGTCCCAA[[CG[CACTTTGGGGAGGGAGAGCTTCC[CG[[CG[GATC[CG[CCTGGGTTTGGGAGGAC[CG[GGGTC

CACTCTGCAC[CG[GCCAGGGCCTGAGGGGCCCAGCAGCTGGAATACAGCAATCTCC[CG[CCCACCTGCT[CG[C

AG[CG[[TACAGAGCACAACAT[CG[CTCACCTG[CG[GCCCCCAGGGCCAGAAGAGAACTCCCTCCTA[CG[GAG[[

CG[[AAGGCAAGAGGCCT[CG[AACCCTTTTGGGACC[CG[GAACCCATCAAAAGTGACCCACAAAGGC[CG[GAA

G[G[GCC[G[GGGGGTCTAAGAACCAGCC[G[[CG[[CG[GGG[CG[CACTTC[CG[[CG[GC[CG[CTCTAGGAAG

GGAG[CG[AAAGGGGCTTTCAACT[CG[GTAGTGTTTC[CG[[CG[[CG[[TCTA[CG[TGAGAGGAAGGTTGATGGCT

TTCAGGCC[CG[CTGGTAAATGGAA[CG[GGTTTATCTTCTCCTCTTCTTTACCCAGCCATTGTCCACACTTCCCC[

CG]ACC[CG[ATGGGTGGT[CG[AGGCTTGTAGAACTGATCTTAAGACAGGGAAATCCCTTG[CG[TCTCCATTCA

CTTTGGGATTCTGTGTCTCTGAGGTTAGAGATGCCTCAAAGGGATGTTCTC[CG[GGGGA

SEQ ID NO: 757

TGTCCCAA[[CG[[CACTTTGGGGAGGGAGAGCTTCC[CG[[CG[GATC[CG[CCTGGGTTTGGGAGGAC[CG[GGGTC

CACTCTGCAC[CG[GCCAGGGCCTGAGGGGCCCAGCAGCTGGAATACAGCAATCTCC[CG[CCCACCTGCT[CG[C

AG[CG[[TACAGAGCACAACAT[CG[CTCACCTG[CG[GCCCCCAGGGCCAGAAGAGAACTCCCTCCTA[CG[GAG[[

CG[[AAGGCAAGAGGCCT[CG[AACCCTTTTGGGACC[CG[GAACCCATCAAAAGTGACCCACAAAGGC[CG[GAA

GGAG[CG[AAAGGGGCTTTCAACT[CG[GTAGTGTTTC[CG[[CG[[[CG[[TCTA[CG[TGAGAGGAAGGTTGATGGCT

TTCAGGCC[CG[CTGGTAAATGGAA[CG[GGTTTATCTTCTCCTCTTCTTTACCCAGCCATTGTCCACACTTCCCC[

CG]ACC[CG[ATGGGTGGT[CG[AGGCTTGTAGAACTGATCTTAAGACAGGGAAATCCCTTG[CG[TCTCCATTCA

CTTTGGGATTCTGTGTCTCTGAGGTTAGAGATGCCTCAAAGGGATGTTCTC[CG[GGGGA

SEQ ID NO: 758

AGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGCTGCAGAG[CG[[CG[[CG[[CG[TCAAGTC[CG[[CG[

GAAAGTTTTACTAGTCAGCTCCTCCAG[G[[CG[CACAG[CG[G[CG[A[CG[TTGGACC[CG[GACC[CG[ACTCTGG

AAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAGGATGTCTG[CG[ATGCTTAAGAGT

GTC[G[GGGTGTT[G[GGGCT[CG[[CG[TCC[CG[AGTTCATGGT[CG[GC[CG[GGCTGGGG[CG[GTC[CG[GC

TGTC[CG[TTG[CG[CTAGGCTC[[CG[CAAA[CG[CCTGGGCCCCAGTGCT[CG[[GCTCCCAATC[CG[GGCCCCCA

GCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG[AGTCC[CG[TGTGCCCCTCCTCCTG[CG[CCCCCACCTCTCC

ACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTACAGGCTGGGGCAGG[[

CG[[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGGCTGCTC[CG[[CG[CTG[CG[

GGG[CG[CTGCAC[CG[TGCACAGTCAGGC[CG[GGCCATACCTCCAGA[CG[CTGTATGC[CG[C[CG[ACTCCC[C

G[CCTAGC[CG[C

SEQ ID NO: 759

AGTC[CG[[CG[ACCTTGC[CG[GCTCTATACCTTCAGAGGGCTGCAGAG[CG[[CG[[CG[[CG[TCAAGTC[CG[[CG[

GAAAGTTTTACTAGTCAGCTCCTCCAG[CG[[CG[CACAG[CG[G[CG[A[CG[TTGGACC[CG[GACC[CG[ACTCTGG

AAGCTG[CG[G[CG[CAGAGGGTGCT[CG[GGGGACCATG[CG[[CG[GGGCTAGGATGTCTG[CG[ATGCTTAAGAGT

GTC[G[GGGTGTT[G[GGGCT[CG[[CG[[TCC[CG[AGTTCATGGT[CG[GC[CG[GGCTGGGG[CG[GTC[CG[GC

TGTC[CG[TTG[CG[CTAGGCTC[CG[[CAAA[CG[CCTGGGCCCCAGTGCT[CG[GCTCCCAATC[CG[GGCCCCCA

GCCT[CG[GACC[CG[CCCC[CG[GCTCTGGGCC[CG[AGTCC[CG[TGTGCCCCTCCTCCTG[CG[CCCCCACCTCTCC

ACCC[CG[GGC[CG[[CG[GTGGATCTGGAGCTCCTAGATGTC[CG[GGGAGGGTATTTCTACAGGCTGGGGCAGG[[

CG[[[CG[GAGAGCAGAAGC[CG[ACCAAACTACCCACCAGAGCAGGGCCA[CG[GGGCTGCTC[CG[[CG[CTG[CG[

GGG[CG[CTGCAC[CG[TGCACAGTCAGGC[CG[GGCCATACCTCCAGA[CG[CTGTATGC[CG[C[CG[ACTCCC[C

G]CCTAGC[CG[C

SEQ ID NO: 760

ACCCCTCCC[CG[CTGACCTCACT[CG[AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCATCTGAAG

AGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[GATCC[CG

]AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCTCTCCTTC[

CG[CAGA[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCACCTT[CG[GTTCTCTGAG

AGCTTCCTGGAGAACAGGGC[CG[GTGCACAGG[[CG[[GG[CG[CTGTGCT[CG[CACCCC[CG[GGTCCTCCC[CG[A

G[G[CAGG[G[GGGACC[G[A[CG[GGAGGCA[CG[G[CG[[CG[GGCACAT[CG[GAGGCTCT[CG[CTGCTGGGC

ACTCAGGT[CG[CCAGAGTC[CG[CAG[CG[[CG[GGGTGGGAGCTC[CG[[CG[GCACCCCCTGCCTGGGTGC[CG[C[

CG[GACAGAGCTGGGTATTCAGGG[CG[T[CG[GCCTGAGAACCTGGGAGTT[CG[AATCCCAATCTCAA[CG[CTA

GAAATAGAATTTTAG[CG[TTGAAGTTAGGATTTTAG[CG[[TTAGAATCAGATTCCTGGCTTAGTCATGAAAG

SEQ ID NO: 761

ACCCCTCCC[CG[CTGACCTCACT[CG]AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[CG[GCCCATCTGAAG

AGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[[CG[CTGCAGACTCCTGACCTGC[CG[ACTG[CG[[GATCC[CG

]AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CCCCAACCCCTCTCCTTC[

CG[CAGA[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCACCTT[CG[GTTCTCTGAG

AGCTTCCTGGAGAACAGGGC[CG[GTGCACAGG[[CG[[GG[CG[CTGTGCT[CG[CACCCC[CG[GGTCCTCCC[CG[A

G[G[CAGGC[G[GGGACC[G[A[G[GGAGGCA[G[G[CG[[CG[GGCACAT[CG[GAGGCTCT[CG[CTGCTGGGC

ACTCAGGT[CG[CCAGAGTC[CG[CAG[CG[[CG[GGGTGGGAGCTC[CG[[CG[GCACCCCCTGCCTGGGTGC[CG[C[

CG[GACAGAGCTGGGTATTCAGGG[CG[T[CG[GCCTGAGAACCTGGGAGTT[CG[AATCCCAATCTCAA[CG[CTA

GAAATAGAATTTTAG[CG[TTGAAGTTAGGATTTTAG[CG[[TTAGAATCAGATTCCTGGCTTAGTCATGAAAG

SEQ ID NO: 762

CAAGCAATTCTCCTGCCTCAGCCTCCCAAGTAGCTGGGACTACAGG[CG[CACACCACCATGCC[CG[GCTAATTT

TTGTATTTTTAGTAGAGA[CG[GGGGTTTCACCATATTGGTCAGGC[CG[GTCT[CG]AGCTCCTGACCTCAGGTGA

TCCACC[CG[CCT[CG[GCCTCCCAAAGTGCTGGGATTACAGG[CG[TGGGCCAC[CG[CTCC[CG[G[CG[GGGCC[CG

]AGTTTCTTGAATGAAGTCCCCCCAGCATGGC[CG[TTGCCATG[CG[GGTCCTGGGTTGTGGAGAGATG[CG[G[C

G[GTACTTGC[CG]ACAG[CG[G[CG[G[CG[CTTGGGGTCCTGGGCTCC[CG[GCCA[CG[CTACAT[CG[C[CG[GTCT

GGGG[G[[G[GAGA[G[[G[TCTGATCC[CG[CC[CG[C[CG[GGCAGAGTTG[CG[GGCTT[CG[CT[CG[GCT[CG

]GGGTTCCCCA[CG[ATCTCTCACCCTGTGTTT[CG[G[CG[GAGTTG[CG[GGGGTTCCCTCTGCTCC[[CG[GGTCCC

TGAGATCCCTGATCC[CG[CTCTCAGGGCAGGGAATTC[CG[GGGTT[CG[CCCCTCTGGGCTTCCC[CG[[CG[ATCC

CAGAGCC[CG[[CG[TTCCAACAGAATTGGGAGGGTTTATTG[CG[CTAGAGGAGTCTTCAGG

SEQ ID NO: 763

CAAGCAATTCTCCTGCCTCAGCCTCCCAAGTAGCTGGGACTACAGG[CG[CACACCACCATGCC[CG[GCTAATTT

TTGTATTTTTAGTAGAGA[CG[GGGGTTTCACCATATTGGTCAGGC[CG[GTCT[CG]AGCTCCTGACCTCAGGTGA

TCCACC[CG[CCT[CG[GCCTCCCAAAGTGCTGGGATTACAGG[CG[TGGGCCAC[CG[CTCC[CG[G[CG[GGGCC[CG

]AGTTTCTTGAATGAAGTCCCCCCAGCATGGC[CG[TTGCCATG[CG[GGTCCTGGGTTGTGGAGAGATG[CG[G[C

G]GTACTTGC[CG[ACAG[CG[G[CG[G[CG[CTTGGGGTCCTGGGCTCC[CG[GCCA[CG[CTACAT[CG[C[CG[GTCT

GGGAG[G[[G[GAGA[G[[G[TCTGATCC[CG[CC[CG[C[CG[GGCAGAGTTG[CG[GGCTT[CG[CT[CG[GCT[CG

]GGGTTCCCCA[CG[ATCTCTCACCCTGTGTTT[CG[G[CG[GAGTTG[CG[GGGGTTCCCTCTGCTCC[[CG[[GGTCCC

TGAGATCCCTGATCC[CG[CTCTCAGGGCAGGGAATTC[CG[GGGTT[CG[CCCCTCTGGGCTTCCC[CG[[CG[ATCC

CAGAGCC[CG[[CG[TTCCAACAGAATTGGGAGGGTTTATTG[CG[CTAGAGGAGTCTTCAGG

SEQ ID NO: 764

AGGGG[CG[AGGCT[CG[AGGGTCCCTAGGGGTGGTGGGA[CG[CAAGGCCCATGCC[CG[TCTATGGCCTCT[CG[C

CG]AGGGCA[CG[CTCC[CG[GGGCTCTTGGC[CG[CCCCT[CG[CCCAC[[CG[[GGCTCTGGGTAGCCCCTCACCA

GGCTCTTG[G[GCCACCTAGCC[G[G[CG[CC[CG[GCCCCCTG[CG[GC[CG[GCCCATTTAGTGTGAATCCTGG

ATC[CG[GCAG[CG[G[CG[G[CG[GCTTCTTCAGGGGTAGCTGATGC[[CG[[GGGCCTTGGAGAGGGA[CG[CTTTGG

GAGGGTCCTGGGGG[G[G[CG[[CG[G[CG[AGCAAAGGGGGCAAGAAGGG[CG[TGCTGTGCTCC[CG[CCTGGC

TCC[CG[GGG[CG[T[CG[TTTGGGGG[CG[GC[CG[GGGAGTTTTCTACTTGGAAGCCCCTCTGAAGCCAC[CG[[[CG

]TCTCCTTTGCC[CG[GCCT[CG[TCTC[CG[CTGCCCA[CG[CAGGCTGC[CG[[CG[CTCTGGCCT[CG[GCCC[CG[GCT

C[CG[AGAGGCAGC

SEQ ID NO: 765

GCCCT[CG[G[CG[GGGCTGGAGCCTG[CG[TGTC[CG[G[CG[GGGCCC[CG[GGGGCTGGGAGCTGGGC[CG[GGCTT

CG[GGTCTCC[CG[CTGCCTCTGCAGAGCCC[CG[[CG[GGC[CG[GATTGCCAGCTTTGCTCTG[CG[CCTGG[CG]AG

GTG[G[[G[GCC[CG[[CG[GGGGCAGAGAG[CG[[CG[G[CG[GCTC[CG[GGGG[CG[CCCCTGGG[CG[GAGG[CG[G

AGGGG[CG[G[CG[GGAGTTGCAGGAACCCCCTCT[CG[TGGC[CG[AT[CG[GCCT[CG[CTGCCTTCTCC[CG[GGC

AG[CG[CTGTTGTAACCT[CG[GAAATAAACAAGTGCCAG[CG[G[CG[GGAGGCC[CG[CTC[CG[AGGC[CG[[CG[G

GG[CG[CTGGGGGA[CG[[CG[CTGGGCACA[CG[CTT[CG[GG[CG[GG[CG[GAAACTTTCCTGGG[CG]AGTTGAGCC

TCCCAC[CG[GGCTG[CG[GGTG[CG[ATTTGGAGCTT[CG[TGGC[CG[ATGAAGAAAGC[CG[[CG[GTTTAGAGCTT

TT[CG[TAAGGAATGACCCTG[CG[TCC[CG[CTCTCCTCCCT[CG[GTGCTGGGGGTAGAGGGG[CG[CCCTC[CG[[C

G[GTGC[CG[G[CG[T[CG[GGAAGCC

SEQ ID NO: 766

AGGGG[CG]AGGCT[CG]AGGGTCCCTAGGGGTGGTGGGA[CG[CAAGGCCCATGCC[CG[TCTATGGCCTCT[CG[C

CG]AGGGCA[G[CTCC[CG[GGGCTCTTGGC[CG[CCCCT[CG[CCCAC[[CG[[GGCTCTGGGTAGCCCCTCACCA

GGCTCTTGG[G[GCCACCTAG[G[G[CG[[CC[CG[GCCCCCTG[CG[GC[CG[GCCCATTTAGTGTGAATCCTGG

ATC[CG[GCAG[CG[G[CG[G[CG[GCTTCTTCAGGGGTAGCTGATGC[[CG[[GGGCCTTGGAGAGGGA[CG[CTTTGG

GAGGGTCCTGGGGG[G[G[CG[[CG[G[CG[AGCAAAGGGGGCAAGAAGGG[CG[TGCTGTGCTCC[CG[CCTGGC

TCC[CG[GGG[CG[T[CG[TTTGGGGG[CG[GC[CG[GGGAGTTTTCTACTTGGAAGCCCCTCTGAAGCCAC[CG[[CG

[TCTCCTTTGCC[CG[GCCT[CG[TCTC[CG[CTGCCCA[CG[CAGGCTGC[CG[[CG[CTCTGGCCT[CG[GCCC[CG[GCT

CT[G[GAGCTGCC[G[[G[GGCT[G[GGTCT[G[CCTCCAGCCCCCAGG[G[GCC[CG[[CG[G[CG[GATCC

C[CG[AGAGGCAGC

SEQ ID NO: 767

GCCCT[CG[G[CG[GGGCTGGAGCCTG[CG[TGTC[CG[G[CG[GGGCCC[CG[GGGGCTGGGAGCTGGGC[CG[GGCTT

CG[GGTCTCC[CG[CTGCCTCTGCAGAGCCC[CG[[CG[GGC[CG[GATTGCCAGCTTTGCTCTG[CG[CCTGG[CG]AG

GTG[G[[G[GCC[G[[G[GGGGCAGAGAG[G[[CG[G[CG[GCTC[CG[GGGG[CG[CCCCTGGG[CG[GAGG[CG[G

AGGGG[CG[G[CG[GGAGTTGCAGGAACCCCCTCT[CG[TGGC[CG[AT[CG[GCCT[CG[CTGCCTTCTCC[CG[GGC

AG[CG[CTGTTGTAACCT[CG[GAAATAAACAAGTGCCAG[CG[G[CG[GGAGGCC[CG[CTC[CG[AGGC[CG[[CG[G

GG[CG[CTGGGGGA[CG[[CG[CTGGGCACA[CG[CTT[CG[GG[CG[GG[CG[GAAACTTTCCTGGG[CG[AGTTGAGCC

TCCCAC[CG[GGCTG[CG[GGTG[CG[ATTTGGAGCTT[CG[TGGC[CG[ATGAAGAAAGC[CG[[CG[GTTTAGAGCTT

G|GTGC[CG[G[CG[T[CG[GGAAGCC

SEQ ID NO: 768

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[CG[[ACC[CG[[CG[[CCTGCACA[[CG[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[CG[[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CGAATG[G[TCCTCCTGG[G[GTGATGGTCTGGA[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[[CG[[GAGACAC

TAC[G[AGAACCAGATGT[G[[G[CC[CG[[CG[[TGGTCATCCTGCTGCTGC[CG[[TTTGC[CG[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG[AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTA

CCTGCAGCC[CG[[[[CG[CAG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 769

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[[CG[ACC[CG[[CG[[CCTGCACA[[CG[[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[[TGGTGC[[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[[CG[[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CG]AATG[G[TCCTCCTGG[G[GTGATGGTCTGGA[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACAC

TAC[G[AGAACCAGATGTT[G[[G[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[[CG[[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTA

CCTGAGCC[G[[CG[CAG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 770

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG]ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[[CAGAGGAG[[CG[[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GTGTGG[G[GTG[G[[G[[ACC[CG[[CG[[CCTGCACA[CG[[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CG]AATG[G[TCCTCCTGG[G[GTGATGGCTCTGGAC[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[[CG[[GAGACAC

TAC[G[AGAACCAGATGTT[G[[G[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTA

CCTGCAGCC[G[[CG[CAG[CG[[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 771

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[CG[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CGAATG[G[TCCTCCTG[G[GTGATGGTCTGGA[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACAC

TAC[G[AGAACCAGATGT[G[[G[CC[CG[[CG[[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG[AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[[GCT[CG[GCCATCTACACCTA

CCTGCAGCC[G[[CG[CAG[CG[[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 772

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[CG[ACC[CG[[CG[[CCTGCACA[[CG[[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACAC

TAC[G[AGAACCAGATGTT[G[[CG[CC[CG[[CG[[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[[CG[GCCATCTACACCTA

CCTGCAGCC[G[[[CG[CAG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 773

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[[CAGAGGAG[CG[CTTTCTCCTGCTGGGTTTCTC[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[CG[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

GAATG[G[TCCTCCTGG[G[GTGATGGTCTGGA[G[[G[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[CG[CTGGCCAG[CG[[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[[GAGACAC

TAC[G[AGAACCAGATGTT[G[[CG[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTA

CCTGCAGCC[G[[CG[CAG[CG[[CTACAACCAGGCA[CG[[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 774

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GCTGCTGG[G[GTG[G[[CG[[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[[GAGACAC

TAC[G[AGAACCAGATGT[G[[CG[CC[CG[[CG[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[CG[GCT[CG[[GCCATCTACACCTA

CCTGCAGCC[CG[[CG[CAG[CG[CTACAACCAGGCA[CG[GGGCAAGTT[CG[TAT[CG[CTCTTCTACAC[CG[T

GGTCACACCTGCTCTCAACC[CG[CTCATCTACACCCTCAGGAATAAGAAAGTGAAGGGGGCAG[CG[AGGAGG

CTGCTG[CG[GAGTCT

SEQ ID NO: 775

CAAGGTTTTCCCTTTGCTTATAAGGGGTAGTCACCCTTTTTTATTT[CG[ACCTTCCAAACATTCTGGGAGTTTTC

CTCCTTTAGGCCAACTACAG[CG[CAGAGGAG[[CG[CTTTCTCCTGCTGGGTTTCTC[CG[[ACTGGCCTTCCCT

GCAGC[CG[GTCCTCTT[CG[CCCTTGTCCTCCTGTGCTACCTCCTGACCTTGA[CG[GGCAACT[CG[G[CG[CTGGT

GTGTGG[G[GTG[G[[CG[ACC[CG[[CG[[CCTGCACA[CG[CCCATGTACTACTTCCTCTGCCACCTGGC

CTTGGTAGA[CG[[CG[GGCTTCACTACTAG[CG[[TGGTGC[CG[C[CG[CTGCTGGCCAACCTG[CG[[CG[GACCA

G[CG[CTCTGGCTGC[CG[[CG[CAGCCACTGCA[CG[GCCCAGCTGTG[CG[CAT[CG[CTGGCTCTGGGTTC[CG[C[

GAATG[G[TCCTCCTGG[G[GTGATGGTCTGGAC[G[[CG[[CG[GC[CG[CAGTGTGC[CG[CC[CG[CTG[CG[

CTATG[CG[GGGCT[CG[TCTCCC[CG[[CG[CCTATGT[CG[CA[[CG[CTGGCCAG[CG[CCTCCTGGCTAAG[CG[GC

TGCTGGACCACTTCATCTGTGAGCTGC[CG[G[CG[TTGCTCAAGCTGGCCTG[CG[GAGG[CG[A[CG[GAGACAC

TAC[G[AGAACCAGATGTT[G[[G[CC[CG[[[CG[[TGGTCATCCTGCTGCTGC[CG[TTTGC[CG[[TCATCC

TGGCCTCCTA[CG[GTGC[CG[TGGCC[CG]AGCTGTCTGTTGCATG[CG[GTTCAG[CG[GAGGC[CG[[GAGGAGGG[

CG[GTGGGCA[CG[TGTGGGTCCCACCTGACAGC[CG[TCTGCCTGTTCTA[[CG[[GCT[CG[G[CG[[[CG]][[CG]]

[[CG]]

SEQ ID NO: 776

GTCTTCCCCTTCTTCTCTTTGCTAAA[CG[ACCCCTCCAAGATAATTTTTAAAAAACCTTCTCCTTTGCTCACCTTT

GCTTCCCAGCCTTCCCATCCCCCCAC[CG]AAAGCAAATCATTCAA[CG[ACCCC[CG[ACCCTC[CG[A[CG[GCAG

GAGGG[CG[[CG]AGCACAGC[CG[AGGCCATGGAGGTGA[CG[G[CG[GACCAGC[CG[[CG[CTGGGTGAGCCACC

ACCACCC[CG[C[CG[TGCTCAA[CG[GGCAGCACC[CG[[GACA[CG[CACCACC[CG[GGCCTCAGCCACTCCTACA

TGGA[CG[[CG[G[CG[CAGTACC[CG[CTGC[CG[GAGGAGGTGGATGTGCTTTTTAACAT[CG[A[CG[GTCAAGGCA

ACCA[CG[TCC[CG[CCCTACTA[CG[GAAACT[CG[GTCAGGGCCA[CG[GTGCAGAGGTACCCTC[CG[ACCCACCA[

CGGTGAGTG[G[[G[GGGTGC[G[GGGCTCC[CG[C[CG[GC[CG[CTTCAGC[CG[TCC[CG[GCT[CG[GGGAG

GT[CG[GGAGGGACCTGAGGG[CG[GGGAGAGGTCAAG[CG[AAAGCCCCCATCTGC[CG[TTCCTGGTTCATTTA

SEQ ID NO: 777

GTCTTCCCCTTCTTCTCTTTGCTAAA[CG[ACCCCTCCAAGATAATTTTTAAAAAACCTTCTCCTTTGCTCACCTTT

GCTTCCCAGCCTTCCCATCCCCCCAC[CG[AAAGCAAATCATTCAA[CG[ACCCC[CG[ACCCTC[CG[A[CG[GCAG

GAGGG[CG[[CG[AGCACAGC[CG]AGGCCATGGAGGTGA[CG[G[CG[GACCAGC[CG[[[CG[CTGGGTGAGCCACC

ACCACCC[CG[C[CG[TGCTCAA[CG[GGCAGCACC[CG[[GACA[CG[CACCACC[CG[GGCCTCAGCCACTCCTACA

TGGA[CG[[CG[G[CG[CAGTACC[CG[CTGC[CG[GAGGAGGTGGATGTGCTTTTTAACAT[CG[A[CG[GTCAAGGCA

ACCA[CG[TCC[CG[CCCTACTA[CG[GAAACT[CG[GTCAGGGCCA[CG[GTGCAGAGGTACCCTC[CG[ACCCACCA[

CG[GTGAGTG[CG[CC[CG[GGGTGC[CG[GGGCTCC[CG[C[CG[GC[CG[CTTCAGC[CG[TCC[CG[GCT[CG[GGGAG

GT[CG[GGAGGGACCTGAGGG[CG[GGGAGAGGTCAAG[CG[AAAGCCCCCATCTGC[CG[TTCCTGGTTCATTTA

SEQ ID NO: 778

TCCCTTTGCCCCCTACA[CG[[CG[TGTTCT[CG[TCAACAGATCTCCAGAGGTGGTGCAGAAA[CG[ACCC[CG[[CG[

[G[[G[CCCCATCCTG[G[GCCAGTGCCT[G[[G[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCC

CAGATTTC[G[GAGGAGAGG[G[GG[CG[GGGTCC[CG[[CG[GGGC[CG[GCTGC[CG[TCAG[CG[CCCCTTCC[C

G[[G[[G[[CG[[ACCCCTCCC[CG[CTGACCTCACT[CG[AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[

CG[GCCCATCTGAAGAGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[CG[CTGCAGACTCCTGACCTGC[CG[

ACTG[CG[GATCC[CG[AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CC

CCAACCCCTCTCCTTC[CG[CAGA[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCA

CCTT[CG[GTTCTCTGAGAGCTTCCTGGAGAACAGGGC[CG[GTGCACAGG[[CG[GG[CG[CTGTGCT[CG[CACCC

C[CG[GGTCCTCCC[CG]AG[CG[CAGGC[CG[GGGACC[CG[A[CG[GGAGGCA[CG[G[CG[[CG[GGCACAT[CG[GAG

GCTCT[CG[CTGCTG

SEQ ID NO: 779

TCCCTTTGCCCCCTACA[CG[[CG[TGTTCT[CG[TCAACAGATCTCCAGAGGTGGTGCAGAAA[CG[ACCC[CG[[CG[

[G[[G[CCCCATCCTG[G[GCCAGTGCCTC[G[[CG[CCC[CG[GCTC[CG[GTCCCCAC[CG[TCCC[CG[CCC

CAGATTTC[CG[GAGGAGCAGG[CG[GG[CG[GGGTCC[CG[[CG[GGGC[CG[GCTGC[CG[TCAG[CG[CCCCTTCC[C

G[[G[[G[[CG[[ACCCCTCCC[CG[CTGACCTCACT[CG]AGC[CG[C[CG[CCTGG[CG[CAGATATAAG[CG[G[

CG[GCCCATCTGAAGAGGGCT[CG[GCAGG[CG[CC[CG[GGGTCCTCAG[[CG[CTGCAGACTCCTGACCTGC[CG[

ACTG[CG[GATCC[CG[AGTCCC[CG[GATCC[CG[GACCCATCCTGTGGAGCCCACTCCTGGCAGGTAAC[CG[CC

CCAACCCCTCTCCTTC[CG[CAGA[CG[GTGTC[CG[GGAGCACTGGAAAGGGAGCCCTCT[CG[GCC[CG[CCCTCA

CCTT[CG[GTTCTCTGAGAGCTTCCTGGAGAACAGGGC[CG[GTGCACAGG[[CG[GG[CG[CTGTGCT[CG[CACCC

GCTCT[CG[CTGCTG

SEQ ID NO: 780

TGCTGAGGATGACAGGGAGC[CG[GGAGC[CG[GAGGATGGAGGATGGTGCAGGCTGGGGAGATGC[CG[GTACC

TTTCCCTGGGTCATGGTGC[CG[[TCTCT[CG[[GGGAAGGGGTCCCTGAGGCC[CG[GGTGGC[CG[CTTGGGTAAC

[CG[CAGCCTGCCTG[CG[TCTCTTCCTTCCTC[CG[[CG[TGGGTTCTAGCAACATCCACTGCAGC[CG[GGCCAGG[C

G]AG[G[G[G[[CG[TACCAT[CG[G[CG[[CG[GGGGGAGGAGAGGGC[CG[GGCCTGGGAAGATGCTG[CG[GAG

CCCCCCCACCC[CG[CCCCCCAC[CG[C[CG[CCCTTAGCCCTCCCC[CG[GGATGAGAGAGAGT[CG[[CG[CTG[CG[

GAGCAACCCCAGTGGATGGGTC[CG[[CG[GGGGCTGAG[CG[GG[CG[GAGGA[CG[[CG[GGAACTC[CG[[TGACA

C[CG[ACCAGCTGA[CG[CTGCC[CG[[CG[TGAAACCAGAGC[CG[GGCATCAGGGCCTCATCTCCACTGTCTCTGC

ACCTCTCTGCAGCTCCAGCTG[CG[CCTCTGCCTTTTCCTCCTCCCTCTTTGGATG[CG[GCCCTGATTTCTGTCTC

SEQ ID NO: 781

TGCTGAGGATGACAGGGAGC[CG[GGAGC[CG[GAGGATGGAGGATGGTGCAGGCTGGGGAGATGC[CG[GTACC

TTTCCCTGGGTCATGGTGC[[CG[[TCTCT[[CG[GGGAAGGGGTCCCTGAGGCC[CG[GGTGGC[CG[CTTGGGTAAC

[CG[CAGCCTGCCTG[CG[TCTCTTCCTTCCTC[CG[[CG[TGGGTTCTAGCAACATCCACTGCAGC[CG[GGCCAGG[C

GAG[G[[G[[G[TACCAT[G[G[CG[[CG[GGGGGAGGAGAGGGC[CG[GGCCTGGGAAGATGCTG[CG[GAG

CCCCCCCACCC[CG[CCCCCCAC[CG[C[CG[CCCTTAGCCCTCCCC[CG[GGATGAGAGAGAGT[CG[[CG[CTG[CG[

GAGCAACCCCAGTGGATGGGTC[CG[[CG[GGGGCTGAG[CG[GG[CG[GAGGA[CG[[CG[GGAACTC[CG[[TGACA

C[CG[ACCAGCTGA[CG[CTGCC[CG[[CG[TGAAACCAGAGC[CG[GGCATCAGGGCCTCATCTCCACTGTCTCTGC

ACCTCTCTGCAGCTCCAGCTG[CG[CCTCTGCCTTTTCCTCCTCCCTCTTTGGATG[CG[GCCCTGATTTCTGTCTC

SEQ ID NO: 782

[G[[G[CAGCAATTGGC[G[[G[GGTCC[CG[GC[CG[CCC[CG[GTAGAGGCTGGGTACAG[CG[AGGGGGC[C

GGG[G[[G[GGCAGGA[G[GG[CG[[CG[G[CG[GGTGGGGCCTGGC[CG[TCTCCCCCTGCCCT[CG[GGGC[CG

]AACA[CG[CACAG[CG[AGAGTCTAG[CG[T[CG[G[CG[TGGCTG[CG[GCCAGC[CG[GGTCCCCCTGGAGGCCTC[C

TCCCACCTGGTCC[CG[GTTCTC[CG[TC[CG[CTAGGCTGGC[CG[[CG[GGGCCCCTGGGGCC[CG[ACCTTCC[CG[G

GGTGCCCCAACCTG[CG[GCAAGGC[CG[AGGTCC[CG[CTGAGGCATGAGTCC[CG[GGT[CG[GGGAC[CG[CTCTG

GGC[CG[ACCCC[CG[GAGGA[CG[GACTAGGC[CG[ATCCCCAGAGGGAAGGGGGCCAGGC[CG]AGGCCATGGCA

G[CG[[CG[TTCCCTGATCC[CG[TGTTCT[CG[GCTCCT[CG[[CG[TCCCACTAT[CG[GCTGTCCCTTT[CG[TG[CG[GG

ACTGA[CG[GCTCACAGAA

SEQ ID NO: 783

[C[[G[CAGCAATTGG[G[[G[GGTCC[CG[GC[CG[CCC[CG[GTAGAGGCTGGGTACAG[CG]AGGGGGC[C

GGG[G[[G[GGCAGGA[CG[GG[CG[[CG[G[CG[GGTGGGGCCTGGC[CG[TCTCCCCCTGCCCT[CG[GGGC[CG

]AACA[CG[CACAG[CG[AGAGTCTAG[CG[T[CG[G[CG[TGGCTG[CG[GCCAGC[CG[GGTCCCCCTGGAGGCCTC[C

TCCCACCTGGTCC[CG[GTTCTC[CG[TC[CG[CTAGGCTGGC[CG[[CG[GGGCCCCTGGGGCC[CG[ACCTTCC[CG[G

GGTGCCCCAACCTG[CG[GCAAGGC[CG]AGGTCC[CG[CTGAGGCATGAGTCC[CG[GGT[CG[GGGAC[CG[CTCTG

GGC[CG[ACCCC[CG[GAGGA[CG[GACTAGGC[CG[ATCCCCAGAGGGAAGGGGGCCAGGC[CG]AGGCCATGGCA

G[CG[[CG[TTCCCTGATCC[CG[TGTTCT[CG[GCTCCT[CG[[CG[TCCCACTAT[CG[GCTGTCCCTTT[CG[TG[CG[GG

ACTGA[CG[GCTCACAGAA

SEQ ID NO: 784

GTCTGGCATTTTGCTGATGGTATCTGGGTGAGGGAGAAAGG[CG[TGTTGTTGG[CG[T[CG[GGGAAGGGGCCTC

CCCAATTGCCAAGGGGGTCCCTGGGGG[CG[G[CG[GGAAGGGGGGTAG[CG[GCCTCAGGGTCTTGGGGGTGCT

GAGGGGCAGAAAGGGGCAAAGGAG[CG[TGGAGGAG[CG[GAAGT[CG]AGAGTGGGACAGAAGTGGAG[CG[CT

GGG[CG[GCAA[CG[AGGAAACTAAAGCCACAGAAGCC[CG[G[CG[CAGGG[CG[GGAAG[CG[TGGGAAGGCCC

CTTCCT[G[[G[[G[AGGTGCCCCCCT[G[CC[CG[AAA[CG[C[CG[GCCCAGGCC[CG[CCTC[CG[GCTCCC

AGGC[CG[TCACCTCCTCCTCCCC[CG[C[CG[[CG[GGTCATCCACTGG[CG[TC[CG[CT[CG[GTGGGCCT[CG[[CG[G

CCTGG[G[GCCTGGAG[G[TACCA[G[[CG[G[CG[GAG[CG[G[CG[GGTTGGGG[CG[T[CG[CA[CG[GTGAGAA

AGG[G[GGGCCTGAGAAAAA[G[[G[[CG[GT[CG[C[CG[GGGCAA[CG[GGA[CG[GGGCA[CG[TGCCC

CCCC[CG[CCAGAGC[CG[GAAG[CG[GCAGGCT[CG[TG[CG[TCCCTCCTGAGCT[CG]AAGCCAACCAGGCCT[CG[

AG[CG[GCT[CG[CTGC

SEQ ID NO: 785

GTCTGGCATTTTGCTGATGGTATCTGGGTGAGGGAGAAAGG[CG[TGTTGTTGG[CG[T[CG[GGGAAGGGGCCTC

CCCAATTGCCAAGGGGGTCCCTGGGGG[CG[G[CG[GGAAGGGGGGTAG[CG[GCCTCAGGGTCTTGGGGGTGCT

GAGGGGCAGAAAGGGGCAAAGGAG[CG[TGGAGGAG[CG[GAAGT[CG[AGAGTGGGACAGAAGTGGAG[CG[CT

GGG[CG[GCAA[CG[AGGAAACTAAAGCCACAGAAGCC[CG[G[CG[CAGGG[CG[GGAAG[CG[TGGGAAGGCCC

TTCCTT[G[[G[[G[AGGTGCCCCCCT[G[CC[CG[AAA[CG[C[CG[GCCCAGGCC[CG[CCTC[CG[GCTCCC

AGGC[G[TCACCTCCTCCTCCCC[CG[[CG[[CG[GGTCATCCACTGG[CG[TC[CG[CT[CG[GTGGGCCT[CG[[CG[G

CCTGG[G[GCCTAG[G[TACCA[G[[G[G[CG[GAG[CG[G[CG[GGTTGGGG[CG[T[CG[CA[CG[GTGAGAA

AGG[G[GGGCCTGAGAACAA[G[[G[[G[GT[CG[C[CG[GGGCAA[CG[GGA[CG[GGGCA[CG[TGCCC

CCCC[CG[CCAGAGC[CG[GAAG[CG[GCAGGCT[CG[TG[CG[TCCCTCCTGAGCT[CG[AAGCCAACCAGGCCT[CG[

AG[CG[GCT[CG[CTGC

SEQ ID NO: 786

[CG[TCTGTGGGGAGTAGCTAGGGGCCTGCC[CG[G[CG[GGGG[CG[CAGGAACC[CG[GTTG[CG[GTGC[CG[GG

AGGAGGGT[CG[GGAGGGTCTCAGCCCCCTCCTTGCTCCCAGGCTTCCACTCCTTGAGGTATTTCCACACCACCA

TGTCC[G[[G[[G[[CG[[CG[GATCCC[CG[CTTCCTCTC[CG[TGGG[CG[A[CG[TGGA[CG[ACA[CG[CAGT

G[G[TG[G[GCT[G[ACAG[CG[A[CG[CCA[CG]AGTCCCAGGATGGAGC[CG[[CG[GG[CG[C[CG[TGGATGGAG

CAGGAGGGGC[CG[GAATATTGGGAAGAGGAGACAGGGAC[CG[[CCAAGGCCAAAGCACAGTTTTAC[CG[[AG

TGAACCTG[CG[GACCCTGAG[CG[GCTACTACAACCAGAGTGAGGCCTGTGAGTGACAC[CG[GC[CG[GGGG[[

CG[[CAGGTCACTACCCCTCCACATCCCCCA[CG[GAC[CG[CC[CG[GGTCTCCC[CG]AGTCTCTGGGTC[CG[AGAT

CCA[CG[C[CG[AGGCAG[CG[GGACCTGGAGACCCTTGACC[CG[GGAGAGGCCCAGGAGC[CG[TTACC[CG[GTT

TCATTTTCAGCCAAAATCCC[CG[CAGGTTGGTCCTGG[CG[[AGGG[CG[GGGCT[CG[[GTGGG[CG[[GGGCTGG

C[CG[[CG[G

SEQ ID NO: 787

[CG[TCTGTGGGGAGTAGCTAGGGGCCTGCC[CG[G[CG[GGGG[CG[CAGGAACC[CG[GTTG[CG[GTGC[CG[GG

AGGAGGGT[CG[GGAGGGTCTCAGCCCCCTCCTTGCTCCCAGGCTTCCACTCCTTGAGGTATTTCCACACCACCA

TGTCC[G[GCC[G[GC[CG[[CG[[CG[GATCCC[CG[CTTCCTCTC[CG[TGGG[CG[A[CG[TGGA[CG[ACA[CG[CAGT

G[G[[G[GCT[G[ACAG[G[A[CG[CCA[CG[AGTCCCAGGATGGAGC[CG[[CG[GG[CG[C[CG[TGGATGGAG

CAGGAGGGGC[CG[GAATATTGGGAAGAGGAGACAGGGAC[CG[[CCAAGGCCAAAGCACAGTTTTAC[CG[[AG

TGAACCTG[CG[GACCCTGAG[CG[GCTACTACAACCAGAGTGAGGCCTGTGAGTGACAC[CG[GC[CG[GGGG[[

CG[[CAGGTCACTACCCCTCCACATCCCCCA[CG[GAC[CG[CC[CG[GGTCTCCC[CG[AGTCTCTGGGTC[CG[AGAT

CCA[CG[C[CG]AGGCAG[CG[GGACCTGGAGACCCTTGACC[CG[GGAGAGGCCCAGGAGC[CG[TTACC[CG[GTT

TCATTTTCAGCCAAAATCCC[CG[CAGGTTGGTCCTGG[CG[[AGGG[CG[GGGCT[CG[GTGGG[CG[GGGCTGG

C[CG[[CG[G

SEQ ID NO: 788

A[G[CC[CG[G[CG[GCCC[CG[GCTT[CG[[CG[GCCAC[CG[G[CG[TTGTCTCCACTCT[CG[C[CG[[CG[GGCAGTGGC

]GACCAGAGCTGCTGCCCCAGCAGGG[CG[G[CG[GCAGAGG[CG[GTGAGATGCAGGTGGAAGC[CG[GAGGGAC

AGGAGT[CG[C[CG[GG[CG[CAGCCCCCAATCACCCAGGAA[CG[[CG[GGGA[CG[[CCTGGGCCACTGCTC[CG[G

C[CG[ATGGTTCCAGAGGAAGC[CG[TCCCCTTGCTAAGGGTTCC[CG[GGAGGAGGTGAAGG[CG[C[CG[[CG[GGC

TGGGGGGT[CG[G[CG[GCTGAAGACCTC[CG[GCTGCCCAGCACCTCCTT[CG[[CG[CTGAC[CG[GGGACT[CG[GC

CCACAACCAAGCCATGGTGCACTGGT[CG[GGACACAACAGCAG[CG[TGAGTACCCACC[CG[G[CG[G[CG[GGT

C[CG[CCTGTTTCCTGACAC[CG[AAGGGGAATGGGGGGGTGGGTGGGAG[CG]AGGGACAGATAGTTGCT[CG[G

GGGT[CG[AGG[CG[G

SEQ ID NO: 789

[G[[G[[CG[GCCC[CG[GCTT[CG[[CG[GCCAC[CG[G[CG[TTGTCTCCACTCT[CG[C[CG[[CG[GGCAGTGGC

CAGCCAGTGGC[G[GAGGAGCTGG[G[[G[[G[[CG[GAGAGC[CG[C[CG[TGCTGGGG[CG[C[CG[GGC[CG

]GACCAGAGCTGCTGCCCCAGCAGGG[CG[G[CG[GCAGAGG[CG[GTGAGATGCAGGTGGAAGC[CG[GAGGGAC

ATCAC[CG[GCAGG[CG[AG[CG[G[CG[GGGC[CG[GGGCATCCCAGCTCCTGCCAAGCTTGG[CG[G[CG[[CG[AGG

AGGAGT[G[C[CG[GG[CG[CAGCCCCCAATCACCCAGGAA[CG[[CG[GGGA[[CG[[CCTGGGCCACTGCTC[CG[G

C[CG[ATGGTTCCAGAGGAAGC[CG[TCCCCTTGCTAAGGGTTCC[CG[GGAGGAGGTGAAGG[CG[C[CG[[CG[GGC

TGGGGGGT[CG[G[CG[GCTGAAGACCTC[CG[GCTGCCCAGCACCTCCTT[CG[[CG[CTGAC[CG[GGGACT[CG[GC

CCACAACCAAGCCATGGTGCACTGGT[CG[GGACACAACAGCAG[CG[TGAGTACCCACC[CG[G[CG[G[CG[GGT

C[CG[CCTGTTTCCTGACAC[CG[AAGGGGAATGGGGGGGTGGGTGGGAG[CG]AGGGACAGATAGTTGCT[CG[G

GGGT[CG]AGG[CG[G

SEQ ID NO: 790

GGTGGGGTGGGGTGGGCAATGGGCAATGAGA[CG[GAGGG[CG[GGGC[CG[GGACCTAATATGG[CG[GGTCAGG

AGGGTCTGGAAGA[[CG[[AAGAAGAGGGACAGGCAATGCCAGGTCTAGGACTAGGAGGGAGG[CG[[CG[GG[CG

AGGGG[CG[[CG[[CG[ACCCTCCCTT[CG[[GTCTGGCTCCAAAGACCTAGCAGCACTGACTTCACCCAGCTGTGG

TTCCA[C[[G[GGTCCAG[G[GCT[G[GCC[G[G[CG[C[CG[TCCTCCTGCTGGCCCAACAGGCC[CG[C

CAGCC[CG[CCCCTGTA[CG[TCTGTGATTGGA[CG[G[CG[G[CG[GCCACTGATGTTCAAG[CG[ACAGGTCCTGGC

C[CG[[GGAGCCAATCTGCAGGTGTTGAGGCCCAGGCTC[CG[AGAG[CG[GGC[CG[AGGAGG[CG[TGGATACCC

TGATTCCTAGGGGGCAGGCCTGGTTCCCC[CG[AGGAGGACC[CG[GCCTATGAATGACTGGAGTTCTGGGGTTC

TGGC[CG[AAAGAGGAAGTGGGACAGGGC[CG[GGTGTGATGGGGCCTAGAGTCACAGAGCCTTG[CG[GC

SEQ ID NO: 791

GGTGGGGTGGGGTGGGCAATGGGCAATGAGA[CG[GAGGG[CG[GGGC[CG[GGACCTAATATGG[CG[GGTCAGG

AGGGTCTGGAAGA[CG[[AAGAAGAGGGACAGGCAATGCCAGGTCTAGGACTAGGAGGGGG[CG[[CG[GG[CG

GTATTAG[G[GCTGGGGGGCTT[G[GGAGG[G[GC[G[A[CG[GC[CG[C[CG[CCTGGTGCTACCCACCC

AGGGG[CG[[CG[[CG[ACCCTCCCTT[[CG[[GTCTGGCTCCAAAGACCTAGCAGCACTGACTTCACCCAGCTGTGG

TTCCA[G[[G[GGTCCAG[G[GCT[G[GCC[CG[G[CG[C[CG[TCCTCCTGCTGGCCCAACAGGCC[CG[C

CAGCC[CG[CCCCTGTA[CG[TCTGTGATTGGA[CG[G[CG[G[CG[GCCACTGATGTTCAAG[CG[ACAGGTCCTGGC

C[[CG[[GGAGCCAATCTGCAGGTGTTGAGGCCCAGGCTC[CG[AGAG[CG[GGC[CG[AGGAGG[CG[TGGATACCC

TGATTCCTAGGGGGCAGGCCTGGTTCCCC[CG]AGGAGGACC[CG[GCCTATGAATGACTGGAGTTCTGGGGTTC

TGGC[CG[AAAGAGGAAGTGGGACAGGGC[CG[GGTGTGATGGGGCCTAGAGTCACAGAGCCTTG[CG[GC

SEQ ID NO: 792

G[G[[CG[ATG[CG[CAG[CG[[CG[TTGGCA[CG[CTCCAGC[CG[GGTG[CG[GCCCTTCCCAG[CG[[CG[CCCAG[CG[

GGTGCCAGCTCC[CG[CAGCTCAATGAGCTCAGGCTCCCC[CG[ACATGGCC[CG[GTTGGGCC[CG[TGCTT[CG[CT

GGCTTTGGG[G[CTAGCAAG[CG[[CG[GGC[CG[GG[CG[GGGCCACAGGG[CG[GGCCC[CG[ACTTCAG[CG[CCTC

CCCCAGGATCCAGACTGGG[CG[G[CG[GGAAGGAGCTGAGGAGAGC[CG[[CG[CAATGGAAACCTGGGTGCAGG

GACTGTGGGGCC[G[AAGG[G[GGGCTGGG[CG[[CG[CTCT[CG[CAGAGCCCCCCC[CG[CCTTGCCCTT

CCTTCCCTCCTT[CG[TCCCCTCCTCACACCCCACCC[CG[GA[CG[GCCACAA[CG[A[CG[G[CG[AC[CG[CAAAGCA

CCA[CG[[[CG[[GAGATACC[CG[TGTTTCTGGAGGCCAGCTTTACTGTGCTAGAGGAAGAGGGTCCCCACATC[C

G[GCCCTGGCCCTCCTGGTC[[CG[[GTTTGCTGAAGCAACACACTTGGCCTACCCACTGGGTGGGGCAGGAAGTC

T[CG[[AGCCTTCACTTGGGGTGAGGAGGAGGGAGAT[CG[GTCAGCAGCTTTAC[CG[CC[CG[CTCTGCTCTCCA

SEQ ID NO: 793

G[G[[CG[ATG[CG[CAG[CG[[CG[TTGGCA[CG[CTCCAGC[CG[GGTG[CG[GCCCTTCCCAG[CG[[CG[CCCAG[CG[

GGTGCCAGCTCC[CG[CAGCTCAATGAGCTCAGGCTCCCC[CG[ACATGGCC[CG[GTTGGGCC[CG[TGCTT[CG[CT

GGCTTTGGG[CG[CTAGCAAG[CG[[CG[GGC[CG[GG[CG[GGGCCACAGGG[CG[GGCCC[CG[ACTTCAG[CG[CCTC

CCCCAGGATCCAGACTGGG[CG[G[CG[GGAAGGAGCTGAGGAGAGC[CG[[CG[CAATGGAAACCTGGGTGCAGG

GACTGTGGGGCC[CG[AAGG[CG[[GGGCTGGG[CG[[CG[CTCT[CG[CAGAGCCCCCCC[CG[CCTTGCCCTT

CCTTCCCTCCTT[CG[TCCCCTCCTCACACCCCACCC[CG[GA[CG[GCCACAA[CG[A[CG[G[CG[AC[CG[CAAAGCA

CCA[CG[[[[CG[GAGATACC[CG[TGTTTCTGGAGGCCAGCTTTACTGTGCTAGAGGAAGAGGGTCCCCACATC[C

G[GCCCTGGCCCTCCTGGTC[[CG[[GTTTGCTGAAGCAACACACTTGGCCTACCCACTGGGTGGGGCAGGAAGTC

T[CG[[AGCCTTCACTTGGGGTGAGGAGGAGGGAGAT[CG[GTCAGCAGCTTTAC[CG[CC[CG[CTCTGCTCTCCA

SEQ ID NO: 794

[CG[CTGCAGATCAA[CG[C[CG[GTGGCAAGAAGGGGC[CG[CAAGGGTTTC[CG[CAGACACCCACACATGCAGG[

[CG[[TTCCCACAGAGGGTACCAGGGATTTCCCAGACCCCCACCAGCCCTCAGGAATAG[CG[TAGAGAGAGGAA

[CG[T[CG[CCTGGCTGAGAAAGGTGGATGGGCATACCCATGTACCTTTGTGTATTAAGTACCCACAACCTC[CG[

AACTTAGC[CG[TCCCTGTCC[CG[GCC[CG[CCCAACTGCTGC[CG[C[CG[CATCTGCAGAAACCACT[CG[TGTTG

AGGCCT[CG[GAGCAGC[CG[GGAGCACCA[[CG[CTGGAGCAAAAAAGC[CG[GAGGG[CG[CAGGGCTCCAGCC[

GCC[G[A[G[[CG[CT[CG[[CG[GACTAGTTCCTCAGACTGTGGGACTCCCTAGTGC[CG[GCTTTGCCCAGGGC

TTTCCAAGGCTGTCTCATGCCCTAGATCTGCCCCAGCAGCTCAGGCCTTGGACTG[CG]AACCCAGTATCC[CG]A

GACAC[CG[ATTCCATCAGTCCCCATCC[CG[ACCCCTCTCCAGC[CG[GGTTCATC[CG[CCT

SEQ ID NO: 795

[CG[CTGCAGATCAA[CG[C[CG[GTGGCAAGAAGGGGC[CG[CAAGGGTTTC[CG[CAGACACCCACACATGCAGG[

[CG[[TTCCCACAGAGGGTACCAGGGATTTCCCAGACCCCCACCAGCCCTCAGGAATAG[CG[TAGAGAGAGGAA

[CG[T[CG[CCTGGCTGAGAAAGGTGGATGGGCATACCCATGTACCTTTGTGTATTAAGTACCCACAACCTC[CG[

AACTTAGC[CG[TCCCTGTCC[CG[GCC[CG[CCCAACTGCTGC[CG[C[CG[CATCTGCAGAAACCACT[CG[TGTTG

AGGCCT[CG[GAGCAGC[CG[GGAGCACCA[[CG[CTGGAGCAAAAAAGC[CG[GAGGG[CG[CAGGGCTCCAGCC[

GCC[G[A[CG[C[CG[CT[CG[[CG[GACTAGTTCCTCAGACTGTGGGACTCCCTAGTGC[CG[GCTTTGCCCAGGGC

TTTCCAAGGCTGTCTCATGCCCTAGATCTGCCCCAGCAGCTCAGGCCTTGGACTG[CG[AACCCAGTATCC[CG[A

GACAC[CG[ATTCCATCAGTCCCCATCC[CG[ACCCCTCTCCAGC[CG[GGTTCATC[CG[CCT

SEQ ID NO: 796

ATAAATATTAATGTCAGCAAGAGTGTGCTGTTGGCAGGA[CG[TAT[CG[[CG[AGCCTGGAGATTTTGGTGGC[CG

]CAGTTGGTAAGTGGCTACAATCCAGAAAGTAGGAT[CG]AGTTGCTCCCCTTGTCTTATCAGTGTAT[CG[TTTCT

[CG[GG[CG[[[CG[GGTCTAACACCTTACAAGTGGTAATTTC[CG[CTCA[CG[GCAGCTTTGTCTCTCTTCTACCAT

CCCCAGACCCAGCCTTGCACTCCAAGGCTG[CG[CAC[CG[CCAGCCACTATCATGTCCACTCC[CG[GGGTCAATT

[CG[TC[CG[CCTCCTTGAGCCC[CG[[AC[CG[GCTGAACAGCCCAGTGACCATCC[CG[G[CG[GTGATGTTCATCTT

[CG[GGGTGGTGGGCAACCTGGTGGCCAT[CG[TGGTGCTGTGCAAGT[CG[[CG[CAAGGAGCAGAAGGAGA[CG[

ACCTTCTACA[CG[CTGGTATGTGGGCTGGCTGTCAC[CG[ACCTGTTGGGCACTTTGTTGGTGAGCC[CG[GTGAC

CAT[CG[CCA[CG[TACATGAAGGGCCAATGGCC[CG[GGGGCCAGC[CG[CTGTG[CG]AGTACAGCACCTTCATTC

