KR102192455B1 - A cancer diagnosis marker based on ATAC-Seq and Method using the same - Google Patents

Abstract

The present invention relates to a cancer diagnostic marker and use thereof using transferase-accessible chromatin using sequencing (ATAC sequencing), and the open chromatin structural variation marker according to the present invention has high structural variation of chromatin. Since it can be checked with accuracy, it is useful as a cancer diagnostic marker, and when a chromatin structural variation is detected using a composition for detecting the marker, it can be utilized as a new cancer diagnostic marker.

Description

A cancer diagnosis marker based on ATAC-Seq and Method using the same, using individual transferase-accessible chromatin sequencing information

The present invention relates to a cancer diagnostic marker selected using transferase-accessible chromatin using sequencing (ATAC sequencing) and uses thereof, and more particularly, to a biological sample after treatment with a transfer enzyme, The present invention relates to an open chromatin structure mutation marker obtained by extracting DNA to obtain sequence information, dividing a chromosome region into a predetermined section, and comparing the distribution of the number of reads by section with a reference group, and a cancer diagnosis method using the same.

Due to cancer, deaths are increasing not only in Korea but also worldwide, and there are various cancer patients in Korea such as stomach cancer, breast cancer, thyroid cancer, lung cancer, and colon cancer. The causes of cancer are divided into congenital, genetic mutations, and acquired causes. Rather than being caused by mutations in a part of a specific gene, it is caused by a combination of various causes. As methods of treating cancer, transplantation and removal through surgery and chemotherapy and radiation therapy are used. Recently, the recurrence rate of cancer is gradually decreasing through such a method, but researches to find the root cause and predict the prognosis in advance are ongoing.

Next-generation nucleotide sequencing (NGS) is a sequencing method that divides chromosomes into small pieces and analyzes the genetic information of each piece in parallel. With the development of genetic analysis technology, NGS is being used for gene mutation detection because of its relatively low test time and cost, and its high resolution capable of detecting single nucleotide polymorphism (SNP) and indels (INDELs). However, due to the principle characteristics of NGS, which analyzes chromosomes by dividing them into small pieces, there are technical limitations in detecting large-scale chromosomal structural changes or CNVs (Yohe S, Thyagarajan B. 2017, Arch Pathol Lab Med. Vol. 141(11), pp. .1544-1557).

To date, genome analysis and whole-genome analysis related to specific risk factors have been performed for research on specific genes related to various cancers. There are genetic risk factors for specific genes related to various cancers, but most of them exist in non-coding regions rather than coding regions, and it takes a lot of time to analyze them. A new approach was needed.

To solve this problem, an epigenome research technique was applied to analyze the function of the genetic factor in the non-death area. The histone modification study using ChIP-Seq (Chromatin ImmunoPrecipitation Sequencing), one of the representative epigenetic analysis techniques, indicates the activity of the non-transcribed region of chromatin, so the epigenetic genome map in cancer-related cell lines or tissues It is used as a method to investigate the molecular mechanism of cancer-causing genetic mutations through writing (Nevedomskaya et al., Genomics data vol. 2 195-8. 8 Jul. 2014).

However, this method is too dependent on the antibody (Antibody) used to sediment a specific protein, and has a problem in making more precise predictions with about 150 markers used in epigenetic studies. In addition, studies have reported that gene regulatory factors in non-transcribed regions often regulate other genes farther than nearby genes, and this is due to the tertiary structure of chromatin, even if they are far away on the DNA, DNA folding allows genes in space. Because regulators and distant genes can be close together, it is difficult to clarify the role of risk factors for predicting the underlying cause and prognosis of cancer only by mapping epigenetic genomes (Mishra et al., Genome medicine vol. 9,1 87 . 30 Sep. 2017).

Therefore, in order to solve this problem, a study based on the tertiary structure of chromatin is required to understand the mechanism of cancer-specific gene regulation, and a new research technique is needed for this.

Techniques for studying the structure of chromatin include ATAC-Seq (Assay for Transposase-Accessible Chromatin using sequencing) and Hi-C using NGS. Hi-C is a representative technology that studies the structure of chromatin at high resolution based on 3C (Chromosome Conformation Capture), and is a technology that captures the physical binding of chromatin on the genome (Belton et al., Methods (San Diego, Calif). .) vol. 58,3 (2012)). ATAC-Seq is a technique that detects open areas of chromatin using Transposon. It can be fully tested with a small amount, and has the advantage of being able to use it for rare cell lines or patients. It is cost-effective compared to -C (Buenrostro et al., Nature methods vol. 10,12, 2013).

Accordingly, the present inventors have made diligent efforts to develop an ATAC-Seq-based open chromatin structure mutation marker, and as a result of dividing by section with high enrichment using the ATAC-Seq result, the number of reads is compared with a reference group to select a marker candidate group. , By setting a statistically significant marker compared to the reference group, and confirming the structure of the chromatin in the marker, it was confirmed that cancer can be diagnosed with high accuracy, and the present invention was completed.

The information described in the background section is only for improving an understanding of the background of the present invention, and thus does not include information forming the prior art known to those of ordinary skill in the art to which the present invention belongs. May not.

An object of the present invention is to provide a composition for diagnosing breast cancer capable of detecting a chromatin structural variation marker.

Another object of the present invention is to provide a method for diagnosing breast cancer using the composition for diagnosing breast cancer.

In order to achieve the above object, the present invention is a transfer enzyme (transposase); And it provides a composition for diagnosing breast cancer comprising a primer pair specific to any one nucleic acid selected from the group consisting of SEQ ID NO: 1 to 100.

The present invention also includes the steps of obtaining a nucleic acid fragment by treating a nucleic acid isolated from a biological sample with a transposase; And amplifying the processed nucleic acid fragment using a primer pair specific to any one or more nucleic acids selected from the group consisting of SEQ ID NOs: 1 to 100, and detecting the chromatin structure of the nucleic acid. Provides a method of providing.

The open chromatin structural variation marker according to the present invention is useful as a cancer diagnostic marker because it can confirm the structural variation of chromatin with high accuracy, and when detecting chromatin structural variation using a composition for detecting the marker, a new cancer diagnostic marker It can be used as

1 is an overall flow chart of a method for screening an open chromatin structure variant marker of the present invention.
FIG. 2 is a graph showing the distribution of chromatin structure mutation candidate markers for normal and triple negative breast cancer detected according to an embodiment of the present invention.
3 is a graph showing a flow chart for detecting a region having a large structural difference between normal and triple negative breast cancer among the triple negative breast cancer-specific gene structure mutation markers detected according to an embodiment of the present invention.
FIG. 4 is a graph showing differences in structural mutation markers between normal and triple-negative breast cancer using a heatmap according to an embodiment of the present invention.
5 is a graph showing a genome-wide example of a triple negative breast cancer-specific gene structure mutation marker detected according to an embodiment of the present invention.

Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by an expert skilled in the art to which the present invention belongs. In general, the nomenclature used in this specification is well known and commonly used in the art.

In the present invention, it was attempted to confirm whether cancer can be diagnosed with an open chromatin structure mutation marker screened using ATAC-seq.

In the present invention, when the chromatin structure mutation marker opened with ATAC-seq is selected by comparing it with a normal reference group, and the possibility of cancer occurrence in the sample is detected using the marker, cancer is detected using the open chromatin structure mutation marker with high accuracy. It was confirmed that it can be diagnosed.

That is, in an embodiment of the present invention, DNA is extracted from cells treated with a transposase to perform NGS, and then aligned based on the reference chromosome Hg19 sequence, to confirm the quality, and read the chromosome with high enrichment. A chromatin structural variation marker that opens a different section by dividing it into a certain section (bin), selecting the section that is above the reference value by graphing the matching lead amount for each section, and then comparing the lead peak value of the selected section with the reference group Was selected as. After the selected marker was treated with a transfer enzyme to another sample, the result of detection by real-time PCR using a primer capable of amplifying the marker showed that cancer diagnosis can be performed based on a three-dimensional chromatin structure with high accuracy. It was confirmed (Fig. 1, Fig. 3).

Therefore, in one aspect, the present invention,

Transposase; And

It relates to a composition for diagnosis of breast cancer comprising a primer pair specific to any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100.

In the present invention, the primer pairs specifically binding to each of the nucleic acids are 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, selected from the group consisting of SEQ ID NOs: 1 to 100 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 may be characterized as a primer pair that specifically binds to each of the nucleic acids, preferably SEQ ID NO It may be characterized by including a primer pair specific to each of the nucleic acids represented by the sequence of 1 to 20.

In the present invention, the primer pair may be characterized in that it includes a primer pair specific to each of the nucleic acids represented by the sequence of SEQ ID NOs: 21 to 40.

In the present invention, the primer pair may be characterized in that it includes a primer pair specific to each of the nucleic acids represented by the sequence of SEQ ID NOs: 41 to 60.

In the present invention, the primer pair may be characterized in that it includes a primer pair specific to each nucleic acid represented by the sequence of SEQ ID NOs: 61 to 80.

In the present invention, the primer pair may be characterized in that it includes a primer pair specific to each nucleic acid represented by the sequence of SEQ ID NOs: 81 to 100.

In the present invention, the term "breast cancer" refers to cancer in the breast, and may also be referred to interchangeably as "mammary cancer". The breast cancer may include mammary gland breast cancer, lobule breast cancer, or a combination thereof. Depending on the site of occurrence, breast cancer can be largely divided into two types: cancer that occurs in the epithelium of the ducts and leaves, and cancer that occurs in the matrix. The breast cancer may include a complex carcinoma (CC) or a type of tubular carcinoma (DC). Coronary carcinoma is a type of breast cancer that exists primarily in the duct of an individual.

In the present invention, the term "diagnosis" refers to determining the name of the disease, and may include the name of the breast cancer, the state of the disease, the stage, the etiology, the presence or absence of complications, prognosis, and recurrence.

In the present invention, the term "transposase" refers to binding to the end of a transposon and moving to another part of the genome by cut and paste, or replicative transposition. It refers to an enzyme that catalyzes. The transfer enzyme may be an enzyme classified under the EC number EC 2.7.

In the present invention, the transferase may be a Tn5 transferase. Tn5 transferase is one of the RNase superfamily that contains retroviral integrase. Tn5 transferase can be translocated by cleavage and insertion. Tn5 transferase can be used in a genome sequencing method using fragmentation of DNA, a so-called ATAC-seq technique.

In the present invention, the term "amplification" refers to a reaction to amplify a nucleic acid molecule. Various amplification reactions have been reported in the art, which are polymerase chain reaction (hereinafter referred to as PCR) (U.S. Patent Nos. 4,683,195, 4,683,202, and 4,800,159), reverse transcription-polymerase chain reaction (hereinafter referred to as RT-PCR). (Sambrook et al., Molecular Cloning.A Laboratory Manual, 3rd ed. Cold Spring Harbor Press (2001)), method of WO 89/06700 and EP 329,822, ligase chain reaction; LCR, WO 90/01069 ), repair chain reaction (EP 439,182), transcription-mediated amplification (MA, WO 88/10315), self-sustained sequence replication (WO 90/06995), Selective amplification of target polynucleotide sequences (US Pat. No. 6,410,276), consensus sequence primed polymerase chain reaction (CP-PCR, US Pat. No. 4,437,975), arbitrary Arbitrarily primed polymerase chain reaction (AP-PCR, U.S. Patent Nos. 5,413,909 and 5,861,245), nucleic acid sequence based amplification (NASBA, U.S. Patent Nos. 5,130,238, 5,409,818) , 5,554,517, and 6,063,603), strand displacement amplification and loop-mediated thermostatic amplification isothermal amplification; LAMP), but is not limited thereto.

Other amplification methods that can be used are described in US Pat. Nos. 5,242,794, 5,494,810, 4,988,617 and US 09/854,317.

PCR is the most well-known nucleic acid amplification method, and its many modifications and applications have been developed. For example, touchdown PCR, hot start PCR, nested PCR and booster PCR have been developed by modifying traditional PCR procedures to enhance the specificity or sensitivity of PCR. In addition, real-time PCR, differential display PCR (D-PCR), rapid amplification of cDNA ends (RACE), DL-PCR (PC), inverse polymerase chain reaction (inverse polymerase chain reaction: IPCR), vectorette PCR, and thermal asymmetric interlaced PCR (TAIL-PCR) have been developed for specific applications. For more information on PCR, see McPherson, M.J., and Moller, S.G. PCR. BIOS Scientific Publishers, Springer-Verlag New York Berlin Heidelberg, N.Y. (2000), the teachings of which are incorporated herein by reference.

In the present invention, the multiplex amplification is a multiplex PCR (Polymerase Chain Reaction) amplification. According to an embodiment of the present invention, the multiplex PCR amplification has an annealing temperature condition of 57-61°C, and according to another embodiment of the present invention, the multiplex PCR amplification is an annealing of 58-60°C. It has a temperature condition, and according to a specific embodiment of the present invention, the multiplex PCR amplification has an annealing temperature condition of 58.5-59.5°C.

The multiplex PCR amplification requires an appropriate number of cycles to perform PCR. According to an embodiment of the present invention, the multiplex PCR amplification is performed in 27-30 cycles. When the multiplex PCR amplification of the present invention was performed in 26 cycles or less, peaks of 500 RFU or less were formed, and peaks of 2,000 RFU or more were formed in 31 cycles, but noise increased and incomplete A insertion occurred, which is not suitable.

In the present invention, the composition may include one or more adapters (adaptor). The adapter refers to a short and synthesized oligonucleotide used in genetic engineering. The transferase may be a transferase complex to which one or two adapters are conjugated. The adapter may be inserted into either or both ends of the nucleic acid fragment by cleavage and insertion of a transfer enzyme. The adapter may include a sequence identical to or complementary to a primer for amplifying a nucleic acid.

In the present invention, the nucleic acid includes genomic DNA, chromatin, and fragments thereof. The nucleic acid may comprise an open reading frame (ORF) and a regulatory region. The regulatory region may include a promoter, an enhancer, a silencer, and an untranslated region (UTR).

In the present invention, the term'primer' refers to a single template that can serve as an initiation point for template-directed DNA synthesis under suitable conditions (i.e., 4 different nucleoside triphosphates and polymerases) in a suitable buffer at a suitable temperature. It refers to the oligonucleotide of the strand The suitable length of a primer varies depending on various factors, eg temperature and application of the primer, but is typically 15 to 30 nucleotides Short primers form a sufficiently stable hybridization complex with the template. It may generally require a lower temperature to form. The terms "forward primer" and "reverse primer" refer to the 3'end of a certain site of the template that is amplified by polymerase chain reaction and It means a primer that binds to each of the 5'ends. The sequence of the primer does not have to have a sequence that is completely complementary to some of the sequences of the template, and it is hybridized with the template to have sufficient complementarity within the range that can perform its own function. Therefore, the primer set according to one embodiment does not need to have a sequence that is completely complementary to the nucleotide sequence as a template, and it is sufficient if it has sufficient complementarity within the range capable of hybridizing to this sequence to function as a primer. The design of such a primer can be easily performed by a person skilled in the art by referring to the base sequence of the polynucleotide used as a template, for example, a primer design program (eg, PRIMER 3, VectorNTI program). You can use it.

In the present invention, the primer pair can be used without limitation as long as it is a primer pair capable of amplifying any one of SEQ ID NOs: 1 to 100, but preferably any one selected from the group consisting of SEQ ID NOs: 101 to 300 It may be characterized as being a primer pair.

For example, the forward primer for amplifying the BC3M_102 marker sequence represented by SEQ ID NO: 1 of the present invention is represented by SEQ ID NO: 101, and the reverse primer is represented by SEQ ID NO: 102. The forward primer for amplifying the BC3M_11 marker sequence represented by SEQ ID NO: 2 of the present invention may be represented by SEQ ID NO: 103, and the reverse primer may be represented by SEQ ID NO: 104.

In the present invention, the primer pair is in the primer pair represented by SEQ ID NOs: 101 to 300, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 , 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65 , 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90 , 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 , 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140 , 141, 142, 143, 144, 145, 146, 147, 148, 149, or 150 pairs of primers may be characterized, preferably, it may be characterized in that the primer pairs represented by 101 to 140.

In the present invention, the primer pair may be characterized in that the primer pair represented by SEQ ID NOs: 141 to 180.

In the present invention, the primer pair may be characterized in that the primer pair represented by SEQ ID NOs: 181 to 220.

In the present invention, the primer pair may be characterized in that the primer pair represented by SEQ ID NOs: 221 to 260.

In the present invention, the primer pair may be characterized in that the primer pair represented by SEQ ID NOs: 261 to 300.

All marker sequences used in the present invention are shown in Table 2, and all primer sequences are shown in Table 3.

In the present invention, the marker sequence may be characterized by screening by the following method:

(a) obtaining DNA sequence information (reads) by processing the nucleic acid isolated from the biological sample with a transfer enzyme;

(b) aligning the sequence information (reads) with a reference genome database of a reference group;

(c) selecting sequence information by checking a sequencing quality score for the aligned sequence information (reads);

(d) The open section of the standard chromosome is divided into a predetermined section (bin) with high read enrichment, and the number of reads of each section is checked for the selected sequence information (reads), and the value calculated by Equation 1 (RPKM) Excluding sections less than 5;

Equation 1=

(e) comparing the quantified values of the reference group and selecting a section in which a statistically significant difference occurs as an open chromatin structural variation marker candidate group;

(f) determining a candidate representing an open chromatin structure different from the reference population as an open chromatin structure mutation marker by confirming the selected marker through real-time PCR;

In the present invention, the term "reads" refers to one nucleic acid fragment obtained by analyzing sequence information using various methods known in the art. Therefore, in the present specification, the terms "sequence information" and "lead" have the same meaning in that they are a result of obtaining sequence information through a sequencing process.

In the present invention, the term “bin” is used with the same meaning as a certain section or section, and means a part of the entire chromosome sequence.

In the present invention, the term “reference group” is a reference group that can be compared like a standard sequence database, and refers to a group of people who do not currently have a specific disease or condition. In the present invention, the standard nucleotide sequence in the standard chromosome sequence database of the reference group may be a reference chromosome generated using the normal tissue of a breast cancer patient provided by Seoul National University Hospital.

In the present invention, the term "RPKM" stands for reads per kilobase of transcript per million mapped reads, and means a normalized peak value.

It means the normalized peak value for the open region (Open Chromatin) in chromatin. This is a quantification of the region based on the total number of mapped reads of the entire genome for reads mapped to the open region.

In the present invention, the chromatin includes euchromatin and heterochromatin. The chromatin may include nucleosomes in which DNA is wound about two turns around eight histone protein cores. The DNA regions between nucleosomes may have a "open chromatin" structure. Transcription factors, polymerases, etc. may be attached to open chromatin to initiate transcription. The DNA region wrapped around the histone protein core may have a "closed chromatin" structure. In closed chromatin, DNA and histone proteins are bound, so transcription factors and polymerases cannot attach. The structure of the chromatin may be changed according to intracellular signal transmission or the like.

In the present invention, the step (a)

(a-i) obtaining a cell nucleus from a biological sample;

(a-ii) adding a transferase complex containing a transferase and an adapter to the nucleus of the obtained cell, thereby generating a nucleic acid fragment labeled with the adapter at either or both ends;

(a-iii) Protein, fat, and other residues are removed from the resulting nucleic acid fragment using a salting-out method, a column chromatography method, or a beads method, Obtaining a purified nucleic acid;

(a-iv) preparing a single-end sequencing or pair-end sequencing library for the purified nucleic acid;

(a-v) reacting the produced library to a next-generation sequencer; And

(a-vi) It may be characterized in that it is carried out by a method comprising the step of obtaining sequence information (reads) of the nucleic acid in the next generation gene sequence tester.

In the present invention, between the (a-iii) and (a-iv) steps, the nucleic acid purified in the (a-ii) step is randomized by enzymatic cleavage, pulverization or a hydroshear method. It may be characterized in that it is performed by a method further including the step of producing a single-end sequencing or pair-end sequencing library by random fragmentation.

In the present invention, the next-generation sequencer is not limited thereto, but the Illumina Company's Hiseq system, the Illumina Company's Miseq system, and the Illumina Company's genome An analyzer (GA) system, a Roche Company's 454 FLX, an Applied Biosystems Company's SOLiD system, and a Life Technology Company's Ion Torrent system, but are not limited thereto.

In the present invention, the alignment step is not limited thereto, but may be performed using the BWA algorithm and the Hg19 sequence.

In the present invention, the BWA algorithm may include BWA-mem, BWA-ALN, BWA-SW or Bowtie2, but is not limited thereto.

In the present invention, the term "selecting sequence information" in the step (c) refers to whether to perform additional analysis based on the data or to terminate the analysis by checking whether a quality score, for example, a sequencing quality score satisfies a certain requirement. Means the procedure to determine.

In the present invention, the step (c)

(c-i) specifying a region of each aligned nucleic acid sequence; And

(c-ii) selecting a region in which a sequencing quality score of 30 or higher is greater than 80% of the entire nucleic acid sequence region in the region is performed.

In the present invention, step (c) may be characterized in that it additionally includes selecting a sequence that satisfies a reference value of a mapping quality score in the selected region.

In the present invention, in the step of specifying the region of the nucleic acid sequence in step (c-i), the region of the nucleic acid sequence is not limited thereto, but may be 1 kb to 1 MB.

In the present invention, in the step (c-ii), the sequencing quality score within the region may vary according to a desired criterion, but specifically, the region where the sequencing quality score is 30 or higher is the entire nucleic acid sequence Among the areas of the, the area exceeding 70%, more specifically exceeding 75%, and most specifically exceeding 80% is selected.

In the present invention, in the step (c-iii), the reference value may vary according to a desired criterion for the mapping quality score, but specifically 15 to 70, more specifically 30 to 65, Most specifically, it may be 60.

In the present invention, a predetermined interval (bin) in which the read enrichment in step (d) is high may be 15 kb to 50 kb. That is, in the present invention, the predetermined period (bin) is not limited thereto, but may be 1 kb to 1 MB, specifically 1 kb to 500 kb, more specifically 15 kb to 100 kb, more specifically 15 kb to 50 kb, and most specifically 15 kb. .

In the present invention, the statistically significant difference in step (e) may be characterized in that the p-value calculated by Equation 2 below is less than 0.05, and the fold change calculated by Equation 3 is 1.5 times or more:

Equation 2=

Here, X1 and X2 are the average RPKM values for each group (1: control group, 2: comparison group), and n1 and n2 indicate the number of samples corresponding to each group.

For example, when comparing two groups, Normal and Cancer, if 10 normal samples and 10 cancer samples are said, X1 is the average value of 10 normal samples, and X2 is the average value of 10 cancer samples.

Equation 3=

Here, control means a control group, and treatment means a control group.

In the present invention, the control group may preferably be a normal cell group or a cell group having a disease other than the target disease, and the control group may be a target disease cell group, preferably a specific cancer cell group.

In the present invention, the step (f) is

(f-i) treating the nucleic acid isolated from the biological sample with a transfer enzyme to obtain a nucleic acid fragment; And

(f-ii) amplifying the nucleic acid fragment by using a primer capable of amplifying the nucleic acid fragment, and detecting the chromatin structure of the nucleic acid.

The term "standard chromosome" of the present invention is a combination of genetic information from multiple donors that are genetically determined to be normal, and may be, for example, GRCh37 (Hg19) data provided by NCBI.

The present invention from another point of view,

Treating the nucleic acid isolated from the biological sample with a transfer enzyme to obtain a nucleic acid fragment; And

Amplification of the processed nucleic acid fragment using a primer pair specific to any one or more nucleic acids selected from the group consisting of SEQ ID NOs: 1 to 100, and detecting the chromatin structure of the nucleic acid. It is about how to provide.

In the present invention, the primer pair is in the primer pair represented by SEQ ID NOs: 101 to 300, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 , 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65 , 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90 , 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 , 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140 , 141, 142, 143, 144, 145, 146, 147, 148, 149, or 150 pairs of primers may be characterized, preferably, it may be characterized in that the primer pairs represented by 101 to 140.

In the present invention, the primer pair may be characterized in that it further comprises a primer pair represented by SEQ ID NOs: 141 to 180.

In the present invention, the primer pair may be characterized in that it further comprises a primer pair represented by SEQ ID NOs: 181 to 220.

In the present invention, the primer pair may be characterized in that it further comprises a primer pair represented by SEQ ID NOs: 221 to 260.

In the present invention, the primer pair may be characterized in that it further comprises a primer pair represented by SEQ ID NOs: 261 to 300.

In the present invention, the biological sample may be blood, bone marrow fluid, lymph fluid, saliva, tear fluid, mucous membrane fluid, amniotic fluid, or cells isolated therefrom. The biological sample may be cells isolated from blood. For example, the cells are peripheral blood mononuclear cells (PBMCs).

