CN110241220B - Peripheral blood transcriptional gene marker for breast cancer detection and application thereof - Google Patents

Abstract

The invention discloses a peripheral blood transcription gene marker for detecting breast cancer, which comprises: blood cell characteristic gene sequences of the breast cancer shown by SEQ ID NO. 1-SEQ ID NO. 10. The invention also discloses application of the gene marker in preparation of a breast cancer detection product. The invention carries out early screening detection on the breast cancer by analyzing the expression condition of the transcriptional gene markers related to the breast cancer in the peripheral blood in a combined manner, has the advantages of high sensitivity and strong specificity, takes the peripheral blood which is most easily collected clinically as a detection sample, is safe and simple to sample, is very suitable for early screening and auxiliary diagnosis of the breast cancer of large-scale people, and has wide application prospect.

Description

Peripheral blood transcriptional gene marker for breast cancer detection and application thereof

Technical Field

The invention relates to the technical field of molecular biology, in particular to a blood cell transcription gene marker for breast cancer detection and application thereof.

Background

Breast cancer is a common malignant tumor in adult women and is also one of the leading causes of cancer death in adult women. Breast cancer accounts for the first and second new morbidity and mortality among female malignancies worldwide. There are approximately 7.9 million new cases per year, accounting for 21% of the total number of malignancies in all women. The annual average incidence rate of breast cancer is 30.30/10 ten thousand worldwide, and the adjustment rate (the world regulation rate) of the world population is 32.97/10 ten thousand. Nearly 60% of new cases of breast cancer occur in developed countries. In developed countries, the number of new breast cancer cases is about 25% of all female malignancies. The incidence rate is 79.09/10 ten thousand, and the world adjustment rate is 56.40/10 ten thousand. In developing countries, the number of new cases of breast cancer is about 17% of all malignant tumors, the incidence rate is 15.89/10 ten thousand, and the frequency of the occurrence is 20.33/10 ten thousand. The incidence of breast cancer in China is at a low level, but the incidence is on a rapid growth trend in recent years, and particularly the rising trend in rural areas is obvious in the last 10 years. In 2013, the incidence rate of breast cancer of women in China reaches 21.6/10 ten thousands of people, and the lung cancer is the first place.

Early detection of breast cancer and timely treatment are critical to ensure a good prognosis, since, in 90% of breast cancer deaths, distant metastasis is associated. At present, the screening means for breast cancer mainly comprises patient self-examination, doctor palpation (CBE), ultrasonic Screening (US) and breast molybdenum target X-ray examination (MAM), both of which belong to palpation, and are generally possible to be found after the tumor is larger than 2cm, while the US can only find tumor mass of more than 0.5cm, and the MAM is less advantageous for young women. Therefore, clinically accepted breast cancer patients are all imagewise detectable, with about 1/3 of the patients having had distant lymph node metastasis and 2/3 of the patients being locally advanced or advanced.

With the progress of treatment methods and clinical medicines for breast cancer, the survival rate of breast cancer patients is effectively improved, the 5-year survival rate reaches 90%, but the mortality rate of all female malignant tumors is still the second place. Because the mammary gland is an important characteristic of women, breast cancer surgery is a better treatment means, but has serious damage to the quality of life and the psychology of women. Therefore, how to safely and effectively discover early patients, perform early non-operative treatment or early breast protection operation, and improve the cure rate and the life quality of the patients is a focus of attention at home and abroad at present.

Blood is the largest tissue organ of the human body, and blood cells are few, and are cell types capable of exchanging information with almost all tissue cells. When abnormal tumor cells are generated in vivo, the immune system performs immune monitoring function, and blood cells (including immune cells such as leucocytes) participate in signal transmission and communication of the whole body immune system, and the gene expression of the blood cells changes correspondingly. The gene expression change of blood cells is far earlier than the obvious sign change of an organism caused by diseases, so that micro information of malignant diseases such as in vivo tumors and the like can be sensitively captured by closely monitoring the gene expression signal of the blood cells, and reliable evidence is provided for early detection and monitoring of the tumors. In addition, the blood cell transcriptional gene marker detection is used as a simple and noninvasive detection mode, so that the detection is easy to accept by a detected person, the detection compliance is high, and the method has a very great application value in early screening/diagnosis of malignant tumors such as breast cancer.

Disclosure of Invention

The invention provides a blood cell transcription gene marker combination for detecting breast cancer, aiming at the problem that the breast cancer is difficult to find and diagnose in early stage at present, the gene marker combination is used for screening and diagnosing in early stage of breast cancer, has high sensitivity and specificity, and is safe and simple to take samples because peripheral blood which is most easily collected in clinic is adopted for detection, thereby being very suitable for screening and auxiliary diagnosis in early stage of breast cancer of large-scale crowds.

In order to solve the technical problems, the invention is realized by the following technical scheme:

in one aspect of the invention, a combination product comprising a plurality of polynucleotides or fragments thereof is provided, the polynucleotides are differentially expressed in peripheral blood cells of a population with normal distribution of the same age, and the sequences of the polynucleotides are blood cell characteristic gene sequences of the breast cancer shown in SEQ ID NO. 1-SEQ ID NO. 10.

In another aspect of the invention, a composition is provided, which comprises primers and/or probes for detecting differential expression of genes in peripheral blood cells of a population with normal age distribution and breast cancer, wherein the sequences of the genes comprise blood cell characteristic gene sequences of the breast cancer shown in SEQ ID NO. 1-SEQ ID NO. 10.

In another aspect of the invention, the use of the above combination product comprising a plurality of polynucleotides or fragments thereof for the preparation of a product for the detection of breast cancer is also provided.

Preferably, the product for detecting breast cancer comprises: the product for detecting the breast cancer by using real-time quantitative PCR, RNA sequencing or gene chip.

The product for detecting the breast cancer by using the real-time quantitative PCR comprises a primer for specifically amplifying a blood cell characteristic gene sequence of the breast cancer shown by SEQ ID NO. 1-SEQ ID NO. 10.

The product for detecting the breast cancer by RNA sequencing comprises messenger RNA sequences for detecting blood cell characteristic gene sequences of the breast cancer shown by SEQ ID NO. 1-SEQ ID NO. 10.

The product for detecting breast cancer by using the gene chip comprises: a probe hybridized with blood cell characteristic gene sequences of the breast cancer shown in SEQ ID NO. 1-10. The gene chip is preferably a gene expression profiling chip.

In another aspect of the invention, the invention also provides a kit for detecting the breast cancer, which comprises a primer specific to the blood cell characteristic gene sequence of the breast cancer shown in SEQ ID NO. 1-SEQ ID NO. 10.

Preferably, the sequence of the primer is shown in SEQ ID NO. 11-SEQ ID NO. 30.

In another aspect of the invention, the invention also provides a kit for detecting the breast cancer, which comprises a probe specifically aiming at the blood cell characteristic gene sequence of the breast cancer shown in SEQ ID NO. 1-SEQ ID NO. 10.

Preferably, the sequence of the probe comprises a nucleotide sequence shown in SEQ ID NO. 31-SEQ ID NO. 40.

In another aspect of the invention, the invention also provides a gene chip for detecting the breast cancer, which comprises oligonucleotide probes hybridized with blood cell characteristic gene sequences of the breast cancer shown in SEQ ID NO. 1-SEQ ID NO. 10.

The kit or the gene chip can detect the expression condition of the breast cancer characteristic gene sequences shown by SEQ ID NO. 1-SEQ ID NO.10 in peripheral blood cells of a detected person, and then a prediction model is constructed by combining statistical methods such as a boosting algorithm and the like according to the up-regulation or down-regulation information of the gene expression to judge the probability of the breast cancer suffered by the detected person, thereby realizing the purposes of early screening and diagnosing the breast cancer.

In the present invention, the terms "blood cell transcriptional gene marker" or "blood cell characteristic gene of breast cancer" or similar terms are used interchangeably, and they have the same meaning and all represent genes that can be used for early screening and diagnosis of breast cancer, and significant changes in the expression levels of the genes can be used as an index for diagnosis of breast cancer.

The term "blood cell" refers to an immune cell such as a leukocyte in peripheral blood of a human body. The information exchange between the disease tissue and the leucocyte in blood is realized, so that the in vivo immune response and repair mechanism are activated, the gene expression of the leucocyte is specifically changed, the response of the immune system to the disease is usually earlier than the tissue response, and the breast cancer can be screened and diagnosed at an early stage by detecting the gene expression specific change of the leucocyte and other immune cells in peripheral blood.

The term "primer" refers to an oligonucleotide that, when paired with a strand of DNA, initiates primer extension synthesis product in the presence of a suitable polymerization reagent. To maximize amplification efficiency, the primer is preferably single-stranded. The length of the primer depends on many factors, including: application area, temperature employed, template reaction conditions, other reagents and primer sources. The skilled person can design the primers autonomously according to the breast cancer signature genes and specific requirements of the present invention.

The term "probe" refers to a molecule that binds to a specific sequence or subsequence or other portion of another molecule. Unless otherwise indicated, the term "probe" generally refers to a polynucleotide probe that is capable of binding to another polynucleotide (often referred to as a "target polynucleotide") by complementary base pairing. Depending on the stringency of the hybridization conditions, a probe can bind to a target polynucleotide that lacks complete sequence complementarity to the probe. The probe may be directly or indirectly labeled.

Those skilled in the art can design other probes that can be used to implement the present invention according to the breast cancer characteristic genes of the present invention and specific requirements, and are not limited to the probes specifically used in the embodiments of the present invention.

The term "gene chip" refers to a substrate having oligonucleotide probes deposited with different known sequences at known discrete locations on the surface of the substrate. The substrate may be silicon or glass, have the thickness of a glass slide or cover slip, or may be composed of other synthetic polymers.

The peripheral blood transcription gene marker combination for early screening and diagnosing breast cancer adopts an ROC curve (receiver operating characteristic curve) tool to measure the performance of the gene marker combination. Disease diagnosis is the problem of distinguishing between patients and normal persons, and is mathematically a dichotomous problem, i.e., dividing instances into positive or negative, so that a combination of genetic markers essentially behaves as a classifier. In the case of correct classification, four situations occur: true Positive (TP) if an instance is Positive and is predicted to be Positive; if the example is negative but predicted to be Positive, it is called False Positive (FP). Accordingly, if an instance is Negative and predicted to be Negative, it is referred to as True Negative (TN), and if an instance is positive but predicted to be Negative, it is False Negative (FN). The classification ability of a classifier is measured in terms of sensitivity (sensitivity) and specificity (specificity). The sensitivity is a True Positive Rate (TPR), and the calculation formula is TPR = TP/(TP + FN), which indicates the proportion of the positive examples identified by the classifier to all the positive examples. The specificity is True Negative Rate (TNR), and the calculation formula is TNR = TN/(FP + TN), which represents the proportion of the negative examples identified by the classifier to all negative examples.

The marker genes of the invention can be used to design specific oligonucleotide probes and corresponding primers. Such probes and primers can be of any length that specifically hybridizes to a marker gene sequence and is at least about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 50, 75, 100, 150, 200, 300, 400, 500 nucleotides in length, and the probes can be up to the full length of the marker gene sequences of the present invention. The probe may also comprise other sequences at its 5 'and/or 3' end so as to be capable of extending beyond the target sequence to which it is hybridised.

When a nucleic acid amplification method is used, these probes and primers enable rapid analysis of peripheral blood samples, i.e., detection or quantitative determination of the transcription products (mainly mRNA) of the marker genes. Such methods include any method or technique known in the art or described herein for replicating or increasing the copy number or content of a target nucleic acid or its complement.

The blood cell transcription gene marker disclosed by the invention is used for detecting breast cancer, has the advantages of high sensitivity and strong specificity, takes peripheral blood which is most easily collected clinically as a detection sample, is safe and simple to sample, is suitable for early screening and auxiliary diagnosis of breast cancer of large-scale crowds, is beneficial to early discovery of breast cancer, improves the cure rate, and has important significance for human health development.

Drawings

The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.

FIG. 1 is a boxplot of 107 cases of breast cancer (breast loss) and 44 cases of Normal Control (Normal Control) screened by the blood cell characteristic gene combinations according to the present invention;

FIG. 2 is a ROC AUC graph of breast cancer diagnosis using a prediction model constructed using 10 peripheral blood cell transcriptional gene markers (10-gene panel) according to the present invention. As a control, ROC AUC curves for breast cancer diagnosis of individual gene markers are also listed.

Detailed Description

The invention is based on the quantitative analysis of the whole gene expression profile of blood cells, through the quantitative analysis of the gene expression status of total RNA of peripheral blood, compare the difference of the blood cell gene expression of breast cancer and normal population, through the characteristic recursion Elimination (recurved feature Elimination) method to screen out 10 blood cell gene expression signals (transcription gene markers, messenger RNA) that are characteristic of breast cancer from the blood cell gene expression profile: DDIT4, APP, FKBP1A, PBX2, YWHAQ, HERC2P2, LUC7L3, WSB1, BCLAF1, FAM126B. Based on the 10 breast cancer transcriptional gene markers obtained by screening, quantitatively detecting the relative expression data of the 10 breast cancer transcriptional gene markers in the peripheral blood of a detected person by a fluorescent quantitative RT-PCR (reverse transcription-polymerase chain reaction), a gene expression profile chip or an RNA (ribonucleic acid) sequencing technology, constructing a breast cancer diagnosis model by adopting a logistic regression algorithm to obtain a decision score (decision score) of a sample, and if the decision score is greater than or equal to 0, judging the sample as breast cancer; and if the decision score is less than 0, judging the result to be normal.

Example 1 screening of peripheral blood characteristic Gene markers for Breast cancer

The screening of the breast cancer peripheral blood characteristic gene comprises the following steps:

1) Using PAXgene^TM55 samples of peripheral Blood confirmed to be diagnosed as breast cancer patients and 50 normal people by pathological examination were collected from Blood RNA Tube Blood collection tubes, and each sample was collected2-3mL of peripheral blood was collected.