TGCTCTTCTTCAGCCTGTC[CG[GCCTCAGCATCATCTG[CG[CCATGAG

SEQ ID NO: 797

ATAAATATTAATGTCAGCAAGAGTGTGCTGTTGGCAGGA[CG[TAT[CG[[CG]AGCCTGGAGATTTTGGTGGC[CG

]CAGTTGGTAAGTGGCTACAATCCAGAAAGTAGGAT[CG]AGTTGCTCCCCTTGTCTTATCAGTGTAT[CG[TTTCT

[CG[GG[CG[[[CG[GGTCTAACACCTTACAAGTGGTAATTTC[CG[CTCA[CG[GCAGCTTTGTCTCTCTTCTACCAT

CCCCAGACCCAGCCTTGCACTCCAAGGCTG[CG[CAC[CG[CCAGCCACTATCATGTCCACTCC[CG[GGGTCAATT

[CG[TC[CG[CCTCCTTGAGCCC[CG[[AC[CG[GCTGAACAGCCCAGTGACCATCC[CG[G[CG[GTGATGTTCATCTT

[CG[GGGTGGTGGGCAACCTGGTGGCCAT[CG[TGGTGCTGTGCAAGT[CG[[CG[CAAGGAGCAGAAGGAGA[CG[

ACCTTCTACA[CG[CTGGTATGTGGGCTGGCTGTCAC[CG[ACCTGTTGGGCACTTTGTTGGTGAGCC[CG[GTGAC

CAT[CG[CCA[CG[TACATGAAGGGCCAATGGCC[CG[GGGGCCAGC[CG[CTGTG[CG[AGTACAGCACCTTCATTC

TGCTCTTCTTCAGCCTGTC[CG[GCCTCAGCATCATCTG[CG[CCATGAG

SEQ ID NO: 798

GGGAAGTAAA[CG[GCCCCAA[CG[CAAGCCTGACTG[CG[AGA[CG[TGCCCAAGGGAGGTAGGT[CG[AATGAAG

AGGGTTGTGTGAGTTTTG[CG[[CG[GGCAGG[CG[GGATAA[CG[GAGGAGGGAGGCC[CG[[CG[GC[CG]AGGCT[C

GGG[G[GG[G[GGGGGGGGGGGG[G[GGGTT[G[[CG[G[CG[[CG[CACTCCCAGGCAGGCCC[CG[CCCC

CT[CG[GC[CG[GCTGTG[CG[[CG[CTGATTGGCCCCTGC[CG[GCCT[CG[[CG[CTCCCT[CG[CTC[CG[GGTTGG[CG[

GGAGACCTTAGAG[CG[GGTAC[CG[CTGCTGGCTAG[CG[AC[CG[A[CG[JAGCAAC[CG[TCTGAGGCCAGGAG[C

G]CTG[CG[A[CG[GAGCCTTGAC[CG[C[CG[TTGCC[CG[GCCCTCTCC[CG[[CG[CAGCCC[CG[GGCTTC[CG[CAG

GTACCTGTGCT[CG[CCCC[CG[GGAAGGGGCCT[CG[CAGG[CG[AATCTCCAGTTT[CG[AGTGTGCC[CG[GTCCCT

GGGTT[G[CT[G[[G[G[CG[ACCCCAC[CG[CC[CG[CCTTAGATGAGAAGGCAG[CG[CTCCAGCCT[CG[TCC

TCA[G[[G[CCCC[G[GGG[G[CCCTAGCTGCTT[G[[CG[G[CG[A[CG[ACACA[CG[[CG[CTCCC[CG[CA

G[CG[GGCTCTGGGCTGAG

SEQ ID NO: 799

GGGAAGTAAA[CG[GCCCCAA[CG[CAAGCCTGACTG[CG[AGA[CG[TGCCCAAGGGAGGTAGGT[CG[AATGAAG

AGGGTTGTGTGAGTTTTG[CG[[CG[GGCAGG[CG[GGATAA[CG[GAGGAGGGAGGCC[CG[[CG[GC[CG[AGGCT[C

GGG[G[GG[G[GGGGGGGGGGGG[G[GGGTT[G[[G[G[CG[[CG[CACTCCCAGGCAGGCCC[CG[CCCC

CT[CG[GC[CG[GCTGTG[CG[[CG[CTGATTGGCCCCTGC[CG[GCCT[CG[[CG[CTCCCT[CG[CTC[CG[GGTTGG[CG[

GGAGACCTTAGAG[CG[GGTAC[CG[CTGCTGGCTAG[CG]AC[CG[A[CG[[AGCAAC[CG[TCTGAGGCCAGGAG[C

GCT[G[[G[GAGCCTTGAC[G[[CG[TTGCC[CG[GCCCTCTCC[CG[[CG[CAGCCC[CG[GGCTTC[CG[CAG

GTACCTGTGCT[CG[CCCC[CG[GGAAGGGGCCT[CG[CAGG[CG[AATCTCCAGTTT[CG[AGTGTGCC[CG[GTCCCT

GGGTT[G[CT[G[[G[G[CG[ACCCCAC[CG[CC[CG[CCTTAGATGAGAAGGCAG[CG[CTCCAGCCT[CG[TCC

TCA[G[[G[CCCC[G[TGGG[CG[CCCTCAGCTGCCTT[G[[CG[G[CG[A[CG[ACACA[CG[[CG[CTCCC[CG[CA

G[CG[GGCTCTGGGCTGAG

SEQ ID NO: 800

[G[[G[GGG[G[[G[[G[[CG[C[CG[CAAG[CG[CCCCCTGCAG[CG[[CG[GGAAGC[CG[CCCTACAGC

GCATCTACAAGTTCATCAC[CG]AG[CG[CTTCCCCTTCTAC[CG[[CG[]ACAACCCCAAAAAGTGGCAGAACAGC

TAAGGGCAACTACTGGG[CG[CTTGACCCCAA[CG[[CG[GAGGACATGTT[CG[AGAG[CG[GCAGCTTCCTG[CG[

[G[[CG[CAAG[CG[CTTCAAG[CG[CT[CG[GACCTCTCCACCTACC[CG[GCTTACATGCA[G[A[CG[[CG[G[CG

[G[[G[[G[CCTCCAGTCTACTAC[G[[G[[CG[T[CG[CC[CG[GCCCTTGC[CG[[CG[TCTT[CG[GCCTGGT

TCCTGAG[CG[GC[CG[CTCAGCCCAGAGCTGGG

SEQ ID NO: 801

[G[[G[GGG[G[[G[GG[G[G[CG[C[CG[CAAG[CG[CCCCCTGCAG[CG[[CG[GGAAGC[CG[CCCTACAGC

GCATCTACAAGTTCATCAC[CG]AG[CG[CTTCCCCTTCTAC[CG[[CG[]ACAACCCCAAAAAGTGGCAGAACAGC

TAAGGGCAACTACTGGG[CG[CTTGACCCCAA[CG[[CG[GAGGACATGTT[CG[[AGAG[CG[GCAGCTTCCTG[CG[

[G[[CG[CAAG[CG[CTTCAAG[CG[CT[CG[GACCTCTCCACCTACC[CG[GCTTACATGA[G[A[CG[[CG[G[CG

[G[[C[[G[CCTCCAGTCTACTAC[G[[G[[CG[T[CG[CC[CG[GCCCTTGC[CG[[CG[TCTT[CG[GCCTGGT

TCCTGAG[CG[GC[CG[CTCAGCCCAGAGCTGGG

SEQ ID NO: 802

[CG[CC[CG[CCCCTC[CG[[CG[CTGGGCAGGGCCCCAGCAGTTGTCCTCCTCC[CG[CTCC[CG[GGCT[CG[GCC[CG[

GGCTCCATGGGGCTCCAGG[CG[GG[CG[GCAG[CG[GCCAG[CG[GTCCCCTGAAGGGC[CG]AGTCCTCCCTTCCC

TCCTCCTGCTCCTCCCC[G[[G[[CG[GT[CG[C[CG[AGGG[CG[AGAC[CG[ACTTTTGC[CG[CAAGGTGCAGG[CG[

GCC[G[GG[G[G[CG[G[CG[GCT[CG[GGAAA[CG[CATGGCCCTGGGGA[CG[[CG[G[CG]AGGACAGGAGAGCC[

CGGCTG[G[AGGT[G[GGACCCTAGGCCCAGGGG[G[GGT[G[[CG[G[CG[TG[CG[GGGCCCTGG[CG[GC

TCCTCTGTGTG[G[CTGGGCTC[G[GG[CG[[CG[[CG[GGATG[CG[GGCAG[CG[G[CG[GGA[CG[GTCCACA[CG[

GG[CG[GGG[CG[GC[CG[GGTTCACCCTCCTGTTCCACC[CG[[CG[GGGTCTCCTTCACT[CG[CAGC[CG[CCAT[CG[

CCAGCCCTCAGCT[CG[GTCC[CG[[GCTACACTTGAGAGTT[CG[GAGGATTAATGGGAAAATGTGTGTAAAGTG

CATTGGAAATGAGGGATTGT[CG[GCAGTTTCTCCTCCTGTTCCTCTGCC[[CG[[GCTCTTT[CG[TCTCCCTCCAG[

CG[CAAAGC

SEQ ID NO: 803

[CG[CC[CG[CCCCTC[CG[[CG[CTGGGCAGGGCCCCAGCAGTTGTCCTCCTCC[CG[CTCC[CG[GGCT[CG[GCC[CG[

GGCTCCATGGGGCTCCAGG[CG[GG[CG[GCAG[CG[GCCAG[CG[GTCCCCTGAAGGGC[CG[AGTCCTCCCTTCCC

TCCTCCTGCTCCCCCC[G[[G[[CG[GT[CG[C[CG[AGGG[CG[AGAC[CG[ACTTTTGC[CG[CAAGGTGCAGG[CG[

GC[G[[G[[G[G[CG[GCT[CG[GGAAA[CG[CATGGCCCTGGGGA[CG[[CG[G[CG]AGGACAGGAGAGCC[

TCCTCTGTGTG[G[CTGGGCT[G[GG[G[[CG[[CG[GGATG[CG[GGCAG[CG[G[CG[GGA[CG[GTCCACA[CG[

GG[CG[GGG[CG[GC[CG[GGTTCACCCTCCTGTTCCACC[CG[[CG[GGGTCTCCTTCACT[CG[CAGC[CG[CCAT[CG[

CCAGCCCTCAGCT[CG[GTCC[CG[[GCTACACTTGAGAGTT[CG[GAGGATTAATGGGAAAATGTGTGTAAAGTG

CATTGGAAATGAGGGATTGT[CG[GCAGTTTCTCCTCCTGTTCCTCTGCC[[CG[GCTCTTT[CG[TCTCCCTCCAG[

CG[CAAAGC

SEQ ID NO: 804

[CG[[CG[G[CG[G[CG[TTTCCTGGGGCAACAGCAATGG[CG[GCCT[CG[CTGTC[CG]AG[CG[GCTCTTCT[CG[CTGG

AGCTGCTGGTGGACTGGGTG[[CG[[TTTGGAAGCC[CG[GCTGCTGC[CG[TCCCC[CG[CTGC[CG[CAGTGGAGCA

GGAGGAGGAAGAGGAGGAAAAGGGGGGGGAGGCCT[G[[G[[CG[[CG[[CG[GTCTGTGCCC[CG[C[CG[

G[C[CG[AAC[CG[TGGCC[CG[GTGTCATC[CG[CTT[CG[GT[CG[[CG[[GCAAGTCCTGCCTCTTC[CG[CCTGCAGC

CTGCTACCCTGCACTGC[CG[GCTCCTG[CG[GACCC[CG[CTTGCCACCTTGCTGCTGCAGCTGCCCCCTGGG[CG

]CC[CG[A[CG[CCCACCCCACAGCTCCTGGGGGCCTG[CG[ACATTT[CG[CTGGCCAC[CG[CAG[CG[CACAGGGT[

CG]TGGGGC[CG[GC[CG[CCTC[CG[GATGCTCCCAC[CG[TCAC[CG[GGGA[CG[TTTCCCCCTGCATAAT[CG[AGT

GGG[CG[AG[CG[GACTGGGGACATTGCACTGGCCTAC[CG[CCTGACTGACCTGGGAAGC[CG[CCTGCTGAGCC

A

SEQ ID NO: 805

[CG[[CG[G[CG[G[CG[TTTCCTGGGGCAACAGCAATGG[CG[GCCT[CG[CTGTC[CG[AG[CG[GCTCTTCT[CG[CTGG

AGCTGCTGGTGGACTGGGTG[[CG[[TTTGGAAGCC[CG[GCTGCTGC[CG[TCCCC[CG[CTGC[CG[CAGTGGAGCA

GGAGGAGGAAGAGGAGGAAAAGGAGAGGGGGAGGCT[G[[CG[[CG[[CG[[CG[GTCTGTGCCC[CG[C[CG[

G[C[CG[AAC[CG[TGGCC[CG[GTGTCATC[CG[CTT[CG[GT[CG[[[CG[[GCAAGTCCTGCCTCTTC[CG[CCTGCAGC

CTGCTACCCTGCACTGC[CG[GCTCCTG[CG[GACCC[[CG[CTTGCCACCTTGCTGCTGCAGCTGCCCCCTGGG[CG

]CC[CG[A[CG[CCCACCCCACAGCTCCTGGGGGCCTG[CG[ACATTT[CG[CTGGCCAC[CG[CAG[CG[CACAGGGT[

CG[TGGGGC[CG[GC[CG[CCTC[CG[GATGCTCCCAC[CG[TCAC[CG[GGGA[CG[TTTCCCCCTGCATAAT[CG[AGT

GGG[CG[AG[CG[GACTGGGGACATTGCACTGGCCTAC[CG[CCTGACTGACCTGGGAAGC[CG[CCTGCTGAGCC

A

SEQ ID NO: 806

GG[G[[CG[G[CG[CTAGG[CG[GC[CG[CTGGC[CG[TT[CG[G[CG[ATGGCCTCTGCAAGCTCAGCAGCTT[CG[[CG

CTGG[G[GGCA[G[[G[CTG[G[[CG[GG[CG[[CG[CTGCTGCTGG[CG[GGCATGAG[CG[TGGAC[CG[CTACCT

GGC[G[TGGTGAAGCTGCT[G[AGG[G[AGGCCACTG[G[CACCC[CG[[CG[CTG[CG[[CG[CTGGCCT[CG[TGC

TG[CG[G[CG[TCTGGGC[CG[TGG[CG[CTGCTGGC[CG[GCCTGCCCTCCCTGGTCTAC[CG[GGGGTTGCAGCCCCT

GCCTGGGGGCCAGGACAGCCAGTG[CG[G[CG]AGGAGCCCTCCCA[[CG[[CCTTCCAGGGCCTCAGCTTGCTGCT

GCTGCTGCTGACCTT[CG[TGCTGCCCCTGGT[CG[TCACCCTCTTCTGCTACTGC[CG[CATCT[CG[[CG[C[CG[CCT

[G[[G[GC[G[C[CG[CA[CG[TGGGT[CG[GGCC[CG[GAGGAACT[CG[CTG[CG[CATCATCTT[CG[CCAT[CG

]AGAGCA[CG[TTTGTGGGCTCCTGGCTGCCCTTCAG[CG[CCCTG[CG[GGC[CG[TCTTCCACCTGG[CG[[CG[TCTG

GGGG[CG[CTGC[CG[CTGC[CG[TGCCCCCTGCTGCTGG[CG[CTG[CG[CTGGGGCCTCACCATTGCCACCTGCCTG

GCCTT

SEQ ID NO: 807

CAAGTGGCTCAGAAGTTCA[CG[GG[CG[GCAT[CG[GAAACAAACTGTG[CG[GTGAGTGCCCAGGGAC[CG[GGG[

CG[GCCAAGGT[CG[GCC[CG[[CG[GGGTCCAAGCAGTCTTCTCACCTC[CG[CATCCCAGTCAG[CG[GAGT[CG[GG

GTTTCCTGGCTG[CG[GGTAGG[CG[GGAG[CG[[AGGGAGC[CG[GGCC[CG[G[CG[GAGGATTGA[CG]AGGCC[CG

][CG[TT[CG[GTGTCCTTACCCAGCCCTGCTCTA[CG[GAGA[CG[C[CG[AGAAGC[CG[G[CG[GAGAG[CG[G[CG[G

GAGCCAACCCC[G[[G[[G[[CG[CC[CG[GAAGGC[CG[CCTG[CG[CCTG[CG[ACCAGAAGCCCTGCAGC

TGCTCCAAAGTGGATGTCAACTA[CG[[CG[TTTCTCCATGCAACAGGTAAAGACTCAG[CG[[GGGAGCCC[CG[G

GACAGGGG[CG[T[CG]AGGTGGCAG[CG[GAGG[CG[[GGACCTGCCAGAATCTTCAGATAAAAG[CG[AGAAATG

[CG[GGACCTGCC[CG[CTGGGTCCAAGCCCC[CG[AACCTGGCCT[CG[GAGCTCCAAGAGGGCTCTGAGGC[CG[

TGG[CG[CTCTTC

SEQ ID NO: 808

CC[CG[[CG[GGGTCCAAGCAGTCTTCTCACCTC[CG[CATCCCAGTCAG[CG[GAGT[CG[GGGTTTCCTGGCTG[CG[

GGTAGG[CG[GGAG[CG[AGGGAGC[CG[GGCC[CG[G[CG[GAGGATTGA[CG]AGGCC[CG[[CG[TT[CG[GTGTCC

TTACCCAGCCCTGCTCTA[CG[GAGA[CG[C[CG]AGAAGC[CG[G[CG[GAGAG[CG[G[CG[GGAGCCAACCCC[CG[[

GGG[G[[CG[CC[CG[GAAGGC[CG[CCTG[CG[CCTG[CG[ACCAGAAGCCCTGCAGCTGCTCCAAAGTGGA

TGTCAACTA[CG[[CG[TTTCTCCATGCAACAGGTAAAGACTCAG[CG[[GGGAGCCC[CG[GGG[CG[CCCCTGCCC

CTCTCTCTGCCC[G[CCCC[G[[CG[GC[CG[GTG[CG[GGTC[CG[G[CG[CTGAGAGC[CG[GACAGGGG[CG[T[CG

]AGGTGGCAG[CG[GAGG[CG[GGACCTGCCAGAATCTTCAGATAAAAG[CG[AGAAATG[CG[[GGACCTGCC[C

G[CTGGGTCCAAGCCCC[CG[AACCTGGCCT[CG[GAGCTCCAAGAGGGCTCTGAGGC[CG[TGG[CG[CTCTTCCCC

CAG[G[[G[GCCCTTGGGATGG[G[GGTGGC[CG[A[CG[ATCCAGG[CG[CT[CG[TG[CG[CTCACTGAAT[CG[AT

GA[CG[GCTGGCTTC

Cancer-Related CpGs for Analysis

In any of the assays described herein, in a sample which has been taken from an individual, the sample comprises a population of DNA molecules.

The assay of the invention further comprises determining in the population of DNA molecules in the sample the methylation status of a panel of:

- (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
- (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG

A cancer index value is then derived based on the methylation status of the one or more CpGs in the panel, which is used to assess the presence, absence or development of cancer in the individual based on the cancer index value.

In any of the assays described herein, in DNA derived from cells in the sample the methylation status of each CpG in a panel of

- (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
- (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG;
- is determined.

In any of the assays described herein, in DNA derived from cells in the sample the methylation status of each CpG in a panel of one or more CpGs from a panel of CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, is determined.

In any of the assays described herein, the panel of one or more CpGs may comprise at least 50 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having a receiver operating characteristics (ROC) area under the curve (AUC) of at least 0.92. The panel of one or more CpGs may comprise at least the CpGs identified in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having an ROC AUC of at least 0.95.

In any of the assays described herein, the panel of one or more CpGs may comprise at least 100 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having a ROC AUC of at least 0.93. The panel of one or more CpGs may comprise at least the CpGs identified in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having a ROC AUC of at least 0.96.

In any of the assays described herein, the panel of one or more CpGs may comprise at least 150 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having a ROC AUC of at least 0.93. The panel of one or more CpGs may comprise at least the CpGs identified in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having a ROC AUC of at least 0.96.

In any of the assays described herein, the panel of one or more CpGs may comprise at least 200 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93. The panel of one or more CpGs may comprise at least the CpGs identified in SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, preferably wherein the assay is characterised as having a ROC AUC of at least 0.96.

In any of the assays described herein, the panel of one or more CpGs may comprise at least the 500 CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and further wherein the assay is characterised as having a ROC AUC of at least 0.97.

In any of the above-described assays, the assay may be characterised as having a ROC AUC of 0.60 or more, 0.61 or more, 0.62 or more, 0.63 or more, 0.64 or more, 0.65 or more, 0.66 or more, 0.67 or more, 0.68 or more, 0.69 or more, 0.70 or more, 0.71 or more, 0.72 or more, 0.73 or more, 0.74 or more, 0.75 or more, 0.76 or more, 0.77 or more, 0.78 or more, 0.79 or more, 0.80 or more, 0.81 or more, 0.82 or more, 0.83 or more, 0.84 or more, 0.85 or more, 0.86 or more, 0.87 or more, 0.88 or more, 0.89 or more or 0.90 or more.

- 1, the assay is characterised as having an ROC AUC (AUC) of at least 0.95, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62;
- 2, the assay is characterised as having an AUC of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62;
- 3 the assay is characterised as having an ROC AUC (AUC) of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62;
- 4, the assay is characterised as having an ROC AUC (AUC) of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62;
- 5, the assay is characterised as having an ROC AUC (AUC) of at least 0.95, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62;
- 6, the assay is characterised as having an ROC AUC (AUC) of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62;
- 7, the assay is characterised as having an ROC AUC (AUC) of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62;
- 8 the assay is characterised as having an ROC AUC (AUC) of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62;
- 9, the assay is characterised as having an ROC AUC (AUC) of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62; or
- 10, the assay is characterised as having an ROC AUC (AUC) of at least 0.92, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62.