In the present invention, a method of obtaining a nucleus of a cell from the biological sample may be performed using a method commonly used in the art. For example, a cell membrane digestion solution can be used to separate the nuclei.

In the present invention, the method includes the step of generating a nucleic acid fragment by adding a transfer enzyme to the nucleus of the obtained cell.

The transferase can bind to open chromatin. The transferase may non-specifically bind to open chromatin, thereby cleaving open chromatin between nucleosomes in the nucleus of the cell.

The method includes amplifying the nucleic acid fragment in the presence of a primer specific for any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100, and detecting the chromatin structure of the nucleic acid.

When any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100 has an open chromatin structure, a transfer enzyme may bind to chromatin to generate a fragment of the nucleic acid. When the generated nucleic acid fragment is specifically amplified on any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100, an amplification product may be generated from the nucleic acid. When any one selected from the group consisting of 1 to 100 has a closed chromatin structure, a transferase cannot bind to the nucleic acid and a fragment of the nucleic acid cannot be generated. When a reaction product is specifically amplified on any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100, there is no fragment of the nucleic acid, so that the amplification product may not be produced or less.

That is, if the amplification amount of any one nucleic acid selected from the group consisting of SEQ ID NOs: 1 to 100 is statistically significant compared to the reference group, it means that the object in which the biological sample is detected has a high probability of developing breast cancer.

Hereinafter, the present invention will be described in more detail through examples. These examples are for illustrative purposes only, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not construed as being limited by these examples.

Example 1. Preparation and Sequencing of ATAC Library for each carcinoma.

About 20 mg of frozen tissue was crushed to separate nuclei using NIB (Nuclei isolation buffer), and then a large tissue mass was removed through filtering. Tagmentation was performed using TD buffer and Tn5 transferase (addgene, pTXB1-Tn5 vector). Then, using a HiFi Hotstart ReadyMix (KAPA: KK2601) kit, the nextera PCR primer was attached and then PCR amplification was performed. After making an ATAC library using PCR amplified DNA, it was purified using a Qiagen PCR purification kit. The sequence was read using a next-generation nucleotide sequence instrument, which is an Illumina Hiseq4000 system.

Primer sequence for NGS _{Sequence number Tagmentation index primer Sequence Sequence number Tagmentation index primer Sequence Ad1_noMX 313 Ad2.13 GTCGTGAT 301 Ad2.1 TAAGGCGA 314 Ad2.14 ACCACTGT 302 Ad2.2 CGTACTAG 315 Ad2.15 TGGATCTG 303 Ad2.3 AGGCAGAA 316 Ad2.16 CCGTTTGT 304 Ad2.4 TCCTGAGC 317 Ad2.17 TGCTGGGT 305 Ad2.5 GGACTCCT 318 Ad2.18 GAGGGGTT 306 Ad2.6 TAGGCATG 319 Ad2.19 AGGTTGGG 307 Ad2.7 CTCTCTAC 320 Ad2.20 GTGTGGTG 308 Ad2.8 CAGAGAGG 321 Ad2.21 TGGGTTTC 309 Ad2.9 GCTACGCT 322 Ad2.22 TGGTCACA 310 Ad2.10 CGAGGCTG 323 Ad2.23 TTGACCCT 311 Ad2.11 AAGAGGCA 324 Ad2.24 CCACTCCT 312 Ad2.12 GTAGAGGA}

Example 2. Pre-Processing analysis

Before searching for an open area of chromatin using sequence information (Read), first perform a sequence quality check using FastQC, a representative sequence test program, to check whether the DNA sequence was read correctly using Illumina Hiseq4000. Performed. When some sequences were read from Adapt and Primer, or when the quality of the sequence was low, the misread sequence and the sequence of low quality (Q20 or less) were removed using a removal program such as Trim_galore and Trimmomatic.

In order to confirm where the short sequences that had been tested for quality were derived from the known human reference genome sequence, the mapping (Mapping, Alignment) process was performed using Bowtie2, a representative mapping program.

Afterwards, sorting and indexing were performed using the Samtools program for downstream analysis. Among the mapped sequences, since there is biased data generated during the experiment (PCR), the duplicated sequence generated during PCR was removed using Picard (MarkDuplicates) to remove this.

Example 3. Peak Calling & Classification

In order to detect the open area of chromatin for each carcinoma, the open area of chromatin was detected using Genrich tool. More accurate information for each region was described through annotation of the open regions of the chromatin extracted in this way.

In order to confirm the change in the chromatin structure of the enhancer region, peaks present in the intergenic region were extracted, and among them, objects that were 2 kb or more and 50 kb or less from the TSS (transscription start site) were used. In order to classify specific and common chromatin structural changes for normal and breast cancer tissues, this was classified using Homer (MergePeak). To solve the problem of recognizing some biases as peaks, the peak that does not exceed the threshold value (threshold value: RPKM <5, Equation 1) is removed, and then statistically significant difference between the two groups (p-value <0.05 Equation 2). , Fold change 1.5 times or more, Equation 3) was reclassified.

Equation 1=

Equation 2=

Here, X1 and X2 are the average values of RPKM for each group (1: control group, 2: comparison group), and n1 and n2 indicate the number of samples corresponding to each group.

Equation 3=

Here, control means a control group, and treatment means a control group.

As a result, breast cancer-specific open chromatin structure mutation markers were confirmed (FIGS. 3, 4, and 5).