2) Total RNA of the peripheral Blood sample was extracted using PAXgene Blood RNA Kit extraction Kit. The RNA samples were tested for fragment integrity (RIN) using an Agilent Bioanalyzer 2100 and for purity using a Nano1000 micro-UV spectrophotometer. All RNA samples must meet the following quality control conditions: the RNA yield is more than 2 micrograms, the ratio of 28S/18S peak is more than 1, the RIN value is more than 7, and the absorbance ratio of 260nm/280nm is more than 1.8.

3) The Gene expression signal of the RNA sample was detected by Affymetrix Gene Profiling Array cGMP U133P2 chip (human whole Gene expression Profiling chip).

4) The MAS5 statistical method in Affymetrix Expression Console software is used for carrying out Normalization processing (Normalization) on the detection result of the gene Expression profile chip of each sample, and genes with proper Expression in all samples are selected for subsequent analysis.

5) Blood cell gene expression signals with modest expression in all samples were selected for subsequent analysis.

6) A characteristic recursion elimination method is used for screening blood cell characteristic gene expression signals caused by the breast cancer, and 10 genes with the highest prediction accuracy (accuracycacy) on the breast cancer are obtained and used as gene markers.

7) The blood cell characteristic genes of the 10 breast cancers are detected by a real-time fluorescent quantitative PCR method, and the result shows that the expression up-regulation or down-regulation trends of all the 10 characteristic genes on a PCR platform and an expression profile chip platform are consistent. The sequences of 10 breast cancer transcriptional gene markers are shown in table 1 below.

TABLE 1 Gene sequences of 10 Breast cancer Gene markers

8) Based on the 10 gene markers obtained by screening, a logistic regression algorithm is utilized to construct a breast cancer diagnosis model:

wherein, P is the risk probability of the subject suffering from breast cancer; b₀To b₁₀Respectively corresponding logistic regression model parameters; delta Ct₁To Δ Ct₁₀Difference values of quantitative PCR cycle number Ct values of 10 breast cancer gene markers and an internal reference gene respectively; x is a decision score (decision score), also known as logistic regression log likelihood ratio (log likelihood ratio). Judging the detection result with the decision score X value being more than or equal to 0 as positive, namely, judging the patient with breast cancer; value of X<The result of detection of 0 is judged as negative, i.e., normal.

Example 2 detection of Breast cancer Using the selected markers for the peripheral blood characteristic genes of Breast cancer

1. The method comprises the following steps:

1) Collecting peripheral blood samples of the sample to be detected: use of PAXgene^TMBlood RNA Tube collected 2ml subjects of elbow vein peripheral Blood;

2) Extracting and purifying total RNA in a peripheral blood sample of a sample to be detected: extracting and purifying total RNA in peripheral Blood by using a PAXgene Blood RNA Kit extraction Kit, identifying the integrity and yield of the extracted total RNA fragment by using an Agilent BioAnalyzer model 2100 micro electrophoresis analyzer, and detecting the purity of an RNA sample by using a Nano1000 micro ultraviolet spectrophotometer;

3) Reverse transcription reaction: performing Reverse Transcription reaction by using a High-Capacity cDNA Reverse Transcription kit of Life Techonlgy company and taking Olig (dT) as a Reverse Transcription primer by using total RNA as a template to synthesize cDNA;

TABLE 2 reaction System for reverse transcription Synthesis of cDNA

4) Fluorescent quantitative RT-PCR detection: according to messenger RNA (mRNA) sequences of 10 blood cell characteristic genes of breast cancer, specific primers SEQ ID NO. 11-SEQ ID NO.30 are designed (wherein, the primers SEQ ID NO. 11-SEQ ID NO.12 are used for specifically amplifying the gene marker of SEQ ID NO.1, the primers SEQ ID NO. 13-SEQ ID NO.14 are used for specifically amplifying the gene marker of SEQ ID NO.2, the primers SEQ ID NO. 15-SEQ ID NO.16 are used for specifically amplifying the gene marker of SEQ ID NO.3, the primers SEQ ID NO. 17-SEQ ID NO.18 are used for specifically amplifying the gene marker of SEQ ID NO.4, the primers SEQ ID NO. 19-SEQ ID NO.20 are used for specifically amplifying the gene marker of SEQ ID NO.5, the primers SEQ ID NO. 21-SEQ ID NO.22 are used for specifically amplifying the gene marker of SEQ ID NO.6, and the primers SEQ ID NO. 23-SEQ ID NO.24 are used for specifically amplifying the gene marker of SEQ ID NO.7, primers SEQ ID NO. 25-SEQ ID NO.26 are used for specifically amplifying the gene marker SEQ ID NO.8, primers SEQ ID NO. 27-SEQ ID NO.28 are used for specifically amplifying the gene marker SEQ ID NO.9, primers SEQ ID NO. 29-SEQ ID NO.30 are used for specifically amplifying the gene marker SEQ ID NO. 10), specific probes SEQ ID NO. 31-SEQ ID NO.40 are designed (wherein SEQ ID NO. 31-SEQ ID NO.40 are respectively probe sequences of the characteristic gene sequences of SEQ ID NO. 1-SEQ ID NO. 10), the primers SEQ ID NO. 11-SEQ ID NO.30 are used as primers, the probes SEQ ID NO. 31-SEQ ID NO.40 are used as probes or SYBR Green dye capable of nonspecifically combining with PCR amplification fragments is used, cDNA obtained by reverse transcription is used as an amplification template to perform real-time fluorescent quantitative RT-PCR reaction, the relative mRNA content of the 10 gene markers in the peripheral blood samples was obtained.

The sequence of the fluorescent quantitative PCR amplification primer is as follows:

DDIT4 gene

A forward primer: 5 'CACTTCTGAGTTCAGCAAACG 3' (SEQ ID NO. 11)

Reverse primer: 5'ACGAGAAGCGGTCCCAAAG 3' (SEQ ID NO. 12)

APP Gene

A forward primer: 5'CCGCTCTGCAGGCTGTTC 3' (SEQ ID NO. 13)

Reverse primer: 5'TCTGCGCGGACATACTTCTTT 3' (SEQ ID NO. 14)

FKBP1A gene

A forward primer: 5'GGATGCTTGAAGATGGAAAGAAA 3' (SEQ ID NO. 15)

Reverse primer: 5 'CCTGCTTGCTTGCTAGCATAAACTTAAA 3' (SEQ ID NO. 16)

PBX2 gene

A forward primer: 5 'CTGCGCGCTCCCGTTTCCT 3' (SEQ ID NO. 17)

Reverse primer: 5 'GGACCTCAGTGCCTGTTTG 3' (SEQ ID NO. 18)

YWHAQ gene

A forward primer: 5 'CCTGGAGGGTCATCTAGCAT 3' (SEQ ID NO. 19)

Reverse primer: 5 'ACTTTCTCCCGATTAGTCCTTATCAG 3' (SEQ ID NO. 20)

HERC2P2 gene

A forward primer: 5 'GGGAAGACCCAGGTGGTAGCTT 3' (SEQ ID NO. 21)

Reverse primer: 5 'CCAAATACTGGCCAACAAAA 3' (SEQ ID NO. 22)

LUC7L3 gene

A forward primer: 5 'TGATGGAAGTGTGTTTATGAATTAT 3' (SEQ ID NO. 23)

Reverse primer: 5 'ATGGGCCGCTCAAACA 3' (SEQ ID NO. 24)

WSB1 gene

A forward primer: 5 'GGTCCCTAGCCCTGCAACATTT 3' (SEQ ID NO. 25)

Reverse primer: 5 'ATCGGCCAGCTCCTGAACTTC 3' (SEQ ID NO. 26)

BCLAF1 gene

A forward primer: 5 'CCTTCACCTATTGCTACACCACTA 3' (SEQ ID NO. 27)

Reverse primer: 5 'GAACCAGACCTTTCAG 3' (SEQ ID NO. 28)

FAM126B gene

A forward primer: 5'GTGGTGCCAAAAATCAATAGCTT 3' (SEQ ID NO. 29)

Reverse primer: 5 'CCCCAATGCGTTACTTGCT 3' (SEQ ID NO. 30)

The fluorescent quantitative PCR probe sequence is as follows:

DDIT4 gene

The probe sequence is as follows: 5 'CCTGGGCGTCTGTCCTCACCATGC 3' (SEQ ID NO. 31)

APP Gene

The probe sequence is as follows: 5'TCCTCGGCCTCGTCACGTGTTCA 3' (SEQ ID NO. 32)

FKBP1A gene

The probe sequence is as follows: 5 'TCCTCCCGGGGACAGAAACAAGCC 3' (SEQ ID NO. 33)

PBX2 gene

The probe sequence is as follows: 5'ATGCCAGACGAAAGCGCCGTAACTT 3' (SEQ ID NO. 34)

YWHAQ gene

The probe sequence is as follows: 5 'AGCAGAAGACCGACACCTACTCCGACAAG 3' (SEQ ID NO. 35)

HERC2P2 gene

The probe sequence is as follows: 5 'AGACACCCGGGAACCCGGAATCCATGCACG 3' (SEQ ID NO. 36)

LUC7L3 gene

The probe sequence is as follows: 5 'CAGCTGATCTACCATACCTACCACACACACGTTG 3' (SEQ ID NO. 37)

WSB1 gene

The probe sequence is as follows: 5 'AATCCGAAGAGTGGATGCCCACCAC 3' (SEQ ID NO. 38)

BCLAF1 gene

The probe sequence is as follows: 5 'AGTTCATCTTTGCTCTGATGCTCCCCATGC 3' (SEQ ID NO. 39)

FAM126B gene

The probe sequence is as follows: 5 'TCTAATCCGGACAGCCAGTGCTTCTC 3' (SEQ ID NO. 40)

TABLE 3 real-time fluorescent quantitative PCR reaction System

Reagent	Concentration of	Volume of
			Breast cancer characteristic gene primer	800nM	2μL
Fluorescent probe for breast cancer characteristic gene	200nM	0.5μL
			2X PCR MasterMix	2X	12.5μL
cDNA template	2.67ng/μL	7.5μL
			TOTAL	10μL	25μL

5) And (3) diagnosis of the result of the sample to be detected: the relative mRNA content of 10 gene markers, namely DDIT4, APP, FKBP1A, PBX2, YWHAQ, HERC2P2, LUC7L3, WSB1, BCLAF1 and FAM126B in peripheral blood samples is detected by real-time fluorescent quantitative PCR and substituted into a logistic regression model:

calculating a decision score X value of the sample, and judging that the detection result with the decision score X value being more than or equal to 0 is positive, namely the breast cancer patient; the detection result with the X value of less than 0 is judged to be negative, namely normal.

2. Results

Collecting 107 breast cancer (breast loss) and 44 Normal Control (Normal Control) peripheral blood samples, detecting the relative expression quantity of 10 transcriptional gene markers of the breast cancer in the peripheral blood by using fluorescent quantitative RT-PCR (reverse transcription-polymerase chain reaction), calculating a decision score X value of each sample, and judging as a positive detection result, namely the breast cancer, when the decision score X value is more than or equal to 0; otherwise, the result is a negative detection result, namely normal. The detection result is compared with the pathological detection result, and the result shows that the sensitivity (TP, true positive rate) of the composition based on 10 blood cell transcription gene markers to the breast cancer detection reaches 100%, the specificity (TN, true negative rate) is 93%, the detection accuracy is 98%, and the specific detection result is shown in table 4 and figures 1-2.

TABLE 4 sensitivity, specificity and ROC AUC values for Breast cancer detection

The above-mentioned embodiments only express the implementation manner of the present invention, and the description thereof is specific and detailed, but not to be understood as the limitation of the patent scope of the present invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the spirit of the invention, and these changes and modifications are all within the scope of the invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Sequence listing

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agagtctgtg gaagaggtgg ttcgagaggt gtgctctgaa caagccgaga cggggccgtg 1080