In any of the assays described herein, the panel of one or more CpGs may comprise:

- 1. at least 50 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.95, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62;
- 2. at least 100 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62;
- 3. at least 150 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62;
- 4. at least 200 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62;
- 5. at least 250 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62;
- 6. at least 300 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62;
- 7. at least 350 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62;
- 8. at least 400 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.96, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62;
- 9. at least 450 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.97, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62; or
- 10. at least 500 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.97, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500.

In any of the assays described herein, the panel of one or more CpGs may comprise:

- 1. at least 50 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.92, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62;
- 2. at least 100 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62;
- 3. at least 150 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62;
- 4. at least 200 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62;
- 5. at least 250 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.93, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62;
- 6. at least 300 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62;
- 7. at least 350 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62;
- 8. at least 400 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.94, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62;
- 9. at least 450 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.95, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified in SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62; or
- 10. at least 500 CpGs selected from the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, preferably wherein the assay is characterised as having an AUC of at least 0.97, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500.

In any of the assays described herein, the step of determining the methylation status of the one or more CpGs in the panel may comprise determining the methylation status of one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein selected CpGs in each DMR are denoted by CG. The nucleotide sequences of the 308 DMRs are defined respectively by the nucleotide sequences of SEQ ID NO: 501 to 808 as set out in Table 1, accepting that variation in the nucleotide sequence of any given DMR may exist due to sequencing errors and/or variation between individuals. In each sequence shown below the cytosine of the CG dinucleotide motifs identified in square brackets and double square brackets is a cytosine of a CpG which may be included in a panel of CpGs when performing the assays of the invention.

The step of determining the methylation status of a panel of one or more CpGs may comprise determining a cancer index value of one or more of the CpGs denoted by CG within any one of the DMRs 1 to 308, or within any combination of two or more DMRs of 1 to 308.

The step of determining the methylation status of a panel of one or more CpGs may comprise determining a cancer index value of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more of the CpGs denoted by CG within any one of the DMRs 1 to 308, optionally within any combination of two or more DMRs of 1 to 308.

The panel of one or more CpGs may comprise two or more CpGs of the DMR(s), three or more CpGs of the DMR(s), four or more CpGs of the DMR(s) or all CpGs of the DMR(s).

The step of determining the methylation status of a panel of one or more CpGs may comprise determining a cancer index value of least two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more of the CpGs denoted by CG within any one of the DMRs 1 to 308, or within:

- a. any combination of two, three, four, five, six, seven, eight, or nine or more of DMRs 1 to 308;
- b. any combination of ten, twenty, thirty, forty, fifty, sixty, seventy, eighty, or ninety or more of DMRs 1 to 308;
- c. all 308 of DMRs 1 to 308;
- d. one DMR defined by SEQ ID NO: 501, two DMRs defined by SEQ ID NOs: 501 to 502, three DMRs defined by SEQ ID NOs: 501 to 503, four DMRs defined by SEQ ID NOs: 501 to 504, five DMRs defined by SEQ ID NOs: 501 to 505, six DMRs defined by SEQ ID NOs: 501 to 506, seven DMRs defined by SEQ ID NOs: 501 to 507, eight DMRs defined by SEQ ID NOs: 501 to 508, or nine DMRs defined by SEQ ID NOs: 501 to 509; or
- e. ten DMRs defined by SEQ ID NOs: 501 to 510, twenty DMRs defined by SEQ ID NOs: 501 to 520, thirty DMRs defined by SEQ ID NOs: 501 to 530, forty DMRs defined by SEQ ID NOs: 501 to 540, fifty DMRs defined by SEQ ID NOs: 501 to 550, sixty DMRs defined by SEQ ID NOs: 501 to 560, seventy DMRs defined by SEQ ID NOs: 501 to 570, eighty DMRs defined by SEQ ID NOs: 501 to 580, or ninety DMRs defined by SEQ ID NOs: 501 to 590; or
- f. ten DMRs defined by SEQ ID NOs: 501 to 510, SEQ ID NOs: 511 to 520, SEQ ID NOs: 521 to 530, SEQ ID NOs: 531 to 540, SEQ ID NOs: 541 to 550, SEQ ID NOs: 551 to 560, SEQ ID NOs: 561 to 570, SEQ ID NOs: 571 to 580, SEQ ID NOs: 581 to 590, SEQ ID NOs: 591 to 600, SEQ ID NOs: 601 to 610, SEQ ID NOs: 611 to 620, SEQ ID NOs: 621 to 630, SEQ ID NOs: 631 to 640, SEQ ID NOs: 641 to 650, SEQ ID NOs: 651 to 660, SEQ ID NOs: 661 to 670, SEQ ID NOs: 671 to 680, SEQ ID NOs: 681 to 690, SEQ ID NOs: 691 to 700, SEQ ID NOs: 701 to 710, SEQ ID NOs: 711 to 720, SEQ ID NOs: 721 to 730, SEQ ID NOs: 731 to 740, SEQ ID NOs: 741 to 750; SEQ ID NOs: 751 to 760; SEQ ID NOs: 761 to 770; SEQ ID NOs: 771 to 780; SEQ ID NOs: 781 to 790; SEQ ID NOs: 791 to 800 or SEQ ID NOs: 801 to 808.

In any of the assays described herein, the step of determining the methylation status of a panel of one or more CpGs may comprise determining the methylation status of one or more CpGs within any one or more DMRs selected from the group of DMRs consisting of DMRs 1 to 308 as defined by SEQ ID NOs 501 to 808, including:

- 1. one or more CpGs within DMR 1 as defined by SEQ ID NO: 501 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.911, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 2. one or more CpGs within DMR 2 as defined by SEQ ID NO: 502 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.903, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 3. one or more CpGs within DMR 3 as defined by SEQ ID NO: 503 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 4. one or more CpGs within DMR 4 as defined by SEQ ID NO: 504 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 5. one or more CpGs within DMR 5 as defined by SEQ ID NO: 505 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 6. one or more CpGs within DMR 6 as defined by SEQ ID NO: 506 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.897, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 7. one or more CpGs within DMR 7 as defined by SEQ ID NO: 507 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.894, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 8. one or more CpGs within DMR 8 as defined by SEQ ID NO: 508 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.894, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 9. one or more CpGs within DMR 9 as defined by SEQ ID NO: 509 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.892, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 10. one or more CpGs within DMR 10 as defined by SEQ ID NO: 510 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.891, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 11. one or more CpGs within DMR 11 as defined by SEQ ID NO: 511 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.89, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 12. one or more CpGs within DMR 12 as defined by SEQ ID NO: 512 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.888, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 13. one or more CpGs within DMR 13 as defined by SEQ ID NO: 513 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.888, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 14. one or more CpGs within DMR 14 as defined by SEQ ID NO: 514 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.888, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 15. one or more CpGs within DMR 15 as defined by SEQ ID NO: 515 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.888, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 16. one or more CpGs within DMR 16 as defined by SEQ ID NO: 516 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.888, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 17. one or more CpGs within DMR 17 as defined by SEQ ID NO: 517 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 18. one or more CpGs within DMR 18 as defined by SEQ ID NO: 518 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 19. one or more CpGs within DMR 19 as defined by SEQ ID NO: 519 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.885, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 20. one or more CpGs within DMR 20 as defined by SEQ ID NO: 520 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.884, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 21. one or more CpGs within DMR 21 as defined by SEQ ID NO: 521 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.882, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 22. one or more CpGs within DMR 22 as defined by SEQ ID NO: 522 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.881, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 23. one or more CpGs within DMR 23 as defined by SEQ ID NO: 523 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.88, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 24. one or more CpGs within DMR 24 as defined by SEQ ID NO: 524 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.879, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 25. one or more CpGs within DMR 25 as defined by SEQ ID NO: 525 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.878, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 26. one or more CpGs within DMR 26 as defined by SEQ ID NO: 526 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.878, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 27. one or more CpGs within DMR 27 as defined by SEQ ID NO: 527 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.877, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 28. one or more CpGs within DMR 28 as defined by SEQ ID NO: 528 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.875, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 29. one or more CpGs within DMR 29 as defined by SEQ ID NO: 529 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.875, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 30. one or more CpGs within DMR 30 as defined by SEQ ID NO: 530 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 31. one or more CpGs within DMR 31 as defined by SEQ ID NO: 531 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 32. one or more CpGs within DMR 32 as defined by SEQ ID NO: 532 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 33. one or more CpGs within DMR 33 as defined by SEQ ID NO: 533 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 34. one or more CpGs within DMR 34 as defined by SEQ ID NO: 534 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.873, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 35. one or more CpGs within DMR 35 as defined by SEQ ID NO: 535 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.873, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 36. one or more CpGs within DMR 36 as defined by SEQ ID NO: 536 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.873, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 37. one or more CpGs within DMR 37 as defined by SEQ ID NO: 537 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.873, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 38. one or more CpGs within DMR 38 as defined by SEQ ID NO: 538 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.873, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 39. one or more CpGs within DMR 39 as defined by SEQ ID NO: 539 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.872, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 40. one or more CpGs within DMR 40 as defined by SEQ ID NO: 540 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.872, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 41. one or more CpGs within DMR 41 as defined by SEQ ID NO: 541 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.871, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 42. one or more CpGs within DMR 42 as defined by SEQ ID NO: 542 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.871, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 43. one or more CpGs within DMR 43 as defined by SEQ ID NO: 543 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.87, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 44. one or more CpGs within DMR 44 as defined by SEQ ID NO: 544 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.87, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 45. one or more CpGs within DMR 45 as defined by SEQ ID NO: 545 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.869, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 46. one or more CpGs within DMR 46 as defined by SEQ ID NO: 546 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.869, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 47. one or more CpGs within DMR 47 as defined by SEQ ID NO: 547 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.869, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 48. one or more CpGs within DMR 48 as defined by SEQ ID NO: 548 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.867, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 49. one or more CpGs within DMR 49 as defined by SEQ ID NO: 549 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.867, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 50. one or more CpGs within DMR 50 as defined by SEQ ID NO: 550 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.867, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 51. one or more CpGs within DMR 551 as defined by SEQ ID NO: 551 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.867, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 52. one or more CpGs within DMR 52 as defined by SEQ ID NO: 552 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.865, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 53. one or more CpGs within DMR 53 as defined by SEQ ID NO: 553 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.864, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 54. one or more CpGs within DMR 54 as defined by SEQ ID NO: 554 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.864, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 55. one or more CpGs within DMR 55 as defined by SEQ ID NO: 555 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 56. one or more CpGs within DMR 56 as defined by SEQ ID NO: 556 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 57. one or more CpGs within DMR 57 as defined by SEQ ID NO: 557 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 58. one or more CpGs within DMR 58 as defined by SEQ ID NO: 558 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 59. one or more CpGs within DMR 59 as defined by SEQ ID NO: 559 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 60. one or more CpGs within DMR 60 as defined by SEQ ID NO: 560 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.861, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 61. one or more CpGs within DMR 61 as defined by SEQ ID NO: 561 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.861, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 62. one or more CpGs within DMR 62 as defined by SEQ ID NO: 562 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.861, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 63. one or more CpGs within DMR 63 as defined by SEQ ID NO: 563 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.86, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 64. one or more CpGs within DMR 64 as defined by SEQ ID NO: 564 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.86, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 65. one or more CpGs within DMR 65 as defined by SEQ ID NO: 565 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.86, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 66. one or more CpGs within DMR 66 as defined by SEQ ID NO: 566 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.86, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 67. one or more CpGs within DMR 67 as defined by SEQ ID NO: 567 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 68. one or more CpGs within DMR 68 as defined by SEQ ID NO: 568 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 69. one or more CpGs within DMR 69 as defined by SEQ ID NO: 569 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 70. one or more CpGs within DMR 70 as defined by SEQ ID NO: 570 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 71. one or more CpGs within DMR 71 as defined by SEQ ID NO: 571 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 72. one or more CpGs within DMR 72 as defined by SEQ ID NO: 572 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.858, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 73. one or more CpGs within DMR 73 as defined by SEQ ID NO: 573 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.857, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 74. one or more CpGs within DMR 74 as defined by SEQ ID NO: 574 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.857, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 75. one or more CpGs within DMR 75 as defined by SEQ ID NO: 575 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.856, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 76. one or more CpGs within DMR 76 as defined by SEQ ID NO: 576 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.856, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 77. one or more CpGs within DMR 77 as defined by SEQ ID NO: 577 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.856, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 78. one or more CpGs within DMR 78 as defined by SEQ ID NO: 578 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.855, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 79. one or more CpGs within DMR 79 as defined by SEQ ID NO: 579 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.855, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 80. one or more CpGs within DMR 80 as defined by SEQ ID NO: 580 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.855, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 81. one or more CpGs within DMR 81 as defined by SEQ ID NO: 581 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.854, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 82. one or more CpGs within DMR 82 as defined by SEQ ID NO: 582 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.854, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 83. one or more CpGs within DMR 83 as defined by SEQ ID NO: 583 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.854, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 84. one or more CpGs within DMR 84 as defined by SEQ ID NO: 584 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.854, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 85. one or more CpGs within DMR 85 as defined by SEQ ID NO: 585 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 86. one or more CpGs within DMR 86 as defined by SEQ ID NO: 586 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 87. one or more CpGs within DMR 87 as defined by SEQ ID NO: 587 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 88. one or more CpGs within DMR 88 as defined by SEQ ID NO: 588 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 89. one or more CpGs within DMR 89 as defined by SEQ ID NO: 589 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.852, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 90. one or more CpGs within DMR 90 as defined by SEQ ID NO: 590 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.852, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 91. one or more CpGs within DMR 91 as defined by SEQ ID NO: 591 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.852, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 92. one or more CpGs within DMR 92 as defined by SEQ ID NO: 592 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 93. one or more CpGs within DMR 93 as defined by SEQ ID NO: 593 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 94. one or more CpGs within DMR 94 as defined by SEQ ID NO: 594 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 95. one or more CpGs within DMR 95 as defined by SEQ ID NO: 595 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 96. one or more CpGs within DMR 96 as defined by SEQ ID NO: 596 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.85, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 97. one or more CpGs within DMR 97 as defined by SEQ ID NO: 597 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 98. one or more CpGs within DMR 98 as defined by SEQ ID NO: 598 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 99. one or more CpGs within DMR 99 as defined by SEQ ID NO: 599 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 100. one or more CpGs within DMR 100 as defined by SEQ ID NO: 600 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 101. one or more CpGs within DMR 101 as defined by SEQ ID NO: 601 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 102. one or more CpGs within DMR 102 as defined by SEQ ID NO: 602 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.848, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 103. one or more CpGs within DMR 103 as defined by SEQ ID NO: 603 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.847, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 104. one or more CpGs within DMR 104 as defined by SEQ ID NO: 604 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.847, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 105. one or more CpGs within DMR 105 as defined by SEQ ID NO: 605 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.847, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 106. one or more CpGs within DMR 106 as defined by SEQ ID NO: 606 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.847, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 107. one or more CpGs within DMR 107 as defined by SEQ ID NO: 607 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.846, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 108. one or more CpGs within DMR 108 as defined by SEQ ID NO: 608 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.845, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 109. one or more CpGs within DMR 109 as defined by SEQ ID NO: 609 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.845, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 110. one or more CpGs within DMR 110 as defined by SEQ ID NO: 610 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.845, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 111. one or more CpGs within DMR 111 as defined by SEQ ID NO: 611 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.845, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 112. one or more CpGs within DMR 112 as defined by SEQ ID NO: 612 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.844, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 113. one or more CpGs within DMR 113 as defined by SEQ ID NO: 613 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.843, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 114. one or more CpGs within DMR 114 as defined by SEQ ID NO: 614 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.843, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 115. one or more CpGs within DMR 115 as defined by SEQ ID NO: 615 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.842, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 116. one or more CpGs within DMR 116 as defined by SEQ ID NO: 616 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.842, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 117. one or more CpGs within DMR 117 as defined by SEQ ID NO: 617 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.841, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 118. one or more CpGs within DMR 118 as defined by SEQ ID NO: 618 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.841, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 119. one or more CpGs within DMR 119 as defined by SEQ ID NO: 619 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.841, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 120. one or more CpGs within DMR 120 as defined by SEQ ID NO: 620 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.84, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 121. one or more CpGs within DMR 121 as defined by SEQ ID NO: 621 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.839, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 122. one or more CpGs within DMR 122 as defined by SEQ ID NO: 622 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.839, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 123. one or more CpGs within DMR 123 as defined by SEQ ID NO: 623 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.838, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 124. one or more CpGs within DMR 124 as defined by SEQ ID NO: 624 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.838, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 125. one or more CpGs within DMR 125 as defined by SEQ ID NO: 625 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.838, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 126. one or more CpGs within DMR 126 as defined by SEQ ID NO: 626 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.835, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 127. one or more CpGs within DMR 127 as defined by SEQ ID NO: 627 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.835, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 128. one or more CpGs within DMR 128 as defined by SEQ ID NO: 628 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.833, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 129. one or more CpGs within DMR 129 as defined by SEQ ID NO: 629 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.832, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 130. one or more CpGs within DMR 130 as defined by SEQ ID NO: 630 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.832, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 131. one or more CpGs within DMR 131 as defined by SEQ ID NO: 631 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.832, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 132. one or more CpGs within DMR 132 as defined by SEQ ID NO: 632 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.831, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 133. one or more CpGs within DMR 133 as defined by SEQ ID NO: 633 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.831, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 134 one or more CpGs within DMR 134 as defined by SEQ ID NO: 634 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.83, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 135. one or more CpGs within DMR 135 as defined by SEQ ID NO: 635 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.83, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 136. one or more CpGs within DMR 136 as defined by SEQ ID NO: 636 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.83, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 137. one or more CpGs within DMR 137 as defined by SEQ ID NO: 637 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.829, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 138. one or more CpGs within DMR 138 as defined by SEQ ID NO: 638 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.829, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 139. one or more CpGs within DMR 139 as defined by SEQ ID NO: 639 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.829, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 140. one or more CpGs within DMR 140 as defined by SEQ ID NO: 640 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.829, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 141. one or more CpGs within DMR 141 as defined by SEQ ID NO: 641 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.828, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 142. one or more CpGs within DMR 142 as defined by SEQ ID NO: 642 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.828, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 143. one or more CpGs within DMR 143 as defined by SEQ ID NO: 643 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.828, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 144. one or more CpGs within DMR 144 as defined by SEQ ID NO: 644 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.828, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 145. one or more CpGs within DMR 145 as defined by SEQ ID NO: 645 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.828, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 146. one or more CpGs within DMR 146 as defined by SEQ ID NO: 646 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.825, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 147. one or more CpGs within DMR 147 as defined by SEQ ID NO: 647 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.825, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 148. one or more CpGs within DMR 148 as defined by SEQ ID NO: 648 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.824, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 149. one or more CpGs within DMR 149 as defined by SEQ ID NO: 649 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.824, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 150. one or more CpGs within DMR 150 as defined by SEQ ID NO: 650 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.824, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 151. one or more CpGs within DMR 151 as defined by SEQ ID NO: 651 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.824, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 152. one or more CpGs within DMR 152 as defined by SEQ ID NO: 652 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.823, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 153. one or more CpGs within DMR 153 as defined by SEQ ID NO: 653 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.82, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 154. one or more CpGs within DMR 154 as defined by SEQ ID NO: 654 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.82, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 155. one or more CpGs within DMR 155 as defined by SEQ ID NO: 655 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.819, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 156. one or more CpGs within DMR 156 as defined by SEQ ID NO: 656 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.816, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 157. one or more CpGs within DMR 157 as defined by SEQ ID NO: 657 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.816, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 158. one or more CpGs within DMR 158 as defined by SEQ ID NO: 658 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.814, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 159. one or more CpGs within DMR 159 as defined by SEQ ID NO: 659 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.814, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 160. one or more CpGs within DMR 160 as defined by SEQ ID NO: 660 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.814, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 161. one or more CpGs within DMR 161 as defined by SEQ ID NO: 661 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.813, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 162. one or more CpGs within DMR 162 as defined by SEQ ID NO: 662 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.812, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 163. one or more CpGs within DMR 163 as defined by SEQ ID NO: 663 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.811, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 164. one or more CpGs within DMR 164 as defined by SEQ ID NO: 664 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.811, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 165. one or more CpGs within DMR 165 as defined by SEQ ID NO: 665 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.81, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 166 one or more CpGs within DMR 166 as defined by SEQ ID NO: 666 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.809, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 167. one or more CpGs within DMR 167 as defined by SEQ ID NO: 667 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.808, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 168. one or more CpGs within DMR 168 as defined by SEQ ID NO: 668 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.807, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 169. one or more CpGs within DMR 169 as defined by SEQ ID NO: 669 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.807, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 170. one or more CpGs within DMR 170 as defined by SEQ ID NO: 670 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.806, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 171. one or more CpGs within DMR 171 as defined by SEQ ID NO: 671 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.806, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 172. one or more CpGs within DMR 172 as defined by SEQ ID NO: 672 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.805, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 173. one or more CpGs within DMR 173 as defined by SEQ ID NO: 673 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.805, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 174. one or more CpGs within DMR 174 as defined by SEQ ID NO: 674 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.803, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 175. one or more CpGs within DMR 175 as defined by SEQ ID NO: 675 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.803, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 176. one or more CpGs within DMR 176 as defined by SEQ ID NO: 676 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.801, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 177. one or more CpGs within DMR 177 as defined by SEQ ID NO: 677 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.799, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 178. one or more CpGs within DMR 178 as defined by SEQ ID NO: 678 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.799, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 179. one or more CpGs within DMR 179 as defined by SEQ ID NO: 679 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.799, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 180. one or more CpGs within DMR 180 as defined by SEQ ID NO: 680 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.799, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 181. one or more CpGs within DMR 181 as defined by SEQ ID NO: 681 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.798, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 182. one or more CpGs within DMR 182 as defined by SEQ ID NO: 682 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.797, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 183. one or more CpGs within DMR 183 as defined by SEQ ID NO: 683 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.796, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 184. one or more CpGs within DMR 184 as defined by SEQ ID NO: 684 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.793, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 185. one or more CpGs within DMR 185 as defined by SEQ ID NO: 685 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.792, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 186. one or more CpGs within DMR 186 as defined by SEQ ID NO: 686 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.792, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 187. one or more CpGs within DMR 187 as defined by SEQ ID NO: 687 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.791, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 188. one or more CpGs within DMR 188 as defined by SEQ ID NO: 688 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.79, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 189. one or more CpGs within DMR 189 as defined by SEQ ID NO: 689 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.79, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 190. one or more CpGs within DMR 190 as defined by SEQ ID NO: 690 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.789, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 191. one or more CpGs within DMR 191 as defined by SEQ ID NO: 691 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.788, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 192. one or more CpGs within DMR 192 as defined by SEQ ID NO: 692 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.788, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 193. one or more CpGs within DMR 193 as defined by SEQ ID NO: 693 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.787, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 194. one or more CpGs within DMR 194 as defined by SEQ ID NO: 694 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.787, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 195. one or more CpGs within DMR 195 as defined by SEQ ID NO: 695 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.787, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 196. one or more CpGs within DMR 196 as defined by SEQ ID NO: 696 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.784, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 197. one or more CpGs within DMR 197 as defined by SEQ ID NO: 697 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.784, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 198. one or more CpGs within DMR 198 as defined by SEQ ID NO: 698 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.783, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 199. one or more CpGs within DMR 199 as defined by SEQ ID NO: 699 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.781, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 200. one or more CpGs within DMR 200 as defined by SEQ ID NO: 700 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.78, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 201. one or more CpGs within DMR 201 as defined by SEQ ID NO: 701 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 202. one or more CpGs within DMR 202 as defined by SEQ ID NO: 702 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 203. one or more CpGs within DMR 203 as defined by SEQ ID NO: 703 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 204. one or more CpGs within DMR 204 as defined by SEQ ID NO: 704 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 205. one or more CpGs within DMR 205 as defined by SEQ ID NO: 705 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 206. one or more CpGs within DMR 206 as defined by SEQ ID NO: 706 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 207. one or more CpGs within DMR 207 as defined by SEQ ID NO: 707 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.777, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 208. one or more CpGs within DMR 208 as defined by SEQ ID NO: 708 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.776, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 209. one or more CpGs within DMR 209 as defined by SEQ ID NO: 209 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.776, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 210. one or more CpGs within DMR 210 as defined by SEQ ID NO: 710 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.776, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 211. one or more CpGs within DMR 211 as defined by SEQ ID NO: 711 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.775, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 212. one or more CpGs within DMR 212 as defined by SEQ ID NO: 712 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.775, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 213. one or more CpGs within DMR 213 as defined by SEQ ID NO: 713 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.775, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 214. one or more CpGs within DMR 214 as defined by SEQ ID NO: 714 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.771, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 215. one or more CpGs within DMR 215 as defined by SEQ ID NO: 715 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.769, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 216. one or more CpGs within DMR 216 as defined by SEQ ID NO: 716 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.767, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 217. one or more CpGs within DMR 217 as defined by SEQ ID NO: 717 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.762, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 218. one or more CpGs within DMR 218 as defined by SEQ ID NO: 718 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.76, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 219. one or more CpGs within DMR 219 as defined by SEQ ID NO: 719 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.758, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 220. one or more CpGs within DMR 220 as defined by SEQ ID NO: 720 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.757, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 221. one or more CpGs within DMR 221 as defined by SEQ ID NO: 721 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.751, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 222. one or more CpGs within DMR 222 as defined by SEQ ID NO: 722 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.742, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 223. one or more CpGs within DMR 223 as defined by SEQ ID NO: 723 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.738, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 224 one or more CpGs within DMR 224 as defined by SEQ ID NO: 724 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.73, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 225. one or more CpGs within DMR 225 as defined by SEQ ID NO: 725 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.726, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 226. one or more CpGs within DMR 226 as defined by SEQ ID NO: 726 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.726, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 227. one or more CpGs within DMR 227 as defined by SEQ ID NO: 727 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.72, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 228. one or more CpGs within DMR 228 as defined by SEQ ID NO: 728 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.715, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 229. one or more CpGs within DMR 229 as defined by SEQ ID NO: 729 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.713, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 230. one or more CpGs within DMR 230 as defined by SEQ ID NO: 730 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.713, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 231. one or more CpGs within DMR 231 as defined by SEQ ID NO: 731 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.708, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 232. one or more CpGs within DMR 232 as defined by SEQ ID NO: 732 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.707, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 233. one or more CpGs within DMR 233 as defined by SEQ ID NO: 733 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.704, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 234. one or more CpGs within DMR 234 as defined by SEQ ID NO: 734 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.697, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 235. one or more CpGs within DMR 235 as defined by SEQ ID NO: 735 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.697, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 236. one or more CpGs within DMR 236 as defined by SEQ ID NO: 736 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.693, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 237. one or more CpGs within DMR 237 as defined by SEQ ID NO: 737 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.638, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 238. one or more CpGs within DMR 238 as defined by SEQ ID NO: 738 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.903, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 239. one or more CpGs within DMR 239 as defined by SEQ ID NO: 739 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.903, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 240. one or more CpGs within DMR 240 as defined by SEQ ID NO: 740 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 241. one or more CpGs within DMR 241 as defined by SEQ ID NO: 741 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 242. one or more CpGs within DMR 242 as defined by SEQ ID NO: 742 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 243. one or more CpGs within DMR 243 as defined by SEQ ID NO: 743 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 244. one or more CpGs within DMR 244 as defined by SEQ ID NO: 744 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 245. one or more CpGs within DMR 245 as defined by SEQ ID NO: 745 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.899, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 246. one or more CpGs within DMR 246 as defined by SEQ ID NO: 746 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.895, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 247. one or more CpGs within DMR 247 as defined by SEQ ID NO: 747 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.895, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 248. one or more CpGs within DMR 248 as defined by SEQ ID NO: 748 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.893, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 249. one or more CpGs within DMR 249 as defined by SEQ ID NO: 749 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.893, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 250. one or more CpGs within DMR 250 as defined by SEQ ID NO: 750 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.891, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 251. one or more CpGs within DMR 251 as defined by SEQ ID NO: 751 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.891, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 252. one or more CpGs within DMR 252 as defined by SEQ ID NO: 752 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 253. one or more CpGs within DMR 253 as defined by SEQ ID NO: 753 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 254. one or more CpGs within DMR 254 as defined by SEQ ID NO: 754 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 255. one or more CpGs within DMR 255 as defined by SEQ ID NO: 755 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.886, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 256. one or more CpGs within DMR 256 as defined by SEQ ID NO: 756 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.878, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 257. one or more CpGs within DMR 257 as defined by SEQ ID NO: 757 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.878, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 258. one or more CpGs within DMR 258 as defined by SEQ ID NO: 758 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.875, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 259. one or more CpGs within DMR 259 as defined by SEQ ID NO: 759 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.875, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 260. one or more CpGs within DMR 260 as defined by SEQ ID NO: 760 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 261. one or more CpGs within DMR 261 as defined by SEQ ID NO: 761 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.874, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 262. one or more CpGs within DMR 262 as defined by SEQ ID NO: 762 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.865, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 263. one or more CpGs within DMR 263 as defined by SEQ ID NO: 763 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.865, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 264. one or more CpGs within DMR 264 as defined by SEQ ID NO: 764 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 265. one or more CpGs within DMR 265 as defined by SEQ ID NO: 765 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 266. one or more CpGs within DMR 267 as defined by SEQ ID NO: 767 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.863, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 267. one or more CpGs within DMR 268 as defined by SEQ ID NO: 768 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 268. one or more CpGs within DMR 269 as defined by SEQ ID NO: 769 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 269. one or more CpGs within DMR 270 as defined by SEQ ID NO: 770 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 270. one or more CpGs within DMR 271 as defined by SEQ ID NO: 771 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 271. one or more CpGs within DMR 272 as defined by SEQ ID NO: 772 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 272. one or more CpGs within DMR 273 as defined by SEQ ID NO: 773 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 273. one or more CpGs within DMR 274 as defined by SEQ ID NO: 774 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 274. one or more CpGs within DMR 275 as defined by SEQ ID NO: 775 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.862, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 275. one or more CpGs within DMR 276 as defined by SEQ ID NO: 776 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.861, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 276. one or more CpGs within DMR 277 as defined by SEQ ID NO: 777 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.861, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 277. one or more CpGs within DMR 278 as defined by SEQ ID NO: 778 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.860, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 278. one or more CpGs within DMR 279 as defined by SEQ ID NO: 779 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.860, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 279. one or more CpGs within DMR 280 as defined by SEQ ID NO: 780 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 280. one or more CpGs within DMR 281 as defined by SEQ ID NO: 781 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.859, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 281. one or more CpGs within DMR 282 as defined by SEQ ID NO: 782 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 282. one or more CpGs within DMR 283 as defined by SEQ ID NO: 783 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.853, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 283. one or more CpGs within DMR 284 as defined by SEQ ID NO: 784 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 284. one or more CpGs within DMR 285 as defined by SEQ ID NO: 785 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.851, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 285. one or more CpGs within DMR 286 as defined by SEQ ID NO: 786 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 286 one or more CpGs within DMR 287 as defined by SEQ ID NO: 787 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.849, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 287. one or more CpGs within DMR 288 as defined by SEQ ID NO: 788 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.846, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 288. one or more CpGs within DMR 289 as defined by SEQ ID NO: 789 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.846, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 289. one or more CpGs within DMR 290 as defined by SEQ ID NO: 790 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.842, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 290. one or more CpGs within DMR 291 as defined by SEQ ID NO: 791 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.842, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 291. one or more CpGs within DMR 292 as defined by SEQ ID NO: 792 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.841, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 292. one or more CpGs within DMR 293 as defined by SEQ ID NO: 793 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.841, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 293. one or more CpGs within DMR 294 as defined by SEQ ID NO: 794 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.838, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 294. one or more CpGs within DMR 295 as defined by SEQ ID NO: 795 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.838, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 295. one or more CpGs within DMR 296 as defined by SEQ ID NO: 796 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.833, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 296. one or more CpGs within DMR 297 as defined by SEQ ID NO: 797 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.833, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 297. one or more CpGs within DMR 298 as defined by SEQ ID NO: 798 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.832, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 298. one or more CpGs within DMR 299 as defined by SEQ ID NO: 799 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.832, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 299. one or more CpGs within DMR 300 as defined by SEQ ID NO: 800 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.831, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 300. one or more CpGs within DMR 301 as defined by SEQ ID NO: 801 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.831, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 301. one or more CpGs within DMR 302 as defined by SEQ ID NO: 802 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.826, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 302 one or more CpGs within DMR 303 as defined by SEQ ID NO: 803 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.826, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 303. one or more CpGs within DMR 304 as defined by SEQ ID NO: 804 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.806, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 304. one or more CpGs within DMR 305 as defined by SEQ ID NO: 805 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.806, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 305. one or more CpGs within DMR 306 as defined by SEQ ID NO: 806 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.911, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 306. one or more CpGs within DMR 307 as defined by SEQ ID NO: 807 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.905, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]];
- 307. one or more CpGs within DMR 308 as defined by SEQ ID NO: 808 and denoted by CG, preferably wherein the assay is characterised as having an ROC AUC of at least 0.905, and more preferably wherein the panel of one or more CpGs comprises at least the CpGs denoted by [[CG]], preferably wherein the methylation status of the one or more CpGs in the panel is preferably determined by a β-value analysis, and the cancer is endometrial cancer of ovarian cancer.

In any of the assays described herein, the step of determining the methylation status of a panel of one or more CpGs comprises determining the methylation status of two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, or nine or more, or all of the CpGs denoted by CG within any combination of:

- i. one or more DMRs defined by SEQ ID NOs: 525, 756 and 757, preferably within all of SEQ ID NOs: 525, 756 and 757;
- ii. one or more DMRs defined by SEQ ID NOs: 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs: 503, 504, 526, 740, 741, 743 and 744; and
- iii. one or more DMRs defined by SEQ ID NOs: 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744, preferably within all of SEQ ID NOs: 525, 756, 757, 503, 504, 526, 740, 741, 743 and 744.

In any one of the assays described herein, the step of determining the methylation status of the one or more CpGs in the panel may comprise or may additionally comprise determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809 to 919.

In any one of the assays described herein, the step of determining the methylation status of the one or more CpGs in the panel may preferably comprise or may preferably additionally comprise determining the methylation status of each CpG within one or more of the sequences identified by SEQ ID NOs 809, 746, 883, 811, 848, 885, 813, 850, and 887. More preferably, in any one of the assays described herein, the step of determining the methylation status of the one or more CpGs in the panel may comprise or may additionally comprise determining the methylation status of each CpG within all of the sequences identified by SEQ ID NOs 809, 746, 883, 811, 848, 885, 813, 850, and 887.

The invention also provides a variety of assays, each comprising any 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more (or any range derivable therein) of a variety of steps and in no particular order, including methods of the following: measuring in a sample; analyzing a sample; assessing a sample; evaluating a sample; measuring nucleic acids in a sample; assessing nucleic acids in a sample; detecting nucleic acids in a sample; measuring methylation in nucleic acids in a sample; analyzing nucleic acids in a sample; assessing nucleic acids in a sample; measuring methylation at one or more CpG dinucleotides in a sample; detecting methylation at one or more CpG dinucleotides in a sample; assaying methylation at one or more CpG dinucleotides in a sample; assessing methylation at one or more CpG dinucleotides in a sample; measuring a methylation status in a sample; assaying a methylation status in a sample; detecting methylation status in a sample; determining methylation status in a sample; identifying methylation status in a sample; measuring one or more DNA methylation markers in a sample; assessing one or more DNA methylation markers in a sample; detecting one or more DNA methylation markers in a sample; measuring the presence of methylation at one or more markers in a sample; detecting the presence of methylation at one or more markers in a sample; assessing the presence of methylation at one or more markers in a sample; assaying the presence of one of more markers in a sample; measuring one or more DNA methylation markers in a sample but excluding the measuring of one or more other DNA methylation markers in the sample; assessing one or more DNA methylation markers in a sample but excluding the assessing of one or more other DNA methylation markers in the sample; analyzing one or more DNA methylation markers in a sample but excluding the analyzing of one or more other DNA methylation markers in the sample; detecting one or more DNA methylation markers in a sample but excluding the detecting of one or more other DNA methylation markers in the sample; measuring methylation status in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; detecting methylation status in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; analyzing methylation status in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; assessing methylation status in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; measuring methylation at one or more CpG dinucleotides in a sample but excluding the measuring of methylation at one or more CpG dinucleotides in the sample; assessing methylation at one or more CpG dinucleotides in a sample but excluding the assessing of methylation at one or more CpG dinucleotides in the sample; analyzing methylation at one or more CpG dinucleotides in a sample but excluding the analyzing of methylation at one or more CpG dinucleotides in the sample; detecting methylation at one or more CpG dinucleotides in a sample but excluding the detecting of methylation at one or more CpG dinucleotides in the sample; measuring methylation at one or more CpG dinucleotides in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; detecting methylation at one or more CpG dinucleotides in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; analyzing methylation at one or more CpG dinucleotides in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; assessing methylation at one or more CpG dinucleotides in nucleic acids from a sample from tissue from an individual other than tissue from the individual suspected of, or at risk for, being cancerous; treating an individual for cancer when the individual has been determined to have a methylation status at one or more methylation markers; treating an individual for cancer when the individual has been determined to have methylation at one or more CpG dinucleotides;

- wherein any of the aforementioned methods, or any other methods encompassed by the disclosure, may comprise any one or more of the following method steps:
- measuring methylation status, wherein the measuring identifies the methylation status of one or markers from nucleic acids in a sample;
- measuring methylation status, wherein the measuring identifies the presence of one or more markers from nucleic acids in a sample;
- measuring the presence of one or more methylation markers from a sample;
- providing DNA from a sample;
- providing nucleic acids from a sample;
- determining whether one or more methylation markers from nucleic acids from a sample are methylated;
- measuring whether one or more methylation markers from nucleic acids from a sample are methylated;
- performing a sequencing step on nucleic acids from a sample;
- determining a sequence of nucleic acids from a sample;
- performing bisulphite conversion on one or more markers;
- performing bisulphite conversion on one or more CpG dinucleotides;
- hybridizing DNA to an array comprising probes capable of determining methylated versus non-methylated markers;
- hybridizing DNA to an array comprising probes capable of determining methylated versus non-methylated CpG dinucleotides;
- hybridizing DNA to an array comprising probes capable of discriminating between methylated and non-methylated markers;
- hybridizing DNA to an array comprising probes capable of discriminating between methylated and non-methylated CpG dinucleotides;
- performing an amplification step on sequence from nucleic acids from a sample;
- performing an amplification step on sequence from nucleic acids using methylation-specific primers;
- performing amplification of sequence comprising one or more regions suspected of having methylation or in need of determination of a methylation status;
- performing PCR on sequence comprising one or more regions suspected of having methylation or in need of determination of a methylation status;
- performing a capturing step;
- performing a binding step;
- performing a purification step;
- performing a capturing step comprising binding of polynucleotides comprising one or more methylation markers to binding molecules specific to the one or more methylation markers and collecting complexes thereof;
- stratifying the grade of a cancer;
- determining the risk of cancer;
- determining the risk of recurrence of cancer;
- obtaining a sample from an individual;
- obtaining DNA from a sample from an individual;
- administering a treatment to an individual;
- providing DNA from a sample;
- determining whether one or more methylation markers from a panel of methylation markers comprises a specific sequence; and/or obtaining data that identifies whether each one of a group of methylation markers from a panel comprises a specific sequence.