Breast cancer specific open chromatin structure mutation marker Sequence number name order One BC3M_102 GGGATCCCTCAGCAGCTCCGGACCTCATCTGCCCCACTTCGGCATCCCGCGCGGGAATATGACCATGTAGGAGTAACCCGGGGCTCTCAAGGACTCTACGGTTTGTCACGGTTTGAACGCAAGCGCAGGGCCTGGGGCGGGTGCAGGTGGAGGGTCGGCCTCTTTCTGCCCTTGGGAACGCCCCTTTCTGGATGTGGACCGGCGAGGCGGTCTCTCCTTTCTGCCCTCGCCTGGTGAAATGTGGGCACTGCTGCCAGGAGAAAAAAAACTGAAGCTGTGAATTCAGTTCATCACCCTTCC 2 BC3M_11 AGCGGGGCTAGACGGAGTCAGGGGCGGACCGCCACAGCCTGCACCAATCAGGACCCGGTTGATAGGCAGAGCCTGGCGACTTCGAAGACTCGCCCCCAGTCAAAGAGCCCCGGGGATTCGTTTCCGTACGCAGCCTGGAAACCAGCCTGGGCCTATCCTGCGCGCCGCTGCGGGCTACTATTGGCTGCCAAGAAACCCCGCCCATCTTCCTGCTCATTGGCCGGTGCGGTTTACGTAAGAGGAGCCTGTTGCTGAGCGAAAAGTCTGTTCTGCAATTTTCGCTAAGGAGTTGTTAACGCT 3 BC3M_117 GTACACTGACTTTGGAACAAATGCCACAGGCCCTAATTGCAGGCTCCAAGGGGCGGGCGCGCCCTGGCGCGGCTGCGCGCGCGGCTAGCCTTCCACTTTCAGGACCCGGACCTGCCCTTCCCCCACGCGGTCCCGCCCAGCCAGTCTCTCTCCCTGGCCACAGAGCGCGCTCACAAAGGCTCAGGCCCTGCAGGGCGGGCGCTGCCTGTAGG 4 BC3M_119 CTAGGAGACAAGTACCCTGCTGAGCAGACAAATAGCCTGGACTTTGTAACAGCCAAAGTGGCCCACATGGCACTCGCGGGGCTGTGCAGCATCCAGGCAGGGGACACTGCCTGGCATTCTAAAGGCCTGTGCTGAGTCATCTTTCACCCAGGAACCAGCTTCTCAAGTCCCCCAGGCTTGCCCTCCCTCAGGCAGTCAGTCTCAGTCAGTCAGTCAGTCAGTCAGTCAGTCAGCCAGGCAGTCAGCCAGGCAGTCAGTCAGCCAGGCAGCCTCAGCCAGGCAGTCAGCCAGGCAGTCAGCCTCAGCTAGCCGCAGCCAGCCAGGCAGGCAGCCAGCCAGCT 5 BC3M_125 CCACCTCTAGACCAAGTGCCTGCCTGGAATGTCCTGTCCAACTTATCCACCAGCTAGCTACTGACTGACCTAGCTAGCCACTCCATCTCTGAAGCCACCCCATGCTCATGACTCTCCCTGACGCAGGTTCCCGACACACCGGGTGACTCAGCTGCAGTGTCCCCTGAACAGCAGCTAGATCCTGTCACGAGCTAGACTGAA 6 BC3M_132 TCTGGAAGCAAGTTACCCACAGGTTTAGTTTGCCTGGAGAGAGAAACAGGCCTGACTGACTGACTGACTGACTACTGACTGACTGACTGACTGACTGACTGACTGACTGACTAGACTGCGGCCTCCCTAGGGTCTTCTGACGGCAAATTCCTCCAGCTCAGTGGCTGCTGGGCAGCAGCACAGCCGGTTTCTCTCAAGGGCTCACACCCCACACACACCGCGTCAC 7 BC3M_137 TAATTTCTCCGAGGCCAGCCAGAGCAGGTTTGTTGGCAGCAGTACCCCTCCAGCAGTCACGCGACCAGCCAATCTCCCGGCGGCGCTCGGGGAGGCGGCGCGCTCGGGAACGAGGGGAGGTGGCGGAACCGCGCCGGGGCCACCTTAAGGCCGCGCTCGCCAGCCTCGGCGGGGCGGCTCCCGCCGCCGCAACCAATGGATCTCCTCCTCTGTTTAAATAGACTCGCCGTGTCAATCATTTTCTTCTTCGTCAGCCTCCCTTCCACCGCCATATTGGGCCACTAAAAAAAGGGGGCTCGT 8 BC3M_139 CCTGACTGTGAAAGCCAGGCCCCAGCCCAAGAAGGCTTCACAGACCCCTAGGTGTGCCCTCTGTGTGAGCCAAGTGTTGACCCTGGCGATGATGCCAACAGCCCGACTCTGCCCAGCTTTCAGCCGCATGAGTGTGAACCAGCTGAGCGGCACCAGCTCAGGGCAAGGCAGAAGGCCAGGTGCACTGTCTCTAGGCAGGCAGGATGAACAGCAGCACCTGATGTCACAGCGGCCGGGGAACCACCCTGGTTGGGGCATGCTAACCCACCCTGCTAATATGCTTTGGGTCCTAATTTCCTT 9 BC3M_142 ggctcacaccctccaggggctaccctggtcactcagggtaaaagccacagcccttccagtggccttcaaggccctggtgatctgctcgcccctcccctttccactcacaccttgcccccccactcctggcaacccgtctctgctccagccacacacttgcttcattgctgttcctggaaaatactgggcatgttctggcctcggggcctttgcctcttttgtgcctgctgccaggacatctgttcctccggaaagcagcctggatcattcccttctctccttcagggctttattcaaaaa 10 BC3M_146 GGATGAGTCACTGGATCCGTTTTCAGTTCGTTCCACCCACAGATCCGTCCTTTGCAGGCGCCCCAGAAAAGATTGCTTCAGAGCTGGCACCAATGGAGAAGGGACAGAGGCCCAGCAACAGGGCGGGATTGGCAGGCGGAAGGGAGCGTGTGATGAGCTGAGCTCACAAAGGGCCGGGGTGCTGGGCTGCAGCTGGGGAGGGCGGGGTTGGATCAGCGCCTGCTCCTCCGCCTTCGTTTTTCCCCTCCCCCTAAGGATTCAGTTCCCCCTTCTGAAATTCACCACCTTGTATGTGACTTA 11 BC3M_154 cacctttcccaagatgacgacatacctaattttgcatagcacctgagattgtAGGCACCCTGCATGCCTGACTTGCACTGACTGACTGTCAGGTACTGACTGTGGTGGGGGAACCCTTGGTGACTTGCTGTGTTGTGTTGGCCAGTGTTAACACTCACTTCCCCTTAACAGCCCTCCAAACCCAAAAGGTCCCATGTCAAATCCAGTCCCTCAGTTCCCAGTACTCCCTGACTGACTGAGCCCGCTC 12 BC3M_168 GAACTCATGAGTCAGGGTCAGTCAGCCCAGAGCTGCAATGTGTACGTGCTAGCTAGCTAGCTAGCTACCTAGCTAGCTAGCTAAGCCTACGCATGCACCCCTGCAGGCACTTACCAGCCTCCTCATCCGTATATCCTGGAAAGGGTGCAAGCATGCCTGGCTTAGTCATCCATCCACAGGAAGGAAGTTGTTGCACAGCTAGCTACGTAGCACAGAGCTAGCTACCTAGCTAGCTAGCTACCT 13 BC3M_171 CAGACAGAGGCCGCTGAATTAACCCGTGGAGGCGTCTCTCTGAGCAGAGCCCGCAATGCGCCTGCTTGGGGCTCCCTGCAGCCTCTGGGGGAGGCAGGGCGGCCCAGAGCAGGCCTGTGCTGGAAAGGAACGCGAAGCCCTGTAACCAAGCCTGTACCTCTGCAGTGCTAGTCCCAAGGGGCCTCCGAGCTGTTTGTCACCATGTGATTGGCTCAGGAGAGGGGTGGAGAAATGAAAACACTCTGCCCAGGATATATTTAGTTGAAGTGCAGCTGGGGAAGTGCTTAAACAAGGGAGCTT 14 BC3M_172 TCTTGGATTTCTGAATATGCAGTTCTGTTCCTAACCAGTGTGTCCCAACCAGAAAGTCACTGTAATTTTTGGTTTTGTTCCCAATCTCCCTCCAAATGTCATTAGTCATATCCTCCTTCCCATttctgccttgaataggcagtcattatgatgaagggggggggggcttgcccctccgaggggggctgcccctccagggggggt 15 BC3M_173 aTTGGTGAGGCGCCGCGCCTCGGTGTCGCAGCGAATCCGCAGATCCTCAAGCCAGGTGGGGGCGCCCACTGCGCGTGTGCAGCGCCTGATAGCCAGGCTAGCTGAGGGCGGGGAGCAGCTGCGGCACCTGGGACACAGCGATTGGCTGGGACCAGGAGAGGGCGGGAAGAAGAACTTGGCGGAGCGCGCTCATATCTCTGATTGGCTGCCAAGGGTAGCCCTTGACAGCTGCCGGGTGGGACCCGTAGACCGCGAGCGCACTGGCCCGTGATTGGTTGGGGTGCGGCGGCGAGCATCTGC 16 BC3M_178 agcacttcccgggcgccccgcctcagtttccccatctataaagtggggagatgataataGCATTCAGTGGCACTGATCTAAGGGCTCAGGGACACCATTCAGTGTAAGCCCCATACACTCCCTGCAAGAGAGGAAGCTGGTTCTGACTCAGCCTTGAGGCTGGCGCGATGCATGCAGGTGGCTGACTGCATGACGT 17 BC3M_179 CCCCCGACACCACCACCTCCTTCTTCGCCTTGCATCGGTACGATAAGGCACTTGCTTGACGGGAAAGAGAAACTCAGCTGCCAGCTGGGGTTCATTTGCACTTTCCCCCGCCTGGTCTGCGGTCTGGCTGTGCAGCTAGCCGCTCTGACGGGGAGGAGGGGCCCAAAGCCACTGCCTGCCGCCTGGGCAGGGGAGAGGGGCACGTGAGGCTCATGGCAGAGGCACAGCCAGCTTCTTGCATGTGCCCTCCCCGGGGAATGTCTGCAGAGCCCAAGACTGCCACGCCGTGGGCACAGCCCT 18 BC3M_182 GGGAAACCTTGCAGACTGTGGGGTCCTGCACACCTAGACTTGCTCCTTTTAGAAGCCATGGAGGAGGTTGATAATGGGAATaacatttattgtagcttatctctatgccttgagcaatgtgctcacactggctggttccctcctcacatcagcctgatgagtcagatcctgttattacttctcactttacagatgaggaaGTAGCAGTAAATCCATTACCCTTTTCAAGCGGAGGTTGCAAGAGGTTGCAAGCGGAGGCAGAATAAACACTTGAAACAGtgagtcagatcctgttatcac 19 BC3M_199 GGAACCCTAGGATCTGATTTAGGACATTTGGAATCTTTAAGGCACATTCGATCTGCATGACTGACTGCTACTGACTGACTGACTGACTGACTGACTGACTGACTGACTGACTGACTGACTGACTGACAGTGACTGACAGTGACTGACTGACAGAGAGGATGATTTTACAGTATAGGGTTTGTGTGGAAATCCCCTTCAGCAGTAATCAACCCAGGTGTCCAACCTGTTTGTTAACCATTTC 20 BC3M_20 tcgTGTGGGCCTGGGCCGCTTGCTATTACTAATAAAACAGCAGCAACCACAGGACAGCTTCACTTCCGGAAACTCCCTCTGTCACGTGCTTTGCATGAATCCTCACACCGTCTCACTAGGGGCGCTCTCCCCGTTTCACCAGTGACTTGGTGACAACCAGCCTTGCTCACGAAGCGTCAGCCGTATCCTTTCTGTGTGCAGTGGGGTGTGGGTTGTGTGGAGCCGCGGTGTCTGTGGAATTCACAGGCTGGGGCCGGAATCCATGGCCCCCGTCGCCGCTGCCACCCCCCAGGTGCTGGG 21 BC3M_203 AGGTGGTGCGCCGGCGGTTCGCAGCTGCTGTGCCCGCTGGCCTGGGCGCAGCCGGGGACAGCGACGCGTTTCCTGCCCGGGAAGGGCCCGAGCGCAGGGCCGGCTATAGCGGTCCCGCAGCTGCCTGCTTCGATTTTAGCACTGCTGCTCCCTAGAGGGAGCAACGCGGCCCTCTGTCCCTCGTAGGGCTTGAAATGTAAATTATTCATATCAGGGGAATGTGTGCTTCAAAAAGCAAGCTGGACAAGAACCGACGGGTAATCCTCGCCAAATTCTTCTATTTAACCCTCACCATTAAAA 22 BC3M_206 TGAATGTCATGAGTCAGGAAAAAAGAATTTGAGCGCAGTCTGGAAATGAAATTTCCTGCCTGTGGTTTGACTCACGTCTGTCTGTCTCGAAATCTACCCCAAGGACATTTATTCCACTGTGACAGGGCTCATCTCTGAGGAGCACCAGACTCCTGCGGTGGGGAGGGAAGATTATCCGCGCTGCAGAGACTAGCTGGCCTCCGGAAGCCGCCTCCTGACCCCGCGTCAAGCACCGCGGTGGATGGCGCAACCCAGCTTTGGGAATTAATTACCCAAGGCGCGTTTCCGTGCAGTCTGGCC 23 BC3M_212 AATGCCCTGCCCGATCCAGTTCCGGCCTCCCATCTCCCCTTCCCGCGTCTCCACGCTCTTTCCTTCCCCGGTTCTGCCGTGAATGCTCCCAAGTCCTAGAGCACCGGAACTCCCCGCGCGCCTTGGCTCCTGGGCCCCAGCTCCGTGCAGTCCTGGACTGGGGCTCCAGGTCCACCAGGGGGCGCCCGCTGCCCAAGCTGGGTATCGCTGCGGAGAAAAGGGGCCCAGAGTGATTGTTCCTCAGGGGAGGGAGGGGGAGGTCCCCAGAGGGAAGGGCCTGAGTTTCCTCTTGGGGGATGG 24 BC3M_22 aaactaacagggaatggtgttgccacctgtagccccagctacttgagagccccccagctacttgagagactgaagcaggaaaatcccttgaagccggcaggcaaagattgcTCACTACAGTCTAGTCTAAAACCCCACTTCCAAAAAAAAAAAAACGCTCACACTCACACCATTACAACAGCCCAAAAAACGCACACTCACACACCATTACAACAGCCCAAAAAACGCTCACACTCACACACCATTACAACACAGCCCAAAAAACGCTCACACTCACACACACACGCACACTCACACACACGCTCACACTCACACACACGCTCACACTCACACACACGCTCACACTCACACACACACGCACACTCACACACACACGCACACTCACACACAATGATACACACACAACACTTACCCACACACACAACACTTACCCACACACAACAAATTACACtccACACACACAACA 25 BC3M_221 cccaaagtactgtgatgagctactacgcctggtcATTGTCCCTGCGGCTGCGCCCGCGCACGGCTGCACGCACGCACGGCTGCACTGCGCACGCACGCACGCACGCACGCACGCGCGCACGCGCGCACGCGCACGCGCACGCCACACATCCCTCAACTTCCCAGTGGTTCCACGATGACTAAGCCAGCCAGCCCTGTCCCTGAGGCTGG 26 BC3M_224 ttacccaagatcaTTCGGTGCGGCCTCAGCGCTGGCGCTGAGTCCTCTTCTGCCCCACCCCTCAGGCTCCCAGTCCTGGTCTAGATCCCTAGCCACGTAGCGTAGAAGGGGGCGTCGACGGGGGTTGGGCTAGAGTTGGAGCGGGGAGGAGATGAGCTAAAGCGGGGCTGGCTGTGCGAGAGGCAGTAGCAGCGGCGTGTGTCCTGGGGCGCCCCCCGGTGGCCTGTGCTGGGGTCGTCGGCCGGGATCCCCTGTTCGACGTACTCCGGGGCTGAATGGGAAACAGACAGTCCCAGACCC 27 BC3M_226 aaaaaagaCTAAGTGGAGATGAGGGTTCAGTGCACCCCCCCATCTCTCCTGGCCCTGCTGCCTGCCGGGCGCGCGCGCGCGCGCGCGCGCGCGCTGGCCATGAGCCAGACCCTGAGCTGACAGATTGGTGCCCATTTCCTCTTATGGATTGATACGGGGCTCTTACCTCTGGGTTTGCTCAGCCCAGCAGCAGGCAGTCAGAGCCGCAGGCGGACGGTCTGGCGATGACAACCGG 28 BC3M_230 AGGGGCAGGGCCAGGGCGGTTGGTGGACTGGGCCTGGCTGTACGTAGGTGCTCTGAGAAGCCCCCGGCGAGAGGGGCGGGGCCAGAGCAACAGTGGGCGGGGACAGGCTGTGCGTCGGAGCTCCGCGGGGCCTGCGGCGGGGTGGGTGGGGCCAGGGCGGCGGTGGGCGGGCCGTGCTGTGCGTAGGGGCGCTGAGAGGCCCGCAATGTGAGAGGGGCGGGGCCGGAACAGCGGTGGACGGGGTCTGTAGTTCAACTGTGCCGTGGCGTCTTCTTCGCGGCGAGATCTGAGTGCCTCGCA 29 BC3M_231 GGAGCGGTGCAAAGGTTCTTATCCTATTTATCGGAGCCAGTGTCCAGAAAAGTGATTGACTGATACTGATAAATCCGGTTCCAAGAGCACGAGGTAGGACTCTGAATCCGATGTGGTTTCTGTTCTCGGTGATGGTGTGCAGAGCTGTGAGCCAGTGTCCCTAGTTGATTGACATTCCTAGTAGTGATACATT 30 BC3M_232 GGCCTCTTGGGGGCGCGGTGAGTAGGTGGCCTCTCCAAGCACCACTCCCGATGTGCGCATGAGCGCAGCCGCCCCTACGCAGCGCGTGCGCACGTGCACTCACCACGTCCATCCCAGACGTGCGGACCCGGGTGTCTGCAAGGTTCAGTCTCCACACCCCAGCGCCCGACCCTGCGCGGGGACATGCGCACAAGCGCGCGTCCTGACCACCCGGACGTGCTGGCCCACACGCACACGCGTGCGCATTACCCCCGCCCCATCCGCGCCTGCGCTCAACCCCGCCTACACCTGCTCCGTGGC 31 BC3M_235 GGTCCTGGACCGGGACTTAGGTCCACACCCACGTGCTGACGTCGGGCAGGCTCAGCGGCCTCCCGCGCCTGCGCAGCACCGCCCTTTTCGGGCGCGGCGCCCAGTCCCTACACCCCACAATCCCCCGCGCCGTTCCGGAGGCGCGCTAGGAGTGGGTGTGGCCTCTGCCTCCACATTGGAACAAGGTGAGGCAGAGGGTGTCGCGTGGTCTTCTGGGAAATGTAGTTCGTCTGCCAGGCCGGAACCACCGCTCAACCGGCTCGCGAGACTATGCACCCCACAATGCGCCGCGCGCGCAGC 32 BC3M_239 TCTAAGTCTGTGCATGCATTTGTGGTCAGAGTCTGGGGAGCTGGGGGCGTGAATGGGCTGCTTCAGACACTGCTTTGAGGGTGTGACCAGGACCTGAGGGTGTGGTTAAGGTGTAGGGGTGGGGCTAGGCCCTTGGGGGTGGGACCACAGTCCCAGAGGCGACCACAGTCCCAGAGAGGCGTCCCCGGCCAGAGTCGAAGGTCCCCGGCCAGGTAGGTAGTCCCGGCCAG 33 BC3M_241 GTGGCCCGCTGTAGCCCCGCCCCGTGGCCCGCCCGCAGTAGGCCCGATTCAAATCTGGCCAATGATAGTGTGTAAACAAACCCAGGCCCCGCCTCCCGACGAATAATCCCCCGACCGGCGAGAGGCCCATTTAACCCGATGGGGTTTGGGGTTGGGACGGTGATGGAGTCGTGGCTCCGCCCCCAGACCTGGGCCAATAGGCGGCTGGGCTCCGCCCCCGGCACTTGCCGCGCTGAGGACCCGAGGCAGGGCTGGGCGCGCAGTTGCCTGATTTCGTGGCGGCTCGCAGTCTGGGCGCTC 34 BC3M_245 cctccaaaagtgctgggattactggcgtgagccaccgcgcccggccTCAGGGCGCGCTTTTAAGGAGAGTTCCTGACATGACGGTGGGCTTTTCCTGCAGATGCACCTCTGGGTAGCGCCCTCTTTACAGCCTTGAAACCTGGTCAACTACATTACTCAGAAAGCTCTGCGTTGAATGAATGCCGTCAGAGCCAATGAGGGCTCGGAAAGAAGCATTTCCGTGTGTGCGCCTAATGTAGGGCCGAGACTTCCGGGGTCCTCTTGTAGCGGCCACGTTGATCTGCGATACGCGTGTTTGCC 35 BC3M_247 ACAGCCTTTTGGAAGTCGCGCTAACCTTGGCCTGAGACCTGCAAACTTGCCCAGGCTGGGGCGTGTGAACCGGCGAGCGCGCAGCGGAAACGGGGCGGGGCACCTGAGGCTGGGAATGCAGAGGAGCCTTCCGGGGGGCGGGGCGGGGCCTCCCGTGCAGACCAATGGTGGAGTAGATGCAGATGTCAAAACGCGCGCTCAAgtggcttccgccaggaatcccgacgcttagggaggcggagggaggatcgcttgagaccagcctgggcaaacaagcgagaccctcgtctgtttacttaa 36 BC3M_250 AGGCTCCAAGGAGTTCAGCATAGCACGAGCTTTTAATTTGCGTGCAGACTAGTGACTGCCTGACTGACTGACTGACTGACTGACTGACTGAGTCTGAGTCTGTTATTTCCCAATGACCTGAGAGCCCGAAGTTTATGTTAAGCCTTGGGTTATGGCAGCTTGCACGCAAGGCCCTGCAGCTAGTGCCTGCAGGCAATTAGAGTGCCTGACGGAC 37 BC3M_252 aacacacacaacacacacacacacacTCTTTCAAGGTCTAGCAAAACCCATCAGGAGAGGTTGGGCCCTGGAGGTGCTGTGGCTTCCTGCTGCCCCGCTCCCTCCCGCCTCCTCCCTGCAGGGCTCCTCCTGGGGAGGCCTGTCCAGCTGCCAGGCCCCGCCCCGCCACAGCCCCCGCTGTCCTCCTCCCTCCCTCAGCCGTGCCAGCAGCGGCACAGAACTGGAATTGCCCTGGACGGCCACAGCTCTGCATATCCCCCAGGAGTGTGGACAAGAAAAAATAAACACAATTAGAGTTCA 38 BC3M_253 AAGAGAAGCCTGTCAGTCCAGCTCGGGCTACACACTGGGTGAGCCATGCACCACCCAGGAATTTCCAGGGCACGTGCCACGTAAGGGGCACACCCGACAGAGTCCAATGGGGTTCCCCACTGGGCCTCCCACTGAGTTGCTCAGCCTGGGCCGGAAAAGGGTGAGTCACCCTGGGGGTGGGGCTCTCCAGGGTAGAGGCCAAAGGAGTGACTACCATGACAATTCTCCGGAGGGCCTGAGGCGGCGGTGGACAGCCCCGGCAACAGTGGGCCCTCCCCGCAGAACTGTGGTTCCAATCCC 39 BC3M_255 gcgtgcttgtgtgtgggtgtgtggtggggtatgtgtgtgtCCGGGGCTGCCGATTCAACTGAAAAACAAAAGCGGCTCTGAGTCTGAAGCTAAGGTTTAACAAGTGACCAAGATGACTCATGCTGCTTGGCTGCAAAGGCCACAGGGCTGCCACCCCCAGCGGGGCGGGGCCTGGGTGGGAAGAGTCACAGGTACAGAGGCTCCTGTGACATTCACACTCTGCCCCTGCATCGGCTGCCTTTGGGGCCAAATACTTTTGTGAAAATTAAGACAGAAggccgggtgcggtggttcacgcgt 40 BC3M_257 AAACCTGCGGGCCCCGGTCCAGGCGTGGTCCCGCTCGCACGAGGGAGCGGTCGCCCAGGGTGCCGGGAAGTCGGGGACCGGCCAGCCGCCGACCGGCCGCACCCCTCCCCGCCGAGCTCGCGCGCCCGCCTCGTCAGCACCTTTCCCGCAGCGCAGCCCCACAGTGGTCACGAGGCGGGCGCGGCCCGGTCAGCCCTGGCTAGACTAGGCATCGGCACCACCCACCTCGCCCCTCCCCGTCCCGCTGGTTTcccctccccctccttcccctccccctctctgttctccttcccctcccGATCCCCGGGCGGGCCGCAGCGCGCCACGTACCTGGCCCCGCCCCTGCGAGCCACGCAGGGAACCCCGGTGACGTCACCACCCTCCGGCGCTCTCATTCCCG 41 BC3M_260 cctgattagccagaactataggtgcacaccaccacccgcctggctaatttatttttgtatttttttgtagagacagggtttcaacatactgcccaagctggtcttgaactcctgggctcaaatgatccgctctccttggcctgccaaagtgcagggccccccccccccccccgcccattcccattcccattcccattcccattatttttgtatttttttgtagagacag 42 BC3M_265 TGTTTCTAGCTAGTTATAATTGGCAGGCAACCAGAAGCCTCATCTGCCAAGGGCGGAAGTCATGTCTGGAACAGGTTTCCCTCTTAAGACTGTGGGCTAACCCAGCATCTTGCCACTTTGTGTGGGACTTCCTCATTCTTAGTACATATCTCACTTCGTTTGACCCTACTGTCCCTCGGTAACTAGTCGATCCCTCGGTAACTAGTCACACTCTCGGTA 43 BC3M_266 AAGGAGAGATGATGGAGGCAACACTTACAGGTCCTGAAAACTGCTCAAGGAGGCACTGCATGCATGACTGACTGAAACGAAGGATGCCTGAAAATAATGATGATGCAAAAACTAAGCTAGGTAGGGCAGCAGGAAGAACCGGTTTGGTGGGAAGATGATGAATTTGGCTTGAGGTGAGTCCCTGACGGAGACTGACTGACTGACTGACGCAG 44 BC3M_267 CCCATGCAACTGTGTGATGAAACAGCCCCACACATCCGGGAGCACAGCCAAGGCGTCCTGTGCCACCTCCCTGGTAGAATCTGGCTTTTCAACTTGCTCACCCATGAGAGGAAAGCGGTTTTAGACATCAGGCTTACCCCTCTCCTAAGCCACACCCTTTTCTCATTCCCAGCTGAGGAACTGAGCCTGAGACACTGAGGTTCCCAGCTGCCTCCATGATTCGCCAGCACCCAGCTTCAGTTTCACATCCTCCCAATCGTCATAGCCAGGACAGCATGCCTCACTGACCACGAGGGAATG 45 BC3M_268 AGGCGCCGCCGCTGAGGGCAGGCAGCCCGGCAGCCACTACACACGGACCCGTGACGTCGGGCGTAGCGCGGCGCACGTCACGGCCGCTCGCTCGTGCGCGCGCACCCCTCCGCCCGGCGGTAGCGGAAcccgccgcgggcgcgcgcccggcccAGGGGAGTGGGTCGGCGCCTGCGCAGAGGCCCGCCACGCCCACACACAGGCCACCGCCCCCACCGGCCGGACGGCGCGGGGATTCCCAGTCCTGGCTCCGccccggcctcggccccgcccccgcccctgccccGGGGCAGCCTGTGCTGTTCCGTGTGCGCGGCGCATACGCACCTGGGTTGTCTCGAGCCTGCGGTAGTGGCCAGATCCCAGACATCCGAGTAGATCCCGTGAAAAGGTCTCCCAC 46 BC3M_269 ccagccactgtgagtactggctgctcctgactcacagctgcaccctttgagggagtgaggggcgttacccttggctgacaggatatgattagaaagcctggaaggcggctggtggtggcccatggccaatgagtcactgtgcgagtgtatactagcccagccctcttgcctccaggcaggaaaacctctgtgtgaagtgctctacttgctccatgctctggcgctctctgtacctacgcaggctgaagctgagcctagacatctcctgaaaccacacctttgactcgcttcttccccttc 47 BC3M_27 AACTTGAAACAAATAAAGCAGGTTGAAGATCACAGTGTGTGCTGCTGGGCCTGTGGGGGCGCTGGGCAGCAGAAAGGCACACTCTGCCTGCAGCCTCGGGATCTGGTCGCCTGTGTGGGAGTAGGGAGGAGTCCTGACGTACCCTCTCTAAGACTGGCTGCTCTGCACCTCCCTCCAAGCCAGGCTGGCCAGTAAAGAAATCTAGCTGTGGACAGGAAACGAGTGGTTTTTGTGATCTGAGCAGAAAGGGCGTTTTAGGCCTGGAGCAGAGTGGAGGCCCTGAGCCACGGCCCAGGAAGT 48 BC3M_275 tttgtgtgcatgtgcgtgtgtgtCTGGGGGAAGGAGGTAGAGGAAGTGAGATGATGGTGACAGTGACAGCAGCTTGGAGAAGACAGGGGGGTGGGTCTACTTCTGAGGAAGTCCTTGGCTGAGGTAGGGCCGCAGAGAGGCAGGGTGAGGGTGGAGCCTGTGGTTTCAGAGAGGAGTTTTAATGGCTGCCAAGAATGTGCACATGAAGCCGAAAGGGAGTGCGGCCTGGAGCTGCAGTCAGCCCAGAGGGCGGGTGGAGCCTGTCCCAGGGCACTAGGATCGCAGAGAACGACAGGAGGG 49 BC3M_277 AAGGTATTCGAATCGAATGAAATGGAATCGAATTGAAGGGGTATgaatggaatggaatggaatggaatcgaatcgaatttaatggaattgaataggaaagaatcaaatggaatggaatcaacccgagtggaatggaatggaatggaaaggaatggaatggaatggaatggaatggaatggaatggaatggaatggactccagtggaaaagactggaatggaacggtttcgaatgaaattgaatcgaatgaaatggaatggaatgcaatggaatcaaatggaatggacttgaatggaatgg 50 BC3M_283 CCCATCGTGTTGCGAAAGCATTCAGGTTGAACAGTGTTCAGGAAGAATACTCAAGCAAAAACTGGTTTGCAGCCAAATAcagagactgcaaaccccagtggcttcaggggccaggcagggaaagtaaacatgtgaaacaatagggagtagtcctgcctgtggggaacaggggagttctcatgccccagcctaaTAAATGAAAAAATTATTTATACACCACAGTGGAACCGGAGATGCACCTAAAGCCATTGGGATGTGGTTtctctttttcatctcactgctctgtctctgatgtggctt 51 BC3M_284 AGCTTGGATGCTGCACCCAGGACTGAAAGGGGGACCTGTGGGCGGCCTCTGCCTCTCCCCGCGCAGCGTCAGGACACAGGCCCACATTCCCTCCTGGCTTCTCCCTGAAGGGAGAGAGAATAATAGTTGGTTCAAATGTCAGGCCTGCTCCGTGCTGGTGGGGAGACTGGTTGAGCAGGTCCGCAGGAGGGACGGAGGGAGGAAATTATTAATAATTGCAAAGCAACCAGCCACACTACAGGCCTTGAGTTGTGTCTGCGTTTGTCTTTGGAGGTGTGGAGTTGGGGGTGCTGATCCTGG 52 BC3M_290 CTGGGGGACTGTTGGGTCAGAAAGTGTTCAGGGAGCAGCTGTTgcgccctccctcggccccgccgctcggagacgccccgccccctgccttcaccggccgccccgccccctgccttcaccggccgcccggccacgccccacaccgccccggccccgccccagcgcccacgtgactagcataggcgcgcccctgctccgccccccgccgccgactccgcctccgGGACGGGAGCGAGCGGCGAGCGCGCGCACTCCCAGTTCTCGCTCGGCGACTCCCGCGCACGCGCGCGCCGTGCCACC 53 BC3M_291 CTTTTTCCTTTAAAGAATACACTTCTTATGTAATTTGTTTTGCATTTCTGGAATGAGGAACTTTTCTGCTCATATTGTTGTTAAAATCTAGACAACACGCCCGTGTGATAGATCACCCTGAGCCTTGGAAGGAAATGATTCACCACAATACTGTAACTGAAAGTCGTCTAACACCAGGGCTGGAAGGCAGGCTATGAACCGCTGCATTACCTGCGTGCAGCAGCAATGGGAGGCAGCCAGAGGTTCCCTCGGCCTGCCTAGCTCACTTCAGCTTTGTTCCTGTTCTGTTTCCTCCGTCCG 54 BC3M_292 CATCAAGGGACCCAGAGATCACAGAATAGCCAGCCCTTCATTTTCAGGTGAGGGCCTCTGTGGGAAGGTGCGTTCCAAGCCACACAGTTGGAAGTTGAGCGAACTGAACCAAGGCTGGGCTTTTGTGTTTGCTGTTTAAACAGTGTGTGTGGTTTTACTCACCTACCATAGTGCTCCTCCTGTATTTCGGTGCATTCCTTACTT 55 BC3M_295 TAGCAACATGAGGCAACCTTGTCTGCGAAAGAGGAGGTGACCGCAGCTCCTGGGGATGTGCCAACTCTGGGATGTGACGGGAAGACAAAGGGCTTCTGTCCCCTTCTGCCTGGCGGTAAGAGAGCCGGCCGCCCGGCAGGCATGCCCCAGCCTGTGGTTCTGGAATGCGGGCAAGCCACCGTCCCCAGAGACCTGTGTTGGTGGCCAGGCCAGCCCACACACCCGATTGGCACATACTCTTGTGCTTGCCCAGGAGCGGAGTCAGACCATTCACGCTGCCTTCATGGGAGTTGAACAGTT 56 BC3M_307 TGCCCCCACATCGCCATCCTGCCTGTCCTTCTGGGCCTGCACGTTTGTTGTGTTTGGAAGGAGCCACCAAGGAGGAGGATGTCAATGTGCAAGTTCTCAGGGAAGCAGGCCCCGCAGCCTCCGTCAGTGTCTTCCGTCCGCAGGAAGAACCCAGGCCTGGGTGATTCATCGGGGCCTCAGGGCCGGGAGGCACTAAATCTTCTGCAGATGTGGTAAGATCCTATCACAGCAGAAAGGGAAGGGCTAGAGTCTCAGGGAAGGTTTTGCTAGGGAGACGGGCTTGGAGGGGGCTGAGGCTCA 57 BC3M_321 caaaaaatactgagcacaaataaatattcaCTGTAAGGCAGGAGGCagccgggaccagactccagatcagatcgaagactggcggaaactgaggagaggcgcttaaagcccctctccataagacacgcccaccaccacctccatgacagccccccccattgccccgtgcccccccccctccccgcccctcccctcc 58 BC3M_323 tggtctctatctcctgatcttgtgatacgccggccgcggcctcccaaagtgccgggattacaggcatgagccaccaggcacggcTGAACAGGGTTTTTTTAAAGTTCCTGAACTGGGTGGCTGCCCACAAGAGGGCACTCATGCCTCTGCGTGTGAGTGTGGAACCTGGTCGACTGCTGTGACACTCTTTGGGAAGACAGTCGGCATTTTCCACTTCCAGCAGCAGGTGGCAGTATGGGCAAGAGTATCATCACCCATCTTTCATCTACCACCCATGTGCTTACATCTGGGCTGCTGAGA 59 BC3M_326 CTCACCCGTAACACACACACACACATGCGCGCCCTCTCCTCTTGCATGACTCCTCTCTCAGGGCTGAGCTGTTTTTCTGAGGGTGCCACAATGAATCAGCTGCTTAGTCATCTCTGGAGTGCGGGAGCTAGCAGAACAGCAAAGAGGCATTACAAACCCAATAGCGGGTTTCACTTCCTTGAGCAGTATTTATTCTGCTCTCTACCTCATGCTGCCCAAACTGTTGGAGAGGCCCTATCCACTCTCCCTGCCTTTTCAGCCCTTATTCTCCCAAATGCAGCCACAGAGGAGGTAAGAGAG 60 BC3M_334 TTTTTGTGGTTGAGTTCTGAATTAAAAAGTGTCGTACTATATATTTGTTTGGTCATTACTGCATTACTTACACTAGACTAGAGACTTGAGACTGACTGACTTACTTACTTACTCTATGACTTCAGCACTCTCAAAGACTTGGACAGAAGCATAAATAAGAGGCAGTGTGAGCATTCTCCAAGTAATCATTCCAAGTTGGTGAGTTCATACTCCACCTAGACCTCATTGGGCCTCGCCACTCTCTCAGTGTCAAACTAG 61 BC3M_353 AGGGCATTTGCTGAGTTTTGCTTTAtgtgactggatgggactggccttggagacactaataagcacgtgagggtttttggacaatgcgaagagttggtgccaagccacaagtgggagatgttgaacttcctgcgaatctggtgtgttgtagcctgagtcggtttcaatatgaaaaataagagtgacagtgccttccttgtatgctaatctggcgaagtggctcatgctggCCATGTAACAACCTGGCAGCCTCCTACAGAAGCAAGTGGGGTGTGGCATTCCTGCTGTCTGCATCTTCTG 62 BC3M_360 TGAGTGAGCTGGCAAGGGAAGGAAGGTTGGTGAGAGTAAGTCGTAAGTATCTTTTTAGAAAAAGAAAAAAAAAAAAAtagcagaggatggtttcgatccatcgacctctgggttatgggcccagcacgcttccgctgcgccactctgctCTATACGGTAGTGATATTTGCAGTGAATTCTTTATGATGTTTTCCTCAAAACTTGGTGGGGATTCTGGTTTTTTGGTATGGTTAAACAAATCTGATTTCCACACCCCACCAAGGGCCACTAGTTCTATTTATGCTGCAAACATGAGGATGA 63 BC3M_362 agacactcgtgccctcaagaacttacaatttagGTTTGTTTGAAAGTTAACTGAGAATTCCAAGTCTAAGGGTGCTGGTGAGAGTGGCCTGGCAAAGCCAGCCCAGGAAGAGCTGCTGAGCAGGTTGTAAGGAACGAGGATGCCCCACCCCCCCTCCTTGGCAAAGCAGAGGATGGTATTCCAGACAGGTCACAAACAGCTCAAGCAAAGACGTGGTGACAGGGATGAGGAAGGCACGCTTGCGGATCGCTAGAATGGAGGTTGCCTGGGCACAGACACCTTGGAGGATCCGATTAGCAA 64 BC3M_367 GCAGCACCCAGTTCAGAACTTTGCAGATTGCTGGAATTGCTGGGGAGCTGCCAGAGGGCTTTCAGAACTCAGCATGAGTGCAGTGAGTGCGGCAGCCAGCTCCCAAAGGGGATGGCCTCAGCATAGTTTCCAGCTCTCGGCTCTCTTAACAGGAaggcgttgcggtgtcgcagacacaatctgaagtgggggttcaaacagacacaacttcacatactggttttgcaacttgctggcaaatgagtgaattttactcaatcccaatttttctcatctgtaaaacagccataaaatcgaccc 65 BC3M_37 CCTTCCCTCGACCTCCCTTCTACCCCTTCGCCTTAGATGGAGATTTTCTCTTTCTGAACCCGGAACCGCTCCCTCCTCCCCGCCCGGCTATAGCTGGCAGGACAGGGATTGGATGCCACGGCCGGTGCGAGCCTTCGCTCTCCGCCGAGGGTAGTGACACAGGCGAGGACGGGCCCCGCAGGTCACATGAGGGCGGGGCCTGGCGGGCTCGTGACCTTCCCGTAGGCGGGGTCCCTCCCCTCCCAGCTCGGGCCGACAGCGTCGTCACCAGCTTTTATGGGGCACGTGGCGGCTGATGCA 66 BC3M_380 TTCACTGTCTGCTGGGGCAGGAGGCAGGGCAGGGGCAGGAGGGAGGCAACCCCAGCCTGTGCCCGGCTTCCCCGAGGCGTGTGCCTTGTGCGGCTGCTGAAGGAGTGACTCCTGAGGAAACCAGCTTTTCCAGGGAGGCAAGGGATGGGAGAAGAGGGTGGAGAAGGAAGTGGTCACACCACTTGCCTTCTGCCAATACTGTCCCTTTCTTACGCGTTAACCTTCCACTCTGAGCTATGACACTTTCAGTACTAGTGTGGTAAGTTCTACAGGAAACAGGAAACATGGTTTAACAGACAT 67 BC3M_39 GCGGGGCTCACGAGTGACGAAGGGCAGAAGGGCGGGGCGGGACgagaggaggggaggggcgagcggaggggagggacgagaggaggggcgggacgagaggggggcgggacgagaggaggggcggggCTCACGAGTGACGCAGGGCAGAAGGGCGGGGCGCAAGAGAGACTGAGAGCACTACgcgggtgagaggaggggcggggcgtgggagtgacggggcgtgggagtgactgggcgcggagaggccggagccggaggcgaggcgaggcgTGAGAGTGAATGAGGGAGGAGGGCTGTGAG 68 BC3M_393 agcaggcacttctgagcctgcagaggaaaggggacttcccggggcccccgagagcacagggatgcccggtttgggagccttggctaggcagctgcagctgcgcaggagggtggggcttccgccccgccgactcagaagcgggcggggcttcggcctcttcccggctcccgccagctccgtggagcctggagccccagccgcgcctccctggctgcagctgctgtattcacagcagccgcttcaggcgggccgccacggcgatcagtttttcatggcctccaggttctgatgaagcgtggg 69 BC3M_402 TAGCATCAGGGTACCTGCTCTGGGCTTGGCTCCTCTTGGCCTTGGCTCCTCTGGTGCCGCACGGTCTTACTCAGGAGGAGCAGACACCTCGCCAGCCGGGGTGTGTCTGAGCCCCAGGAATCCTGCCTCGCAGGGAGGATTCTCTCTGAGTAGAGGTGATGTGTTCCTCAGCCGTGACTACGCATTTCGATCAGCCGTGACT 70 BC3M_406 acaagctctgacacagcgtatactcagtaaacatggagtgaatcagttcattcaatgaatgaaCGAATGAATGAAACGCCAGAGCCCGCCACAGGGGTCCGCTGCCGCTCCACGCCCGGGCCTCTCACCGGCCAATCAACACTGTGACTCGTACGCCCTGCCCCCTGATGCCACGCCCATCACTCGCCCCTCTGGATTCCCTCCGGCTGCGTGGAAATCCCGGAGCACTGGATTTCCCAGAGGCGCCTCCGGTAGCAGTGCGCATGCTCCAGCGCCGGTAGCTGAGGCATCAATTTCCCG 71 BC3M_410 GCGCCTGCGCCGTGGCGGCCGAACTGGCGCTCAACAGACGGGCGGGGCCGAGCGTGAGGCGGAGTCTGCGCACTGCTGCTTTGCAAATGAAGGTGGGCGGGGTGGAGCGAGCGTGAGAGACGTGCCCCCGACCAATAAGTGCAGAGATCGCTCGGGGGCGGGGACCTGCTGCCGCGCTCCAGGCTGCGGGTGGCCAGAAGGCAGCGGGGGCGGGCTCGGCGCGCGCGGCTCCGCCCACTCCGGGCCCCTGCTGGGCGGGAAGGCGGCGCCCCGGCCGAGGTGGCGGCGGCTCCTCAGGTA 72 BC3M_414 acagaagcaatctgacaaagtttttgtgatgtgtgtgcattcatctcgcagagtAGATTAGTAtagAATTAGacttagAAaccttaatttcgattgagcagtttttgaaacactccttttgtagaatctgtaagtggacatttggagcgctttgaggcctaaggtgaaaaaggaaatatcttcccataaaaaggaaaacttgATTACATTAGATacttgtttacgagATTAGATact 73 BC3M_417 ACCTGAGGACGCTCAGCGCTGGAGCTCCGAGCAGGAGTTAAAGTACCCGCAGTGGAGCTGGCCCGCTGCCTTTCCAGACTGCAAGGCCCGCAGTGCACCGCGCGGGTGACGTGTAACAGGGGCGGGCGGGACCGCTGGAGAGCCTATGAGCACAGCGCAAGCACCCCGAGGGGCCGCCTTCCGGCCCTATTGGTGAATCCGATTAGGGGTGGGACCGAGCCGTGGTGATTGGCGGCCGGAGGGATGGCAAAGCTGCCACGCGCACGGGGGTGCAGGCTGCGGGACTGCGATCGCTGCCGG 74 BC3M_47 CTGCTGAGGCTGCTCCTGCAGCAGGGGCCATCTTGTTGCTCGGcctcctcttcctcctcctcgtcctccGCCGCCCAGTCGCTCGTTGTCCTCGTCCCCTTCCTCTTCCTCAGGCTCCGGCCCGCCCCGGAGACTGGGGCGGAGACGAGGGCGAGGATCCTCCCTCAGGAGGCGGGGCGGGCGGAGGGGAGGGGCGGGCGCGGGAGCAAAGCTCTGAGTCACCGGCCACCAACGCCCGGAGGGAGACCGGCGACGCTCTCCGCCGCGACCGAAAGTCTCACACGCCCTGAGCAGATGAAC 75 BC3M_48 CTTCCTGGGAATGAGTGTCTCACAGCAGCCAGAGAGGTTGAGGCTTTGTCGGTGGCGGGCGGTGAGGGTGAGGGTGAGGGTCAGGGAGGCAGACTTGCCTCAGGGCCCCTGCTTGTTTGAGACAGGGCATTCAGTTTGCCTGAGTCAGGCAGGCTGGGGCGGAGGGAGGAGGTGAGGGTGAGGGAGTG 76 BC3M_49 AAGTTGGGCAGGGCAGGGGCTAGTCTGCCTTCTTCTGGGCCCAACCCTCCCGGCCGGCACCACAGGCATTACAGGTACTCTGTGCACTCAGGCTGCGCAGACCCGCAGCTTCCTATCCTGTAGCTCACTTTCCTCTGAGGCGGGCTGGAGGCGGAGCTTGTCCGCTGGGGGTGGGGCTCAAAGCTGGGGCGGGGATACGGAGCAAAACTTAAGAGGAAGATGAGAAGCCTGGTTGGCCAGGAGGCTTATCTGTCAGGACAGGGGGCGGGGCCTGGGGGGCCGTACCTTTGCTTACCGCGA 77 BC3M_52 TCATTtttattattagaatctactatttgccaggtactctgaggcaccaggaatatacaaataacaagtgcagaaactgaccagtctagttggacaggcagacgcataaatcagcaatcacaaggcagtgtgactaatagaggaggtatggcagcacagagagaagtgagcagttactcagcctgccttgtaggcagggcactcagagaagcttctcagaggtggtgacatgagagagagctgagccAGTGATACAGAAGCATGTAGCAAGAGTGGGGGTACACTGGCCTGGCAGTGTGA 78 BC3M_55 ACCCACGTCCCTCAATCCCCACGAGCAGCTGACTGGGACCTGAAAGTGCCACCAGACGCCCTCACAAGTCTGCTTTCTTTGCTGGGCGCTTTCTTTGCTGGGAAACAGCAGCCGCGCCGCAGCCTCCGCCCGCTCTGGGGAAGCCCCACCTTGGCAACAAGCCGCTGATTGGGCCCCCAGCCGCTGATTGGCGCGCGGCCGCGCGGGCGGCCGCGCGGCCGCGCGGGCGGGCGCGGGCCCAGGCGGACGCAGACGCCCTCACAAGG 79 BC3M_58 CAAGAGTGGAAAACCTGCCCTCACAGGCCCAGCTGGCCAGAGGGCTTGTCTCTTTCAGTCGCCCTCCCCCAGAGGGAGCAGGAGCAGACAATGGCCACCATGACTCACCAGTGAGCCATCTTCCCCTCCCCACCCCTCCAGCCTGGCCCATGACAGCTTAGCTTGTCCTCCAAGGGAGCTGCAGCCCAGCCTCCCAGGGCCGCCAGCTTCCTCTCTCTTCACCCAACCTGGCTCCCCCCCTGCTTGTGCAACACCACATCAGAGGGTTGTGAAGTGGAGAGGGAGGAGTTTGACAGCTGC 80 BC3M_61 GGGGCTAGCAGGAGAGCCAGAATAAGCAGATTTGGCTTCTAATCTGACTCACCCAACTGGTTCAGAATGCAGCCAAACCGGGGAAATTTGGGTGAGCTCCTCCTCTTCCCCTCCCTCACTTGCTCTCGCAGTTGTCCTCTAGCACCTCTCTCTATCCCTCCCTCCCCGTCCCCCCGCCCCACTCCCCCAGCTCTGGGAGCGCATGCGGGGGCGGGGTCCTAGGAGGATGTGAGCCCATGGACACGCGGGCGGGATGTTTTTCTCCTCGTCATTGTTCTCCCATGCCCATTGTGTGCGCTG 81 BC3M_66 AGCCACTCACTGCAGAAGGGGCTGGTGAGAGACATGCTCGTCATCTCCGAGGGCCTGGCTCTGCGCCAGCCACACACTTATCTGCCTGCTCCATCTCCGGAGTTTCTGTCTCTCTGAGCTTTGGCAATGTGGAAGTTGTGCTTCCACTATTAGTCAACACCGAGGGGCTGCCgggtcggggttttccggtccgccgttt 82 BC3M_67 CTATTGTTTGGGCTTTGCTTTTGACTTCACATCCTGAAATAAATGGTCGTTGCATGCATGCCGCACTGACGCACTGACTGACTGACGCACTGGCACGTGAGCAGGAAGTGGGCAGGGCTTAAAACACAGAGAAGTCATAACCTCTGCGGTTTGGTTCATGTTGTAATATGAAAACCAGGATCAGCTTATCTTGCAGGACCTCCCTCGGAGGCAGGATCCCTCATGGAG 83 BC3M_69 ACCAGATAAGCACCCACTGCACTCAAGGCCTCTCTGATCAAGTCCCACGACCAGGCTCTCCAAGTCCTGACACCGCGGAGACCCCCAAAAGAGGAGGATGGAGCAGAGGGCAAGGCTCTCAGCTCCGCGGACTCACACCCAGCTGCAGAGGCAGGGGGAGCCGCCCTTTCTGTGGCCGGGGAAATTGAGGTCACTTCCTGTCTCGCTTCCCTCTCTCTGTGCTGGCTGCATCCTTCAGAAGGGGGGTGGGTGGCTGCAGGGCAGCGCCAGGCAAGGCTGCGGAGAAGCCGGTGCTCCCTG 84 BC3M_7 tctgcctgcAAGCTCCAGGTCTTGCAAAGCCTGAGAACTGGTATGGCAAGGGCAGAGTGAGAGCAGGGAAGAAATGGAGTCAAGCTGAACAGAGACTTCCGCATCATGAGGGTGGTGGGAGGTGGGGAGGAAGTTCTGAAACCACACACATTTATCATTGTTATTGAGTCAGACAGACAGTGCCTGCTGACATGTAACTGTCAGGCGTTGCCAAGGCACAGTAGGGTTGCAAAGGCTGAGTGTCCACTTCCTCCCAATGAGTCAGGAAGAACCCTTGGATAATTCTCCAAAATAGTTTCA 85 BC3M_70 CAGGCACAGTTCTAAGTAATTGaagtctactgaggtaggtatcaatattattcccattctctagatgacgaaactggtgcatgtagcagttaggaaatatgcccaaaggtacactgctcgtaagcggcagagcaggaatatgaatccagccagtctggttccggagtctgcattcttgatcactgcactataccaactttcactttgttgtgagcacctgcctatctcagacatcagtcagtaagtcccttgaaggcaagaactgtcctttgatccttattcctgagccctaggcattac 86 BC3M_71 GGTGTATGTACTGATGTACTGAATGGGCGACCATTTCCTTCCAGAAAGGCTGGACTGACTGCCTGACTGACTGTCTGTCTGTGTGACTGTCTGCACACCACTGCCCTCCACTGGACACTGAATCAAAGCTGCCCCAGACCCACGTTCCCGTGTCAGGACTCCCTCAGGTTTCCTTCCCTCCCTCCCTCGATGCCGGACTT 87 BC3M_74 AGGGCATTTCTTGAGCCTGGCAGGAGGCCAGGGGTTTTACAGGGCAGGAAGGAACCTGGAGGAACCGAGGAGCCACGTTGTTGGTTGGAAAGAAGGGTGGCCAGGTGGGGAGGAGTCTGGCAAAGGGTCCCAGACAGCAGGAAGGGCACCTGTGAAGCCGCCCTGCCGAGTGTGTGGTAGAGGCGGGGTGAAATGAGCACTGCTCATAAAAGTGACTGTTGTGAttttttatgagatggagtctcgctctgtcgcccaggctggagtgcaggggagcaacctcggctcactgcaacctcc 88 BC3M_76 gatcgcggtgaatatcctgcaggtcatgctacgcccacttgctttgaggttgggaaagcagcctcttgaccttcagccacttgagcccagcaggtggagctatttgccctcactggagcctgctttctcgctaaggggaaatctgctaaccattacacagatagcaggtaagtatttggagttgctcatgattttggaatgttgtggaaacaGGTTTCCTCACTTTCAATAATGAACCTTATGATTTATTATATGCAATACAAATACCTGCTGCTGTGGCCATGATAAAGGTTCCAGGCC 89 BC3M_80 CTGAAGGAGTTAAAACAGTCCCCACCCCCACTCCCGATTTCTAGAACACCCCACGATAAATTGGGTAAATATGTATTCCATTCATTGGTGCATCTGACCTTGGTCTGTGACAGAGAGGAAAGGCGTGTCTTCTCATACTGTTCCCTATGAACAAAAGGCAAGTCCCCACCCCCACTCCCGATTTCTAGAACCCCACGATACCACTAAACACTACATACATTAA 90 BC3M_82 AAACAAACACTGGGTTTAGGCATTCTGCTCTCCCAGCACCGCATGGCTGAGGGTGGAAAAAAATAACATCTGAAACAGGCCGGGCTTTTGATGATACCTCCTTATGACAGACACATCGAAAACCACCGACGGTGAGTCACCCACATTCTGTGCATACCCTCTCCGAGGAGCAGGAAGTGTGGCTATTTTAAACCCTGAGGCAATGAGAAGTTTTCAGATGCGTCCTAAGGCGCTCCGGCCAGCGCCCTGCATGCACACGAGGGCCTTCCTCAGTGTGGCCCCAGCACATCTGTAGACCTG 91 BC3M_84 ATTTTGACTCACAATGTTGAAACCAGATTATAAATGAGTCATCAGTGAATCGACCACAAAGAGCCTTTGCGGAGGTGATTTACAGGAGAGCTCTGATGTCTGCTGTCCCCTGCACACGCTTCACAGAGATGCTGTCAGACGCAGAGCTGGTCTGGGGCATCTGTTGCCGCGTCAGCTCAAAAGGATGCTGTGTTGTCACCAATGGGATTCCCCAGCCCAGGCGGTGTTGCGGTCCCACCCACACAAGGAAGGCGGCCATCACTGAATAATGCTTGTGGTTACATCATCATTGCTGGTTTC 92 BC3M_86 gggatttcctctgctttttcaactaaaatcagctctttcccaaaagcctgtgctgcctgttgtgttttctctgtgtgtgttttgaaatggccttgcgcaccctccagactctctgcctccggggcaagtctgccttttccctgtttccactttgcatactgcataacttccttctctgccccacatggacacacgccctcttattcatgcatccgcggctcttgctgcattcgctcggcagcaaagccacaggctcccttgtggatgtcccttgtggagatttgtacttttttaccccac 93 BC3M_87 GAGCACAGAAGACGACCCAGCTGAGGCTGGCAGGAGAGACGAAGGCCCCGCCAGATCCCGGAAGCCGCGCCCTTCTGTCCGGCTGCACGCCCGATTGGACGGTTCCTACGTCAGCGCCCCTGATTGGATAGGGCTCCAGGCCCCGCCCCCTCAGTCCCTGAGTGACGGAGGATGTGATCGGACGCTGGGCTGAGGGCGACAAAGTGACAGGTTCTTGGCTGCAGCCTTTTCATGCAGGGCTTCCTGCTTGCGCTGGGCCTGGCCCAGCCCAGGGGGCATTTTCATTTAACCTTTTGTATA 94 BC3M_9 AGTTTGGATGTTCTCTGTGGAGAGGGAATAAAACCATTGCCTGTTCCCTGGAGGGAATTGGATGCTGAAGCTTCTACCTTTAACAGGGGCATGGGTGCAGTTCCAGCCTCTGCCAGCAGGCTGGGCCCTGTGCCCACTTTTGAAAGACCTTCAGGGCTGTGGGGCATGAGATGAGAGAGGGAGGGAAGATAATCTGGCTCACtgccgggcactttatgtgacttacctccttaattcccccgggcacagccctgagaggaggttggcagtgtctgcattttacagatggggaacttgagg 95 BC3M_92 aaacttcgtctcaaaaacaaaacaaaacaaagcgaaaaaacaaaAAAAGTTTCATTGTTTCACCTCCACACACAGCTCTGTCTGCATTTTGAGCAATGGCCACCAGAGGGCAGGAAGAACCAATCTATAAAGCACACAAGGGTTTCACCAACTTTGAAGTCCTCCGTACACATTCCAATGTAGCAGACTGACTGAATGTAGCAGAGACTGAATGTAGACAG 96 BC3M_96 GAAGCagccagaagacctggttctcccaagcctgctacttgctggccatgtaaccttgagcaagttatttcctcctctgcaaaaggaagacaataccctcctgcctacttcactcagacgttctgaagatcgatgtagcaatgtggtgtagacatgcttttgtaaCGTGGACACACCCAGACAGGAATAAGTCTTGTCCAGGGAATATTTTTTGACAAACACTGCTTAACTGGTTTGTCCTCTGAGTGTCACAACTTTTGGCAGAACTTGGTAGTTGGAGGTCAGTGGTTGGCTGGTTCA 97 BC3M_23 CAGCCCTTCCTCACCTCATCACTCCCCATCCCCCCAAGATATAGAAAGGCCGTGACAGCTGCCAGCCCTGCACATGCTCTTGTTTCAACAGCGGCGATTGCACATCACGTAGTCCCCACGTGACCTGTCGGGCCTAGGGCAAGCGCAAAGCTTTCGGAAACCCGAATTATTGCAACCTTGACTTCCTGCCTGTCTCTGAGGCTCCCGGGctgtgctttaagctggacaggcacctgctttacagggaaaaggaccaaggtccggagaggaaaggggcttgtcccaggatacgcagcaagt 98 BC3M_103 CTAGGAGCTCTGTGCGGAACCGCGTCCAGCCGCCGACTCACTGACACATCACAATGAGTCACGTGCTCTGTGCACCGGGCGGATTTGTCAGATCCGCTGCTGCATCACGGCTCGGCAGGGCTCTCTGGGTTCTCAGTGCCCTCCTAGGTCTGCAATGCAGTGCGGGAGAGGAGGAATATGGGCTTGTGGGGGCAGGGGCAGCGCCCGGACTCCTCCCGGGGCAGGACTCCCAGAAACGCAGGAAGCGATGACGCTGCTCAGATAAACCCTGGCGCTCTGCGCTGGCGTCCTGGTCAGGAG 99 BC3M_44 CATGTGAGCTCAATTAATACAACATATGGTTACTGTACGCCCAAAGGCAACGCATTCAAATTGCTTTGTACCATGTAAAACACACACTCTTGAAAAACAGACGCCTAGTGCGGAATCCTGTGCACGCCTTTAACTCCTCCAAACGAGCAGGGGGCGTCATGGATTAGCATGTCCCGGGGTTCGGGAATCAGCATTTCCGAGGAAAGGGGCGCTCAGGAGATATCCCCACCCCCGATGAGGGGCACTGTCGTGGATGAGTTTAAACCACGCCATAGGCAGCCAAGAACTGAGCTCCCGATG 100 BC3M_219 GGGACCAATCCAGAAGCAGCACCCAGACCGGTTTACCCGGTTCCAGGACCTTGGGCGAAGTCCACCCGCCCGAGGGCAGGGACGACGCAGGCCACGCCGCGGCCCAGTTGCTAGCCAGGCAGGGTGGGGATTTGATCTTGCCAAGGAAATGTGAGCGGGAGGCCGAGCGTTGGAGGTGGGTAAGTCGTCACTATGCAGGGCGGAGCCATCCTGTGTCTATCACGCCCAAGGGCGGTGCATGCAAATTGACTCCCGCATTTGGCTTTTCCCCGGGCTCCGTCTCCGCGCGCTGCAACCCGC