ccgagcaatg atctcccgct ggtactttga tgtgactgaa gggaagtgtg ccccattctt 1140

ttacggcgga tgtggcggca accggaacaa ctttgacaca gaagagtact gcatggccgt 1200

gtgtggcagc gccattccta caacagcagc cagtacccct gatgccgttg acaagtatct 1260

cgagacacct ggggatgaga atgaacatgc ccatttccag aaagccaaag agaggcttga 1320

ggccaagcac cgagagagaa tgtcccaggt catgagagaa tgggaagagg cagaacgtca 1380

agcaaagaac ttgcctaaag ctgataagaa ggcagttatc cagcatttcc aggagaaagt 1440

ggaatctttg gaacaggaag cagccaacga gagacagcag ctggtggaga cacacatggc 1500

cagagtggaa gccatgctca atgaccgccg ccgcctggcc ctggagaact acatcaccgc 1560

tctgcaggct gttcctcctc ggcctcgtca cgtgttcaat atgctaaaga agtatgtccg 1620

cgcagaacag aaggacagac agcacaccct aaagcatttc gagcatgtgc gcatggtgga 1680

tcccaagaaa gccgctcaga tccggtccca ggttatgaca cacctccgtg tgatttatga 1740

gcgcatgaat cagtctctct ccctgctcta caacgtgcct gcagtggccg aggagattca 1800

ggatgaagtt gatgagctgc ttcagaaaga gcaaaactat tcagatgacg tcttggccaa 1860

catgattagt gaaccaagga tcagttacgg aaacgatgct ctcatgccat ctttgaccga 1920

aacgaaaacc accgtggagc tccttcccgt gaatggagag ttcagcctgg acgatctcca 1980

gccgtggcat tcttttgggg ctgactctgt gccagccaac acagaaaacg aagttgagcc 2040

tgttgatgcc cgccctgctg ccgaccgagg actgaccact cgaccaggtt ctgggttgac 2100

aaatatcaag acggaggaga tctctgaagt gaagatggat gcagaattcc gacatgactc 2160

aggatatgaa gttcatcatc aaaaattggt gttctttgca gaagatgtgg gttcaaacaa 2220

aggtgcaatc attggactca tggtgggcgg tgttgtcata gcgacagtga tcgtcatcac 2280

cttggtgatg ctgaagaaga aacagtacac atccattcat catggtgtgg tggaggttga 2340

cgccgctgtc accccagagg agcgccacct gtccaagatg cagcagaacg gctacgaaaa 2400

tccaacctac aagttctttg agcagatgca gaactagacc cccgccacag cagcctctga 2460

agttggacag caaaaccatt gcttcactac ccatcggtgt ccatttatag aataatgtgg 2520

gaagaaacaa acccgtttta tgatttactc attatcgcct tttgacagct gtgctgtaac 2580

acaagtagat gcctgaactt gaattaatcc acacatcagt aatgtattct atctctcttt 2640

acattttggt ctctatacta cattattaat gggttttgtg tactgtaaag aatttagctg 2700

tatcaaacta gtgcatgaat agattctctc ctgattattt atcacatagc cccttagcca 2760

gttgtatatt attcttgtgg tttgtgaccc aattaagtcc tactttacat atgctttaag 2820

aatcgatggg ggatgcttca tgtgaacgtg ggagttcagc tgcttctctt gcctaagtat 2880

tcctttcctg atcactatgc attttaaagt taaacatttt taagtatttc agatgcttta 2940

gagagatttt ttttccatga ctgcatttta ctgtacagat tgctgcttct gctatatttg 3000

tgatatagga attaagagga tacacacgtt tgtttcttcg tgcctgtttt atgtgcacac 3060

attaggcatt gagacttcaa gcttttcttt ttttgtccac gtatctttgg gtctttgata 3120

aagaaaagaa tccctgttca ttgtaagcac ttttacgggg cgggtgggga ggggtgctct 3180

gctggtcttc aattaccaag aattctccaa aacaattttc tgcaggatga ttgtacagaa 3240

tcattgctta tgacatgatc gctttctaca ctgtattaca taaataaatt aaataaaata 3300

accccgggca agacttttct ttgaaggatg actacagaca ttaaataatc gaagtaattt 3360

tgggtgggga gaagaggcag attcaatttt ctttaaccag tctgaagttt catttatgat 3420

acaaaagaag atgaaaatgg aagtggcaat ataaggggat gaggaaggca tgcctggaca 3480

aacccttctt ttaagatgtg tcttcaattt gtataaaatg gtgttttcat gtaaataaat 3540

acattcttgg aggagcaaaa aaaaaaaaaa aa 3572

<210> 3

<211> 1514

<212> DNA

<213> human (Homo sapiens)

<400> 3

gctgttggtc cacgccgccc gtcgcgccgc ccgcccgctc agcgtccgcc gccgccatgg 60

gagtgcaggt ggaaaccatc tccccaggag acgggcgcac cttccccaag cgcggccaga 120

cctgcgtggt gcactacacc gggatgcttg aagatggaaa gaaatttgat tcctcccggg 180

acagaaacaa gccctttaag tttatgctag gcaagcagga ggtgatccga ggctgggaag 240

aaggggttgc ccagatgagt gtgggtcaga gagccaaact gactatatct ccagattatg 300

cctatggtgc cactgggcac ccaggcatca tcccaccaca tgccactctc gtcttcgatg 360

tggagcttct aaaactggaa tgacaggaat ggcctcctcc cttagctccc tgttcttgga 420

tctgccatgg agggatctgg tgcctccaga catgtgcaca tgaatccata tggagctttt 480

cctgatgttc cactccactt tgtatagaca tctgccctga ctgaatgtgt tctgtcactc 540

agctttgctt ccgacacctc tgtttcctct tcccctttct cctcgtatgt gtgtttacct 600

aaactatatg ccataaacct caagttattc attttatttt gttttcattt tggggtgaag 660

attcagtttc agtcttttgg atataggttt ccaattaagt acatggtcaa gtattaacag 720

cacaagtggt aggttaacat tagaatagga attggtgttg gggggggggt ttgcaagaat 780

attttatttt aattttttgg atgaaatttt tatctattat atattaaaca ttcttgctgc 840

tgcgctgcaa agccatagca gatttgaggc gctgttgagg actgaattac tctccaagtt 900

gagagatgtc tttgggttaa attaaaagcc ctacctaaaa ctgaggtggg gatggggaga 960

gcctttgcct ccaccattcc cacccaccct ccccttaaac cctctgcctt tgaaagtaga 1020

tcatgttcac tgcaatgctg gacactacag gtatctgtcc ctgggccagc agggacctct 1080

gaagccttct ttgtggcctt tttttttttt catcctgtgg tttttctaat ggactttcag 1140

gaattttgta atctcataac tttccaagct ccaccacttc ctaaatctta agaactttaa 1200

ttgacagttt caattgaagg tgctgtttgt agacttaaca cccagtgaaa gcccagccat 1260

catgacaaat ccttgaatgt tctcttaaga aaatgatgct ggtcatcgca gcttcagcat 1320

ctcctgtttt ttgatgcttg gctccctctg ctgatctcag tttcctggct tttcctccct 1380

cagccccttc tcaccccttt gctgtcctgt gtagtgattt ggtgagaaat cgttgctgca 1440

cccttccccc agcaccattt atgagtctca agttttatta ttgcaataaa agtgctttat 1500

gccggctttt ctca 1514

<210> 4

<211> 3229

<212> DNA

<213> human (Homo sapiens)

<400> 4

ctcctccctc ctccctctct ctcacacaca cccccgcttg ggcctcctct ctctctccgg 60

ctccattttc tccgccgccg ggggccgggg tctcctgtgg ggggcccagc cggtatccca 120

ggtctccctt cagtgccggg gtgaaccccc gggggagccg ggagccgggg gcagacgggc 180

gggggttggg gcggagggag cagcggcccc agcgagtttg gggggagaag taaccaggcg 240

gggggagggg cggagcaggg agggggcctc agggcccccc cccagctatg gacgaacggc 300

tactggggcc gccccctcca ggcgggggcc gggggggcct gggattggtg agtggggagc 360

ctgggggccc tggcgagcct cccggtggcg gagaccccgg tgggggtagc gggggggtcc 420

cgggaggccg agggaagcaa gacatcgggg acattctgca gcagataatg accatcaccg 480

accagagcct ggacgaggcc caggccaaga aacacgccct aaactgccac cgaatgaagc 540

ctgctctctt tagcgtcctg tgtgaaatca aggagaaaac tggcctcagc attcggagct 600

cccaggagga ggagccggtg gacccacagc tgatgcgctt ggacaacatg cttctggcag 660

agggtgtggc tgggcccgag aaagggggcg gctcagcagc agcagctgca gccgctgcag 720

cctctggtgg tggtgtgtcc cctgacaact ccatcgaaca ctcggactat cgcagcaaac 780

ttgcccagat ccgtcacata taccactcgg agctggagaa gtatgagcag gcatgtaatg 840

agttcacgac ccatgtcatg aacctgctga gggagcagag ccgcaccagg cccgtggccc 900

ccaaagagat ggaacgcatg gtgagcatca tccatcgaaa gttcagcgcc atccagatgc 960

agctgaagca gagcacctgc gaggctgtga tgatcctgcg ctcccgtttc ctggatgcca 1020

gacgaaagcg ccgtaacttc agcaaacagg ccactgaggt cctaaatgag tatttctact 1080

cccacctgag taacccatat cctagtgagg aggccaagga ggagcttgcc aagaagtgtg 1140

gcatcaccgt gtctcaggtc tccaactggt ttggcaacaa gaggattcgc tataagaaaa 1200

acatcggaaa gttccaagag gaggcaaaca tctatgctgt caagaccgcc gtgtcagtca 1260

cccagggggg ccacagccgc accagctccc cgacaccccc ttcctctgca ggctctggcg 1320

gctctttcaa tctctcagga tctggagaca tgtttctggg gatgcctggg ctcaacggag 1380

attcctattc tgcttcccag gtggaatcac tccgacactc gatggggcca gggggctatg 1440

gggataacct cgggggaggc cagatgtaca gcccacggga aatgagggca aatggcagct 1500

ggcaagaggc tgtgaccccc tcttcagtga catccccaac ggagggacca gggagtgttc 1560

actctgatac ctccaactga tcttgcccct cagggtcaca ggggtggggg ctctcacaag 1620

gcgacttgaa gaggacgcag gcttccagag gacaaacccc aatacaggag aagcacaaga 1680

cagagaaggg ccaatggggt catcccctcc ctaacgagac tctctgtgct gggggtgcta 1740

attacatggc aggaagaatg gggcctctaa ggggagtgtg gggtctgtct ctcccttttt 1800

tccatctttt tcctctctcg ctttctttct tacacagaaa catacacata ccgagaaacc 1860

tatttctcag accccttttt ctcctctgtc tttctctctc cctctcccac acctcacaca 1920

cacatactcc cacttgcaac tattctgttt ctctcctggg ctcccccact ttcccttccc 1980

caccccactt gtatgctctg gaatctgtgg agacgccagc cctgcccaat cagagatgcc 2040

aaaaatgggg acatgacttc tggacagagg acatgggcca cgcccccatg catccccacc 2100

cccgcccctc cggacggctt acttacctca tacgcagctc atcttaaacc aatagaatcg 2160

ctcggtggac gagagtgtct gactcagata tctacctcgg agggagtttc tgctacttta 2220

gggaattatt gactgggctt tggggttgaa cttttttttt tttaaagaaa gaaaaagaaa 2280

ccctgggatc catctgtttt ttttgttgtt gttgttgttt ttgttgttgt tggtggtggt 2340

ggtggtggtg gttcttaatt tttaatttag tttggggaag tagcttgttt ttttttttat 2400

aaatatgttg atttcttgtc tttttttttt tttatttctt actttcccat attaggggtg 2460

atagccaaag gggttctggt aagagaaagg gggacaaaca gaactggtaa agaggccccc 2520

ctggctccag gcctgtccat caggaagtaa attttacagg gcaccaagct ttgcccccta 2580

aaatccctta ggtgttcttt gttcatgcag gcaggtttct gccgcatttg atgtggaggc 2640

agtgaagggc ttgccctgct ggcctctcat cccccttctt cccacaaccc ttgggcaggg 2700

ctggactcag taattttgag gaaattgaag atgccatctt cccctgtgag tgacatgtct 2760

ttaatttttt aaaaaactac tatttgaaaa ttggaggggg aagaatggga agggagttat 2820

tgccaaatat gttaaatatg ggttggggtg cttgtatatg tatcttcctc aatttcccca 2880

taaatgaggt atctttttgt cacaccaaaa tcaaggggta gggagaggga ggaggttgca 2940

aaaagccaga tgtgggggaa aagtaacatc aacactgtcc catcctcagc cctgaactag 3000

ctaccatctg atcccctcag acattctcag gattttacaa gactgtcaga gtggggaacc 3060

cctcccatta aagatccggg caggactggg gacaggttgg aagtgtgatg ggtggggggg 3120

tgggaggcat gggccggggg cagttctctc ctcacttgta aacttgtgta gtttcacaga 3180

aaaaaaacaa aatgcagttt taaataaaga aatttctttt ttccctggg 3229

<210> 5

<211> 2196

<212> DNA

<213> human (Homo sapiens)

<400> 5

aaagccaaaa gcagatcaaa gtggtgggac tcgcgtcgcg gccgcggaga cgtgaagctc 60

tcgaggctcc tcccgctgcg ggtcggcgct cgccctcgct ctcctcgccc tccgccccgg 120

ccccggcccc gcgcccgcca tggagaagac tgagctgatc cagaaggcca agctggccga 180

gcaggccgag cgctacgacg acatggccac ctgcatgaag gcagtgaccg agcagggcgc 240

cgagctgtcc aacgaggagc gcaacctgct ctccgtggcc tacaagaacg tggtcggggg 300

ccgcaggtcc gcctggaggg tcatctctag catcgagcag aagaccgaca cctccgacaa 360

gaagttgcag ctgattaagg actatcggga gaaagtggag tccgagctga gatccatctg 420

caccacggtg ctggaattgt tggataaata tttaatagcc aatgcaacta atccagagag 480

taaggtcttc tatctgaaaa tgaagggtga ttacttccgg taccttgctg aagttgcgtg 540

tggtgatgat cgaaaacaaa cgatagataa ttcccaagga gcttaccaag aggcatttga 600

tataagcaag aaagagatgc aacccacaca cccaatccgc ctggggcttg ctcttaactt 660

ttctgtattt tactatgaga ttcttaataa cccagagctt gcctgcacgc tggctaaaac 720

ggcttttgat gaggccattg ctgaacttga tacactgaat gaagactcat acaaagacag 780

caccctcatc atgcagttgc ttagagacaa cctaacactt tggacatcag acagtgcagg 840

agaagaatgt gatgcggcag aaggggctga aaactaaatc catacagggt gtcatccttc 900

tttccttcaa gaaacctttt tacacatctc cattccttat tccacttgga tttcctatag 960

caaagaaacc cattcatgtg tatggaatca actgtttata gtcttttcac actgcagctt 1020

tgggaaaact tcattccttg atttgtgttt gtcttggcct tcctggtgtg cagtactgct 1080

gtagaaaagt attaatagct tcatttcata taaacataag taactcccaa acacttatgt 1140

agaggactaa aaatgtatct ggtatttaag taatctgaac cagttctgca agtgactgtg 1200

ttttgtatta ctgtgaaaat aagaaaatgt agttaattac aatttaaaga gtattccaca 1260

taacttctta atttctacat tccctccctt actcttcggg ggtttccttt cagtaagcaa 1320

cttttccatg ctcttaatgt attccttttt agtaggaatc cggaagtatt agattgaatg 1380

gaaaagcact tgccatctct gtctaggggt cacaaattga aatggctcct gtatcacata 1440

cggaggtctt gtgtatctgt ggcaacaggg agtttcctta ttcactcttt atttgctgct 1500

gtttaagttg ccaacctccc ctcccaataa aaattcactt acacctcctg cctttgtagt 1560

tctggtattc actttactat gtgatagaag tagcatgttg ctgccagaat acaagcattg 1620

cttttggcaa attaaagtgc atgtcatttc ttaatacact agaaagggga aataaattaa 1680

agtacacaag tccaagtcta aaactttagt acttttccat gcagatttgt gcacatgtga 1740

gagggtgtcc agtttgtcta gtgattgtta tttagagagt tggaccacta ttgtgtgttg 1800

ctaatcattg actgtagtcc caaaaaagcc ttgtgaaaat gttatgccct atgtaacagc 1860

agagtaacat aaaataaaag tacattttat aaaccattta ctatggcttt gtaacaattg 1920

catacccata ttttaaggga caggtgaatt tactactttc taaagtttat tgatacttcc 1980

cttttatgta aaatgtagta gtgataccta tatttccaca ttgtgcattg tgacacactt 2040

gtctagggat gcctggaagt gtataaaatt ggactgcatt tcttagagtg ttttactata 2100

gatcagtctc atgggccatc tcttcctcag atgtaaatga tatctggtta agtgttatat 2160

ggaataaagt ggacatttta aaactagcaa agttaa 2196

<210> 6

<211> 6075

<212> DNA

<213> human (Homo sapiens)