Moreover, in some aspects of the invention, an individual who is administered a therapy or treatment has been subjected to any of the methods and steps described herein.

Described herein are assays that utilise a statistically robust panel of one or more CpGs whose methylation status can be determined to provide a reliable prediction of the presence or development of cancer in an individual. By determining the methylation status of each CpG within the panel of one or more CpGs, a cancer index value may be derived thus enabling stratification of individuals according to their risk of developing cancer or of having cancer, particularly endometrial and/or ovarian cancer, with statistically robust sensitivity and specificity. The skilled person would understand that the methylation status of each CpG within a panel of one or more CpGs can be determined by any suitable means in order to thereby derive the cancer index value. Any one method, or a combination of methods, may be used to determine the methylation status of each CpG within a panel of one or more CpGs.

Various exemplary methods for determining the methylation status of each CpG within a panel of one or more CpGs are described herein. For example, in one method a percent methylated reference (PMR) value of a CpG may be determined. In another method the methylation β-values of a CpG may be determined. Different mechanisms may be employed to determine specific values depending on the circumstances, such as PCR-based mechanisms or array-based mechanisms.

Cancer Index Values as Diagnostic and Risk Assessment Tools

In any of the assays described herein, the assessment of the presence, absence or development of cancer in an individual is based on the cancer index value of the individual at the time of testing.

As explained herein, using panels of the specific CpGs disclosed herein, cancer index values can be established which correspond with cancer negative samples, because they are based on values derived from individuals known to be cancer negative and obtained from tissue samples from an anatomical site other than the endometrium or ovary, such as from the cervix, vagina, buccal area, blood and/or urine, particularly from a liquid-based cytology sample, and more preferably a cervical smear sample. Similarly, using panels of the specific CpGs disclosed herein, cancer index values can be established which correspond with cancer positive samples, because they are based on values derived from an anatomical site other than the ovary or endometrium, as noted above, from tissue samples from individuals known to be cancer positive. A user can then apply these cancer index values to assess the presence, absence or development of cancer in any test individual whose cancer status is required to be tested. As also explained herein, the assays of the invention are capable of being performed with a high degree of statistical accuracy.

As explained herein, the described assays particularly relate to the assessment of the presence, absence or development of endometrial cancer and/or ovarian cancer, particularly endometrial cancer.

A skilled person will readily appreciate that a cancer index value provides a value that indicates a “likelihood” or “risk” or “prediction” of any of the assays of the invention correctly assessing the presence, absence or development of cancer in an individual. This is because the assessment is based upon a correlation between DNA methylation profiles of tissue samples and individual disease status. Nevertheless, as demonstrated by data set out in the Examples and elsewhere herein, the assays of the invention provide such correlations with high statistical accuracy, thus providing the skilled person with a high degree of confidence that the cancer index value which is determined for any test individual whose cancer status is required to be tested will provide an accurate correlation with actual disease status for the individual.

In the context of the present invention, “likelihood”, “risk” and “prediction” may be used synonymously with each other.

Any references herein to sequences, genomic sequences and/or genomic coordinates are derived based upon Homo sapiens (human) genome assembly GRCh37 (hg19). The skilled person would understand variations in the nucleotide sequences of any given sequence, particularly DMRs 1 to 308, may exist due to sequencing errors and/or variation between individuals.

The assay of the invention represents a ‘prediction’ because any cancer index value (WID-EC-Index) derived in accordance with the invention is unlikely to be capable of diagnosing every individual as having or not having cancer with 100% specificity and 100% sensitivity. Rather, depending on the cancer index cutpoint threshold applied by the user for positively predicting the presence of cancer in an individual, the false positive and false negative rate will vary. In other words, the inventors have discovered that the assays of the invention can achieve variable levels of sensitivity and specificity for predicting the presence, absence or development of cancer, as defined by receiver operating characteristics, depending on the cancer index cutpoint threshold chosen and applied by the user. Such sensitivity and specificity can be seen from the data disclosed herein to be achievable at high proportions, demonstrating accurate and statistically-significant discriminatory capability.

Similarly, cancer index values which have been pre-determined to correlate with specific cancer phenotypes, such as the presence or absence of cancer, have been defined with a high level of statistical accuracy as explained further herein.

Assessing the ‘development’ of cancer in the context of the invention may refer to assessing whether an individual is likely or unlikely to develop cancer. The inventors have shown that the CpGs assayed in order to derive the cancer index value of the assays of the invention are representative of the cells within normal tissue from an anatomical site other than the endometrium or ovary, such as from the cervix, vagina, buccal area, blood and/or urine, particularly from a liquid-based cytology sample, and more preferably a cervical smear sample. Assessing the development of cancer in accordance with the assays of the invention may refer to assessing an increased or decreased likelihood of cancer and/or CIN3 development, particularly endometrial cancer and ovarian cancer, preferably endometrial cancer. Assessing the development of cancer in accordance with the assays of the invention may refer to assessing progression or worsening of a pre-existing cancer lesion in an individual. Assessment of the development of cancer in accordance with the assays of the invention may refer to predicting the likelihood of recurrence of cancer.

In any of the assays described herein, the step of assessing the presence or development of cancer in an individual based on a cancer index value may involve the application of a threshold value. Threshold values can provide a risk-based indication of an individual's cancer status, whether that is cancer positive, or cancer negative. Threshold values can also provide a means for identifying whether the cancer index value is intermediate between a cancer positive value and a cancer negative value. As explained herein, the cancer index value may be dynamic and subject to change depending upon genetic and/or environmental factors. Accordingly, the cancer index value may provide a means for assessing and monitoring cancer development. Cancer index values may therefore indicate at least a low risk or a high risk that the individual has a cancer positive status or has a status that is indicative of the development of cancer. If the cancer index value of an individual is determined by the assays of the invention at two or more time points, an increase or decrease in the individual's cancer index value may indicate an increased or decreased risk of the individual having or developing cancer, particularly endometrial and/or ovarian cancer, most preferably endometrial cancer.

Throughout the disclosure herein the terms “threshold value”, “cutpoint”, and “cutpoint threshold” are to be considered synonymous and interchangeable.

As explained further herein any assay of the invention is an assay for assessing the presence, absence or development of cancer in an individual. The types of cancer are set out further herein. As explained further herein, the assays of the invention provide means for assessing whether an individual is at risk of having or developing cancer based on specific cutpoint thresholds. Such risk assessments can be provided with a high degree of confidence based on the statistical parameters which characterise the assay. Thus in any of the assays described herein involving cancer index cutpoint thresholds, the cutpoint threshold may be used for risk assessment purposes. Equally, in any of the assays described herein involving cancer index cutpoint thresholds, the cutpoint threshold value may be used to specify whether or not an individual has cancer as a pure diagnostic test. Again, such diagnostic tests can be provided with a high degree of confidence based on the statistical parameters which characterise the assay. Accordingly, in any assay described herein which specifies that a cancer index value for the individual is a specific value or more, or is “about” a specific value or more, the individual may be assessed as having cancer. In any assay described herein which specifies that a cancer index value for the individual is less than a specific value, or is less than “about” a specific value, the individual may be assessed as not having cancer. The term “about” is to be understood as providing a range of +/−5% of the value.

Accordingly, any assay of the invention is an assay for assessing the presence, absence or development of cancer in an individual, the assay comprising:

- a. providing a sample which has been taken from the individual, the sample comprising a population of DNA molecules;
- b. determining in the population of DNA molecules in the sample the methylation status of a panel of:
  - (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
  - (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG;
- c. deriving a cancer index value based on the methylation status of the one or more CpGs in the panel; and
- d. assessing the presence, absence or development of cancer in the individual based on the cancer index value;
- wherein the assay is characterised as having an area under the curve (AUC) of 0.60 or more as determined by receiver operating characteristics (ROC).

Any of the assays of the invention are particularly for assessing the presence or absence of cancer and/or CIN3 in an individual.

Such an assay may be performed in accordance with any of the methods disclosed and defined herein.

As explained further herein, any assay of the invention for assessing the presence, absence or development of cancer in an individual may alternatively be referred to as an assay for stratifying an individual in accordance with their cancer status.

Accordingly, any assay of the invention is an assay for stratifying an individual for the presence, absence or development of cancer in an individual, the assay comprising:

- a. providing a sample which has been taken from the individual, the sample comprising a population of DNA molecules;
- b. determining in the population of DNA molecules in the sample the methylation status of a panel of:
  - (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
  - (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG;
- c. deriving a cancer index value based on the methylation status of the one or more CpGs in the panel; and
- d. stratifying the individual for the presence, absence or development of cancer based on the cancer index value;
- wherein the assay is characterised as having an area under the curve (AUC) of 0.60 or more as determined by receiver operating characteristics (ROC).

Such an assay may be performed in accordance with any of the methods disclosed and defined herein.

Accordingly, any assay of the invention is an assay for stratifying an individual for cancer, the assay comprising:

- a. providing a sample which has been taken from the individual, the sample comprising a population of DNA molecules;
- b. determining in the population of DNA molecules in the sample the methylation status of a panel of:
  - (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
  - (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG;
- c. deriving a cancer index value based on the methylation status of the one or more CpGs in the panel; and
- d. stratifying the individual for cancer based on the cancer index value;
- wherein the assay is characterised as having an area under the curve (AUC) of 0.60 or more as determined by receiver operating characteristics (ROC).

Such an assay may be performed in accordance with any of the methods disclosed and defined herein.

The cancer index value may be derived by any suitable means. Preferably, the cancer index value may be derived by assessing the methylation status of the panel of:

- (i) one or more CpGs selected from a panel of CpGs identified in SEQ ID NOs 1 to 500 wherein the CpGs are identified at nucleotide positions 61 to 62; and/or
- (ii) one or more CpGs selected from within a panel of one or more Differentially Methylated Regions (DMRs) defined by SEQ ID NOs 501 to 808, wherein the CpGs are denoted by CG,
- in a sample provided from an individual. The methylation status of the CpGs may be determined by any suitable means. For example, in any of the assays described herein the step of determining the methylation status of each CpG in the panel of one or more CpGs may comprise:
  - a. performing a sequencing step to determine the sequence of each CpG;
  - b. hybridising DNA to an array comprising probes capable of discriminating between methylated and non-methylated forms of the CpGs and applying a detection system to the array so as to determine the methylation status of each CpG; and/or
  - c. performing a PCR step using methylation-specific primers, wherein the methylation status of the CpG is determined by the presence or absence of a PCR product.

The step of determining in the population of DNA molecules in the sample the methylation status of a panel of one or more CpGs may comprises determining a β value of each CpG. Deriving the cancer index value may involve providing a methylation β-value data set comprising the methylation β-values for each CpG in the panel of one or more CpGs. Additionally, or alternatively, the step of determining in the population of DNA molecules in the sample the methylation status of a panel of one or more CpGs may comprises determining a percent methylated reference value for each of the panel of one or more CpGs. Optionally deriving the cancer index value may also involve estimating the fraction of contaminating DNA within the DNA provided from a sample.

DNA may be DNA originating from a particular source organism, tissue or cell type. Preferably the contaminating DNA originates from one or more different cell types to one or more cell types of interest. A cell type of interest may particularly be an epithelial cell. In some aspects of the invention, it may be preferable to estimate the fraction of contaminating DNA after the step of providing a sample which has been take from an individual. The assays described herein may optionally involve estimating a contaminating DNA fraction within DNA in the sample by any suitable means. Preferably, the contaminating DNA fraction for the sample is estimated via any suitable bioinformatics analysis tool. A bioinformatics analysis tool that may be used to estimate a contaminating DNA fraction may be EpIDISH. As described herein, it may be desirable to estimate the fraction of contaminating DNA from the one or more cell types that are different to the one or more cell types of interest because the cancer index value used for predicting the presence or development of cancer in an individual may, in some instances, only be reliably derived from determining the methylation status of a set of CpGs from DNA of a particular cell type of interest. Particularly, methylation status beta-values may differ in the one or more cell types of interest within a sample relative to methylation status beta-values in contaminating DNA from different cell types within the same sample. Thus, the derived cancer index value may in some instances have a decreased predictive power without estimating and controlling for the contaminating DNA fraction within the DNA provided from the sample. In assays of the invention that involve estimating the fraction of contaminating DNA and accordingly controlling for said contaminating DNA, it is preferable to estimate an immune cell DNA fraction within the DNA provided from the sample. In particular assays of the invention, wherein the individual has an immune cell contamination of over 50% (i.e. wherein more than 50% of the DNA in the sample is deemed to be derived from immune cells), the assay may preferably involve controlling for the immune cell contamination by deriving the cancer index, in accordance with the invention, solely from the DNA molecules derived from epithelial cells.

Any of the assays described herein comprising a step of deriving a cancer index value based on the methylation status of the one or more CpGs in the panel may further comprise applying an algorithm to the methylation beta-value dataset to obtain the cancer index value. Preferably, in any of the assays described herein, the step of deriving the cancer index value based on the methylation status of the panel of CpGs comprises providing a methylation beta-value data set comprising the methylation beta-values for each CpG in the panel and applying an algorithm to the methylation beta-value data set to obtain the cancer index value.

In any of the assays described herein, the step of deriving the cancer index value based on the methylation status of the one or more CpGs in the panel comprises:

- a. providing a methylation β-value data set comprising the methylation β-values for each CpG in the panel;
- b. providing a mathematical model capable of generating the cancer index from the methylation β-value data set; and
- c. applying the mathematical model to the methylation β-value data set, thereby generating the cancer index.

In any of the assays described herein, the cancer index value may be calculated by any suitable mathematical model such as an algorithm or formula. Preferably, the cancer index value is termed Women's risk Identification for Endometrial Cancer Index (WID-EC-index) and wherein the mathematical model which is applied to the methylation β-value data set to generate the cancer index is calculated by an algorithm according to the following formula:

$WID - EC - index = \sum_{i = 1}^{n} \frac{w_{i} β_{i} - μ}{σ}$

wherein:

- 1. β₁, . . . , β_nare methylation beta-values (between 0 and 1);
- 2. w₁, . . . , w₅₀₀are real valued coefficients;
- 3. μ and σ are real valued parameters used to scale the index; and
- 4. n refers to the number of CpGs in the set of test CpGs;
- preferably wherein the cancer is endometrial cancer.

In any of the assays described herein, the WID-EC-index algorithm applies real valued coefficients inferred by initially training on a dataset (this dataset in the exemplary embodiments of the invention described in the Examples consisted of 144 endometrial cancer cases and 572 controls) to fit a ridge classifier using the R package glmnet with a mixing parameter value of alpha=0 (ridge penalty) and binomial response type. Ten-fold cross-validation was used internally by the cv.glmnet function in order to determine the optimal value of the regularisation parameter lambda. The beta values from n CpGs for individual v, β₁^v, . . . , β_n^v, are used as inputs to the ridge classifier. The coefficients w₁, . . . , w_nare obtained from the fitted model. The following quantity was computed for each individual v in the training set:

$x_{v} = \sum_{i = 1}^{n} w_{i} β_{i}^{v}$

Any suitable real valued coefficients may be applied to the WID-EC-Index in any of the assays described herein.

The value of the parameters μ and σ are given by the mean and standard deviation of x_vin the training dataset respectively.

Thus, any suitable μ and σ real valued parameters may be applied to the WID-EC-index in any of the assays described herein. Any suitable training data set may be applied to the assays described herein in order to infer real valued parameters and coefficients that can subsequently be applied to the WID-EC-index formula according to the present invention. Exemplary ways of utilising a training dataset in accordance with the present invention are further described in the ‘Statistical analyses for classifier development’ section of the Materials and Methods section of the Examples.

Exemplary μ and σ real valued parameters are provided in Table 2 for CpG subsets identified in SEQ ID NOs 1 to 500. These real valued parameters may be applied to any of the assays described herein wherein the real parameters correspond to any one of the sets of CpGs identified in SEQ ID NOs 1 to 500 and set out in the left hand column of Table 2.