Example 4. Open area validation of carcinoma specific chromatin.

In order to verify breast cancer-specific regions, a nucleic acid fragment obtained by the method described in Example 1 was amplified using the primers shown in Table 3 below.

Primer sequence for nucleic acid amplification Sequence number name order 101 BC3M_102F GGGGCTCTCAAGGACTCTAC 102 BC3M_102R CGAGGGCAGAAAGGAGAGAC 103 BC3M_11F GTTTCCGTACGCAGCCTG 104 BC3M_11R CAATGAGCAGGAAGATGGGC 105 BC3M_117F AAGGCTCAGTGTGTGTATGC 106 BC3M_117R GGTTACTGACTGCTCCCCAT 107 BC3M_119F TAACCTTCCCTTGGCTTCCA 108 BC3M_119R GAGAGAAGGAAAGGGAGGGG 109 BC3M_125F ACCTCTAGACCAAGTGCCTG 110 BC3M_125R GGTGGCTTCAGAGATGGAGT 111 BC3M_132F CTGACGGCAAATTCCTCCAG 112 BC3M_132R GCTTGTCTGTCATCTGAGGC 113 BC3M_137F GACCAGCCAATCTCCCGG 114 BC3M_137R GAGATCCATTGGTTGCGGC 115 BC3M_139F GTGTGAGCCAAGTGTTGACC 116 BC3M_139R TTCATCCTGCCTGCCTAGAG 117 BC3M_142F ctttccactcacaccttgcc 118 BC3M_142R aggcacaaaagaggcaaagg 119 BC3M_146F GGATGAGTCACTGGATCCGT 120 BC3M_146R GCCTCTGTCCCTTCTCCATT 121 BC3M_154F AATCCAGTCCCAGTTCCCAG 122 BC3M_154R ACTGGCCTCTCAACACCTAC 123 BC3M_168F CCCAGAGCTGCAATGTGTAC 124 BC3M_168R TACGGATGAGGAGGCTGGTA 125 BC3M_171F CCTGTACCTCTGCAGTGCTA 126 BC3M_171R TCCTGGGCAGAGTGTTTTCA 127 BC3M_172F CCTCCTTCCCATttctgcct 128 BC3M_172R ccttttccatttccagcccc 129 BC3M_173F GAATCCGCAGATCCTCAAGC 130 BC3M_173R AAGTTCTTCTTCCCGCCCTC 131 BC3M_178F ACCATTCAGTGTAAGCCCCA 132 BC3M_178R TCTTTCCACCATGCACGTTG 133 BC3M_179F ACACCACCACCTCCTTCTTC 134 BC3M_179R GGAAAGTGCAAATGAACCCCA 135 BC3M_182F tggttccctcctcacatcag 136 BC3M_182R TTGCAACCTCCGCTTGAAAA 137 BC3M_199F TTGGGAAGGCAAGAGGATGA 138 BC3M_199R GTGTTCAAGCCCTCCCTCTA 139 BC3M_20F CTCACACCGTCTCACTAGGG 140 BC3M_20R GAATTCCACAGACACCGCG 141 BC3M_203F CCTCGTAGGGCTTGAAATGT 142 BC3M_203R AGAAGAATTTGGCGAGGATTACC 143 BC3M_206F TTGAGCGCAGTCTGGAAATG 144 BC3M_206R GAGATGAGCCCTGTCACAGT 145 BC3M_212F AAGTCCTAGAGCACCGGAAC 146 BC3M_212R CTTTTCTCCGCAGCGATACC 147 BC3M_22F ggaaaatcccttgaagccgg 148 BC3M_22R TGGGCTGTTGTAATGGTGTG 149 BC3M_221F tgatgagctactacgcctgg 150 BC3M_221R TGGGAAGTTGAGGGATGTGT 151 BC3M_224F CGGGGAGGAGATGAGCTAAA 152 BC3M_224R AGTACGTCGAACAGGGGATC 153 BC3M_226F TGGATTGATACGGGGCTCTT 154 BC3M_226R CGACAGCTGGTTTCACAAGT 155 BC3M_230F CTGAGAGGCCCGCAATGT 156 BC3M_230R CACTCAGATCTCGCCGCG 157 BC3M_231F GAGCGGTGCAAAGGTTCTTA 158 BC3M_231R CCTACCTCGTGCTCTTGGAA 159 BC3M_232F CTCTCCAAGCACCACTCCC 160 BC3M_232R TGTGGAGACTGAACCTTGCA 161 BC3M_235F CAGTCCCTACACCCCACAAT 162 BC3M_235R CATTTCCCAGAAGACCACGC 163 BC3M_239F TGGTTAAGGTGTAGGGGTGG 164 BC3M_239R AGCACAGAGTTACCACCTCC 165 BC3M_241F GTGTAAACAAACCCAGGCCC 166 BC3M_241R GACTCCATCACCGTCCCAA 167 BC3M_245F GCGCGCTTTTAAGGAGAGTT 168 BC3M_245R GGCTCTGACGGCATTCATTC 169 BC3M_247F GATGCAGATGTCAAAACGCG 170 BC3M_247R gagggtctcgcttgtttgc 171 BC3M_250F AGGAGTTCAGCATAGCACGA 172 BC3M_250R CAAGCTGTGCCATAACCCAA 173 BC3M_252F CTGTCCTCCTCCCTCCCTC 174 BC3M_252R TTTCTTGTCCACACTCCTGG 175 BC3M_253F ACACCCGACAGAGTCCAATG 176 BC3M_253R GGTAGTCACTCCTTTGGCCT 177 BC3M_255F CGGCTCTGAGTCTGAAGCTA 178 BC3M_255R GGAGCCTCTGTACCTGTGAC 179 BC3M_257F CCCCACAGTGGTCACGAG 180 BC3M_257R ggggaaggagaacagagagg 181 BC3M_260F gctcaaatgatccgctctcc 182 BC3M_260R gactctgatgctgccatgtg 183 BC3M_265F GCGGAAGTCATGTCTGGAAC 184 BC3M_265R CGAGGCCAGGAAACACTAGT 185 BC3M_266F GGCACAAAGGAAACGAAGGA 186 BC3M_266R CCAAGCACCTCAAGCCAAAT 187 BC3M_267F CCTCCCTGGTAGAATCTGGC 188 BC3M_267R GTGTCTCAGGCTCAGTTCCT 189 BC3M_268F CTGTGCTGTTCCGTGTGC 190 BC3M_268R GAGACCTTTTCACGGGATCT 191 BC3M_269F acctctgtgtgaagtgctct 192 BC3M_269R gcgagtcaaaggtgtggttt 193 BC3M_27F TCTAAGACTGGCTGCTCTGC 194 BC3M_27R AAAACGCCCTTTCTGCTCAG 195 BC3M_275F GGGTGGGTCTACTTCTGAGG 196 BC3M_275R CTCCCTTTCGGCTTCATGTG 197 BC3M_277F tggaatggaatcaacccgag 198 BC3M_277R cgaaaccgttccattccagt 199 BC3M_283F aacaggggagttctcatgcc 200 BC3M_283R agccacatcagagacagagc 201 BC3M_284F GTTCAAATGTCAGGCCTGCT 202 BC3M_284R CACCTCCAAAGACAAACGCA 203 BC3M_290F gcccacgtgactagcatagg 204 BC3M_290R GAGCGAGAACTGGGAGTGC 205 BC3M_291F ATCACCCTGAGCCTTGGAAG 206 BC3M_291R CAGGTAATGCAGCGGTTCAT 207 BC3M_292F CAAGGGACCCAGAGATCACA 208 BC3M_292R ACAGCAAACACAAAAGCCCA 209 BC3M_295F TCTGCGAAAGAGGAGGTGAC 210 BC3M_295R CATTCCAGAACCACAGGCTG 211 BC3M_307F AGCCTCCGTCAGTGTCTTC 212 BC3M_307R TGAGACTCTAGCCCTTCCCT 213 BC3M_321F ctctccataagacacgccca 214 BC3M_321R aagaggcgggtcattcagaa 215 BC3M_323F caaagtgccgggattacagg 216 BC3M_323R TCCCAAAGAGTGTCACAGCA 217 BC3M_326F CCCTCTCCTCTTGCATGACT 218 BC3M_326R ATGCCTCTTTGCTGTTCTGC 219 BC3M_334F TCGCCACTCTCAGTCAAACT 220 BC3M_334R CCCTAGGGCAAAATCAACTGT 221 BC3M_353F tgttgtagcctgagtcggtt 222 BC3M_353R CCCCACTTGCTTCTGTAGGA 223 BC3M_360F GGGAAGGAAGGTTGGTGAGA 224 BC3M_360R ACCGTATAGagcagagtggc 225 BC3M_362F TCCAAGTCTAAGGGTGCTGG 226 BC3M_362R TACCATCCTCTGCTTTGCCA 227 BC3M_367F GAGGGCTTTCAGAACTCAGC 228 BC3M_367R gcaacgcctTCCTGTTAAGA 229 BC3M_37F TTCCCTCGACCTCCCTTCTA 230 BC3M_37R CCCTGTCCTGCCAGCTATAG 231 BC3M_380F GACTCCTGAGGAAACCAGCT 232 BC3M_380R CAGAGTGGAAGGTTAACGCG 233 BC3M_39F GCAAGAGAGACTGAGAGCAC 234 BC3M_39R CCCTCCTCCCTCATTCACTC 235 BC3M_393F gctgcagctgctgtattcac 236 BC3M_393R aggggtacagggcagaaaat 237 BC3M_402F GGAACAAGGAGGAGCAGACA 238 BC3M_402R CTCCATGAGTCAGGCTGAGA 239 BC3M_406F GGCCAATCAACACTGTGACT 240 BC3M_406R TCCAGTGCTCCGGGATTTC 241 BC3M_410F CCGAACTGGCGCTCAACA 242 BC3M_410R CTCTGCACTTATTGGTCGGG 243 BC3M_414F tgtgtgcattcatctcgca 244 BC3M_414R cctcaaagcgctccaaatgt 245 BC3M_417F GCAGGAGTTAAAGTACCCGC 246 BC3M_417R GCTGTGCTCATAGGCTCTCC 247 BC3M_47F CTTCCTCTTCCTCAGGCTCC 248 BC3M_47R CGGTGACTCAGAGCTTTGC 249 BC3M_48F GGCTGGGGAGGTTCTTCTAG 250 BC3M_48R TTCATGTCCACCTCCTCAGC 251 BC3M_49F CCGCAGCTTCCTATCCTGTA 252 BC3M_49R ACCAGGCTTCTCATCTTCCT 253 BC3M_52F atggcagcacagagagaagt 254 BC3M_52R Tggctcagctctctctcatg 255 BC3M_55F AGCTGACTGGGACCTGAAAG 256 BC3M_55R CCCGAGCCAGCCAATCAG 257 BC3M_58F CAAGAGTGGAAAACCTGCCC 258 BC3M_58R GAGGGGAAGATGGCTCACTG 259 BC3M_61F CTCTTCCCCTCCCTCACTTG 260 BC3M_61R CATGGGCTCACATCCTCCTA 261 BC3M_66F AGCCACACACTTATCTGCCT 262 BC3M_66R CCCGAGCTACACTAGATGCA 263 BC3M_67F AAGTGGGCAGGGCTTAAAAC 264 BC3M_67R GGGCTCCACTCCATTCTGAA 265 BC3M_69F AAGAGGAGGATGGAGCAGAG 266 BC3M_69R GAGAGAGGGAAGCGAGACAG 267 BC3M_7F GGTGGGGAGGAAGTTCTGAA 268 BC3M_7R CTTTGCAACCCTACTGTGCC 269 BC3M_70F atgacgaaactggtgcatgt 270 BC3M_70R tcaagaatgcagactccgga 271 BC3M_71F CCCTCCACTGGACACTGAAT 272 BC3M_71R AGAAGCCAACCAAGAAACCG 273 BC3M_74F TTGGAAAGAAGGGTGGCCA 274 BC3M_74R CTCATTTCACCCCGCCTCTA 275 BC3M_76F tttgaggttgggaaagcagc 276 BC3M_76R agcagatttccccttagcga 277 BC3M_80F TGCATCTGACCTTGGTCTGT 278 BC3M_80R GGCCATGAGAAGTCCTGAGT 279 BC3M_82F AGACACATCGAAAACCACCG 280 BC3M_82R GCCTTAGGACGCATCTGAAA 281 BC3M_84F AGGAGAGCTCTGATGTCTGC 282 BC3M_84R GCATCCTTTTGAGCTGACGC 283 BC3M_86F tgtgctgcctgttgtgtttt 284 BC3M_86R atgtggggcagagaaggaag 285 BC3M_87F CAGGAGAGACGAAGGCCC 286 BC3M_87R TCACATCCTCCGTCACTCAG 287 BC3M_9F CTTTAACAGGGGCATGGGTG 288 BC3M_9R TCTCTCATCTCATGCCCCAC 289 BC3M_92F CAGCTCTGTCTGCATTTTGAG 290 BC3M_92R TGGTGGCCATTAATCGTTCC 291 BC3M_96F ctggccatgtaaccttgagc 292 BC3M_96R TGTGTCCACGttacaaaagca 293 BC3M_23F ATAGAAAGGCCGTGACAGCT 294 BC3M_23R GCAGGAAGTCAAGGTTGCAA 295 BC3M_103F GGGAGAGGAGGAATATGGGC 296 BC3M_103R AGGGTTTATCTGAGCAGCGT 297 BC3M_44F GGGCGTCATGGATTAGCATG 298 BC3M_44R CAGTTCTTGGCTGCCTATGG 299 BC3M_219F GACCAATCCAGAAGCAGCAC 300 BC3M_219R GCAAGATCAAATCCCCACCC