<400> 6

tcggcccgcc cctcgggccg cgagaggcgc cgggatcgcg ggcgccggct gagccagcgg 60

ctcttgggag gctgcgtccg cgcgccggcg gggcgaggcg gccgggccct gcgcgtcagg 120

cctgagacct gggaggaagc tggagaaaag atgccctctg aatctttgtg tttggctgcc 180

caggctcgcc tcgactccaa atggttgaaa acagatatac agcttgcatt cacaagagat 240

gggctctgtg gtctgtggaa tgaaatggtt aaagatggag aaattgtata cactggaaca 300

gaatcaaccc agaacggata gctccctcct ggaaaagctt ttgtctggtc ctctgagccc 360

cagtgagagt ttcctgaggt acctcaccct tccacaagac aacaggcttg ccattgatct 420

gcaacaaacg gcggttgttg tcatggccca tttagaccgt ctggctacac cctgtagatg 480

cctcctctgt gtagctctcc gacgtctcat aagagtcatt ttttacaggt cagaactgta 540

gaaataatga gaaagtgaca tttgtacgca tagctgattt ggagaaccat aataacgatg 600

gaggcttctg gactgtgatt gacgggaaag tgtatgatat aaaggacttc cagacacagt 660

cgttaacaga aaatagtatt cttgctcagt ttgcagggga agacccagtg gtagctttgg 720

aagctgcttt gcagtttgaa gacacccggg aatccatgca cgcattttgt gttggccagt 780

atttggagcc tgaccaagaa ggcgtcacca taccagatct ggggagtctc tcctcacctc 840

tgatagacac agagaggaat ctgggcctgc ttctcggatt acacgcttcc tatttagcaa 900

tgagcacacc gctgtctcct gtcgagattg aatgtgccaa atggcttcag tcatccatct 960

tctctggagg cctgcagacc agccagatcc actacagcta caacgaggag aaagacgagg 1020

accactgcag ctccccaggg ggcacacctg ccagcaaatc tcgactctgc tcccacagac 1080

gggccctggg ggaccattcc caggcatttc tgcaagccat tgcagacaac aacattcagg 1140

atcacaacgt gaaggacttt ttgtgtcaaa tagaaaggta ctgtaggcag tgccatttga 1200

ccacaccgat catgtttccc cccgagcatc ccgtggaaga ggtcggtcgc ttgctgttat 1260

gttgcctctt aaaacatgaa gatttaggtc atgtggcatt atctttagtt catgcaggtg 1320

cacttgatat tgagcaagta aagcacagaa cgttgcctaa gtcagtggtg gatgtttgta 1380

gagttgtcta ccaagcaaaa tgttcgctca ttaagactca tcaagaacag ggccgttctt 1440

acaaggaggt ctgcgctcct gtcatcaaac gtttgagatt cctctttaat gaattgagac 1500

ctgctgtttg taatgacctc tctataatgt ctaagtttaa attgttaagt tctttgcccc 1560

attggaggag gatagctcag aagataattc gagaaccaag gaaaaagaga gttcctaaga 1620

agccagaatc tacggatgat gaagaaaaaa ttggaaacga agagagtgat ttagaagaag 1680

cttgcatttt gcctcatagt ccaataaatg tggacaagag acccattgca attaaatcac 1740

ccaaggacaa atggcagccg ctgttgagta ctgttacaga tgttcacaaa tacaagtggt 1800

tgaagcagaa tgtgcagggt ctttatccgc agtctccact cctcagtaca attgctgaat 1860

ttgcccttaa agaagagcca gtggatgtgg aaaagagaaa gtgcctacta aaacagttgg 1920

agagagcaga ggttcgcctg gaagggatag atacaatttt aaaattgtat ctggtgagca 1980

agaatttctt acttccatct gtgccgtatg cgatgttttg tggatggcaa agacttattc 2040

ctgagggaat cgatataggg gaacctctta ctgattgttt aaaggatgtt gatttgatcc 2100

cgccttttaa tcggatgctg ctggaagtca cctttggcaa gctgtacgct tgggctgttc 2160

agaacattcg aaatgttttg gtggatgcca gtgccaaatt taaagagctt ggtatccagc 2220

cggttcccct gcaaaccatc accaatgaga acccatcggg accgagcctg gggaccatcc 2280

cgcaagccca cttcctcctg gtgatgctca gcatgctcac cctgcagcac agcgcaaaca 2340

accttgacct cctgctcaat tccggcacgc tggccctcgc tcagacggca ctgcgcctga 2400

ttggccccag ttgtgacagc gttgaggaag atatgaatgc ttctgcccaa ggtgcttctg 2460

ccacagtttt ggaagaaaca aggaaggaaa cggctcctgt gcagctccct gtttcagggc 2520

cagaactggc tgccatgatg aagattggaa caagggtcat gagaggtgtg gactggaaat 2580

ggggcgatca ggatgggcct cctccaggcc taggccgagt gattggtgag ctgggagagg 2640

acgggtggat aagagtccag tgggacacag gcagcaccaa ctcctacagg atggggaaag 2700

aaggaaaata cgacctcaag ctggcagagc tgccagcccc tgcacagccc tcagcagagg 2760

attcggacac agaggacgac tctgaagccg aacaaactga aaggaacatt caccccactg 2820

caatgatgtt taccagcact attaacttac tgcagactct ttgtctgtct gctggagttc 2880

atgctgagat catgcagagt gaagccacca agactttatg cggactgctg cgaatgttag 2940

tggaaagcgg aacgacggac aagacatctt ctccaaacag gctggtgtac agggagcaac 3000

accggagctg gtgcacgctg gggtttgtgc agagcatcgc tctcacgctg caggtgtgcg 3060

gcgccctcag ctccccgcag tggatcacgc tgctcatgaa ggttgtggaa gggcacgcac 3120

ccttcactgc cacctcgctg cagaggcaga tcttagctgt gcatttgttg caagcagtcc 3180

ttccgtcatg ggacaagacc gaaagggtga gggacatgaa atgcctcatg gagaagctgt 3240

ttgacttctt ggggagcttg ctcactatgt gctcctctga cgtgccgtta ctcagagagt 3300

ccacgctgag gcggcgcagg gtgtgcccgc aggcctcgct gactgccacc cacagcagca 3360

cactggcgga ggaggtggtg gcactgctgc acacgctgca ctccctgact cggtggaatg 3420

ggctcatcaa caagtacatc aactcccagc tccgctccat cacccacagc tttgcgggaa 3480

ggccttccaa aggggcccag ttagatgact acttccctga ttccgagaac cctgaagtgg 3540

ggggcctcat ggcggtcctg gctgtggttg gaggcatcga tggtcgcctg tgcctgggcg 3600

gccaagttgt gcacgatgac tttggagaag tcaccatgac tcgcatcacc ctgaagggca 3660

aaatcaccgt gcagttctct gacatgcgga cgtgtcgcgt ttgcccattg aatcagctga 3720

aaccactccc tgccgtggcc tttaatgtga acaacctgcc cttcacagag cccatgctgt 3780

ctgtctgggc tcagttggtg aacctcgctg gaagcaagtt agaaaagcac aaaataaaga 3840

aatcgactaa acaggccttt gcaggacaag tggacctgga cctgctgcgg cgccagcagt 3900

tgaagctata catcctgaaa gcaggtcggg cgctgttctc ccaccaggat aaactgcggc 3960

agatcctgtc tcagccagct gttcaggaga ctggaactgt tcacacagaa cccatggata 4020

cggagggcta gctgtatatg tttattgctg tggaaacatg aaaacaatga tggagcagtg 4080

gtatcacctg accttgggga catgtctcct gaagggccgc agccccccat gatcctcttg 4140

cagcagctgc tggcctcggc cacccagccg tctcctgtga aggccatatt tgataaacag 4200

gaacttgaga ctgctgcact ggccgttgtg gagtccactc acccttcgag cccaggattt 4260

gaagactgca gctccagtga ggccaccacg cctgtcaacg tgcagcacat ccgccctgcc 4320

agagtgaaga ggcgcaagca gtcacccgtt cccgctctgc cgatcgtggt gcagctcatg 4380

gagatgggat ttcccagaag gaacatcgag tttgccctga agtctctcac tggtgcttcc 4440

gggaatgcgt ccggcttgcc tggtgtggaa gccttggtcg ggtggctgct ggaccactcc 4500

gacatacagg tcacggagct ctcagatgca gacacggtgt ccgacgagta ttctgacgag 4560

gaggtggtgg aggacatgga tgatgccgcc tactccatgt ctactggtgc tgttgtgacg 4620

gagagccaga cgtacaaaaa ccgagctggt ttcttgggta atgatgatta tgctgtatat 4680

gtgagagaga atattcaggt gggaatgatg gttagatgct gccgaacata cgaagaagtg 4740

tgcgaaggtg atgtgatgtt ggcaaagtca tcaagctgga cagagatgga ttgcatgatc 4800

tcaatgtgca gtgtgactgg cagcagaaag ggggcatcta ctggtttagg tacattcatg 4860

tggaacttat aggctatcct ccaccaagaa gttcttctca catcaagatt ggtgataaag 4920

tgcgggtcaa agcctctgtc accacaccaa aatacaaatg gggatctgtg actcatcaga 4980

gtgtgggggt tgtgaaaggt gtgatggatg tcagatgttt cctatcaatg gatccagatt 5040

caaatgcaga aactgtgatg actttgattt ttgtgaaacg tgtttcaaga ccaaaaaaca 5100

caataccagg catacatttg gcagaataaa tgaaccaggc ttcagcagaa gaaacacttc 5160

ctataaatct cgcccaaaca ggaaaggaga agcattaggg tgtccgacta cgtgggtttc 5220

atagctgtgg aaaagccaaa ggggagactc ctgaagaaag gcggtgaaga ctgtgaagag 5280

cgggtcagga agatgagcac agcactgcta ctcctgtggg cacagggaca gcatgtctcc 5340

agccagcgcc accttgttta atacatggga actcactgaa attcattctg tattttgccc 5400

gcaaagtttt aaagctttca tccacagtca ggaattaaac ttataccaat gagagcctca 5460

cacattcaag gatgtactaa gcactacagg cctcacagaa acagagatcc catcttggag 5520

ttttcagtac cacatgggag ataaagggtt ttgaacatga aatgacaaaa acaacagcaa 5580

gaagaaaatt cttgtccttt ttcattacta tcagactcaa ataaatgtct tggctcttac 5640

attacattca ttcttcaacc attgtggtct ggcttccact tccttcactt caccaacatg 5700

gctctgccaa aggaagcccg tgatctctag gccatcactt taattgatct ttctacaaca 5760

tttatcctgg ttgttaagcc ctccttacaa cattcttctc tctttgtttt tatagctcca 5820

tctctcctgc ttctttaact tgataatgca tacttgattt ttctatttgt tatttcataa 5880

accaattaat acacagataa aatgactgta tatcaaacca tgtttgtata gaaaaaatgg 5940

attttggatg cctctcatat gtaattagtt ctattaaaca tattaattgt attgtttaat 6000

ttgtcaggtt tttgacagaa ttttgtttac aagtaataaa aattttatct ccaattttca 6060

ataattacac ccatt 6075

<210> 7

<211> 6882

<212> DNA

<213> human (Homo sapiens)