TABLE 2

Exemplary μ and σ real valued parameters are provided in

Table 2 for CpG subsets identified in SEQ ID NOs 1 to 500

SEQ ID

NOs:
mu
sigma

1-50
2.880073
4.148988

1-100
3.43488
4.076555

1-150
3.897919
4.129713

1-200
3.861902
3.842672

1-250
3.774098
4.12993

1-300
3.807151
4.17154

1-350
3.662246
4.109188

1-400
3.316238
3.984151

1-450
3.351052
3.982014

1-500
3.667061
4.171657

Exemplary w₁, . . . , w_nreal value coefficients are provided below for the CpGs identified at positions 61 to 62 in SEQ ID NOs 1 to 500. These real value coefficients may be applied to any of the assays described herein wherein the real parameters correspond to any one of the sets of CpGs identified in SEQ ID NOs 1 to 500 wherein the 500 real value coefficients below in turn correspond to the CpGs in turn identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500. Accordingly, the listed coefficients are presented below in numerical order corresponding respectively to the CpGs identified in SEQ ID NOs 1 to 5000. Thus the first number below corresponds to SEQ ID NO 1, the second number corresponds to SEQ ID NO 2 etc. The exemplary real value coefficients are as follows:

- 2.32966, 1.95059, 1.87174, 1.86617, 1.65489, 1.60169, −1.52485, 1.4846, 1.48231, 1.47445, 1.47342, 1.4441, 1.40984, −1.40743, 1.3761, 1.32123, −1.29551, 1.29183, −1.26448, 1.26166, −1.2578, −1.23771, 1.23418, −1.19877, 1.16649, 1.16451, 1.1421, 1.13892, −1.13096, 1.12541, 1.08222, 1.04719, 1.02739, 1.0262, 1.01259, 0.94512, 0.93919, 0.93148, 0.90943, 0.9025, 0.89635, 0.89152, −0.89049, −0.88852, −0.88615, 0.88339, −0.88238, −0.84763, 0.84381, 0.84281, −0.81762, −0.80659, 0.80114, −0.79765, −0.77473, −0.77145, 0.76203, −0.75583, 0.75558, 0.7419, 0.73368, 0.73031, −0.72253, −0.71934, −0.7095, 0.70083, 0.69289, −0.68917, −0.68351, −0.67983, 0.67887, 0.67199, −0.67196, −0.67186, 0.6693, −0.66391, 0.66347, −0.64944, −0.6407, 0.63298, 0.6277, 0.6159, −0.61381, −0.61247, 0.60994, −0.60626, −0.59996, 0.58813, 0.58678, −0.58473, 0.58414, 0.57932, 0.57361, 0.56698, 0.56338, 0.55991, −0.55792, −0.5568, −0.55381, 0.54696, 0.54651, 0.54566, −0.54331, 0.54171, 0.53775, 0.53111, −0.52707, 0.52526, 0.52488, 0.52102, −0.51622, −0.51409, −0.50784, −0.50732, −0.5063, −0.5026, 0.4983, −0.49476, 0.49368, −0.49317, 0.49183, −0.49079, −0.4825, −0.47419, −0.47231, 0.47057, −0.46063, −0.45931, −0.4517, −0.45066, 0.45017, 0.44947, 0.44946, 0.44407, 0.44333, 0.44312, −0.44228, 0.4386, −0.43757, 0.43618, −0.43183, 0.43138, 0.42876, −0.42769, −0.42701, −0.42635, −0.42458, −0.42425, 0.4214, −0.41693, 0.41445, 0.41152, −0.40511, 0.4017, −0.4001, −0.39825, 0.39582, 0.3921, −0.39146, −0.39114, −0.39101, 0.39046, −0.38991, 0.38989, −0.38837, −0.38587, −0.38464, 0.38453, −0.37816, 0.37631, −0.37551, 0.37536, −0.3738, 0.37293, 0.3729, 0.37046, −0.36971, 0.36901, 0.36684, −0.36451, 0.36449, −0.36442, 0.36383, −0.36291, 0.35913, −0.35596, 0.35594, −0.35422, −0.35344, 0.35168, 0.35008, 0.34932, 0.3479, 0.33951, −0.33902, −0.33693, 0.33589, 0.33518, −0.33354, −0.32969, −0.32906, 0.32799, −0.32761, −0.32373, 0.32287, −0.32125, −0.32052, 0.31686, 0.31205, 0.30807, −0.30682, −0.30671, −0.3051, −0.30257, −0.30238, 0.29616, −0.29598, 0.29579, 0.29554, 0.29553, 0.29552, −0.29492, −0.29464, 0.29168, −0.29124, −0.29108, 0.29078, 0.28992, 0.28904, −0.28898, 0.28857, 0.28584, 0.28496, −0.28375, 0.28254, −0.28172, 0.28088, 0.28033, 0.28024, 0.27964, 0.27814, 0.27351, −0.27199, −0.26681, −0.26572, −0.26482, 0.26282, −0.26196, 0.26167, −0.25997, 0.25947, −0.2582, −0.25679, −0.25527, 0.25448, −0.25443, 0.25302, 0.25204, 0.25198, −0.25098, −0.24987, −0.24811, −0.24735, 0.24589, 0.24566, −0.24389, 0.24355, 0.2433, −0.24253, −0.24066, −0.23859, 0.2381, 0.23454, −0.23433, 0.23349, −0.2332, −0.23185, −0.23092, 0.22721, 0.22664, −0.22602, 0.22147, 0.22089, 0.21875, 0.21869, 0.21644, −0.2164, −0.21569, −0.21555, 0.21494, −0.21491, 0.21266, −0.21264, −0.21258, −0.21237, 0.20801, 0.2073, −0.2054, −0.20527, 0.20216, −0.20175, 0.20159, 0.19936, −0.19924, 0.19851, −0.19521, 0.19502, −0.19436, 0.1942, −0.19284, −0.19253, −0.19086, −0.19076, 0.18983, −0.18908, −0.18795, 0.18669, 0.18616, 0.18415, 0.18398, −0.18331, 0.18297, 0.1817, 0.18094, −0.17951, −0.17894, 0.17722, −0.17719, 0.1771, 0.17613, −0.17517, −0.1745, −0.1739, −0.17205, 0.17203, −0.17156, −0.17088, 0.17084, −0.16955, −0.16933, −0.16659, 0.16417, −0.16366, −0.16063, −0.15928, −0.15883, −0.15631, −0.15543, −0.15504, −0.15367, −0.15211, 0.15155, −0.15136, −0.14875, −0.14763, −0.14623, 0.14084, −0.14027, 0.13945, −0.13918, −0.13807, 0.13787, 0.13747, −0.13745, −0.1358, −0.1354, 0.13442, 0.13287, −0.13083, −0.13017, −0.12858, −0.12794, 0.1279, −0.12639, 0.12472, 0.12451, −0.12409, −0.12237, 0.12222, −0.12063, 0.1202, −0.1186, −0.11855, −0.11781, 0.1171, 0.11674, 0.11558, −0.11356, −0.11325, −0.11304, 0.11228, −0.11198, −0.11176, −0.11094, −0.11023, 0.10822, 0.10798, −0.10794, 0.10786, −0.10719, −0.10512, 0.10485, −0.10472, 0.10422, −0.10366, −0.10352, 0.10349, 0.10115, 0.09742, 0.09554, 0.09475, −0.09452, 0.09413, 0.09279, 0.09095, −0.09058, −0.08692, 0.08546, 0.08527, 0.08234, 0.08225, 0.08034, −0.07898, −0.07844, 0.07581, 0.07534, −0.07492, −0.07315, −0.06965, −0.06891, −0.06813, −0.06763, 0.06733, −0.06613, −0.06587, 0.06558, −0.0645, −0.06294, 0.06163, −0.06075, −0.06061, 0.05772, 0.05563, −0.05531, −0.05395, −0.05349, −0.05207, −0.05088, −0.04909, 0.04894, 0.04817, −0.0475, 0.04684, −0.0437, −0.04325, 0.04069, 0.04061, 0.03859, −0.0379, −0.03773, 0.03649, 0.03592, −0.03564, 0.03468, 0.03356, −0.03242, 0.03235, 0.02751, −0.0273, −0.02729, 0.02726, −0.02588, −0.02556, −0.02538, −0.02536, −0.02408, 0.02189, 0.01846, −0.01608, 0.01572, 0.01462, −0.01254, −0.0117, 0.01122, −0.01112, −0.01092, −0.00938, −0.00906, −0.00851, −0.00846, −0.00818, −0.00662, −0.00621, −0.00543, 0.00291, 0.00232, 0.00112, −0.00063, −0.00034, and −0.00021.

The predicting the presence, absence or development of cancer in an individual may particularly involve a threshold cancer index value being applied in order to assess or stratify an individual has having or not having cancer or of having a high or low risk of cancer development.

The assays of the invention may involve a threshold index being applied in order to assess the presence or absence of cancer and/or CIN3 in an individual. The assessment may be characterised by receiver operating characteristics, particularly and area under the curve (AUC), sensitivity, and specificity, indicative of the reliability of the threshold being applied in order to assess the presence or absence of cancer and/or CIN3 in an individual.

In any of the assays described herein, wherein when the cancer index value for the individual is about −0.201 or more, the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about −0.201, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, and more preferably wherein the assessing the presence, absence or development of cancer in an individual is based on the WID-EC-Index. The panel of one or more CpGs used to derive the cancer index value may comprise:

- 1. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 76%;
- 2. at least 100 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 3. at least 150 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and specificity is at least 76%;
- 4. at least 200 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 5. at least 250 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 6. at least 300 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 89% and specificity is at least 79%;
- 7. at least 350 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 8. at least 400 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 90% and specificity is at least 79%;
- 9. at least 450 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 89% and specificity is at least 79%; or
- 10. at least 500 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 95% and specificity is at least 76%.

- a. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 88% and the specificity is at least 76%;
- b. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 80%;
- c. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 92% and specificity is at least 79%; or
- d. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 93% and specificity is at least 80%.

- 1. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 80%;
- 2. at least the CpGs defined by SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 79%;
- 3. at least the CpGs defined by SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 92% and specificity is at least 80%;
- 4. at least the CpGs defined by SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 71%;
- 5. at least the CpGs defined by SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 76%;
- 6. at least the CpGs defined by SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 79%;
- 7. at least the CpGs defined by SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 80%;
- 8. at least the CpGs defined by SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 77%;
- 9. at least the CpGs defined by SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 76%;
- 10. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 76%;
- 11. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 80%;
- 12. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 92% and specificity is at least 79%;
- 13. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 93% and specificity is at least 80%;
- 14. at least the CpGs defined by SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 93% and specificity is at least 78%;
- 15. at least the CpGs defined by SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 78%;
- 16. at least the CpGs defined by SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 77%;
- 17. at least the CpGs defined by SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 77%;
- 18. at least the CpGs defined by SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 78%;
- 19. at least the CpGs defined by SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 78%;
- 20. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 76%;
- 21. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 76%;
- 22. at least the CpGs defined by SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 23. at least the CpGs defined by SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 76%;
- 24. at least the CpGs defined by SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 25. at least the CpGs defined by SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 26. at least the CpGs defined by SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 79%;
- 27. at least the CpGs defined by SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 88% and specificity is at least 78%;
- 28. at least the CpGs defined by SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 90% and specificity is at least 79%;
- 29. at least the CpGs defined by SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 89% and specificity is at least 79%; or
- 30. at least the CpGs defined by SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 95% and specificity is at least 76%.

In any of the assays described herein, wherein when the cancer index value for the individual is about 0.269 or more, the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about 0.269, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, and more preferably wherein the assessing the presence, absence or development of cancer in an individual is based on the WID-EC-Index. The panel of one or more CpGs used to derive the cancer index value may comprise:

- 1. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 75% and the specificity is at least 94%;
- 2. at least 100 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 3. at least 150 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 74% and specificity is at least 95%;
- 4. at least 200 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 5. at least 250 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 6. at least 300 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and specificity is at least 97%;
- 7. at least 350 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 8. at least 400 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 77% and specificity is at least 96%;
- 9. at least 450 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 77% and specificity is at least 97%; or
- 10. at least 500 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 79% and specificity is at least 96%.

- a. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 75% and the specificity is at least 94%;
- b. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 98%;
- c. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 98%;
- d. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%.

- 1. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 98%;
- 2. at least the CpGs defined by SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 98%;
- 3. at least the CpGs defined by SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 74% and specificity is at least 96%;
- 4. at least the CpGs defined by SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 77% and specificity is at least 95%;
- 5. at least the CpGs defined by SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 97%;
- 6. at least the CpGs defined by SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 71% and specificity is at least 96%;
- 7. at least the CpGs defined by SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 70% and specificity is at least 97%;
- 8. at least the CpGs defined by SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 9. at least the CpGs defined by SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 71% and specificity is at least 95%;
- 10. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 94%;
- 11. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 98%;
- 12. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 98%;
- 13. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%;
- 14. at least the CpGs defined by SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%;
- 15. at least the CpGs defined by SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 96%;
- 16. at least the CpGs defined by SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 96%;
- 17. at least the CpGs defined by SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%;
- 18. at least the CpGs defined by SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 96%;
- 19. at least the CpGs defined by SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 97%;
- 20. at least the CpGs defined by SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 96%;
- 21. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 75% and specificity is at least 94%;
- 22. at least the CpGs defined by SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 23. at least the CpGs defined by SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 74% and specificity is at least 95%;
- 24. at least the CpGs defined by SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 25. at least the CpGs defined by SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 26. at least the CpGs defined by SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 97%;
- 27. at least the CpGs defined by SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 73% and specificity is at least 96%;
- 28. at least the CpGs defined by SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 77% and specificity is at least 96%;
- 29. at least the CpGs defined by SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 77% and specificity is at least 97%; or
- 30. at least the CpGs defined by SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 79% and specificity is at least 96%.

In any of the assays described herein, wherein when the cancer index value for the individual is about 1.072 or more, the individual is assessed as having cancer and/or CIN3 or as having a high risk of cancer and/or CIN3 development, or wherein when the cancer index value for the individual is less than about 1.072, the individual is assessed as not having cancer and/or CIN3 or as having a low risk of cancer and/or CIN3 development, preferably wherein the assay comprises determining methylation β-values for each CpG in the panel of one or more CpGs, and more preferably wherein the assessing the presence, absence or development of cancer in an individual is based on the WID-EC-Index. The panel of one or more CpGs used to derive the cancer index value may comprise:

- 1. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and the specificity is at least 99%;
- 2. at least 100 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 3. at least 150 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 4. at least 200 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 5. at least 250 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 6. at least 300 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 55% and specificity is at least 99%;
- 7. at least 350 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 8. at least 400 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 9. at least 450 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 59% and specificity is 100%; or
- 10. at least 500 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 64% and specificity is 100%.

- a. at least 50 of the CpGs identified at nucleotide positions 61 to 62 in SEQ ID NOs 1 to 500, and wherein the sensitivity is at least 58% and the specificity is at least 99%;
- b. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is 100%;
- c. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 63% and specificity is 100%;
- d. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%.

- 1. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is 100%;
- 2. at least the CpGs defined by SEQ ID NOs 51 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is at least 99%;
- 3. at least the CpGs defined by SEQ ID NOs 101 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is 100%;
- 4. at least the CpGs defined by SEQ ID NOs 151 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is at least 99%;
- 5. at least the CpGs defined by SEQ ID NOs 201 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 6. at least the CpGs defined by SEQ ID NOs 251 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 7. at least the CpGs defined by SEQ ID NOs 301 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 52% and specificity is 100%;
- 8. at least the CpGs defined by SEQ ID NOs 351 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 56% and specificity is at least 99%;
- 9. at least the CpGs defined by SEQ ID NOs 401 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 52% and specificity is at least 99%;
- 10. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 11. at least the CpGs defined by SEQ ID NOs 1 to 50 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 60% and specificity is 100%;
- 12. at least the CpGs defined by SEQ ID NOs 1 to 100 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 63% and specificity is 100%;
- 13. at least the CpGs defined by SEQ ID NOs 1 to 150 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 14. at least the CpGs defined by SEQ ID NOs 1 to 200 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 15. at least the CpGs defined by SEQ ID NOs 1 to 250 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 16. at least the CpGs defined by SEQ ID NOs 1 to 300 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 17. at least the CpGs defined by SEQ ID NOs 1 to 350 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 18. at least the CpGs defined by SEQ ID NOs 1 to 400 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 63% and specificity is 100%;
- 19. at least the CpGs defined by SEQ ID NOs 1 to 450 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 20. at least the CpGs defined by SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%;
- 21. at least the CpGs defined by SEQ ID NOs 451 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 22. at least the CpGs defined by SEQ ID NOs 401 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 23. at least the CpGs defined by SEQ ID NOs 351 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 24. at least the CpGs defined by SEQ ID NOs 301 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 25. at least the CpGs defined by SEQ ID NOs 251 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 53% and specificity is at least 99%;
- 26. at least the CpGs defined by SEQ ID NOs 201 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 55% and specificity is at least 99%;
- 27. at least the CpGs defined by SEQ ID NOs 151 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 28. at least the CpGs defined by SEQ ID NOs 101 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 58% and specificity is at least 99%;
- 29. at least the CpGs defined by SEQ ID NOs 51 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 59% and specificity is 100%; or
- 30. at least the CpGs defined by SEQ ID NOs 1 to 500 and identified at nucleotide positions 61 to 62, and wherein the sensitivity is at least 64% and specificity is 100%.

In any of the described assays, the methylation status of the one or more CpGs in the panel is preferably determined by a β-value analysis, and the cancer is endometrial cancer of ovarian cancer. Preferably, the cancer is endometrial cancer. The ROC data set out in Tables 3, 4 and 5 corresponding to each specified panel of SEQ ID NOs: 1 to 500 are derived by determining a cancer index value from said panel.

TABLE 3

CpG

Subset

(SEQ ID
AUC (internal
Sensitivity
Specificity
Sensitivity
Specificity
Sensitivity
Specificity

NO)
validation)
(q = 1.072)
(q = 1.072)
(q = 0.269)
(q = 0.269)
(q = −0.201)
(q = −0.201)

1-50
0.95
0.6
1
0.73
0.98
0.9
0.8

51-100
0.94
0.6
0.99
0.73
0.98
0.89
0.79

101-150
0.94
0.58
1
0.74
0.96
0.92
0.8

151-200
0.93
0.6
0.99
0.77
0.95
0.89
0.71

201-250
0.95
0.58
0.99
0.75
0.97
0.9
0.76

251-300
0.93
0.53
0.99
0.71
0.96
0.89
0.79

301-350
0.94
0.52
1
0.7
0.97
0.89
0.8

351-400
0.93
0.56
0.99
0.73
0.96
0.9
0.77

401-450
0.93
0.52
0.99
0.71
0.95
0.88
0.76

451-500
0.92
0.58
0.99
0.75
0.94
0.88
0.76

TABLE 4

CpG

Subset

(SEQ ID
AUC (internal
Sensitivity
Specificity
Sensitivity
Specificity
Sensitivity
Specificity

NO)
validation)
(q = 1.072)
(q = 1.072)
(q = 0.269)
(q = 0.269)
(q = −0.201)
(q = −0.201)

1-50
0.95
0.6
1
0.73
0.98
0.9
0.8

1-100
0.96
0.63
1
0.75
0.98
0.92
0.79

1-150
0.96
0.64
1
0.79
0.97
0.93
0.8

1-200
0.96
0.64
1
0.79
0.97
0.93
0.78

1-250
0.96
0.64
1
0.79
0.96
0.95
0.78

1-300
0.96
0.64
1
0.79
0.96
0.95
0.77

1-350
0.96
0.64
1
0.79
0.97
0.95
0.77

1-400
0.96
0.63
1
0.79
0.96
0.95
0.78

1-450
0.97
0.64
1
0.79
0.96
0.95
0.78

1-500
0.97
0.64
1
0.79
0.96
0.95
0.76

TABLE 5

CpG

subset

(SEQ ID
AUC (internal
Sensitivity
Specificity
Sensitivity
Specificity
Sensitivity
Specificity

NO)
validation)
(q = 1.072)
(q = 1.072)
(q = 0.269)
(q = 0.269)
(q = −0.201)
(q = −0.201)

1-500
0.97
0.64
1
0.79
0.96
0.95
0.76

51-500
0.95
0.59
1
0.77
0.97
0.89
0.79

101-500
0.94
0.58
0.99
0.77
0.96
0.9
0.79

151-500
0.94
0.58
0.99
0.73
0.96
0.88
0.78

201-500
0.94
0.55
0.99
0.73
0.97
0.89
0.79

251-500
0.93
0.53
0.99
0.73
0.96
0.88
0.78

301-500
0.93
0.53
0.99
0.73
0.96
0.88
0.78

351-500
0.93
0.53
0.99
0.74
0.95
0.88
0.76

401-500
0.93
0.53
0.99
0.73
0.96
0.88
0.78

451-500
0.92
0.58
0.99
0.75
0.94
0.88
0.76

The predicting of the presence, absence, or development of cancer in an individual may particularly involve determining the mean β-value across any panel of one or more CpGs defined herein. A threshold mean β-value may be applied in order to stratify an individual as having or not having cancer, or of having a high or low risk of cancer development, preferably wherein the cancer is endometrial or ovarian cancer, more preferably wherein the cancer is endometrial cancer.