As a result, similar to the results of FIGS. 4 and 5, it was confirmed that the amplification product was detected in the marker sequence modified to the open chromatin structure in the cancer-causing patient, and the amplified product was not detected in the marker sequence modified to the closed chromatin structure.

As described above, specific parts of the present invention have been described in detail, and it will be apparent to those of ordinary skill in the art that these specific techniques are only preferred embodiments, and the scope of the present invention is not limited thereby. will be. Accordingly, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

SEQUENCE LISTING <110> Korea Advanced Institute of Science and Technology <120> A cancer diagnosis marker based on ATAC-Seq and Method using the same <130> P19-B293 <150> KR 10-2019-0040056 <151> 2019-04-05 <160> 324 <170> PatentIn version 3.5 <210> 1 <211> 300 <212> DNA <213> BC3M_102 <400> 1 gggatccctc agcagctccg gacctcatct gccccacttc ggcatcccgc gcgggaatat 60 gaccatgtag gagtaacccg gggctctcaa ggactctacg gtttgtcacg gtttgaacgc 120 aagcgcaggg cctggggcgg gtgcaggtgg agggtcggcc tctttctgcc cttgggaacg 180 cccctttctg gatgtggacc ggcgaggcgg tctctccttt ctgccctcgc ctggtgaaat 240 gtgggcactg ctgccaggag aaaaaaaact gaagctgtga attcagttca tcacccttcc 300 <210> 2 <211> 300 <212> DNA <213> BC3M_11 <400> 2 agcggggcta gacggagtca ggggcggacc gccacagcct gcaccaatca ggacccggtt 60 gataggcaga gcctggcgac ttcgaagact cgcccccagt caaagagccc cggggattcg 120 tttccgtacg cagcctggaa accagcctgg gcctatcctg cgcgccgctg cgggctacta 180 ttggctgcca agaaaccccg cccatcttcc tgctcattgg ccggtgcggt ttacgtaaga 240 ggagcctgtt gctgagcgaa aagtctgttc tgcaattttc gctaaggagt tgttaacgct 300 <210> 3 <211> 300 <212> DNA <213> BC3M_117 <400> 3 gtacactgac tttggaacaa atgccacagg ccctaattgc aggctccaag gagttgagat 60 tccatactgg ggttgctgga ggcagaagcc ttcccacttt caggacccgg acctgccctt 120 cccccacgcg gtcccgccca gccagctaca ccctggccac agagcgctca caaaggctca 180 gtgtgtgtat gccgggctga ctcacagtgg ttctgggccc aggcgaggac cttctcagag 240 gggcggaagg ggccctctcc ctcctggcca ttttccatgg ggagcagtca gtaaccagga 300 <210> 4 <211> 300 <212> DNA <213> BC3M_119 <400> 4 ctaggagaca agtaccctgc tgagcagaca aatagcctgg actttgtaac agccaaagtg 60 gcccacatgg cactcgcggg gctgtgcagc atccaggcag gggacactgc ctggcattct 120 aaaggcctgt gctgagtcat ctttcacagg aaccagcttc tcaagtctct gggatcctgt 180 tttacaggct gttactaacc ttcccttggc ttccaggcca aggaagaaga aagaataaat 240 attaaccaaa ggtacggctg tggcagggtg cccagggccc ctccctttcc ttctctcccc 300 <210> 5 <211> 300 <212> DNA <213> BC3M_125 <400> 5 ccacctctag accaagtgcc tgcctggaat gtcctgtcca acttatccac cagctcatcc 60 ttccgggcct aattaaggcc ccactccatc tctgaagcca ccccatgctc atgactctcc 120 ctgacgcagg ttcccgacac accgggtgac tcagctgcag tgtttttcac agtccgtgat 180 gcgtcacagc tatttatagg tgtgcttaac tccctgtgag gaagcacttc aacccccaaa 240 cgcaagttcc agaaatatgc tcataaagat aaagatagag aaaagctctg gaaaaataca 300 <210> 6 <211> 300 <212> DNA <213> BC3M_132 <400> 6 tctggaagca agttacccac aggtttagtt tgcctggaga gaaacaggcc ggagagagac 60 tgcggcctcc ctagggtctt ctgacggcaa attcctccag ctcagtggct gctgggcagc 120 agcacagccg gtttctctca agggcacacc ccacacaccg cgtcactgtg cactagcctc 180 agatgacaga caagcctttc acaagacttt tgtggcactg ttcatttctg agaccttctc 240 tatgatgagc tcaaactgct tacctcagag aagaaactgc gtgcacagaa agctgctgag 300 <210> 7 <211> 300 <212> DNA <213> BC3M_137 <400> 7 taatttctcc gaggccagcc agagcaggtt tgttggcagc agtacccctc cagcagtcac 60 gcgaccagcc aatctcccgg cggcgctcgg ggaggcggcg cgctcgggaa cgaggggagg 120 tggcggaacc gcgccggggc caccttaagg ccgcgctcgc cagcctcggc ggggcggctc 180 ccgccgccgc aaccaatgga tctcctcctc tgtttaaata gactcgccgt gtcaatcatt 240 ttcttcttcg tcagcctccc ttccaccgcc atattgggcc actaaaaaaa gggggctcgt 300 <210> 8 <211> 300 <212> DNA <213> BC3M_139 <400> 8 cctgactgtg aaagccaggc cccagcccaa gaaggcttca cagaccccta ggtgtgccct 60 ctgtgtgagc caagtgttga ccctggcgat gatgccaaca gcccgactct gcccagcttt 120 cagccgcatg agtgtgaacc agctgagcgg caccagctca gggcaaggca gaaggccagg 180 tgcactgtct ctaggcaggc aggatgaaca gcagcacctg atgtcacagc ggccggggaa 240 ccaccctggt tggggcatgc taacccaccc tgctaatatg ctttgggtcc taatttcctt 300 <210> 9 <211> 300 <212> DNA <213> BC3M_142 <400> 9 ggctcacacc ctccaggggc taccctggtc actcagggta aaagccacag cccttccagt 60 ggccttcaag gccctggtga tctgctcgcc cctccccttt ccactcacac cttgcccccc 120 cactcctggc aacccgtctc tgctccagcc acacacttgc ttcattgctg ttcctggaaa 180 atactgggca tgttctggcc tcggggcctt tgcctctttt gtgcctgctg ccaggacatc 240 tgttcctccg gaaagcagcc tggatcattc ccttctctcc ttcagggctt tattcaaaaa 300 <210> 10 <211> 300 <212> DNA <213> BC3M_146 <400> 10 ggatgagtca ctggatccgt tttcagttcg ttccacccac agatccgtcc tttgcaggcg 60 ccccagaaaa gattgcttca gagctggcac caatggagaa gggacagagg cccagcaaca 120 gggcgggatt ggcaggcgga agggagcgtg tgatgagctg agctcacaaa gggccggggt 180 gctgggctgc agctggggag ggcggggttg gatcagcgcc tgctcctccg ccttcgtttt 240 tcccctcccc ctaaggattc agttccccct tctgaaattc accaccttgt atgtgactta 300 <210> 11 <211> 300 <212> DNA <213> BC3M_154 <400> 11 cacctttccc aagatgacga catacctaat tttgcatagc acctgagatt gtaactaagg 60 tggtgggaac ccttggtgac ttgctgtgtt gtgttggcca gtgttaacac tcacttcccc 120 ttaacagccc tccaaaccca aaaggctatg tcaaatccag tcccagttcc cagttccttg 180 tgactgagcc cctcaccccg ctggacattc ctctccaagc aggcagtgct tccttatacc 240 ctccccacac gggtaggtgt tgagaggcca gtactgaggt aaatttcttt cttatgggca 300 <210> 12 <211> 300 <212> DNA <213> BC3M_168 <400> 12 gaactcatga gtcagggtca gtcagcccag agctgcaatg tgtacgtgct tcccggccct 60 gctcttctgg cccgccccca agccttcacg catgcacccc tgcaggcact taccagcctc 120 ctcatccgta tatcctggaa agggtgcaag catgcctggc ttagtcatcc atccacagga 180 agtttgcaca gccctacctg agtgctaaga tcaggctgta aactgccaga atgaaacaaa 240 agagggaaaa taaatatcag cactctccca taaattttgc aatagtcagc tgtagtctag 300 <210> 13 <211> 300 <212> DNA <213> BC3M_171 <400> 13 cagacagagg ccgctgaatt aacccgtgga ggcgtctctc tgagcagagc ccgcaatgcg 60 cctgcttggg gctccctgca gcctctgggg gaggcagggc ggcccagagc aggcctgtgc 120 tggaaaggaa cgcgaagccc tgtaaccaag cctgtacctc tgcagtgcta gtcccaaggg 180 gcctccgagc tgtttgtcac catgtgattg gctcaggaga ggggtggaga aatgaaaaca 240 ctctgcccag gatatattta gttgaagtgc agctggggaa gtgcttaaac aagggagctt 300 <210> 14 <211> 300 <212> DNA <213> BC3M_172 <400> 14 tcttggattt ctgaatatgc agttctgttc ctaaccagtg tgtcccaacc agaaagtcac 60 tgtaattttt ggttttgttc ccaatctccc tccaaatgtc attagtcata tcctccttcc 120 catttctgcc ttgaataggc agtcattatg atgaagccag gcttgtttca gaattccatg 180 agaaccacag tgtcaggctg tgacaactct ggggctggaa atggaaaagg ctgtgatctg 240 gggttggctg gcaccgtccc cgtgagtcat tatggaaaca ctgtccccgg attctgctga 300 <210> 15 <211> 300 <212> DNA <213> BC3M_173 <400> 15 attggtgagg cgccgcgcct cggtgtcgca gcgaatccgc agatcctcaa gccaggtggg 60 ggcgcccact gcgcgtgtgc agcgcctgat agccaggcta gctgagggcg gggagcagct 120 gcggcacctg ggacacagcg attggctggg accaggagag ggcgggaaga agaacttggc 180 ggagcgcgct catatctctg attggctgcc aagggtagcc cttgacagct gccgggtggg 240 acccgtagac cgcgagcgca ctggcccgtg attggttggg gtgcggcggc gagcatctgc 300 <210> 16 <211> 300 <212> DNA <213> BC3M_178 <400> 16 agcacttccc gggcgccccg cctcagtttc cccatctata aagtggagat gataatagca 60 ttcagagtca ctgatctaag ggctcaggga caccattcag tgtaagcccc atacactccc 120 tgcaagagga agctggttct gactcagcct tgaggctggc gtctgaggca accacaagcc 180 caacgtgcat ggtggaaaga tgactgtaag tgggggcaac ctcagctggc cttgggtttg 240 accatggaat gcgaggcaca aaggggccca ttttgcatac tttctcagag gctgtagggc 300 <210> 17 <211> 300 <212> DNA <213> BC3M_179 <400> 17 cccccgacac caccacctcc ttcttcgcct tgcatcggta cgataaggca cttgcttgac 60 gggaaagaga aactcagctg ccagctgggg ttcatttgca ctttcccccg cctggtctgc 120 ggtctggctg tgcagctagc cgctctgacg gggaggaggg gcccaaagcc actgcctgcc 180 gcctgggcag gggagagggg cacgtgaggc tcatggcaga ggcacagcca gcttcttgca 240 tgtgccctcc ccggggaatg tctgcagagc ccaagactgc cacgccgtgg gcacagccct 300 <210> 18 <211> 300 <212> DNA <213> BC3M_182 <400> 18 gggaaacctt gcagactgtg gggtcctgca cacctagact tgctcctttt agaagccatg 60 gaggaggttg ataatgggaa taacatttat tgtagcttat ctctatgcct tgagcaatgt 120 gctcacactg gctggttccc tcctcacatc agcctgatga gtcagatcct gttattactt 180 ctcactttac agatgaggaa gtagcagtaa atccattacc cttttcaagc ggaggttgca 240 agaggttgca agcggaggca gaataaacac ttgaaacagt gagtcagatc ctgttatcac 300 <210> 19 <211> 300 <212> DNA <213> BC3M_199 <400> 19 ggaaccctag gatctgattt aggacatttg gaatctttaa ggcacattcg atctagaaag 60 tggaactgaa ttgctttggg aaggcaagag gatgatttta cagtataggg tttgtgtgga 120 aatccccttc agcagtaatc aacccaggtg tccaacctgt ttgttaacca tttccaaatg 180 actcagagga cctagaggga gggcttgaac acactccagc actgtttcta caatttagcc 240 tttatttgca ttggaaacca cattcctgaa ttcttgaggg ggcaggctct ggcttattct 300 <210> 20 <211> 300 <212> DNA <213> BC3M_20 <400> 20 tcgtgtgggc ctgggccgct tgctattact aataaaacag cagcaaccac aggacagctt 60 cacttccgga aactccctct gtcacgtgct ttgcatgaat cctcacaccg tctcactagg 120 ggcgctctcc ccgtttcacc agtgacttgg tgacaaccag ccttgctcac gaagcgtcag 180 ccgtatcctt tctgtgtgca gtggggtgtg ggttgtgtgg agccgcggtg tctgtggaat 240 tcacaggctg gggccggaat ccatggcccc cgtcgccgct gccacccccc aggtgctggg 300 <210> 21 <211> 300 <212> DNA <213> BC3M_203 <400> 21 aggtggtgcg ccggcggttc gcagctgctg tgcccgctgg cctgggcgca gccggggaca 60 gcgacgcgtt tcctgcccgg gaagggcccg agcgcagggc cggctatagc ggtcccgcag 120 ctgcctgctt cgattttagc actgctgctc cctagaggga gcaacgcggc cctctgtccc 180 tcgtagggct tgaaatgtaa attattcata tcaggggaat gtgtgcttca aaaagcaagc 240 tggacaagaa ccgacgggta atcctcgcca aattcttcta tttaaccctc accattaaaa 300 <210> 22 <211> 300 <212> DNA <213> BC3M_206 <400> 22 tgaatgtcat gagtcaggaa aaaagaattt gagcgcagtc tggaaatgaa atttcctgcc 60 tgtggtttga ctcacgtctg tctgtctcga aatctacccc aaggacattt attccactgt 120 gacagggctc atctctgagg agcaccagac tcctgcggtg gggagggaag attatccgcg 180 ctgcagagac tagctggcct ccggaagccg cctcctgacc ccgcgtcaag caccgcggtg 240 gatggcgcaa cccagctttg ggaattaatt acccaaggcg cgtttccgtg cagtctggcc 300 <210> 23 <211> 300 <212> DNA <213> BC3M_212 <400> 23 aatgccctgc ccgatccagt tccggcctcc catctcccct tcccgcgtct ccacgctctt 60 tccttccccg gttctgccgt gaatgctccc aagtcctaga gcaccggaac tccccgcgcg 120 ccttggctcc tgggccccag ctccgtgcag tcctggactg gggctccagg tccaccaggg 180 ggcgcccgct gcccaagctg ggtatcgctg cggagaaaag gggcccagag tgattgttcc 240 tcaggggagg gagggggagg tccccagagg gaagggcctg agtttcctct tgggggatgg 300 <210> 24 <211> 300 <212> DNA <213> BC3M_22 <400> 24 aaactaacag ggaatggtgt tgccacctgt agccccagct acttgagaga ctgaagcagg 60 aaaatccctt gaagccggca ggcaaagatt gctcactaca gtctagtcta aaaccccact 120 tccaaaaaaa taaaaaacgc acactcacac cattacaaca gcccaaaata aatgttcaaa 180 caaaatgttg tctcacacct cgcaacaaac acacaacttt ctatctgatt tttaaacacc 240 gttgatgaac cccaccaaca tagggcttca aaaaatttgc ttgaaactca aaacggtttc 300 <210> 25 <211> 300 <212> DNA <213> BC3M_221 <400> 25 cccaaagtac tgtgatgagc tactacgcct ggtcattgtc cctctttctc atgactctct 60 ggacatccct ggggtggagg gtggggcagg cacacacatc cctcaacttc ccagtggttc 120 cacgatgact aagccagccc tgtccctgag gctgggagtc tggagctagg atccaccccc 180 atggcctcat atcccaacct tgagcctggg tttctggtca gactggacgg gctagctcgg 240 tctccttaac tctcagagtt gccttgtcca ggcccagcgg gtcccacaca gccaggcaca 300 <210> 26 <211> 300 <212> DNA <213> BC3M_224 <400> 26 ttacccaaga tcattcggtg cggcctcagc gctggcgctg agtcctcttc tgccccaccc 60 ctcaggctcc cagtcctggt ctagatccct agccacgtag cgtagaaggg ggcgtcgacg 120 ggggttgggc tagagttgga gcggggagga gatgagctaa agcggggctg gctgtgcgag 180 aggcagtagc agcggcgtgt gtcctggggc gccccccggt ggcctgtgct ggggtcgtcg 240 gccgggatcc cctgttcgac gtactccggg gctgaatggg aaacagacag tcccagaccc 300 <210> 27 <211> 300 <212> DNA <213> BC3M_226 <400> 27 aaaaaagact aagtggagat gagggttcag tgcaccccca tctcctggcc ctgctgccca 60 tgagccagac cctgagctga cagattggtg cccatttcct cttatggatt gatacggggc 120 tcttacctct gggtttgctc agcccagcag caggcagtca gagccagaag ttgtttgcaa 180 accgaaaccg gtctgcggct tgggccacct acttgtgaaa ccagctgtcg ctgtttttcc 240 tccctgtgag aaagtccccc agtaaagctg cgcgggggag gagaaggagg gtggaggagg 300 <210> 28 <211> 300 <212> DNA <213> BC3M_230 <400> 28 aggggcaggg ccagggcggt tggtggactg ggcctggctg tacgtaggtg ctctgagaag 60 cccccggcga gaggggcggg gccagagcaa cagtgggcgg ggacaggctg tgcgtcggag 120 ctccgcgggg cctgcggcgg ggtgggtggg gccagggcgg cggtgggcgg gccgtgctgt 180 gcgtaggggc gctgagaggc ccgcaatgtg agaggggcgg ggccggaaca gcggtggacg 240 gggtctgtag ttcaactgtg ccgtggcgtc ttcttcgcgg cgagatctga gtgcctcgca 300 <210> 29 <211> 300 <212> DNA <213> BC3M_231 <400> 29 ggagcggtgc aaaggttctt atcctattta tcggagccag tgtccagaaa aggaagcttg 60 tggtttgaga cattctgtaa atccggttcc aagagcacga ggtaggactc tgaatccgat 120 gtggtttctg ttctcggtga tggtgcagag ctgtgagcca gtggtagggt gtcctttaaa 180 ttccagctca gtacactagt taatgaactt ggctgactga taaaaatgtt ttcaggttta 240 gctcatgaac atatcaacat agacctaaat ataattccag tttgtcatga atgttgattt 300 <210> 30 <211> 300 <212> DNA <213> BC3M_232 <400> 30 ggcctcttgg gggcgcggtg agtaggtggc ctctccaagc accactcccg atgtgcgcat 60 gagcgcagcc gcccctacgc agcgcgtgcg cacgtgcact caccacgtcc atcccagacg 120 tgcggacccg ggtgtctgca aggttcagtc tccacacccc agcgcccgac cctgcgcggg 180 gacatgcgca caagcgcgcg tcctgaccac ccggacgtgc tggcccacac gcacacgcgt 240 gcgcattacc cccgccccat ccgcgcctgc gctcaacccc gcctacacct gctccgtggc 300 <210> 31 <211> 300 <212> DNA <213> BC3M_235 <400> 31 ggtcctggac cgggacttag gtccacaccc acgtgctgac gtcgggcagg ctcagcggcc 60 tcccgcgcct gcgcagcacc gcccttttcg ggcgcggcgc ccagtcccta caccccacaa 120 tcccccgcgc cgttccggag gcgcgctagg agtgggtgtg gcctctgcct ccacattgga 180 acaaggtgag gcagagggtg tcgcgtggtc ttctgggaaa tgtagttcgt ctgccaggcc 240 ggaaccaccg ctcaaccggc tcgcgagact atgcacccca caatgcgccg cgcgcgcagc 300 <210> 32 <211> 300 <212> DNA <213> BC3M_239 <400> 32 tctaagtctg tgcatgcatt tgtggtcaga gtctggggag ctgggggcgt gaatgggctg 60 cttcagacac tgctttgagg gtgtgaccag gacctgaggg tgtggttaag gtgtaggggt 120 ggggctaggc ccttgggggt gggaccacag tcccagaggc gtggccaggg cctcgaaggt 180 atggccatag tttgaggcgt ggccgagaaa ctccgttccc aagggaggtg gtaactctgt 240 gctcagagcg ccctcttgtg gctatcctca ggtctccact ttttattcaa tagctttatt 300 <210> 33 <211> 300 <212> DNA <213> BC3M_241 <400> 33 gtggcccgct gtagccccgc cccgtggccc gcccgcagta ggcccgattc aaatctggcc 60 aatgatagtg tgtaaacaaa cccaggcccc gcctcccgac gaataatccc ccgaccggcg 120 agaggcccat ttaacccgat ggggtttggg gttgggacgg tgatggagtc gtggctccgc 180 ccccagacct gggccaatag gcggctgggc tccgcccccg gcacttgccg cgctgaggac 240 ccgaggcagg gctgggcgcg cagttgcctg atttcgtggc ggctcgcagt ctgggcgctc 300 <210> 34 <211> 300 <212> DNA <213> BC3M_245 <400> 34 cctccaaaag tgctgggatt actggcgtga gccaccgcgc ccggcctcag ggcgcgcttt 60 taaggagagt tcctgacatg acggtgggct tttcctgcag atgcacctct gggtagcgcc 120 ctctttacag ccttgaaacc tggtcaacta cattactcag aaagctctgc gttgaatgaa 180 tgccgtcaga gccaatgagg gctcggaaag aagcatttcc gtgtgtgcgc ctaatgtagg 240 gccgagactt ccggggtcct cttgtagcgg ccacgttgat ctgcgatacg cgtgtttgcc 300 <210> 35 <211> 300 <212> DNA <213> BC3M_247 <400> 35 acagcctttt ggaagtcgcg ctaaccttgg cctgagacct gcaaacttgc ccaggctggg 60 gcgtgtgaac cggcgagcgc gcagcggaaa cggggcgggg cacctgaggc tgggaatgca 120 gaggagcctt ccggggggcg gggcggggcc tcccgtgcag accaatggtg gagtagatgc 180 agatgtcaaa acgcgcgctc aagtggcttc cgccaggaat cccgacgctt agggaggcgg 240 agggaggatc gcttgagacc agcctgggca aacaagcgag accctcgtct gtttacttaa 300 <210> 36 <211> 300 <212> DNA <213> BC3M_250 <400> 36 aggctccaag gagttcagca tagcacgagc ttttaatttg cgtgcagaca agcacaaaag 60 gcacaaccgg atatacctgt tatttcccaa tgacctgaga gcccgaagtt tatgttaagc 120 cttgggttat ggcacagctt gcacgcaagg ccctgcagct cctgcaggca attgagaggt 180 ggtggtgtac aggacagagg aacaactctg aagtgacagc acataattta attcccccta 240 agctttccaa gcatgcagac tgttcctttt ttgtcagcgt ataacctaag tgatttgttc 300 <210> 37 <211> 300 <212> DNA <213> BC3M_252 <400> 37 aacacacaca acacacacac acacactctt tcaaggtcta gcaaaaccca tcaggagagg 60 ttgggccctg gaggtgctgt ggcttcctgc tgccccgctc cctcccgcct cctccctgca 120 gggctcctcc tggggaggcc tgtccagctg ccaggccccg ccccgccaca gcccccgctg 180 tcctcctccc tccctcagcc gtgccagcag cggcacagaa ctggaattgc cctggacggc 240 cacagctctg catatccccc aggagtgtgg acaagaaaaa ataaacacaa ttagagttca 300 <210> 38 <211> 300 <212> DNA <213> BC3M_253 <400> 38 aagagaagcc tgtcagtcca gctcgggcta cacactgggt gagccatgca ccacccagga 60 atttccaggg cacgtgccac gtaaggggca cacccgacag agtccaatgg ggttccccac 120 tgggcctccc actgagttgc tcagcctggg ccggaaaagg gtgagtcacc ctgggggtgg 180 ggctctccag ggtagaggcc aaaggagtga ctaccatgac aattctccgg agggcctgag 240 gcggcggtgg acagccccgg caacagtggg ccctccccgc agaactgtgg ttccaatccc 300 <210> 39 <211> 300 <212> DNA <213> BC3M_255 <400> 39 gcgtgcttgt gtgtgggtgt gtggtggggt atgtgtgtgt ccggggctgc cgattcaact 60 gaaaaacaaa agcggctctg agtctgaagc taaggtttaa caagtgacca agatgactca 120 tgctgcttgg ctgcaaaggc cacagggctg ccacccccag cggggcgggg cctgggtggg 180 aagagtcaca ggtacagagg ctcctgtgac attcacactc tgcccctgca tcggctgcct 240 ttggggccaa atacttttgt gaaaattaag acagaaggcc gggtgcggtg gttcacgcgt 300 <210> 40 <211> 400 <212> DNA <213> BC3M_257 <400> 40 aaacctgcgg gccccggtcc aggcgtggtc ccgctcgcac gagggagcgg tcgcccaggg 60 tgccgggaag tcggggaccg gccagccgcc gaccggccgc acccctcccc gccgagctcg 120 cgcgcccgcc tcgtcagcac ctttcccgca gcgcagcccc acagtggtca cgaggcgggc 180 gcggcccggt cagccctggc tagactaggc atcggcacca cccacctcgc ccctccccgt 240 cccgctggtt tcccctcccc ctccttcccc tccccctctc tgttctcctt cccctcccga 300 tccccgggcg ggccgcagcg cgccacgtac ctggccccgc ccctgcgagc cacgcaggga 360 accccggtga cgtcaccacc ctccggcgct ctcattcccg 400 <210> 41 <211> 300 <212> DNA <213> BC3M_260 <400> 41 cctgattagc cagaactata ggtgcacacc accacgcctg gctaattttt gtattttttt 60 gtagagacag ggtttcaaca tactgcccaa gctggtcttg aactcctggg ctcaaatgat 120 ccgctctcct tggcctgcca aagtgcaggg attagaggcg tgagtcacca cgcccagccc 180 attttccttt tcctgtccat aaattcctct ctgaccacat ggcagcatca gagtccctct 240 ggttcaggga gttaccggat tcatgaatca ttctttgctc aattaaactc tgttaacttt 300 <210> 42 <211> 300 <212> DNA <213> BC3M_265 <400> 42 tgtttctagc tagttataat tggcaggcaa ccagaagcct catctgccaa gggcggaagt 60 catgtctgga acaggtttcc ctcttaagac tgtgggctaa cccagcatct tgccactttg 120 tgtgggactt cctcattctt agtacataac tgtgtttgac cctcagggat gactagtgtt 180 tcctggcctc ggtacagttg acttctccag aaactatctg gctcactctc aatttcctgg 240 agccgtatat cctaattaca aaaatgggaa aatcatacct agagtcccat agaaagagaa 300 <210> 43 <211> 300 <212> DNA <213> BC3M_266 <400> 43 aaggagagat gatggaggca acacttacag gtcctgaaaa ctgctcaaat aggcacaaag 60 gaaacgaagg atgcctgaaa ataatgatga tgcaaaaact aagctaggta gggcagcagg 120 aagaaccggt ttggtgggaa gatgatgaat ttggcttgag gtgcttggca agacatgcaa 180 gtctgctgca caggcaatgc aggtcagcaa tttgagagaa aggtaaactt tcacaatcct 240 aatttgagaa gcaacagcac ggagatgatt atggagccat gagggctgag acactcagcg 300 <210> 44 <211> 300 <212> DNA <213> BC3M_267 <400> 44 cccatgcaac tgtgtgatga aacagcccca cacatccggg agcacagcca aggcgtcctg 60 tgccacctcc ctggtagaat ctggcttttc aacttgctca cccatgagag gaaagcggtt 120 ttagacatca ggcttacccc tctcctaagc cacacccttt tctcattccc agctgaggaa 180 ctgagcctga gacactgagg ttcccagctg cctccatgat tcgccagcac ccagcttcag 240 tttcacatcc tcccaatcgt catagccagg acagcatgcc tcactgacca cgagggaatg 300 <210> 45 <211> 400 <212> DNA <213> BC3M_268 <400> 45 aggcgccgcc gctgagggca ggcagcccgg cagccactac acacggaccc gtgacgtcgg 60 gcgtagcgcg gcgcacgtca cggccgctcg ctcgtgcgcg cgcacccctc cgcccggcgg 120 tagcggaacc cgccgcgggc gcgcgcccgg cccaggggag tgggtcggcg cctgcgcaga 180 ggcccgccac gcccacacac aggccaccgc ccccaccggc cggacggcgc ggggattccc 240 agtcctggct ccgccccggc ctcggccccg cccccgcccc tgccccgggg cagcctgtgc 300 tgttccgtgt gcgcggcgca tacgcacctg ggttgtctcg agcctgcggt agtggccaga 360 tcccagacat ccgagtagat cccgtgaaaa ggtctcccac 400 <210> 46 <211> 300 <212> DNA <213> BC3M_269 <400> 46 ccagccactg tgagtactgg ctgctcctga ctcacagctg caccctttga gggagtgagg 60 ggcgttaccc ttggctgaca ggatatgatt agaaagcctg gaaggcggct ggtggtggcc 120 catggccaat gagtcactgt gcgagtgtat actagcccag ccctcttgcc tccaggcagg 180 aaaacctctg tgtgaagtgc tctacttgct ccatgctctg gcgctctctg tacctacgca 240 ggctgaagct