<400> 7

gtcttgtcgg ctcctgtgtg taggagggat ttcggcctga gagcgggccg aggagattgg 60

cgacggtgtc gcccgtgttt tcgttggcgg gtgcctgggc tggtgggaac agccgcccga 120

aggaagcacc atgatttcgg ccgcgcagtt gttggatgag ttaatgggcc gggaccgaaa 180

cctagccccg gacgagaagc gcagcaacgt gcggtgggac cacgagagcg tttgtaaata 240

ttatctctgt ggtttttgtc ctgcggaatt gttcacaaat acacgttctg atcttggtcc 300

gtgtgaaaaa attcatgatg aaaatctacg aaaacagtat gagaagagct ctcgtttcat 360

gaaagttggc tatgagagag attttttgcg atacttacag agcttacttg cagaagtaga 420

acgtaggatc agacgaggcc atgctcgttt ggcattatct caaaaccagc agtcttctgg 480

ggccgctggc ccaacaggca aaaatgaaga aaaaattcag gttctaacag acaaaattga 540

tgtacttctg caacagattg aagaattagg gtctgaagga aaagtagaag aagcccaggg 600

gatgatgaaa ttagttgagc aattaaaaga agagagagaa ctgctaaggt ccacaacgtc 660

gacaattgaa agctttgctg cacaagaaaa acaaatggaa gtttgtgaag tatgtggagc 720

ctttttaata gtaggagatg cccagtcccg ggtagatgac catttgatgg gaaaacaaca 780

catgggctat gccaaaatta aagctactgt agaagaatta aaagaaaagt taaggaaaag 840

aaccgaagaa cctgatcgtg atgagcgtct aaaaaaggag aagcaagaaa gagaagaaag 900

agaaaaagaa cgggagagag aaagggaaga aagagaaagg aaaagacgaa gggaagagga 960

agaaagagaa aaagaaaggg ctcgtgacag agaaagaaga aagagaagtc gttcacgaag 1020

tagacactca agccgaacat cagacagaag atgcagcagg tctcgggacc acaaaaggtc 1080

acgaagtaga gaaagaaggc ggagcagaag tagagatcga cgaagaagca gaagccatga 1140

tcgatcagaa agaaaacaca gatctcgaag tcgggatcga agaagatcaa aaagccggga 1200

tcgaaagtca tataagcaca ggagcaaaag tcgggacaga gaacaagata gaaaatccaa 1260

ggagaaagaa aagaggggat ctgatgataa aaaaagtagt gtgaagtccg gtagtcgaga 1320

aaagcagagt gaagacacaa acactgaatc gaaggaaagt gatactaaga atgaggtcaa 1380

tgggaccagt gaagacatta aatctgaagt gcagcgtaag tatgcacaga tgaagatgga 1440

actaagccga gtaagaagac atacaaaagc ctcttctgaa ggaaaagaca gtgtagtcct 1500

gcaaaacatt ttgaggtaca ttgttttgtc tcagctattt tgtagcagac tcgtgccccc 1560

attagtgtgc ctctttggaa attatcgccc acatttgtaa tatagtcgcc attgaaaagt 1620

taattatcct ttttttaggg attttgatgt catttctttt ttttttttaa taaaaaggtt 1680

gaactgtttt tttttttctt tttggtatta agtccatctt gtgttggtac attggcagag 1740

acatatgctt taaaaactta aatatttcgg aggcacatgt tggactactt tgttttaatt 1800

aaactgctag tatttctttg tcaaggatgt ttctagtttt ttgctttatt gccttgcatt 1860

ctaatgcagt ttgttctgta actcgagagc cagtagcatt ggattgatgg aagtgtaggg 1920

tttatgaatt attgcagctg actaccatac ctcacacagc gttggtgttg tgagcggccc 1980

atgaaaagcc aaattaaaaa tcaaggattc agtcaaacta agcaggtact catgccaggt 2040

actcctttct ctacccacat ccatgtttga atgctattgc ctgtgatctt tacgcttaac 2100

tgttgtgtat cttttttgtt ctttacaaga agtgcagagg ggttttttgt gtattgcgtg 2160

aaaacttata aaacaaatgt taacagaatg gaattttttt tcaactgtat gtagggctgc 2220

agtggtggcc agaattagat atctttaaag aattttaaat acaataaaca cttcatatta 2280

ttcgccttgt tacactcaat gcaattctca agtctataag aggtatgtgc ttaatatttc 2340

ctactgtgta ggagaatttg cagtcagcca taggtatgta ggaatagtca ctcactggct 2400

gatacattta aagcagcagt gtgaatagca aggacagaca ccttcaattt gtgaaatcaa 2460

agaactgatg cactatatag aacgaatttg ggtttttaaa gaaatattaa aagttaggta 2520

ctgtaagtgt tcttaaaacc tgtaaacttc attctgtggg ctagtggtgt gggacaaaat 2580

attcctaatg aaaggaagta ccaattagtt gatttgttgg tggcattccc cttttgggaa 2640

agcaatgtaa ggttatgtct gtgtatgtca ttcacactta ggcaagcata cacaggcaca 2700

tggctttaag aaccacactg atgccttgat aattaaaaag aatacaagca ttccatgtac 2760

acatgttaat tagcagttag tgactgggcc aacactttct cataaaaatt ggccttttac 2820

atgttgtcta attatcattt ttccccaaat tttgcgttgt aggactactg ttcgaagatt 2880

tttggaagaa tactgagaac ggcataaagt gaagatcgac atttaaaaaa tgaggtgaaa 2940

gaaagctata gtggcataga aaaagtataa agctcagtta gtttttttat tattattatt 3000

attaaaagtt aattcaggac tgatgtgacc taccagattt cagaacatgt gttaatagta 3060

tatatgccac tgaaaactta ggtcctgtat catacttttt tctttaagac tttttaagaa 3120

atattactta aacatgtggc ttgctcagtg tttaattgca agttttcaat cttggacttt 3180

gaaaacagga ttaaacgtta gtattcgtgt gaatcagact aagtgggatt tcatttttac 3240

aactctgctc tacttagcct ttggatttag aagtaaaaat aaagtatctc tgactttctg 3300

ttacaaagtt gattgtctct gtcattgaaa agttttagta ttaatctttt tctaataaag 3360

ttattgactc tgaactagtc ccctgtttta aatacaagag ttacactatt actagaggtg 3420

ttggtgtaca gttttatctg atttgttctg tttaagacta atttttatag actttctaat 3480

gttttaaata atggtgcttc aattttaggt ggttatgaat aaatttgaat tttgctttta 3540

atagcaaaga tgtgcagtga actagaatat atttttacat ccctgagaga ttcatttagt 3600

agaaaattcc aagtatcctg acaagcactc tttagctggc tagctatggg atgatgtaga 3660

aaagcattca agagctagtt tttgttaagt cctgtatcaa gattaaccca gctgtgtcag 3720

tttataaatg tatttgtgta tagggtgtgt agtatatatg gcaagggttt tttcccccca 3780

cttaagtgat tatttttgtg tcacatctag gaaaaccggc agcatgtttc tatctatagc 3840

cagcttcttc gactgtataa aagtattctc tccagctacg tatatacaca catacatata 3900

tatcatagca attccttgtg gtttataact tgcaaatact gctatcagtt tataggtaaa 3960

gaaacagtgt gttaaatgac ttatccaggg agggtcctgt ggcttcatgt ttatggagtt 4020

gctaggtctc tgcctcatgg tccagtgcct gttaagccac tgtgttcatt ctaataggca 4080

taatgaattg ttaaagaatt tactaaaatc tcttccacca aactttgaaa aataatgaag 4140

ccgcccccac tttagaggct ctgtatgaaa aaatgctgtg gagacagagc cctcctggct 4200

ccctagctga tcctggagat gcagcaatag atgaatgggt tatctctgaa tttgtaagag 4260

ataattcaca tgaggattaa gataaaatgg gaagtaaaat ctaacaaaca caaagatagc 4320

tcccaggcac tgctttgtgt agtttgacag cattgtggtt gtagcagcaa aggacttaaa 4380

gtgatagttt ttaaaccata ttctgtccct aagtaataaa aaatctagga agttactaaa 4440

ataccagatt tgttctgctc tgcctcatct agaatcaacg tctaactaac ttaaatgaag 4500

tataataaat gagttcatat gaaaaggctt cctctatgga cacttagata tattgtaact 4560

attgaagtta cctgggatgt gggggtggtg ggaggaggac ctgcctcccc aggacatcta 4620

tgactaaggc ctggctttag ttatggagag agacgtagaa gttgaatttt acacccaaaa 4680

ttgatgtgac tgaagaggaa ctgattgttg ctaaccagct cacaagaatc cagtattgag 4740

accagttcac tagaagaaac aaacatttct gccatgcaga ccaaaaagtt attagttggt 4800

gaatatgtat tttctctttg gaaggtcttt aaggggagca aaccagtttt aatcaatcag 4860

attgcttggt aagtttggaa tctgcaatca gttggtctta aaaaaaaaaa aactttattt 4920

tggaaattta aagacataca caaaagagga acaatataat taacctctgt taactcatca 4980

ccaacaagac tcatgaccac ttttatactt catgagtgat tgtatttgta tccactgttt 5040

tctattattt tcgagcaagt ctcagacaca ccatttaatc tgtaaataat tcagcatgta 5100

tctctaaaag acaaagacct cttaaataac agttcattag tataaaacaa attgggtaaa 5160

cttttgttgg tcatcaaact atattagcac tggtccaata gtttaatttt cattgagcct 5220

ttcaagagga ccgaccagtc tgctgctcaa gacatcctct cctctggaat gtagagataa 5280

tacatatcat gctccttttt gttaaaacgt ttttttttcc ccttcaaaca cagtccattc 5340

atttttcagt ttgggttgaa acatcctttt cttgatcttg agcttataat aacctagtca 5400

tattgctcag ctcagatatt tttactccct ctccttaggc attctggttc cttaaatata 5460

gttagtgtca cagaggataa ataaccaacc ttatttctaa ggtctgagaa cacttggacc 5520

acatattggt tgagctcagc caccttctga ttaaagtttt cagacttgta agaactgaaa 5580

atttttatgg tggaagttct ctgagccctc atccattctg tttttaaaaa tgcattgcag 5640

atgggctatg tgaatatgtt tttaaacatc tgatatgtgc atgaaacaaa aaacacttga 5700

agttattatg tatacaattc tgtgggatgg gacttcatgc aggattggtt ttcaagtttg 5760

atttcctgag ggatttttta gttgtttgtg aaagaacccc aggtctactt ttgaaatttt 5820

gtattataat tgtaatgttg cccatggtta aaaaaaaaaa gtgttcagtg atctatgtct 5880

cctactactc ctatttctct gtttttcctc tgcaggagct tgctgctgtt aacagttatt 5940

cttccaagtt gttttctttg tggggagatg ggaggtggga ggaaatataa acatatatgt 6000

atagatcttt caaaatatat gacggtatac ccgtatgttc tgagtcttgc tgtttttacc 6060

tggtaatatt tagaaacatt tattttgaga taaaggagag cacttttaag ttgaacctgt 6120

agttttaaaa agtacatttc aagtaagcca aagcagagaa gtaaatgtat ttttcattgt 6180

tgtatcagaa ttttgaattt actattttaa aaattcaaga gttttgtagc tgatctattt 6240

cttcccctca gccatcccaa ataggtcatt tgtcaacaga tttaagaatg tttagaaaca 6300

acaactttgg gaaacgggaa acaatttggt ataagtgggt gtgccataac ctctctcgta 6360

gccattcatt cccggataca taccctagag aaactcttac acatgcgtac caggggatgg 6420

atttaagcat ttgtgtgtaa taggaagaaa agaagaaaaa acccgggaag atcccaagtg 6480

tccaccaaca gtgtgttgga taaatactgt ggtatattcc aacagtggaa ttccacagaa 6540

gtgaaactga actgcagctg tgtatgtgaa catggacaaa actcaacaat agaaggatca 6600

aaaaaagcaa gtcacagaag aatacatcac tatggttcca tttcaatgaa agtcaaaaac 6660

aggctgtcaa atacatgata aaaggaaacg attaagacaa aatttaatgt tagccgtttt 6720

gatggaggga gaggtgatca tgagggcaca ggggtcttca gaagaactgg tgagggtctg 6780

tttctgaagc ctgtgggcat ttcctttttt aatctgtatg tttatgtgct tttgtatgta 6840

tgatatttct taataaaatt taaaaagaag aatgggaaaa aa 6882

<210> 8

<211> 5105

<212> DNA

<213> human (Homo sapiens)

<400> 8

agtgtctcgt ttgcagtcgg cgctttaggg gaactgtctt cctccgcagg cgcgaggctg 60

ggtacagggt ctattgtctg tggttgactc cgtactttgg tctgaggcct tcgggagctt 120

tcccgaggca gttagcagaa gccgcagcgg ccgcccccgc ccgtctcctc tgtccctggg 180

cccgggaggg accaacttgg cgtcacgccc ctcagcggtc gccactctct tctctgttgt 240

tgggtccgca tcgtattccc ggaatcagac ggtgccccat agatggccag ctttcccccg 300

agggtcaacg agaaagagat cgtgagatta cgtactatag gtgaactttt agctcctgca 360

gctccttttg acaagaaatg tggtcgtgaa aattggactg ttgcttttgc tccagatggt 420

tcatactttg cttggtcaca aggacatcgc acagtaaagc ttgttccgtg gtcccagtgc 480

cttcagaact ttctcttgca tggcaccaag aatgttacca attcaagcag tttaagattg 540

ccaagacaaa atagtgatgg tggtcagaaa aataagcctc gtgaacatat tatagactgt 600

ggagatatag tctggagtct tgcttttggg tcatcagttc cagaaaaaca gagtcgctgt 660

gtaaatatag aatggcatcg cttcagattt ggacaagatc agctacttct tgctacaggg 720

ttgaacaatg ggcgtatcaa aatatgggat gtatatacag gaaaactcct ccttaacttg 780

gtagatcata ctgaagtggt cagagattta acttttgctc cagatggaag cttgatcctg 840

gtgtcagctt caagagacaa aactctcaga gtatgggacc tgaaagatga tggaaacatg 900

atgaaagtat tgagggggca tcagaattgg gtgtacagct gtgcattctc tcctgactct 960

tctatgctgt gttcagtcgg agccagtaaa gcagttttcc tttggaatat ggataaatac 1020

accatgatac ggaaactaga aggacatcac catgatgtgg tagcttgtga cttttctcct 1080

gatggagcat tactggctac tgcatcttat gatactcgag tatatatctg ggatccacat 1140

aatggagaca ttctgatgga atttgggcac ctgtttcccc cacctactcc aatatttgct 1200

ggaggagcaa atgaccggtg ggtacgatct gtatctttta gccatgatgg actgcatgtt 1260

gcaagccttg ctgatgataa aatggtgagg ttctggagaa ttgatgagga ttatccagtg 1320

caagttgcac ctttgagcaa tggtctttgc tgtgccttct ctactgatgg cagtgtttta 1380

gctgctggga cacatgacgg aagtgtgtat ttttgggcca ctccacggca ggtccctagc 1440

ctgcaacatt tatgtcgcat gtcaatccga agagtgatgc ccacccaaga agttcaggag 1500

ctgccgattc cttccaagct tttggagttt ctctcgtatc gtatttagaa gattctgcct 1560

tccctagtag tagggactga cagaatacac ttaacacaaa cctcaagctt tactgacttc 1620

aattatctgt ttttaaagac gtagaagatt tatttaattt gatatgttct tgtactgcat 1680

tttgatcagt tgagctttta aaatattatt tatagacaat agaagtattt ctgaacatat 1740

caaatataaa tttttttaaa gatctaactg tgaaaacata catacctgta catatttaga 1800

tataagctgc tatatgttga atggaccctt ttgcttttct gatttttagt tctgacatgt 1860

atatattgct tcagtagagc cacaatatgt atctttgctg taaagtgcaa ggaaatttta 1920

aattctggga cactgagtta gatggtaaat actgacttac gaaagttgaa ttgggtgagg 1980

cgggcaaatc acctgaggtc agcagtttga gactagcctg gcaaacatga tgaaaccctg 2040

tctctactaa aaatacaaaa aaaaaaaaaa ttagccaggc gtggtggtgc acacctgtag 2100

tcctagctac ttgggaggct gaggcaggag aattgcttga acccaggagg tggaggttgc 2160

agtaagccaa gatcacacca ctgcactcca acctggacaa cagagcgaga ctccatctca 2220

aaaaaaaaaa aaaattgtgt tgcctcatac gaaatgtatt tggttttgtt ggagagtgtc 2280

agactgatct ggaagtgaaa cacagtttat gtacagggaa aaggatttta ttatccttag 2340

gaatgtcatc caagacgtag agcttgaatg tgacgttatt taaaaacaac aacaaagaag 2400

gcagagccag gatataacta gaaaaaggat gtcttttttt ttttttttac tccccctcta 2460

aacactgctg ctgccttaat tttagaaagc agcttactag tttacccttg tggtataaag 2520

tattataaat tgttgtgaat ttgaagaatc cgtctactgt attattgcta aatattttgt 2580

ttatactaag ggacaattat tttaagacca tggatttaaa aaaaaaaaaa aaaactctgt 2640

ttctgcaggg gatgatattg gtgagttgcc aaagaagcaa tacagcatat ctgcttttgc 2700

cttctgttgt ttatcttacc tgcagatatt aagaatgtat gcattatgta aaatgctcaa 2760

ttatatattt ttgttgagtt ttttaattaa agacttgtaa aaaaaaaaaa cagtatattg 2820

caaatgtttc ttaaataggt taggtggagt actttctctc tgtctccatt gtaaggttga 2880

tggtacacca caggcaaatt aagcaaaaag gacaatgaag aaagaatgca ggactcaggc 2940

gctgctctag aattcattca gggctccccg agtgcagcag ctcttatggt ggttttgttt 3000

ttaggagaac tgttgtaata atgcatattt taaaagcata gggaagctct agaacacagg 3060

aaggtgacta ctaagcaaga gaaaagtatc ttttagtggg gaactaccag cctatagtaa 3120

gtctatctgg ttaaagtagt tattatgaaa atctagcagt ctgggtcctt tgagaaggca 3180

ttaaaaaagc aaaactctta tgagccatgt gtgattttga agactcattt ccactgagaa 3240

attatttgga agttcctatg gttagctctg ttaaggaatg taaaaattta tagggggtgt 3300

agggttatca atttgaaagc cagtagaaaa tctgctcaag ttacttcttg aggatcatct 3360

gtattttaca aaaagaagca caagaagcat ctaatcttta tacttcttgt gacttttttt 3420

cccctgcatt ttactttgta atatatcggc tttataattt taaaatacac tggccgggcg 3480

cagtggccca cacctataat cccagcactt tgggaggcca aggcaggtgg gtcacttaag 3540

gccgggagtt catgacaagc ctgaccaaca tagtgaaacc cctgtctcta ctaaaattac 3600

aaaaattagc tgggcatggt ggtgggttcc tgtactccta gctacttagg aggctgaggc 3660

aagagaattg cttgaactgg agaaatggag gttgcagtga gctgagatca cgcaactgca 3720

ctccagcctg ggtgacagag taagactcta aataaataag ataccattac ttttcatatc 3780

attgcattat ttttgctttc cacaccaaca tatccagtca agtaaaaaca gcttttttta 3840

ttttttattt tttatttttt ttgagacgga gtctcacact gtcacctggg ctggagtgca 3900

gtggtgcgat cttggctcac tgcagcctcc acctcctggg ttcaagcaat tctcctgcct 3960

cagcctccca agcagctggg attacaggcg ctcccccacc acgcccagct aatttttgtt 4020

gtatttttag gacagacggc gtttcactgt tggccagact ggtctcaaac tcctgacctc 4080

gtgatccgcc cgcctcggcc tcccagagtg ctgggattat aggtgtgagc caccgaacct 4140

ggcccaaaac agcatttttg gaagctacat tctgtgagat gttcacctgt ttgccacctc 4200

ttctcgtgaa aaccatagtg agtgccagtg tgaaaggaag attgcagcgt atatgtcaag 4260

tagaaacatg tttgaatttt ccatttgtct gtggggaaga aggtaataac agtaataaca 4320

gactgaagga ccaaaggaaa atagggaaga cgttgattat ggacttggat cagattctag 4380

ctacatgatt tgaaaatgac actgcctctc ctattttgcc acaagcctgt catttggaga 4440

actggcagat catttatgtt cagatttaat tttctgtttt agaatcccat ggagtacatg 4500

tgaacatagg aaaatcacac tcagcagcca agctatcctt ttgcgataat gaaatcactt 4560

taaaacctat aacttgatct taggttggca aatcttaaac ttaacgatcc ttgaaatttc 4620

ctgcctgctg tgactgtgat gcagttggat tcaactggtt tacactgctc ttgggtcggc 4680

aagaccaaaa aaggttggac tgcactgtag catgcttatg ggttgaggca gtggcagagg 4740

cagaggactt ggccgtcagc cagccagcac aggcgtaaga aaatagcatg agaagtttca 4800

cgagcctgaa accattgaga cagtgattac aacctccata ttaatcagat gagggtttgt 4860

aggtgacata gcattttacc caagtaattc tgaacagact gtggcttatg ataatacatt 4920

ttaactagca agtgtgtgga ctataaaaca aatatctaga gttatatatg gatgtactat 4980

catttggtga taaaagcata gaaaaagcat aagttggagt atactgggtt tttttgttgt 5040

tgttaaattc ttttccatca gaagtaagag ctgttggcag caactaataa aatgcaacct 5100

agtga 5105

<210> 9

<211> 6975

<212> DNA

<213> human (Homo sapiens)