gagcctagac atctcctgaa accacacctt tgactcgctt cttccccttc 300 <210> 47 <211> 300 <212> DNA <213> BC3M_27 <400> 47 aacttgaaac aaataaagca ggttgaagat cacagtgtgt gctgctgggc ctgtgggggc 60 gctgggcagc agaaaggcac actctgcctg cagcctcggg atctggtcgc ctgtgtggga 120 gtagggagga gtcctgacgt accctctcta agactggctg ctctgcacct ccctccaagc 180 caggctggcc agtaaagaaa tctagctgtg gacaggaaac gagtggtttt tgtgatctga 240 gcagaaaggg cgttttaggc ctggagcaga gtggaggccc tgagccacgg cccaggaagt 300 <210> 48 <211> 300 <212> DNA <213> BC3M_275 <400> 48 tttgtgtgca tgtgcgtgtg tgtctggggg aaggaggtag aggaagtgag atgatggtga 60 cagtgacagc agcttggaga agacaggggg gtgggtctac ttctgaggaa gtccttggct 120 gaggtagggc cgcagagagg cagggtgagg gtggagcctg tggtttcaga gaggagtttt 180 aatggctgcc aagaatgtgc acatgaagcc gaaagggagt gcggcctgga gctgcagtca 240 gcccagaggg cgggtggagc ctgtcccagg gcactaggat cgcagagaac gacaggaggg 300 <210> 49 <211> 300 <212> DNA <213> BC3M_277 <400> 49 aaggtattcg aatcgaatga aatggaatcg aattgaaggg gtatgaatgg aatggaatgg 60 aatggaatcg aatcgaattt aatggaattg aataggaaag aatcaaatgg aatggaatca 120 acccgagtgg aatggaatgg aatggaaagg aatggaatgg aatggaatgg aatggaatgg 180 aatggaatgg aatggactcc agtggaaaag actggaatgg aacggtttcg aatgaaattg 240 aatcgaatga aatggaatgg aatgcaatgg aatcaaatgg aatggacttg aatggaatgg 300 <210> 50 <211> 300 <212> DNA <213> BC3M_283 <400> 50 cccatcgtgt tgcgaaagca ttcaggttga acagtgttca ggaagaatac tcaagcaaaa 60 actggtttgc agccaaatac agagactgca aaccccagtg gcttcagggg ccaggcaggg 120 aaagtaaaca tgtgaaacaa tagggagtag tcctgcctgt ggggaacagg ggagttctca 180 tgccccagcc taataaatga aaaaattatt tatacaccac agtggaaccg gagatgcacc 240 taaagccatt gggatgtggt ttctcttttt catctcactg ctctgtctct gatgtggctt 300 <210> 51 <211> 300 <212> DNA <213> BC3M_284 <400> 51 agcttggatg ctgcacccag gactgaaagg gggacctgtg ggcggcctct gcctctcccc 60 gcgcagcgtc aggacacagg cccacattcc ctcctggctt ctccctgaag ggagagagaa 120 taatagttgg ttcaaatgtc aggcctgctc cgtgctggtg gggagactgg ttgagcaggt 180 ccgcaggagg gacggaggga ggaaattatt aataattgca aagcaaccag ccacactaca 240 ggccttgagt tgtgtctgcg tttgtctttg gaggtgtgga gttgggggtg ctgatcctgg 300 <210> 52 <211> 300 <212> DNA <213> BC3M_290 <400> 52 ctgggggact gttgggtcag aaagtgttca gggagcagct gttgcgccct ccctcggccc 60 cgccgctcgg agacgccccg ccccctgcct tcaccggccg ccccgccccc tgccttcacc 120 ggccgcccgg ccacgcccca caccgccccg gccccgcccc agcgcccacg tgactagcat 180 aggcgcgccc ctgctccgcc ccccgccgcc gactccgcct ccgggacggg agcgagcggc 240 gagcgcgcgc actcccagtt ctcgctcggc gactcccgcg cacgcgcgcg ccgtgccacc 300 <210> 53 <211> 300 <212> DNA <213> BC3M_291 <400> 53 ctttttcctt taaagaatac acttcttatg taatttgttt tgcatttctg gaatgaggaa 60 cttttctgct catattgttg ttaaaatcta gacaacacgc ccgtgtgata gatcaccctg 120 agccttggaa ggaaatgatt caccacaata ctgtaactga aagtcgtcta acaccagggc 180 tggaaggcag gctatgaacc gctgcattac ctgcgtgcag cagcaatggg aggcagccag 240 aggttccctc ggcctgccta gctcacttca gctttgttcc tgttctgttt cctccgtccg 300 <210> 54 <211> 300 <212> DNA <213> BC3M_292 <400> 54 catcaaggga cccagagatc acagaatagc cagcccttca ttttcaggtg agggcctctg 60 tgggaaggtg cgttccaagc cacacagttg gaagttgagc gaactgaacc aaggctgggc 120 ttttgtgttt gctgtttaaa cagtgtgtgg ttttactcac ctaccatagt gctcctccta 180 ctggtgggca ccttagagta ggctgaaaac aacgtgtctc actgtccttt tttgtttgtc 240 tctgagtatt tttccttatg atcttgaagt aacatttact taatttgcaa tgaatgaaaa 300 <210> 55 <211> 300 <212> DNA <213> BC3M_295 <400> 55 tagcaacatg aggcaacctt gtctgcgaaa gaggaggtga ccgcagctcc tggggatgtg 60 ccaactctgg gatgtgacgg gaagacaaag ggcttctgtc cccttctgcc tggcggtaag 120 agagccggcc gcccggcagg catgccccag cctgtggttc tggaatgcgg gcaagccacc 180 gtccccagag acctgtgttg gtggccaggc cagcccacac acccgattgg cacatactct 240 tgtgcttgcc caggagcgga gtcagaccat tcacgctgcc ttcatgggag ttgaacagtt 300 <210> 56 <211> 300 <212> DNA <213> BC3M_307 <400> 56 tgcccccaca tcgccatcct gcctgtcctt ctgggcctgc acgtttgttg tgtttggaag 60 gagccaccaa ggaggaggat gtcaatgtgc aagttctcag ggaagcaggc cccgcagcct 120 ccgtcagtgt cttccgtccg caggaagaac ccaggcctgg gtgattcatc ggggcctcag 180 ggccgggagg cactaaatct tctgcagatg tggtaagatc ctatcacagc agaaagggaa 240 gggctagagt ctcagggaag gttttgctag ggagacgggc ttggaggggg ctgaggctca 300 <210> 57 <211> 300 <212> DNA <213> BC3M_321 <400> 57 caaaaaatac tgagcacaaa taaatattca ctgtaaggca ggaggcagcc gggaccagac 60 tccagatcag atcgaagact ggcggaaact gaggagaggc gcttaaagcc cctctccata 120 agacacgccc accacctcca tgacagttta ccattgccgt ggcaacaccc ggaagttact 180 gccccttgcc gcggcaacac cggaagttcc cgcccacttt ctagctaatt ctgaatgacc 240 cgcctcttaa ttagcatgtc ttttaaagtg gacctaaata cgcctacgaa actgccccta 300 <210> 58 <211> 300 <212> DNA <213> BC3M_323 <400> 58 tggtctctat ctcctgatct tgtgatacgc cggccgcggc ctcccaaagt gccgggatta 60 caggcatgag ccaccaggca cggctgaaca gggttttttt aaagttcctg aactgggtgg 120 ctgcccacaa gagggcactc atgcctctgc gtgtgagtgt ggaacctggt cgactgctgt 180 gacactcttt gggaagacag tcggcatttt ccacttccag cagcaggtgg cagtatgggc 240 aagagtatca tcacccatct ttcatctacc acccatgtgc ttacatctgg gctgctgaga 300 <210> 59 <211> 300 <212> DNA <213> BC3M_326 <400> 59 ctcacccgta acacacacac acacatgcgc gccctctcct cttgcatgac tcctctctca 60 gggctgagct gtttttctga gggtgccaca atgaatcagc tgcttagtca tctctggagt 120 gcgggagcta gcagaacagc aaagaggcat tacaaaccca atagcgggtt tcacttcctt 180 gagcagtatt tattctgctc tctacctcat gctgcccaaa ctgttggaga ggccctatcc 240 actctccctg ccttttcagc ccttattctc ccaaatgcag ccacagagga ggtaagagag 300 <210> 60 <211> 300 <212> DNA <213> BC3M_334 <400> 60 tttttgtggt tgagttctga attaaaaagt gtcgtactat atatttgttt ggtcatttct 60 atgacttcag cactctcaaa gacttggaca gaagcataaa taagaggcag tgtgagcatt 120 ctccaagtaa tcattccaag ttggtgagtt catactccac ctagacctca tggcctcgcc 180 actctcagtc aaactggttt ttgtggttgt caaagtccaa catggcaaat ttcccactga 240 tactaagtga gttgaaaact caagttacag ttgattttgc cctagggaat tttaccaaga 300 <210> 61 <211> 300 <212> DNA <213> BC3M_353 <400> 61 agggcatttg ctgagttttg ctttatgtga ctggatggga ctggccttgg agacactaat 60 aagcacgtga gggtttttgg acaatgcgaa gagttggtgc caagccacaa gtgggagatg 120 ttgaacttcc tgcgaatctg gtgtgttgta gcctgagtcg gtttcaatat gaaaaataag 180 agtgacagtg ccttccttgt atgctaatct ggcgaagtgg ctcatgctgg ccatgtaaca 240 acctggcagc ctcctacaga agcaagtggg gtgtggcatt cctgctgtct gcatcttctg 300 <210> 62 <211> 300 <212> DNA <213> BC3M_360 <400> 62 tgagtgagct ggcaagggaa ggaaggttgg tgagagtaag tcgtaagtat ctttttagaa 60 aaagaaaaaa aaaaaaatag cagaggatgg tttcgatcca tcgacctctg ggttatgggc 120 ccagcacgct tccgctgcgc cactctgctc tatacggtag tgatatttgc agtgaattct 180 ttatgatgtt ttcctcaaaa cttggtgggg attctggttt tttggtatgg ttaaacaaat 240 ctgatttcca caccccacca agggccacta gttctattta tgctgcaaac atgaggatga 300 <210> 63 <211> 300 <212> DNA <213> BC3M_362 <400> 63 agacactcgt gccctcaaga acttacaatt taggtttgtt tgaaagttaa ctgagaattc 60 caagtctaag ggtgctggtg agagtggcct ggcaaagcca gcccaggaag agctgctgag 120 caggttgtaa ggaacgagga tgccccaccc cccctccttg gcaaagcaga ggatggtatt 180 ccagacaggt cacaaacagc tcaagcaaag acgtggtgac agggatgagg aaggcacgct 240 tgcggatcgc tagaatggag gttgcctggg cacagacacc ttggaggatc cgattagcaa 300 <210> 64 <211> 300 <212> DNA <213> BC3M_367 <400> 64 gcagcaccca gttcagaact ttgcagattg ctggaattgc tggggagctg ccagagggct 60 ttcagaactc agcatgagtg cagtgagtgc ggcagccagc tcccaaaggg gatggcctca 120 gcatagtttc cagctctcgg ctctcttaac aggaaggcgt tgcggtgtcg cagacacaat 180 ctgaagtggg ggttcaaaca gacacaactt cacatactgg ttttgcaact tgctggcaaa 240 tgagtgaatt ttactcaatc ccaatttttc tcatctgtaa aacagccata aaatcgaccc 300 <210> 65 <211> 300 <212> DNA <213> BC3M_37 <400> 65 ccttccctcg acctcccttc taccccttcg ccttagatgg agattttctc tttctgaacc 60 cggaaccgct ccctcctccc cgcccggcta tagctggcag gacagggatt ggatgccacg 120 gccggtgcga gccttcgctc tccgccgagg gtagtgacac aggcgaggac gggccccgca 180 ggtcacatga gggcggggcc tggcgggctc gtgaccttcc cgtaggcggg gtccctcccc 240 tcccagctcg ggccgacagc gtcgtcacca gcttttatgg ggcacgtggc ggctgatgca 300 <210> 66 <211> 300 <212> DNA <213> BC3M_380 <400> 66 ttcactgtct gctggggcag gaggcagggc aggggcagga gggaggcaac cccagcctgt 60 gcccggcttc cccgaggcgt gtgccttgtg cggctgctga aggagtgact cctgaggaaa 120 ccagcttttc cagggaggca agggatggga gaagagggtg gagaaggaag tggtcacacc 180 acttgccttc tgccaatact gtccctttct tacgcgttaa ccttccactc tgagctatga 240 cactttcagt actagtgtgg taagttctac aggaaacagg aaacatggtt taacagacat 300 <210> 67 <211> 300 <212> DNA <213> BC3M_39 <400> 67 gcggggctca cgagtgacga agggcagaag ggcggggcgg gacgagagga ggggaggggc 60 gagcggaggg gagggacgag aggaggggcg ggacgagagg ggggcgggac gagaggaggg 120 gcggggctca cgagtgacgc agggcagaag ggcggggcgc aagagagact gagagcacta 180 cgcgggtgag aggaggggcg gggcgtggga gtgacggggc gtgggagtga ctgggcgcgg 240 agaggccgga gccggaggcg aggcgaggcg tgagagtgaa tgagggagga gggctgtgag 300 <210> 68 <211> 300 <212> DNA <213> BC3M_393 <400> 68 agcaggcact tctgagcctg cagaggaaag gggacttccc ggggcccccg agagcacagg 60 gatgcccggt ttgggagcct tggctaggca gctgcagctg cgcaggaggg tggggcttcc 120 gccccgccga ctcagaagcg ggcggggctt cggcctcttc ccggctcccg ccagctccgt 180 ggagcctgga gccccagccg cgcctccctg gctgcagctg ctgtattcac agcagccgct 240 tcaggcgggc cgccacggcg atcagttttt catggcctcc aggttctgat gaagcgtggg 300 <210> 69 <211> 300 <212> DNA <213> BC3M_402 <400> 69 tagcatcagg gtacctgctc tgggcttggc tcctcttggc cttggctcct ctggggcatc 60 atgggaacaa ggaggagcag acacctcgcc agccggggtg tgtctgagcc ccaggaatcc 120 tgcctcgcag ggaggattct ctgagtagag gtgatgtgtt atcacagtat cagcatttct 180 cagcctgact catggagggg agtgacttta ctgttagggc ctgaggggaa ataatgagga 240 acttctagac cagtttcatt tttattttta aacccacagt tcacccttgg gccttttgcc 300 <210> 70 <211> 300 <212> DNA <213> BC3M_406 <400> 70 acaagctctg acacagcgta tactcagtaa acatggagtg aatcagttca ttcaatgaat 60 gaacgaatga atgaaacgcc agagcccgcc acaggggtcc gctgccgctc cacgcccggg 120 cctctcaccg gccaatcaac actgtgactc gtacgccctg ccccctgatg ccacgcccat 180 cactcgcccc tctggattcc ctccggctgc gtggaaatcc cggagcactg gatttcccag 240 aggcgcctcc ggtagcagtg cgcatgctcc agcgccggta gctgaggcat caatttcccg 300 <210> 71 <211> 300 <212> DNA <213> BC3M_410 <400> 71 gcgcctgcgc cgtggcggcc gaactggcgc tcaacagacg ggcggggccg agcgtgaggc 60 ggagtctgcg cactgctgct ttgcaaatga aggtgggcgg ggtggagcga gcgtgagaga 120 cgtgcccccg accaataagt gcagagatcg ctcgggggcg gggacctgct gccgcgctcc 180 aggctgcggg tggccagaag gcagcggggg cgggctcggc gcgcgcggct ccgcccactc 240 cgggcccctg ctgggcggga aggcggcgcc ccggccgagg tggcggcggc tcctcaggta 300 <210> 72 <211> 300 <212> DNA <213> BC3M_414 <400> 72 acagaagcaa tctgacaaag tttttgtgat gtgtgcattc atctcgcaga gtggaacctt 60 aatttcgatt gagcagtttt gaaacactcc ttttgtagaa tctgtaagtg gacatttgga 120 gcgctttgag gcctaaggtg aaaaaggaaa tatcttccca taaaaactag acagaagcat 180 tctcagaaac ttgtttacga tgtgtgtact caactaacag agttgaaact ttcttttgat 240 agagcaaaac agtaaattga agtttaaaat aattgtaaca attgcatctt atatatcagg 300 <210> 73 <211> 300 <212> DNA <213> BC3M_417 <400> 73 acctgaggac gctcagcgct ggagctccga gcaggagtta aagtacccgc agtggagctg 60 gcccgctgcc tttccagact gcaaggcccg cagtgcaccg cgcgggtgac gtgtaacagg 120 ggcgggcggg accgctggag agcctatgag cacagcgcaa gcaccccgag gggccgcctt 180 ccggccctat tggtgaatcc gattaggggt gggaccgagc cgtggtgatt ggcggccgga 240 gggatggcaa agctgccacg cgcacggggg tgcaggctgc gggactgcga tcgctgccgg 300 <210> 74 <211> 300 <212> DNA <213> BC3M_47 <400> 74 ctgctgaggc tgctcctgca gcaggggcca tcttgttgct cggcctcctc ttcctcctcc 60 tcgtcctccg ccgcccagtc gctcgttgtc ctcgtcccct tcctcttcct caggctccgg 120 cccgccccgg agactggggc ggagacgagg gcgaggatcc tccctcagga ggcggggcgg 180 gcggagggga ggggcgggcg cgggagcaaa gctctgagtc accggccacc aacgcccgga 240 gggagaccgg cgacgctctc cgccgcgacc gaaagtctca cacgccctga gcagatgaac 300 <210> 75 <211> 300 <212> DNA <213> BC3M_48 <400> 75 cttcctggga atgagtgtct cacagcagcc agaggttgag gctttgtctt aaggtggagg 60 taataaaaac ctgtttgttt tcccagagca agacttgcct cagggcccct gcttgtttga 120 gacagggcat tcagtttgcc tgagtcaggc tggggaggtt cttctagtct ttggaatcct 180 gttgggcagg gtggctgcag gggatctgga agaggtaagg cctgtcccag gggtgggggc 240 tgaggaggtg gacatgaaga actccctgga ttaggacagt ggcccaggag gggaaaagag 300 <210> 76 <211> 300 <212> DNA <213> BC3M_49 <400> 76 aagttgggca gggcaggggc tagtctgcct tcttctgggc ccaaccctcc cggccggcac 60 cacaggcatt acaggtactc tgtgcactca ggctgcgcag acccgcagct tcctatcctg 120 tagctcactt tcctctgagg cgggctggag gcggagcttg tccgctgggg gtggggctca 180 aagctggggc ggggatacgg agcaaaactt aagaggaaga tgagaagcct ggttggccag 240 gaggcttatc tgtcaggaca gggggcgggg cctggggggc cgtacctttg cttaccgcga 300 <210> 77 <211> 300 <212> DNA <213> BC3M_52 <400> 77 tcatttttat tattagaatc tactatttgc caggtactct gaggcaccag gaatatacaa 60 ataacaagtg cagaaactga ccagtctagt tggacaggca gacgcataaa tcagcaatca 120 caaggcagtg tgactaatag aggaggtatg gcagcacaga gagaagtgag cagttactca 180 gcctgccttg taggcagggc actcagagaa gcttctcaga ggtggtgaca tgagagagag 240 ctgagccagt gatacagaag catgtagcaa gagtgggggt acactggcct ggcagtgtga 300 <210> 78 <211> 300 <212> DNA <213> BC3M_55 <400> 78 acccacgtcc ctcaatcccc acgagcagct gactgggacc tgaaagtgcc accagacgcc 60 ctcacaagtc tgctttcttt gctgggaaac agcagccgcg ccgcagcctc cgcccgctct 120 ggggaagccc caccttggca acaagccgct gattggctgg ctcgggggcg gcgcgggcca 180 atccaagccc gccctgacgc cgcggcgttt ggccgagaac tattaagaaa aaaaaaaaaa 240 gaaaaaaaga aaggtggggc cgggcgctag gtggcttccc aacggagttg ctcccccggc 300 <210> 79 <211> 300 <212> DNA <213> BC3M_58 <400> 79 caagagtgga aaacctgccc tcacaggccc agctggccag agggcttgtc tctttcagtc 60 gccctccccc agagggagca ggagcagaca atggccacca tgactcacca gtgagccatc 120 ttcccctccc cacccctcca gcctggccca tgacagctta gcttgtcctc caagggagct 180 gcagcccagc ctcccagggc cgccagcttc ctctctcttc acccaacctg gctccccccc 240 tgcttgtgca acaccacatc agagggttgt gaagtggaga gggaggagtt tgacagctgc 300 <210> 80 <211> 300 <212> DNA <213> BC3M_61 <400> 80 ggggctagca ggagagccag aataagcaga tttggcttct aatctgactc acccaactgg 60 ttcagaatgc agccaaaccg gggaaatttg ggtgagctcc tcctcttccc ctccctcact 120 tgctctcgca gttgtcctct agcacctctc tctatccctc cctccccgtc cccccgcccc 180 actcccccag ctctgggagc gcatgcgggg gcggggtcct aggaggatgt gagcccatgg 240 acacgcgggc gggatgtttt tctcctcgtc attgttctcc catgcccatt gtgtgcgctg 300 <210> 81 <211> 300 <212> DNA <213> BC3M_66 <400> 81 agccactcac tgcagaaggg gctggtgaga gacatgctcg tcatctccga gggcctggct 60 ctgcgccagc cacacactta tctgcctgct ccatctccgg agtttctgtc tctgagcttt 120 ggcaatggaa gttgtgcttc cactattagc caacaccgag ctggactctg gtaactgaca 180 cagccgtgca tctagtgtag ctcgggttga gatgacttgg cttttttttt tttttttttt 240 tttttgagac ggagtctcgc tccgtcaccc aggctggagt gcagtggcgg gatctcggct 300 <210> 82 <211> 300 <212> DNA <213> BC3M_67 <400> 82 ctattgtttg ggctttgctt ttgacttcac atcctgaaat aaatggtcgt tgcagaccag 60 gcacgtgagc aggaagtggg cagggcttaa aacacagaga agtcataacc tctgcggttt 120 ggttcatgtt gtaatatgaa aaccaggaag cttatcttgc aggaggctga tgtgtaaaag 180 ttcagaatgg agtggagccc tccctcttgg caccctatgc gcggagtcac cctttgtctg 240 ccacaggaag cacccaggtc ctggcagcta gaaaactgta acaacttgga aacatttccc 300 <210> 83 <211> 300 <212> DNA <213> BC3M_69 <400> 83 accagataag cacccactgc actcaaggcc tctctgatca agtcccacga ccaggctctc 60 caagtcctga caccgcggag acccccaaaa gaggaggatg gagcagaggg caaggctctc 120 agctccgcgg actcacaccc agctgcagag gcagggggag ccgccctttc tgtggccggg 180 gaaattgagg tcacttcctg tctcgcttcc ctctctctgt gctggctgca tccttcagaa 240 ggggggtggg tggctgcagg gcagcgccag gcaaggctgc ggagaagccg gtgctccctg 300 <210> 84 <211> 300 <212> DNA <213> BC3M_7 <400> 84 tctgcctgca agctccaggt cttgcaaagc ctgagaactg gtatggcaag ggcagagtga 60 gagcagggaa gaaatggagt caagctgaac agagacttcc gcatcatgag ggtggtggga 120 ggtggggagg aagttctgaa accacacaca tttatcattg ttattgagtc agacagacag 180 tgcctgctga catgtaactg tcaggcgttg ccaaggcaca gtagggttgc aaaggctgag 240 tgtccacttc ctcccaatga gtcaggaaga acccttggat aattctccaa aatagtttca 300 <210> 85 <211> 300 <212> DNA <213> BC3M_70 <400> 85 caggcacagt tctaagtaat tgaagtctac tgaggtaggt atcaatatta ttcccattct 60 ctagatgacg aaactggtgc atgtagcagt taggaaatat gcccaaaggt acactgctcg 120 taagcggcag agcaggaata tgaatccagc cagtctggtt ccggagtctg cattcttgat 180 cactgcacta taccaacttt cactttgttg tgagcacctg cctatctcag acatcagtca 240 gtaagtccct tgaaggcaag aactgtcctt tgatccttat tcctgagccc taggcattac 300 <210> 86 <211> 300 <212> DNA <213> BC3M_71 <400> 86 ggtgtatgta ctgatgtact gaatgggcga ccatttcctt ccagaaaggc tggagtcagc 60 cctccgggat ggctgtctct gtgtgactgt ctgcacacca ctgccctcca ctggacactg 120 aatcaaagct gccccagacc cacgttggtg tcaggactcc ctcaggtttc cttccctccc 180 tatctgggac acaacctcct gggcaaaccg gtttcttggt tggcttctct taccaggttt 240 gttttaccct gtctgccttg cattgaatcc atgaaacttg ggaagtacaa gaggaacaat 300 <210> 87 <211> 300 <212> DNA <213> BC3M_74 <400> 87 agggcatttc ttgagcctgg caggaggcca ggggttttac agggcaggaa ggaacctgga 60 ggaaccgagg agccacgttg ttggttggaa agaagggtgg ccaggtgggg aggagtctgg 120 caaagggtcc cagacagcag gaagggcacc tgtgaagccg ccctgccgag tgtgtggtag 180 aggcggggtg aaatgagcac tgctcataaa agtgactgtt gtgatttttt atgagatgga 240 gtctcgctct gtcgcccagg ctggagtgca ggggagcaac ctcggctcac tgcaacctcc 300 <210> 88 <211> 300 <212> DNA <213> BC3M_76 <400> 88 gatcgcggtg aatatcctgc aggtcatgct acgcccactt gctttgaggt tgggaaagca 60 gcctcttgac cttcagccac ttgagcccag caggtggagc tatttgccct cactggagcc 120 tgctttctcg ctaaggggaa atctgctaac cattacacag atagcaggta agtatttgga 180 gttgctcatg attttggaat gttgtggaaa caggtttcct cactttcaat aatgaacctt 240 atgatttatt atatgcaata caaatacctg ctgctgtggc catgataaag gttccaggcc 300 <210> 89 <211> 300 <212> DNA <213> BC3M_80 <400> 89 ctgaaggagt taaaacagtc cccaccccca ctcccgattt ctagaacccc acgataaatt 60 gggtaaatat gtattccatt cattggtgca tctgaccttg gtctgtgaca gaggaaaggc 120 gtgtcttctc atactgttcc ctatgaacaa aaggcaagca aatgagggtg actcaggact 180 tctcatggcc tacacacaac tgaacatttt tctgaatgat tccacgtata cacttaggaa 240 tcaggaagag aaacatttta ctcttcacta accaaataaa accatctata aatcatatgc 300 <210> 90 <211> 300 <212> DNA <213> BC3M_82 <400> 90 aaacaaacac tgggtttagg cattctgctc tcccagcacc gcatggctga gggtggaaaa 60 aaataacatc tgaaacaggc cgggcttttg atgatacctc cttatgacag acacatcgaa 120 aaccaccgac ggtgagtcac ccacattctg tgcataccct ctccgaggag caggaagtgt 180 ggctatttta aaccctgagg caatgagaag ttttcagatg cgtcctaagg cgctccggcc 240 agcgccctgc atgcacacga gggccttcct cagtgtggcc ccagcacatc tgtagacctg 300 <210> 91 <211> 300 <212> DNA <213> BC3M_84 <400> 91 attttgactc acaatgttga aaccagatta taaatgagtc atcagtgaat cgaccacaaa 60 gagcctttgc ggaggtgatt tacaggagag ctctgatgtc tgctgtcccc tgcacacgct 120 tcacagagat gctgtcagac gcagagctgg tctggggcat ctgttgccgc gtcagctcaa 180 aaggatgctg tgttgtcacc aatgggattc cccagcccag gcggtgttgc ggtcccaccc 240 acacaaggaa ggcggccatc actgaataat gcttgtggtt acatcatcat tgctggtttc 300 <210> 92 <211> 300 <212> DNA <213> BC3M_86 <400> 92 gggatttcct ctgctttttc aactaaaatc agctctttcc caaaagcctg tgctgcctgt 60 tgtgttttct ctgtgtgtgt tttgaaatgg ccttgcgcac cctccagact ctctgcctcc 120 ggggcaagtc tgccttttcc ctgtttccac tttgcatact gcataacttc cttctctgcc 180 ccacatggac acacgccctc ttattcatgc atccgcggct cttgctgcat tcgctcggca 240 gcaaagccac aggctccctt gtggatgtcc cttgtggaga tttgtacttt tttaccccac 300 <210> 93 <211> 300 <212> DNA <213> BC3M_87 <400> 93 gagcacagaa gacgacccag ctgaggctgg caggagagac gaaggccccg ccagatcccg 60 gaagccgcgc ccttctgtcc ggctgcacgc ccgattggac ggttcctacg tcagcgcccc 120 tgattggata gggctccagg ccccgccccc tcagtccctg agtgacggag gatgtgatcg 180 gacgctgggc tgagggcgac aaagtgacag gttcttggct gcagcctttt catgcagggc 240 ttcctgcttg cgctgggcct ggcccagccc agggggcatt ttcatttaac cttttgtata 300 <210> 94 <211> 300 <212> DNA <213> BC3M_9 <400> 94 agtttggatg ttctctgtgg agagggaata aaaccattgc ctgttccctg gagggaattg 60 gatgctgaag cttctacctt taacaggggc atgggtgcag ttccagcctc tgccagcagg 120 ctgggccctg tgcccacttt tgaaagacct tcagggctgt ggggcatgag atgagagagg 180 gagggaagat aatctggctc actgccgggc actttatgtg acttacctcc ttaattcccc 240 cgggcacagc cctgagagga ggttggcagt gtctgcattt tacagatggg gaacttgagg 300 <210> 95 <211> 300 <212> DNA <213> BC3M_92 <400> 95 aaacttcgtc tcaaaaacaa aacaaaacaa agcgaaaaaa caaaaaaagt ttcattgttt 60 cacctccaca cagctctgtc tgcattttga gcaatggcca ccagagggca ggaagaacca 120 atctataaag cacacaaggg tttcaccaac tttgaagtcc tccgttagaa ggcaagttgt 180 ccactaatat gtaggaacga ttaatggcca ccagagggca ggaagaacca atctataaag 240 cgcacaaggg tttcaccaac tttgaagtcc tccgttagaa ggcaagttgt ccactaatat 300 <210> 96 <211> 300 <212> DNA <213> BC3M_96 <400> 96 gaagcagcca gaagacctgg ttctcccaag cctgctactt gctggccatg taaccttgag 60 caagttattt cctcctctgc aaaaggaaga caataccctc ctgcctactt cactcagacg 120 ttctgaagat cgatgtagca atgtggtgta gacatgcttt tgtaacgtgg acacacccag 180 acaggaataa gtcttgtcca gggaatattt tttgacaaac actgcttaac tggtttgtcc 240 tctgagtgtc acaacttttg gcagaacttg gtagttggag gtcagtggtt ggctggttca 300 <210> 97 <211> 300 <212> DNA <213> BC3M_23 <400> 97 cagcccttcc tcacctcatc actccccatc cccccaagat atagaaaggc cgtgacagct 60 gccagccctg cacatgctct tgtttcaaca gcggcgattg cacatcacgt agtccccacg 120 tgacctgtcg ggcctagggc aagcgcaaag ctttcggaaa cccgaattat tgcaaccttg 180 acttcctgcc tgtctctgag gctcccgggc tgtgctttaa gctggacagg cacctgcttt 240 acagggaaaa ggaccaaggt ccggagagga aaggggcttg tcccaggata cgcagcaagt 300 <210> 98 <211> 300 <212> DNA <213> BC3M_103 <400> 98 ctaggagctc tgtgcggaac cgcgtccagc cgccgactca ctgacacatc acaatgagtc 60 acgtgctctg tgcaccgggc ggatttgtca gatccgctgc tgcatcacgg ctcggcaggg 120 ctctctgggt tctcagtgcc ctcctaggtc tgcaatgcag tgcgggagag gaggaatatg 180 ggcttgtggg ggcaggggca gcgcccggac tcctcccggg gcaggactcc cagaaacgca 240 ggaagcgatg acgctgctca gataaaccct ggcgctctgc gctggcgtcc tggtcaggag 300 <210> 99 <211> 300 <212> DNA <213> BC3M_44 <400> 99 catgtgagct caattaatac aacatatggt tactgtacgc ccaaaggcaa cgcattcaaa 60 ttgctttgta ccatgtaaaa cacacactct tgaaaaacag acgcctagtg cggaatcctg 120 tgcacgcctt taactcctcc aaacgagcag ggggcgtcat ggattagcat gtcccggggt 180 tcgggaatca gcatttccga ggaaaggggc gctcaggaga tatccccacc cccgatgagg 240 ggcactgtcg tggatgagtt taaaccacgc cataggcagc caagaactga gctcccgatg 300 <210> 100 <211> 300 <212> DNA <213> BC3M_219 <400> 100 gggaccaatc cagaagcagc acccagaccg gtttacccgg ttccaggacc ttgggcgaag 60 tccacccgcc cgagggcagg gacgacgcag gccacgccgc ggcccagttg ctagccaggc 120 agggtgggga tttgatcttg ccaaggaaat gtgagcggga ggccgagcgt tggaggtggg 180 taagtcgtca ctatgcaggg cggagccatc ctgtgtctat cacgcccaag ggcggtgcat 240 gcaaattgac tcccgcattt ggcttttccc cgggctccgt ctccgcgcgc tgcaacccgc 300 <210> 101 <211> 20 <212> DNA <213> BC3M_102F <400> 101 ggggctctca aggactctac 20 <210> 102 <211> 20 <212> DNA <213> BC3M_102R <400> 102 cgagggcaga aaggagagac 20 <210> 103 <211> 18 <212> DNA <213> BC3M_11F <400> 103 gtttccgtac gcagcctg 18 <210> 104 <211> 20 <212> DNA <213> BC3M_11R <400> 104 caatgagcag gaagatgggc 20 <210> 105 <211> 20 <212> DNA <213> BC3M_117F <400> 105 aaggctcagt gtgtgtatgc 20 <210> 106 <211> 20 <212> DNA <213> BC3M_117R <400> 106 ggttactgac tgctccccat 20 <210> 107 <211> 20 <212> DNA <213> BC3M_119F <400> 107 taaccttccc ttggcttcca 20 <210> 108 <211> 20 <212> DNA <213> BC3M_119R <400> 108 gagagaagga aagggagggg 20 <210> 109 <211> 20 <212> DNA <213> BC3M_125F <400> 109 acctctagac caagtgcctg 20 <210> 110 <211> 20 <212> DNA <213> BC3M_125R <400> 110 ggtggcttca gagatggagt 20 <210> 111 <211> 20 <212> DNA <213> BC3M_132F <400> 111 ctgacggcaa attcctccag 20 <210> 112 <211> 20 <212> DNA <213> BC3M_132R <400> 112 gcttgtctgt catctgaggc 20 <210> 113 <211> 18 <212> DNA <213> BC3M_137F <400> 113 gaccagccaa tctcccgg 18 <210> 114 <211> 19 <212> DNA <213> BC3M_137R <400> 114 gagatccatt ggttgcggc 19 <210> 115 <211> 20 <212> DNA <213> BC3M_139F <400> 115 gtgtgagcca agtgttgacc 20 <210> 116 <211> 20 <212> DNA <213> BC3M_139R <400> 116 ttcatcctgc ctgcctagag 20 <210> 117 <211> 20 <212> DNA <213> BC3M_142F <400> 117 ctttccactc acaccttgcc 20 <210> 118 <211> 20 <212> DNA <213> BC3M_142R <400> 118 aggcacaaaa gaggcaaagg 20 <210> 119 <211> 20 <212> DNA <213> BC3M_146F <400> 119 ggatgagtca ctggatccgt 20 <210> 120 <211> 20 <212> DNA <213> BC3M_146R <400> 120 gcctctgtcc cttctccatt 20 <210> 121 <211> 20 <212> DNA <213> BC3M_154F <400> 121 aatccagtcc cagttcccag 20 <210> 122 <211> 20 <212> DNA <213> BC3M_154R <400> 122 actggcctct caacacctac 20 <210> 123 <211> 20 <212> DNA <213> BC3M_168F <400> 123 cccagagctg caatgtgtac 20 <210> 124 <211> 20 <212> DNA <213> BC3M_168R <400> 124 tacggatgag gaggctggta 20 <210> 125 <211> 20 <212> DNA <213> BC3M_171F <400> 125 cctgtacctc tgcagtgcta 20 <210> 126 <211> 20 <212> DNA <213> BC3M_171R <400> 126 tcctgggcag agtgttttca 20 <210> 127 <211> 20 <212> DNA <213> BC3M_172F <400> 127 cctccttccc atttctgcct 20 <210> 128 <211> 20 <212> DNA <213> BC3M_172R <400> 128 ccttttccat ttccagcccc 20 <210> 129 <211> 20 <212> DNA <213> BC3M_173F <400> 129 gaatccgcag atcctcaagc 20 <210> 130 <211> 20 <212> DNA <213> BC3M_173R <400> 130 aagttcttct tcccgccctc 20 <210> 131 <211> 20 <212> DNA <213> BC3M_178F <400> 131 accattcagt gtaagcccca 20 <210> 132 <211> 20 <212> DNA <213> BC3M_178R <400> 132 tctttccacc atgcacgttg 20 <210> 133 <211> 20 <212> DNA <213> BC3M_179F <400> 133 acaccaccac ctccttcttc 20 <210> 134 <211> 21 <212> DNA <213> BC3M_179R <400> 134 ggaaagtgca aatgaacccc a 21 <210> 135 <211> 20 <212> DNA <213> BC3M_182F <400> 135 tggttccctc ctcacatcag 20 <210> 136 <211> 20 <212> DNA <213> BC3M_182R <400> 136 ttgcaacctc cgcttgaaaa 20 <210> 137 <211> 20 <212> DNA <213> BC3M_199F <400> 137 ttgggaaggc aagaggatga 20 <210> 138 <211> 20 <212> DNA <213> BC3M_199R <400> 138 gtgttcaagc cctccctcta 20 <210> 139 <211> 20 <212> DNA <213> BC3M_20F <400> 139 ctcacaccgt ctcactaggg 20 <210> 140 <211> 19 <212> DNA <213> BC3M_20R <400> 140 gaattccaca gacaccgcg 19 <210> 141 <211> 20 <212> DNA <213> BC3M_203F <400> 141 cctcgtaggg cttgaaatgt 20 <210> 142 <211> 23 <212> DNA <213> BC3M_203R <400> 142 agaagaattt ggcgaggatt acc 23 <210> 143 <211> 20 <212> DNA <213> BC3M_206F <400> 143 ttgagcgcag tctggaaatg 20 <210> 144 <211> 20 <212> DNA <213> BC3M_206R <400> 144 gagatgagcc ctgtcacagt 20 <210> 145 <211> 20 <212> DNA <213> BC3M_212F <400> 145 aagtcctaga gcaccggaac 20 <210> 146 <211> 20 <212> DNA <213> BC3M_212R <400> 146 cttttctccg cagcgatacc 20 <210> 147 <211> 20 <212> DNA <213> BC3M_22F <400> 147 ggaaaatccc ttgaagccgg 20 <210> 148 <211> 20 <212> DNA <213> BC3M_22R <400> 148 tgggctgttg taatggtgtg 20 <210> 149 <211> 20 <212> DNA <213> BC3M_221F <400> 149 tgatgagcta ctacgcctgg 20 <210> 150 <211> 20 <212> DNA <213> BC3M_221R <400> 150 tgggaagttg agggatgtgt 20 <210> 151 <211> 20 <212> DNA <213> BC3M_224F <400> 151 cggggaggag atgagctaaa 20 <210> 152 <211> 20 <212> DNA <213> BC3M_224R <400> 152 agtacgtcga acaggggatc 20 <210> 153 <211> 20 <212> DNA <213> BC3M_226F <400> 153 tggattgata cggggctctt 20 <210> 154 <211> 20 <212> DNA <213> BC3M_226R <400> 154 cgacagctgg tttcacaagt 20 <210> 155 <211> 18 <212> DNA <213> BC3M_230F <400> 155 ctgagaggcc cgcaatgt 18 <210> 156 <211> 18 <212> DNA <213> BC3M_230R <400> 156 cactcagatc tcgccgcg 18 <210> 157 <211> 20 <212> DNA <213> BC3M_231F <400> 157 gagcggtgca aaggttctta 20 <210> 158 <211> 20 <212> DNA <213> BC3M_231R <400> 158 cctacctcgt gctcttggaa 20 <210> 159 <211> 19 <212> DNA <213> BC3M_232F <400> 159 ctctccaagc accactccc 19 <210> 160 <211> 20 <212> DNA <213> BC3M_232R <400> 160 tgtggagact gaaccttgca 20 <210> 161 <211> 20 <212> DNA <213> BC3M_235F <400> 161 cagtccctac accccacaat 20 <210> 162 <211> 20 <212> DNA <213> BC3M_235R <400> 162 catttcccag aagaccacgc 20 <210> 163 <211> 20 <212> DNA <213> BC3M_239F <400> 163 tggttaaggt gtaggggtgg 20 <210> 164 <211> 20 <212> DNA <213> BC3M_239R <400> 164 agcacagagt taccacctcc 20 <210> 165 <211> 20 <212> DNA <213> BC3M_241F <400> 165 gtgtaaacaa acccaggccc 20 <210> 166 <211> 19 <212> DNA <213> BC3M_241R <400> 166 gactccatca ccgtcccaa 19 <210> 167 <211> 20 <212> DNA <213> BC3M_245F <400> 167 gcgcgctttt aaggagagtt 20 <210> 168 <211> 20 <212> DNA <213> BC3M_245R <400> 168 ggctctgacg gcattcattc 20 <210> 169 <211> 20 <212> DNA <213> BC3M_247F <400> 169 gatgcagatg tcaaaacgcg 20 <210> 170 <211> 19 <212> DNA <213> BC3M_247R <400> 170 gagggtctcg cttgtttgc 19 <210> 171 <211> 20 <212> DNA <213> BC3M_250F <400> 171 aggagttcag catagcacga 20 <210> 172 <211> 20 <212> DNA <213> BC3M_250R <400> 172 caagctgtgc cataacccaa 20 <210> 173 <211> 19 <212> DNA <213> BC3M_252F <400> 173 ctgtcctcct ccctccctc 19 <210> 174 <211> 20 <212> DNA <213> BC3M_252R <400> 174 tttcttgtcc acactcctgg 20 <210> 175 <211> 20 <212> DNA <213> BC3M_253F <400> 175 acacccgaca gagtccaatg 20 <210> 176 <211> 20 <212> DNA <213> BC3M_253R <400> 176 ggtagtcact cctttggcct 20 <210> 177 <211> 20 <212> DNA <213> BC3M_255F <400> 177 cggctctgag tctgaagcta 20 <210> 178 <211> 20 <212> DNA <213> BC3M_255R <400> 178 ggagcctctg tacctgtgac 20 <210> 179 <211> 18 <212> DNA <213> BC3M_257F <400> 179 ccccacagtg gtcacgag 18 <210> 180 <211> 20 <212> DNA <213> BC3M_257R <400> 180 ggggaaggag aacagagagg 20 <210> 181 <211> 20 <212> DNA <213> BC3M_260F <400> 181 gctcaaatga tccgctctcc 20 <210> 182 <211> 20 <212> DNA <213> BC3M_260R <400> 182 gactctgatg ctgccatgtg 20 <210> 183 <211> 20 <212> DNA <213> BC3M_265F <400> 183 gcggaagtca tgtctggaac 20 <210> 184 <211> 20 <212> DNA <213> BC3M_265R <400> 184 cgaggccagg aaacactagt 20 <210> 185 <211> 20 <212> DNA <213> BC3M_266F <400> 185 ggcacaaagg aaacgaagga 20 <210> 186 <211> 20 <212> DNA <213> BC3M_266R <400> 186 ccaagcacct caagccaaat 20 <210> 187 <211> 20 <212> DNA <213> BC3M_267F <400> 187 cctccctggt agaatctggc 20 <210> 188 <211> 20 <212> DNA <213> BC3M_267R <400> 188 gtgtctcagg ctcagttcct 20 <210> 189 <211> 18 <212> DNA <213> BC3M_268F <400> 189 ctgtgctgtt ccgtgtgc 18 <210> 190 <211> 20 <212> DNA <213> BC3M_268R <400> 190 gagacctttt cacgggatct 20 <210> 191 <211> 20 <212> DNA <213> BC3M_269F <400> 191 acctctgtgt gaagtgctct 20 <210> 192 <211> 20 <212> DNA <213> BC3M_269R <400> 192 gcgagtcaaa ggtgtggttt 20 <210> 193 <211> 20 <212> DNA <213> BC3M_27F <400> 193 tctaagactg gctgctctgc 20 <210> 194 <211> 20 <212> DNA <213> BC3M_27R <400> 194 aaaacgccct ttctgctcag 20 <210> 195 <211> 20 <212> DNA <213> BC3M_275F <400> 195 gggtgggtct acttctgagg 20 <210> 196 <211> 20 <212> DNA <213> BC3M_275R <400> 196 ctccctttcg gcttcatgtg 20 <210> 197 <211> 20 <212> DNA <213> BC3M_277F <400> 197 tggaatggaa tcaacccgag 20 <210> 198 <211> 20 <212> DNA <213> BC3M_277R <400> 198 cgaaaccgtt ccattccagt 20 <210> 199 <211> 20 <212> DNA <213> BC3M_283F <400> 199 aacaggggag ttctcatgcc 20 <210> 200 <211> 20 <212> DNA <213> BC3M_283R <400> 200 agccacatca gagacagagc 20 <210> 201 <211> 20 <212> DNA <213> BC3M_284F <400> 201 gttcaaatgt caggcctgct 20 <210> 202 <211> 20 <212> DNA <213> BC3M_284R <400> 202 cacctccaaa gacaaacgca 20 <210> 203 <211> 20 <212> DNA <213> BC3M_290F <400> 203 gcccacgtga ctagcatagg 20 <210> 204 <211> 19 <212> DNA <213> BC3M_290R <400> 204 gagcgagaac tgggagtgc 19 <210> 205 <211> 20 <212> DNA <213> BC3M_291F <400> 205 atcaccctga gccttggaag 20 <210> 206 <211> 20 <212> DNA <213> BC3M_291R <400> 206 caggtaatgc agcggttcat 20 <210> 207 <211> 20 <212> DNA <213> BC3M_292F <400> 207 caagggaccc agagatcaca 20 <210> 208 <211> 20 <212> DNA <213> BC3M_292R <400> 208 acagcaaaca caaaagccca 20 <210> 209 <211> 20 <212> DNA <213> BC3M_295F <400> 209 tctgcgaaag aggaggtgac 20 <210> 210 <211> 20 <212> DNA <213> BC3M_295R <400> 210 cattccagaa ccacaggctg 20 <210> 211 <211> 19 <212> DNA <213> BC3M_307F <400> 211 agcctccgtc agtgtcttc 19 <210> 212 <211> 20 <212> DNA <213> BC3M_307R <400> 212 tgagactcta gcccttccct 20 <210> 213 <211> 20 <212> DNA <213> BC3M_321F <400> 213 ctctccataa gacacgccca 20 <210> 214 <211> 20 <212> DNA <213> BC3M_321R <400> 214 aagaggcggg tcattcagaa 20 <210> 215 <211> 20 <212> DNA <213> BC3M_323F <400> 215 caaagtgccg ggattacagg 20 <210> 216 <211> 20 <212> DNA <213> BC3M_323R <400> 216 tcccaaagag tgtcacagca 20 <210> 217 <211> 20 <212> DNA <213> BC3M_326F <400> 217 ccctctcctc ttgcatgact 20 <210> 218 <211> 20 <212> DNA <213> BC3M_326R <400> 218 atgcctcttt gctgttctgc 20 <210> 219 <211> 20 <212> DNA <213> BC3M_334F <400> 219 tcgccactct cagtcaaact 20 <210> 220 <211> 21 <212> DNA <213> BC3M_334R <400> 220 ccctagggca aaatcaactg t 21 <210> 221 <211> 20 <212> DNA <213> BC3M_353F <400> 221 tgttgtagcc tgagtcggtt 20 <210> 222 <211> 20 <212> DNA <213> BC3M_353R <400> 222 ccccacttgc ttctgtagga 20 <210> 223 <211> 20 <212> DNA <213> BC3M_360F <400> 223 gggaaggaag gttggtgaga 20 <210> 224 <211> 20 <212> DNA <213> BC3M_360R <400> 224 accgtataga gcagagtggc 20 <210> 225 <211> 20 <212> DNA <213> BC3M_362F <400> 225 tccaagtcta agggtgctgg 20 <210> 226 <211> 20 <212> DNA <213> BC3M_362R <400> 226 taccatcctc tgctttgcca 20 <210> 227 <211> 20 <212> DNA <213> BC3M_367F <400> 227 gagggctttc agaactcagc 20 <210> 228 <211> 20 <212> DNA <213> BC3M_367R <400> 228 gcaacgcctt cctgttaaga 20 <210> 229 <211> 20 <212> DNA <213> BC3M_37F <400> 229 ttccctcgac ctcccttcta 20 <210> 230 <211> 20 <212> DNA <213> BC3M_37R <400> 230 ccctgtcctg ccagctatag 20 <210> 231 <211> 20 <212> DNA <213> BC3M_380F <400> 231 gactcctgag gaaaccagct 20 <210> 232 <211> 20 <212> DNA <213> BC3M_380R <400> 232 cagagtggaa ggttaacgcg 20 <210> 233 <211> 20 <212> DNA <213> BC3M_39F <400> 233 gcaagagaga ctgagagcac 20 <210> 234 <211> 20 <212> DNA <213> BC3M_39R <400> 234 ccctcctccc tcattcactc 20 <210> 235 <211> 20 <212> DNA <213> BC3M_393F <400> 235 gctgcagctg ctgtattcac 20 <210> 236 <211> 20 <212> DNA <213> BC3M_393R <400> 236 aggggtacag ggcagaaaat 20 <210> 237 <211> 20 <212> DNA <213> BC3M_402F <400> 237 ggaacaagga ggagcagaca 20 <210> 238 <211> 20 <212> DNA <213> BC3M_402R <400> 238 ctccatgagt caggctgaga 20 <210> 239 <211> 20 <212> DNA <213> BC3M_406F <400> 239 ggccaatcaa cactgtgact 20 <210> 240 <211> 19 <212> DNA <213> BC3M_406R <400> 240 tccagtgctc cgggatttc 19 <210> 241 <211> 18 <212> DNA <213> BC3M_410F <400> 241 ccgaactggc gctcaaca 18 <210> 242 <211> 20 <212> DNA <213> BC3M_410R <400> 242 ctctgcactt attggtcggg 20 <210> 243 <211> 19 <212> DNA <213> BC3M_414F <400> 243 tgtgtgcatt catctcgca 19 <210> 244 <211> 20 <212> DNA <213> BC3M_414R <400> 244 cctcaaagcg ctccaaatgt 20 <210> 245 <211> 20 <212> DNA <213> BC3M_417F <400> 245 gcaggagtta aagtacccgc 20 <210> 246 <211> 20 <212> DNA <213> BC3M_417R <400> 246 gctgtgctca taggctctcc 20 <210> 247 <211> 20 <212> DNA <213> BC3M_47F <400> 247 cttcctcttc ctcaggctcc 20 <210> 248 <211> 19 <212> DNA <213> BC3M_47R <400> 248 cggtgactca gagctttgc 19 <210> 249 <211> 20 <212> DNA <213> BC3M_48F <400> 249 ggctggggag gttcttctag 20 <210> 250 <211> 20 <212> DNA <213> BC3M_48R <400> 250 ttcatgtcca cctcctcagc 20 <210> 251 <211> 20 <212> DNA <213> BC3M_49F <400> 251 ccgcagcttc ctatcctgta 20 <210> 252 <211> 20 <212> DNA <213> BC3M_49R <400> 252 accaggcttc tcatcttcct 20 <210> 253 <211> 20 <212> DNA <213> BC3M_52F <400> 253 atggcagcac agagagaagt 20 <210> 254 <211> 20 <212> DNA <213> BC3M_52R <400> 254 tggctcagct ctctctcatg 20 <210> 255 <211> 20 <212> DNA <213> BC3M_55F <400> 255 agctgactgg gacctgaaag 20 <210> 256 <211> 18 <212> DNA <213> BC3M_55R <400> 256 cccgagccag ccaatcag 18 <210> 257 <211> 20 <212> DNA <213> BC3M_58F <400> 257 caagagtgga aaacctgccc 20 <210> 258 <211> 20 <212> DNA <213> BC3M_58R <400> 258 gaggggaaga tggctcactg 20 <210> 259 <211> 20 <212> DNA <213> BC3M_61F <400> 259 ctcttcccct ccctcacttg 20 <210> 260 <211> 20 <212> DNA <213> BC3M_61R <400> 260 catgggctca catcctccta 20 <210> 261 <211> 20 <212> DNA <213> BC3M_66F <400> 261 agccacacac ttatctgcct 20 <210> 262 <211> 20 <212> DNA <213> BC3M_66R <400> 262 cccgagctac actagatgca 20 <210> 263 <211> 20 <212> DNA <213> BC3M_67F <400> 263 aagtgggcag ggcttaaaac 20 <210> 264 <211> 20 <212> DNA <213> BC3M_67R <400> 264 gggctccact ccattctgaa 20 <210> 265 <211> 20 <212> DNA <213> BC3M_69F <400> 265 aagaggagga tggagcagag 20 <210> 266 <211> 20 <212> DNA <213> BC3M_69R <400> 266 gagagaggga agcgagacag 20 <210> 267 <211> 20 <212> DNA <213> BC3M_7F <400> 267 ggtggggagg aagttctgaa 20 <210> 268 <211> 20 <212> DNA <213> BC3M_7R <400> 268 ctttgcaacc ctactgtgcc 20 <210> 269 <211> 20 <212> DNA <213> BC3M_70F <400> 269 atgacgaaac tggtgcatgt 20 <210> 270 <211> 20 <212> DNA <213> BC3M_70R <400> 270 tcaagaatgc agactccgga 20 <210> 271 <211> 20 <212> DNA <213> BC3M_71F <400> 271 ccctccactg gacactgaat 20 <210> 272 <211> 20 <212> DNA <213> BC3M_71R <400> 272 agaagccaac caagaaaccg 20 <210> 273 <211> 19 <212> DNA <213> BC3M_74F <400> 273 ttggaaagaa gggtggcca 19 <210> 274 <211> 20 <212> DNA <213> BC3M_74R <400> 274 ctcatttcac cccgcctcta 20 <210> 275 <211> 20 <212> DNA <213> BC3M_76F <400> 275 tttgaggttg ggaaagcagc 20 <210> 276 <211> 20 <212> DNA <213> BC3M_76R <400> 276 agcagatttc cccttagcga 20 <210> 277 <211> 20 <212> DNA <213> BC3M_80F <400> 277 tgcatctgac cttggtctgt 20 <210> 278 <211> 20 <212> DNA <213> BC3M_80R <400> 278 ggccatgaga agtcctgagt 20 <210> 279 <211> 20 <212> DNA <213> BC3M_82F <400> 279 agacacatcg aaaaccaccg 20 <210> 280 <211> 20 <212> DNA <213> BC3M_82R <400> 280 gccttaggac gcatctgaaa 20 <210> 281 <211> 20 <212> DNA <213> BC3M_84F <400> 281 aggagagctc tgatgtctgc 20 <210> 282 <211> 20 <212> DNA <213> BC3M_84R <400> 282 gcatcctttt gagctgacgc 20 <210> 283 <211> 20 <212> DNA <213> BC3M_86F <400> 283 tgtgctgcct gttgtgtttt 20 <210> 284 <211> 20 <212> DNA <213> BC3M_86R <400> 284 atgtggggca gagaaggaag 20 <210> 285 <211> 18 <212> DNA <213> BC3M_87F <400> 285 caggagagac gaaggccc 18 <210> 286 <211> 20 <212> DNA <213> BC3M_87R <400> 286 tcacatcctc cgtcactcag 20 <210> 287 <211> 20 <212> DNA <213> BC3M_9F <400> 287 ctttaacagg ggcatgggtg 20 <210> 288 <211> 20 <212> DNA <213> BC3M_9R <400> 288 tctctcatct catgccccac 20 <210> 289 <211> 21 <212> DNA <213> BC3M_92F <400> 289 cagctctgtc tgcattttga g 21 <210> 290 <211> 20 <212> DNA <213> BC3M_92R <400> 290 tggtggccat taatcgttcc 20 <210> 291 <211> 20 <212> DNA <213> BC3M_96F <400> 291 ctggccatgt aaccttgagc 20 <210> 292 <211> 21 <212> DNA <213> BC3M_96R <400> 292 tgtgtccacg ttacaaaagc a 21 <210> 293 <211> 20 <212> DNA <213> BC3M_23F <400> 293 atagaaaggc cgtgacagct 20 <210> 294 <211> 20 <212> DNA <213> BC3M_23R <400> 294 gcaggaagtc aaggttgcaa 20 <210> 295 <211> 20 <212> DNA <213> BC3M_103F <400> 295 gggagaggag gaatatgggc 20 <210> 296 <211> 20 <212> DNA <213> BC3M_103R <400> 296 agggtttatc tgagcagcgt 20 <210> 297 <211> 20 <212> DNA <213> BC3M_44F <400> 297 gggcgtcatg gattagcatg 20 <210> 298 <211> 20 <212> DNA <213> BC3M_44R <400> 298 cagttcttgg ctgcctatgg 20 <210> 299 <211> 20 <212> DNA <213> BC3M_219F <400> 299 gaccaatcca gaagcagcac 20 <210> 300 <211> 20 <212> DNA <213> BC3M_219R <400> 300 gcaagatcaa atccccaccc 20 <210> 301 <211> 8 <212> DNA <213> Ad2.1 <400> 301 taaggcga 8 <210> 302 <211> 8 <212> DNA <213> Ad2.2 <400> 302 cgtactag 8 <210> 303 <211> 8 <212> DNA <213> Ad2.3 <400> 303 aggcagaa 8 <210> 304 <211> 8 <212> DNA <213> Ad2.4 <400> 304 tcctgagc 8 <210> 305 <211> 8 <212> DNA <213> Ad2.5 <400> 305 ggactcct 8 <210> 306 <211> 8 <212> DNA <213> Ad2.6 <400> 306 taggcatg 8 <210> 307 <211> 8 <212> DNA <213> Ad2.7 <400> 307 ctctctac 8 <210> 308 <211> 8 <212> DNA <213> Ad2.8 <400> 308 cagagagg 8 <210> 309 <211> 8 <212> DNA <213> Ad2.9 <400> 309 gctacgct 8 <210> 310 <211> 8 <212> DNA <213> Ad2.10 <400> 310 cgaggctg 8 <210> 311 <211> 8 <212> DNA <213> Ad2.11 <400> 311 aagaggca 8 <210> 312 <211> 8 <212> DNA <213> Ad2.12 <400> 312 gtagagga 8 <210> 313 <211> 8 <212> DNA <213> Ad2.13 <400> 313 gtcgtgat 8 <210> 314 <211> 8 <212> DNA <213> Ad2.14 <400> 314 accactgt 8 <210> 315 <211> 8 <212> DNA <213> Ad2.15 <400> 315 tggatctg 8 <210> 316 <211> 8 <212> DNA <213> Ad2.16 <400> 316 ccgtttgt 8 <210> 317 <211> 8 <212> DNA <213> Ad2.17 <400> 317 tgctgggt 8 <210> 318 <211> 8 <212> DNA <213> Ad2.18 <400> 318 gaggggtt 8 <210> 319 <211> 8 <212> DNA <213> Ad2.19 <400> 319 aggttggg 8 <210> 320 <211> 8 <212> DNA <213> Ad2.20 <400> 320 gtgtggtg 8 <210> 321 <211> 8 <212> DNA <213> Ad2.21 <400> 321 tgggtttc 8 <210> 322 <211> 8 <212> DNA <213> Ad2.22 <400> 322 tggtcaca 8 <210> 323 <211> 8 <212> DNA <213> Ad2.23 <400> 323 ttgaccct 8 <210> 324 <211> 8 <212> DNA <213> Ad2.24 <400> 324 ccactcct 8