<400> 9

agatcggaag tgacggagac gtgctagcgc gtcgaaggta gctctatggt tttcctcgcg 60

ttcttgagtc gggaaatggc cgctgtgtgg ttgcaacgga gataaattcc cggaaccgcg 120

attcggcgtg tcaggaattc gaatttagag tttaatttct cagagcattc tctccaggaa 180

gaatttttac agtatctcaa agacttcact tgacttcttg atcctgcata aaaccaagga 240

gaaaagaaat gggtcgctcc aattctagat cacattcttc aaggtcaaag tctagatcac 300

agtctagttc tcgatcaaga tcaagatctc attctagaaa gaagcgatac agttctaggt 360

ctcgttccag aacatattca aggtctcgta gtagagatcg tatgtattct agagattatc 420

gtcgcgatta cagaaataat agaggaatga gacgacctta tgggtacaga ggaaggggta 480

gagggtatta tcaaggagga ggaggtagat atcatcgagg tggttataga cctgtctgga 540

atagaaggca ctctaggagt cctagacgag gtcgttcacg ttccaggagt ccaaaaagaa 600

gatccgtttc ttctcaaaga tccagaagca gatctcgccg gtcatataga tcttctaggt 660

ctccaagatc atcctcttct cgttcttcat ccccatatag caaatctcct gtttctaaaa 720

gacgagggtc tcaggaaaaa caaaccaaaa aagctgaagg ggaaccccaa gaagagagtc 780

cgttgaaaag taaatcacag gaggaaccga aagatacatt tgaacatgac ccatctgagt 840

ctatcgatga atttaataag tcatcagcca catccggtga tatttggcct ggcctttcag 900

cttatgataa tagtcctaga tcaccccata gtccttcacc tattgctaca ccacctagtc 960

agagttcatc ttgctctgat gctcccatgc tcagtacagt tcactctgca aaaaatactc 1020

cttctcagca ttcacattcc attcagcata gtcctgaaag gtctgggtct ggttctgttg 1080

gaaatggatc tagtcgatac agtccttctc agaatagtcc aattcatcac atcccttcac 1140

gaagaagtcc tgcaaagaca atcgcaccac agaatgctcc aagagatgag tctaggggcc 1200

gttcctcgtt ttatcctgat ggtggagatc aggaaactgc aaagactggg aagttcttaa 1260

aaagtccccc tctacacaag aatctggatg cacgagaaaa gtctaccttc agagaggaaa 1320

gcccacttag gatcaaaatg atagcgagtg attctcaccg tcctgaagtc aaactcaaaa 1380

tggcacctgt tcctcttgat gattctaaca gacctgcttc cttgactaaa gacaggctgc 1440

ttgctagtac acttgtccat tctgtcaaga aggagcaaga attccgatcc atctttgacc 1500

acattaagtt gccacaggcc agcaaaagca cttcagagtc atttattcaa cacattgtgt 1560

ccttggttca tcatgttaaa gagcaatact tcaagtcagc tgcaatgacc ctaaacgagc 1620

ggttcacttc gtatcagaaa gccactgaag aacatagtac tcggcaaaag agccctgaaa 1680

tacacaggag aattgacatc tcaccaagta ccctgaggaa gcatacccgt ttagcagggg 1740

aagagagagt ttttaaagaa gaaaatcaaa agggagataa aaaattaagg tgtgactctg 1800

ctgaccttcg gcatgacatt gatcgccgta gaaaagaaag aagtaaagaa cggggagatt 1860

ccaagggctc cagggaatcc agtggatcaa gaaagcagga aaaaactcca aaagattaca 1920

aggaatacaa atcttacaaa gatgacagta aacataaaag agagcaagat cattctcgat 1980

cttcatcctc ttcagcatca ccttcttctc ccagttctcg agaagaaaag gagagtaaga 2040

aggaaagaga agaagaattt aaaactcacc atgaaatgaa agaatactca ggctttgcag 2100

gagttagccg accacgagga accttttttc gaattagagg cagaggaaga gccagaggag 2160

tttttgctgg gacaaatact ggtccaaaca actcaaatac tacttttcaa aagagaccga 2220

aggaagagga atgggatcca gaatataccc caaagagcaa gaagtacttc ttgcatgacg 2280

acagagatga tggtgtggat tattgggcca aaagaggaag aggtcgtggt acttttcaac 2340

gtggcagagg gcgctttaac ttcaaaaaat caggtagcag tcctaaatgg actcatgaca 2400

aataccaagg ggatgggatt gttgaagatg aagaagagac catggaaaat aatgaagaaa 2460

agaaggacag acgcaaggaa gaaaaggaat aataaatatg aagtaagatt acaacagagc 2520

agaacttgca cccaccattt tttttacctg atttttgttt tcaaataaga atgtaagcat 2580

tttacttaaa ttttactgtt tgcaagtagt ctatagaaat tttgttttaa gtcttcaaat 2640

atcttgagaa atagtagact gtatgttgaa aattgtactg aaataaagta gaaaattgtt 2700

acgtaccata tttgtaacta tcaactttta aaacttttaa cgtttttgtt acatgcattg 2760

taattctgct ttgtctataa gatatggtca agtacagctc tgtgaaagtt ctgattctct 2820

tccttccctg tttgtcaatg ttttattctg aagtaaacgt tagctctaca tataaatcct 2880

ggaacagaaa ttgtttatag agactacact aattatttta actgtataca tctgtttaat 2940

ttgaacacac tacatcgtag ggtgactgat ttttgaagta taccacagac aaaaagttgt 3000

tactatggta aactaagcta gtttaacact tgagcaaatg cttaagaagg aattaaaaaa 3060

aaaaagcttt gccaatagct aaaaagtaca agctattaaa aatcagattg aaaagttttg 3120

agaaaatgtt atttttactg aaagcaagca gtggcctata aagaacattc ttaggagcct 3180

tttctatttg cgttcaaaac tgtgtgttct ctttctattc ctatttgata gtttgagtca 3240

tggtcttaga tattagctat ttgtgagagg aaactggttt gtaacaatac tgcaaataga 3300

aaccccattt ctactgaaca tcctagtttt aaacagaaga aaaactgtaa tcctggggtt 3360

ggtatgtagg aggtctatcc tgcagaataa gttgatacat tagtacctga tttcatatct 3420

tacatattta tttgagctga acattagttt gtagtgtaac tattagtaaa aatagagaaa 3480

cacagcatac tgttcattaa tagtatttta aaaaaattgt ttttcaaatg tcaccaataa 3540

aagttttggc aggaagcttg ttgcggcatt gatctaacct ttttcccccc catttcagtt 3600

gcagtttttg tagaatggct ttttcttttt cctcttaaga gttctattct tcaggtagat 3660

aatttttcaa atgtgaatta tcttttgtgt ctatattgat agctcttaaa ggagtgaaaa 3720

tctaaaatag taaatttcaa tgttaagtgt ctgctttatg ggcatatata aaagtagaca 3780

catttcattt gttaatttag ttgtgtgtgt gtgttaaaag gagctaatgc ttattctgtt 3840

aatgtaaact tttgaagatc ttaagtgtat tgctctttca tcttaaacac tttcgaggat 3900

ttgcagtgcg tctagcacct agattacagc caggaacatt ggttaagaac tgttggaaac 3960

aaaactaaaa gcaaactcaa catatgtgat gtttatggcc ctcagatcct tagtattgtg 4020

tgattttccc ccgttaacat gtctttctaa aattgtctat taaagcagag gaaatacctg 4080

ccaaaggaag tatgtattgc attaatcagg gcataactaa tattctcctg ttcagaataa 4140

tacttattta cgtgtgaaag caacatggat gtgattccca acacagaatt ttcatgaccc 4200

ttttattgta tacaaataaa taccataaca gttacttggt tagacatcaa atctgtgtgc 4260

atgactatgt gcttatccac ttaagacaat aggtaaaagg ggatctgaga aattatgtaa 4320

tagggagtgg gaataaaact acttaattcc tgtgggcagg ttatatttta agttcaaatg 4380

cattgcttta acctttggtt acttttattc tgttaaacag aattgaagaa agagtattat 4440

accagagtgt agtaggctag ggtgattgta agaactctgt aatagaatgt cattgtggat 4500

gttacctttt tcagatccaa gcatataaaa agcctgtata ttttttaaaa acacatctta 4560

actccacgct ttacgatatt ataaaagttg aatggttcct cttggtaagg atatttgctt 4620

acaagtgcta ggaaataact cactgatacc tgcgttaaca tactttgttt tgcctagaga 4680

ggggcaataa aaatgaacca aaggatattt ccagaaagga ttaagaaagc tgtttaagaa 4740

ggccatgact ctttaggtgt gtatgtgtac ctttcagcat cctaggaatt tttatactaa 4800

aagcaaaatg ttttttccag ttagtcttct tcaaggaatt actattgttc cttttgtcac 4860

aggtaaaatc agtgttggga attataattt gagaaaaata ttacccagta acattgaatg 4920

tagatggcta aacgattctt actcagtgtg atgtataatg atgcaacagg gacccttgta 4980

aattgtcata cgccaataaa atgtcacaag taataactgc tgttgtttgt ttacctgtgt 5040

ctatttcaca catcttattt ctgtggccta ttttagaata tcagcgcatc tgttaggaag 5100

attactggtg tggtaaggct tgataaatgc tttataaact ccctcaaacc tttctttact 5160

gtttttttgt tttgtcttgt ttttgttttt gtttttgttt ttgtttttgt ttttgttttt 5220

cccttgtctc ccctgggaaa atgggaaatt ttacagttgg taaatctaag ccaaaattat 5280

tttgaaataa aggaattctg gatgtccagt ttagtcctcg ttttcttacg ttaatctggg 5340

accttatcac ccataatatg gtgattactt ctctttctaa aaacatagta gctagtaaat 5400

aagtaaaaag aattgtcttt tcattcactt taagtaagat gtggtataat tcttaccatg 5460

tgccatcctg tcagttttaa caaagcattt tcacagaaat ttgtgtacta agacaaactg 5520

acacattttg actcatacaa atggcaaatt agtccttaaa aattctgtga gagaaataac 5580

tctgtgtgta catacatatg catgtaaagt gttgtgtaag atcattggta gcttaattat 5640

actggataat tgtaatgtta tatacaaatt tcttatataa aagtatgctg cattattaac 5700

atttgtttaa cttttcttat ttttcttttt ctgggtttca actggaatcc cattggtggg 5760

gatgtacctt aagtttcctt gtggaataat agactttcac atccagaaag agaagttcag 5820

aggcctttct caatttacag agttgaagag gaaaggcaaa tggaggaata aacttcattg 5880

tcattgggat taatttggct agactcaatc tcttgagcct taaaatgaga aagtaatatc 5940

cattacatgt ttagagttct caaatagttg atactattat taaatgtttc aaattttatt 6000

ggggtagata ctaaaaatta gtacactgtc ctaatgaagt ttaaatgaac aagttttaca 6060

tttcttagga ttcaggaata tatggaatct agttgtattt aattgacttg agagccacag 6120

agattgtgtt gatttatgag ctggactcct attgttttag aaacatgcag taatgattaa 6180

cttgtgtcaa tgatggtaat gagaccaaac ttgtacattt aattaagggt accagttctt 6240

tttatgttac tagactatac cttggccttt aaaaatgaat ctcactgatt aaagagaaca 6300

ggcattatta ggatagcatt ccaccacaac tagaaacatt caaataatgt gtcttaattg 6360

taatctgtat ataggaaaat ttttcctatg gatatttttg gtgttttacc acagtgaact 6420

gatttgtagc acttatgaag tgcagaaggt aatattcttg aaaatagaaa aaggttgggt 6480

gagcaggctt taatgccttt cccccaagaa tatacatcga atttttctta atcttttggg 6540

gttggccagc ttccagattt cattaataat gagctctgcc tttaataaaa gtacatgatc 6600

atagctacac tgtatgttta ggtggtgtga aatgatttat aatcacagct tgaactgtgt 6660

ttgcttggta ctgtcatagt gattacaaat ttcatggaat gcgaagagca acaataaata 6720

aaaaatacca ctcaccctcc agaatagtgg attatttgct accttgagtc cttcactatg 6780

gaaaataatt tttcagtctc atttgtacta gaagggaaaa ctaaactttc tgttgagttc 6840

tcaggatact tgtaaggtgg ccgtgaaaaa gaatgttaaa tgcactttga attatttatt 6900

tatttattta tttatttatt tatttattta ttgagatgga gtcttaccca gactagagtg 6960

cagtggctcg agctc 6975

<210> 10

<211> 9335

<212> DNA

<213> human (Homo sapiens)