Claims (20)

A composition for diagnosing breast cancer comprising:
i) transposase; And
ii) A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 109 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 110 that specifically binds to the BC3M_125 marker.
The composition of claim 1, wherein the transferase is a Tn5 transferase.
The composition for diagnosing breast cancer according to claim 1, further comprising a primer pair that specifically binds to a marker selected from the following:
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 103 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 104 that specifically binds to the BC3M_11 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 101 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 102 that specifically binds to the BC3M_102 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 105 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 106 that specifically binds to the BC3M_117 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 107 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 108 that specifically binds to the BC3M_119 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 111 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 112 that specifically binds to the BC3M_132 marker; And
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 119 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 120 that specifically binds to the BC3M_146 marker.
The composition for diagnosing breast cancer according to claim 3, further comprising a primer pair selected from the group consisting of primers comprising nucleotide sequences represented by SEQ ID NOs: 113 to 118 and SEQ ID NOs: 121 to 300.
delete delete delete delete delete delete delete delete delete (a) treating the nucleic acid isolated from the biological sample with a transfer enzyme to obtain a nucleic acid fragment; And
(b) Amplification of the treated nucleic acid fragment using a primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 109 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 110 that specifically binds to the BC3M_125 marker Thus, a method of providing information for breast cancer diagnosis comprising the step of detecting a chromatin structure of the nucleic acid.
The method of claim 14, wherein the method of detecting the chromatin structure of the nucleic acid comprises detecting the presence or absence of an amplification product.
The method of claim 14, wherein in the step (b), the processed nucleic acid fragment is additionally amplified using a primer pair that specifically binds to a marker selected from the following. .:
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 103 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 104 that specifically binds to the BC3M_11 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 101 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 102 that specifically binds to the BC3M_102 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 105 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 106 that specifically binds to the BC3M_117 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 107 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 108 that specifically binds to the BC3M_119 marker;
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 111 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 112 that specifically binds to the BC3M_132 marker; And
A primer pair consisting of a primer comprising a nucleotide sequence represented by SEQ ID NO: 119 and a primer comprising a nucleotide sequence represented by SEQ ID NO: 120 that specifically binds to the BC3M_146 marker.
The method of claim 14, wherein in step (b), the treated nucleic acid fragment is prepared by using a primer pair selected from the group consisting of primers including nucleotide sequences represented by SEQ ID NOs: 113 to 118 and SEQ ID NOs: 121 to 300. A method of providing information for breast cancer diagnosis, characterized in that amplifying additionally. delete delete delete

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