<400> 10

gcagttggca ggctgctgcg ggaggcggcg gcggtaggaa gccggagaca gcagggtgac 60

agaattggaa aatatttaac tcttaacaaa tgaattcccc acttgaactc tgccgaattc 120

ctgtgccacc tcctccttta gaaaactgat cttaatacag agataaaaga ggagtagaag 180

gtaaaagaaa atgctgggaa ctgaccgttg tgttgtggaa gaatggttat cagaattcaa 240

ggcattacct gacactcaga tcaccagtta tgcagcaact ttacaccgga aaaaaacact 300

tgtaccagcc ctctataaag ttattcaaga ttcaaataat gagctcctgg agcctgtctg 360

ccatcagctg tttgagctct atcgtagctc agaggttcga cttaagaggt tcacactgca 420

gttcttgcca gaattgatgt gggtttattt acggcttaca gttagccgag acagacagag 480

taatggttgc attgaagcac ttctgttagg aatttacaat ttggaaatcg ctgataaaga 540

tgggaacaat aaagttctgt ctttcactat cccctcctta tccaagcctt caatatacca 600

tgaaccttca acaattggat ccatggcttt gacagaaggg gcattgtgtc agcatgatct 660

catcagagtt gtttatagtg atcttcatcc tcagagggaa acattcactg cacagaaccg 720

gtttgaagtc ctgagttttc tcatgctgtg ttataattct gctattgtat atatgcctgc 780

ctcatcttac caatctcttt gtcggatggg ttccagggtt tgtgtgagtg gctttccacg 840

gcaacatgaa aaacactgga aagaactctg tggtcgaata gtattggatc ctgaatttat 900

ggtgcaactt ctcacagggg tttattatgc catgtataat ggacagtggg accttggcca 960

ggaagttctt gatgatatca tttatagagc ccagctagag cttttttctc aaccactatt 1020

ggttgccaat gccatgaaaa actcattacc atttgatgct cctgattcta cacaagaagg 1080

ccagaaagtc cttaaagttg aagtcactcc aacagtgccg aggatttctc ggactgcaat 1140

tacaacagct tcaatccgtc gtcatagatg gagaagagaa ggtgctgagg gtgtaaatgg 1200

aggagaggag tctgtaaacc tgaatgatgc agatgaagga ttttcatcag gggcttccct 1260

cagcagtcag ccaattggga ccaaaccatc ctcctcttct cagaggggaa gcttaaggaa 1320

agtagcaact gggcgttcag ccaaggataa agaaacagcc tctgccatca aatccagtga 1380

gagccctcga gattcagtag ttcgcaagca gtatgtacag caaccaactg atcttagtgt 1440

agattcagtt gagctgacac caatgaagaa acacctgagc ctgcctgctg gccaggtggt 1500

gccaaaaatc aatagcttaa gtctaatccg gacagccagt gcttcctcaa gtaaatcatt 1560

tgactatgta aatggcagtc aagcaagtac cagcattggg gttggcactg agggaggtac 1620

taatttagca gccaacaatg ctaatcgata ctcaactgtc agtctgcagg aagaccggct 1680

aggtcaagct ggcgaaggta aagagctcct cagcccagga gcccccttga ccaagcagtc 1740

tcgatcccca agtttcaata tgcagctaat atcccaggtg tagttttgac atcctccctc 1800

atctttctgc ttacctttta aactgaacat ttcattgtgc aagaagacac ttcatcccac 1860

attgtgaaaa tattggtcac tgttatcaga tttcatttag tttaggtatc ttcatactgt 1920

attttgtatc aaaacagcaa taaggttttc tttatccctc tttcctacat cttctcttca 1980

cctatccctt gtaaatgtgt ttgtgaagca gtataaaatg gttgcctttt ccatgccttc 2040

ctttctcctt gggtgatgtg caatccatcg taggctgatc ggtcccattt caacactgtg 2100

agactgaggg tacattagag gaaatggtgt atatgatccc tatgaaacga ttctttggct 2160

tttgtttaaa aacaaaacgg gtttgttctc ataatctata gaactatgaa gattactgga 2220

tcatattttt ttctcttaac caggagtgcc tcagagattc tgctatgact ttggacttct 2280

ctgagtctgt gcaatcattt tctggagaag catggggaaa ggtggtagac tgctgcactt 2340

tttcattaaa atgagggtag ctctttctcc acccccccat ctcctttatc ccgaagacat 2400

aaatgttcaa ttacggaggc atttaaatca agttgtgacc acctccattg gagggcagga 2460

ctcttgattg tgtaattgat aatgcacttt ctcaatggct gtatagtcat tattaacgtg 2520

tcttccctct tccccacaag gacatataag gtcatttctg tccttcaagt ttggccaact 2580

aacaaatcag aatctgaggg gcatgttcta tttcccagga atgattgaca ctttggtgct 2640

ggggttttgt gggggcgggg ggtagttttt gtttagcttt tgtggagatt gtgtgtgtga 2700

gaggagattt gatttttttt tcttcttttc ctttgtgagc tgatggctga agtgtaacag 2760

tacatcttca ggtaaagaga gggatttctc aatctacttt ctgttatgtc agactataag 2820

agaaaccctt tcagctgctt tctagatgta cctaaattca gtcagacatt ttggattaag 2880

aaacctaaag tcctgataca ttacatactc caaggaaata tatcagggac agacaattgg 2940

ctgaaacact gatacttcaa tgtgacacat ttttatagaa catttctacc agggggtact 3000

gaccttgatt tctcctacaa ggaccacact gcctttgtgt ttaatgtaat gcaatttgtg 3060

taccttctaa tcatatatct gcagttcctc atttttataa aactttgata tcatgccagt 3120

aagctagatg ttgaatgtat gtaagtagca tttggtaact gctaagaggt tacaaaaaca 3180

ttattggtaa aaaaaatttc cttagttctg atctggttgg ataagatttt atcataactt 3240

ttctgggtct caggctctga tgtttgaaaa agaagggaat atattgggtt ttaaaaaagt 3300

gtattgtgac ttaaactgtt ataagttatc cttccacaga atacatcaga gctatcagtg 3360

ctttgtacat ttagatgttt ttacttgatt attgtttaag aaaaatatac tgaatttata 3420

gaaagcaagt attctcctaa ttagcaaaag ttaaaatttt atctctacca ttaaaattac 3480

aatagatttt gataaataac cagaaaaaac gccttttttt ttttcacacc tagcaatcct 3540

cccgttttta ttgtaaggac tttctttttt ccctaagaga ctttctgtta gactctttat 3600

atatgagatg cttgtttaaa tatggtggtc tgtaacattt ttccagctca tgtgaaaatg 3660

gaaaactaga acctgaacta gtatctacaa cattgccaaa gtccagggta aagctaaaag 3720

ttgataagta gacaatttat tgttttgtgt gtgtctgtgt gtgtgtgtgt gtgtgtgtgt 3780

gtgtgtgtat ggtgtgtata tgtatatatc acaaagttgt attttaaata ttttaaatac 3840

cctttctttt aatttaaggg atgtcaaata aatgaaagga gtttaaaaat agccaaaata 3900

aatgagctat aaaggcccat aacatactaa aacaggcagt ttcaggtatg taaggaaagg 3960

aacattatac ttacctagaa agtgagatct aaaaaaaaat taaaaataaa taaaaaataa 4020

aaaagaaagt gagatcttgg ctatggctgg aggtcagtca ctttatggca taaattattt 4080

gggaggtaaa aagactgttt tcaattcaaa ttgtgcattt attggcatct aaatctagca 4140

tgattttggt tagagcacaa aagaaatacc acataatacc aaatcacagc aaatgttaga 4200

attaatacaa caaaattttc ctttggctag aaatcttatg ttatacctga aaaattggtt 4260

ttaaaaaatg ttcatcttgg ccgggcacgg tggctcacgc ctgtaatccc aacactctgg 4320

gaggctgagg tgggtgaatc atgaggtcag gagttcgaga ccagcctggc caacatggtg 4380

aaaccctgtc tctactaaaa atacaaaaaa ttagctgggc gtggtggcag gcgcctgtaa 4440

tcccagctac tcgggaggct gaggcaggag aatctcttga acctgggagg tggaggttgc 4500

agtgagccaa gaatgcacta ctgtactcca gcctaggcaa cagtgcaaga ctccatctct 4560

gaaaaaaaaa aaaaaaaaaa aaaaaaaagt tcatcttaga ggattttatt tatctgtatg 4620

tatatacata tatgtttgta tgtatacata cccacattaa cattttatga ccctgtaaca 4680

tttgttttct attcttttag gtgatgtgaa ttgacctcag tgaagaaaca tttcatttag 4740

tctaagcctt gcattcaggg tcttacaaca gatttcttgt gcaagaatta ttattagtta 4800

aaatggaagg tgttagttta acaaactgag agtcaaattt tctaagtttt taaatatgca 4860

ttttaacatg cattattttt ggcatttaat ttaaaatagt tttgtttcat gtatacaaca 4920

gctgttacag atatatgcca gcaatattca tactttttta acaagctttt gttatatatt 4980

ttctaatctc cataaaagtc taatcatcta tgaaaaagat atttagggag aaaatacttg 5040

ttttctgtaa taaaacaatt aggttggtgc catgtatgcc aagttggata aaagaataca 5100

aagaaacagc tgaaggtttt gggagctcgc tctgacatta attactagaa agcaaactaa 5160

aatgcaaagt gaatagttaa ctcagaagat ttgaattttt tgaaataggg tctcactctg 5220

tcctctaggc tagagtgcag tggcactatc acggctcact gcagcctcaa cctccctggg 5280

ctcaggtgat cttcccacct cagcctctgg agtagctgga actccaggca tgcaccacca 5340

cacctggcta atttttgtat ttttagtaga gacgaggttt tgccatgttg cccaggctgg 5400

tctcgaactc ctgggcttaa gagatccacc cacctggcct cccagaagtg ctaggattac 5460

agacataact accacacctg gcctgaagat ttttaaatgt gaaaatattt taagaagcta 5520

aggggaaaat cgttatttta aaatcctgat ccccttaact ttacccctta ccattcccct 5580

tacctttcca attcactttt gtctatttat tatagaatca gaattgtgct aagaagaaac 5640

cctggagata atctagctag tctcccactc cctcacccca accttcatcc tcaagaaaca 5700

gaggctcaga ggttgtggtg tgatcaagat catataccta aagcagagcc agaatcaaac 5760

ccagtctccc atgggtttgg ggaggcagtg ggttgttaac tccatttttg cagtttcttt 5820

atagttctgg tctagtagtt ggtgaataca acacattaag aaaagtgtta aatccagaaa 5880

aaatgtagag taatctagat ggggaaatgt tggaaatgtt aagtatatct acagatgtaa 5940

ggatcaatac attattctaa tttatgcctt actattttct gccacataac agttgtatgc 6000

tgccatttta tagttgaata catttgttgg gatttattta aatataaaat aaaccctgtg 6060

aaatggcttt gatcagtgtt ttctagttat tttaaagtaa tttttgagtc agccagcttt 6120

cagtcaccag tgtggcaagc taattatatt gcacaataga gtattgcaaa gtaaagatta 6180

aataaatttg attccattac tttttaatgt agaaagagac tgaatcttat gcttagagca 6240

aatgcaagca atatttcctt atatgattga aaaaggttct atagtgtgaa gcttatgatt 6300

ccataatgga acagtgacca tgatgtcatt taaagtgtgt atataccata taaaatgtct 6360

taaatgcggt agtctcagct atataagctc agtatttcca gtctgtattc tcagattcca 6420

tctagtagct ttaaattaat taaaattgtt tattagacac tggaatactg agaataactt 6480

ctttcagatt gttttgtttg caccactttt gtgaatattt taatgaagtg gagtccattt 6540

ttgagtactt cagttgttga caatcagttg tctcgtttaa atctctgcat gttcatttgt 6600

aaataaaaaa tgtagtacct gtctttaggg gtagtcccct atttattaca aacactggca 6660

aggaatatct gtccatttct gaccttggat tacaaagtat gttttgggtt tttccttttt 6720

taatcagtat ttcagttaca tctttgtttt cagctttaaa aagtttaacg ggtcatgcca 6780

atgatcagaa aatctgtaag aattttagag caatttttct atgtacagct atgttaaaca 6840

gtctgaacat gagacttttt ctttcaagtt gaagattatt gtcatcgttt taccactaag 6900

ttggttgaga cacttacttg taatacttta atttttttaa agtgttttta gaaacaagtt 6960

gtttgaaaac caattagaaa ttagaatatt tgccagatta taagcagatg gaatgcagtg 7020

taaaactgtt aacaatgcta ataaaattat gagtcatcag attggtacag ttttccctgc 7080

caagatggtc atattgataa tgtaagacaa attttagtat tacttgcatt atgtgtacct 7140

aataggtata tcatactggt actgagcata tatagaaaat actattcata gaggagtcat 7200

caccacccaa cctccttgcc tgtgtaggca tatttcttct gaacctgacc acacaagtac 7260

aacattttgg taacttcagt cttttcagta tttttgtaat cttagccata gtcctatgag 7320

aaatgtacat aagagcaaac aattcaggat agaaattagc agaaagctgg gaatgatgtg 7380

aaataactgg cagcatagta cagaaatgta aggtatatgt tttgcttctg gatttttaga 7440

aattgtgcta atcatgttta caaattaagg catattcaga tgtctgctat tatgtttaat 7500

attgatttga taaaaaaatg gaattaggtg tagcttagag tataaatgag tctttttaaa 7560

aatgtgtatc tggaagtagg gctaataaag aaatcctttt attttcaaag aaatgaactt 7620

aattggacaa ctcatcccca attacagaat tgatatcaat atggtttgct gtatttgagt 7680

ataaacagct cagtgttaat tatatcaaag gaagttcttt acatcttcat tgattacaaa 7740

atttaccaaa gaaaatgtat ctaccaaata taatttttaa agtacttgtt aaggaatgag 7800

gcctctttaa catataaagt atcttaaaaa tattctctga cctggaaaat aggtttacag 7860

tagctacaag attccatttt aggttttctt atgtcaataa atgtcaatat tttacacttc 7920

cagcaaaagt acccgttaaa gctaaatcta aatattattc ctcatagcac agtttctggt 7980

ctccttaaat taaggatcct actcatcagg attgaataaa aagggggaaa ttcctaaaat 8040

tggtatattg tataatattg tgggttaagt aaaatttagg ggggcattat ggaaatgtac 8100

ctattttaaa gggcagtggc aattactata atattggtta aactggtaaa gtttgttaaa 8160

taatttatgt ccatgatcat tctgagtgtt ttttttcttt gcagaaaaac aggattgggt 8220

taagaaaagc taaaatactc atttttttaa aatgtatagc ccaataagaa ctaaatgatt 8280

tatttcaaaa gttaaataat tttttttgga aatcatggaa tgtatttgca tattgatgtt 8340

ccaaacaggt tttatgtatt gttttttata gcagggagta gttgaaaagt aatgagtata 8400

ttgattagct gtcttggaaa gagaggattg gctttctaac aatcactgat acaggtttgg 8460

gtttgggggg gtttgtttgt ttgtttttaa gttttatcat ccatactgaa ttgagagata 8520

tgctccatgt ttaaaaatat ttgtaataag ttcatctact tgacactgaa tcttttttat 8580

tcttactcta aaattattct ggctttacat tcagtttaag tggttaagtg aaacagtttt 8640

tagggtgcaa aaattatttt cccactgttt ttctcatgat aatttgagtc tcctgagcta 8700

taatttctga aggattttta ctactttggc attatgtaat ctgatctctg tcacaatgat 8760

attaaataag aactatctca ctttcatatg tttgcttcat aaaaggatat ggaatgtaca 8820

catcagctct tttttttttt ttaaactagc atcaacctat aacttggtat aaacttccca 8880

agtatttaga gaatagtgct ggtgaaaatt taaataggat aggcatatag aaattatgac 8940

ttgtattgag tgatgtcctt tcaacctagg actagtgaca accttcattt tttcagagct 9000

gaagaaaaaa ccgtgaattt aagatcatat ttattggtgc atgtaagcca ttatcctgtc 9060

ttaatgaacc gattaatgct gttgattgtt gaaatgtgaa atgtagtcac tgttgacctt 9120

gtaaatatct gccagagatg aaaaaatatt ttaagttatt gtaaataaag atgtataaaa 9180

ttcagtatca gtctgcaatg cagaaacata tcttagatgt taaaatactg tgtttgagag 9240

atgtgtaatt tacccttaga tgtatctagt tacattaaga gtgtaaattt ttttgtacag 9300

tataaaaata cagctctatt tggcttttaa ctgga 9335

<210> 11

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 11

cactctgagt tcatcagcaa acg 23

<210> 12

<211> 19

<212> DNA

<213> Artificial sequence (Artificial)

<400> 12

acgagaagcg gtcccaaag 19

<210> 13

<211> 18

<212> DNA

<213> Artificial sequence (Artificial)

<400> 13

ccgctctgca ggctgttc 18

<210> 14

<211> 21

<212> DNA

<213> Artificial sequence (Artificial)

<400> 14

tctgcgcgga catacttctt t 21

<210> 15

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 15

ggatgcttga agatggaaag aaa 23

<210> 16

<211> 25

<212> DNA

<213> Artificial sequence (Artificial)

<400> 16

cctgcttgcc tagcataaac ttaaa 25

<210> 17

<211> 17

<212> DNA

<213> Artificial sequence (Artificial)

<400> 17

ctgcgctccc gtttcct 17

<210> 18

<211> 20

<212> DNA

<213> Artificial sequence (Artificial)

<400> 18

ggacctcagt ggcctgtttg 20

<210> 19

<211> 22

<212> DNA

<213> Artificial sequence (Artificial)

<400> 19

cctggagggt catctctagc at 22

<210> 20

<211> 26

<212> DNA

<213> Artificial sequence (Artificial)

<400> 20

actttctccc gatagtcctt aatcag 26

<210> 21

<211> 21

<212> DNA

<213> Artificial sequence (Artificial)

<400> 21

gggaagaccc agtggtagct t 21

<210> 22

<211> 22

<212> DNA

<213> Artificial sequence (Artificial)

<400> 22

ccaaatactg gccaacacaa aa 22

<210> 23

<211> 28

<212> DNA

<213> Artificial sequence (Artificial)

<400> 23

tgatggaagt gtagggttta tgaattat 28

<210> 24

<211> 17

<212> DNA

<213> Artificial sequence (Artificial)

<400> 24

atgggccgct cacaaca 17

<210> 25

<211> 21

<212> DNA

<213> Artificial sequence (Artificial)

<400> 25

ggtccctagc ctgcaacatt t 21

<210> 26

<211> 20

<212> DNA

<213> Artificial sequence (Artificial)

<400> 26

atcggcagct cctgaacttc 20

<210> 27

<211> 25

<212> DNA

<213> Artificial sequence (Artificial)

<400> 27

ccttcaccta ttgctacacc accta 25

<210> 28

<211> 22

<212> DNA

<213> Artificial sequence (Artificial)

<400> 28

gaaccagacc cagacctttc ag 22

<210> 29

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 29

gtggtgccaa aaatcaatag ctt 23

<210> 30

<211> 20

<212> DNA

<213> Artificial sequence (Artificial)

<400> 30

ccccaatgct ggtacttgct 20

<210> 31

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 31

cctggcgtct gtcctcacca tgc 23

<210> 32

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 32

tcctcggcct cgtcacgtgt tca 23

<210> 33

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 33

tcctcccggg acagaaacaa gcc 23

<210> 34

<211> 25

<212> DNA

<213> Artificial sequence (Artificial)

<400> 34

atgccagacg aaagcgccgt aactt 25

<210> 35

<211> 26

<212> DNA

<213> Artificial sequence (Artificial)

<400> 35

agcagaagac cgacacctcc gacaag 26

<210> 36

<211> 23

<212> DNA

<213> Artificial sequence (Artificial)

<400> 36

agacacccgg gaatccatgc acg 23

<210> 37

<211> 30

<212> DNA

<213> Artificial sequence (Artificial)

<400> 37

cagctgacta ccatacctca cacagcgttg 30

<210> 38

<211> 24

<212> DNA

<213> Artificial sequence (Artificial)

<400> 38

aatccgaaga gtgatgccca ccca 24

<210> 39

<211> 28

<212> DNA

<213> Artificial sequence (Artificial)

<400> 39

agttcatctt gctctgatgc tcccatgc 28

<210> 40

<211> 27

<212> DNA

<213> Artificial sequence (Artificial)

<400> 40

tctaatccgg acagccagtg cttcctc 27

Claims (11)

1. A combination of peripheral blood transcriptional gene markers for detecting breast cancer, said peripheral blood transcriptional gene markers being differentially expressed in peripheral blood cells of a population having breast cancer and normal distribution at the same age, the sequence of said peripheral blood transcriptional gene markers being SEQ ID NO:1 to SEQ ID NO: shown at 10.

2. The composition consists of primers and/or probes for specifically detecting peripheral blood transcription gene markers which are differentially expressed in peripheral blood cells of breast cancer and people with normal age distribution, wherein the sequence of the peripheral blood transcription gene markers is SEQ ID NO:1 to SEQ ID NO: shown at 10.

3. Use of a combination of peripheral blood transcriptional gene markers according to claim 1 for the preparation of a product for the detection of breast cancer.

4. Use according to claim 3, wherein said product for detecting breast cancer comprises: products for detecting breast cancer by real-time quantitative PCR, RNA sequencing or gene chip.

5. The use according to claim 4, wherein the product for the detection of breast cancer by real-time quantitative PCR comprises the specific amplification of the nucleic acid sequence of SEQ ID NO:1 to SEQ ID NO:10, or a primer having a sequence shown in figure 10.

6. The use according to claim 4, wherein the product for detecting breast cancer by RNA sequencing comprises the nucleic acid sequence of SEQ ID NO: 1-SEQ ID NO:10, or a messenger RNA sequence of the sequence shown in figure 10.

7. The use according to claim 4, wherein the product for detecting breast cancer using gene chip comprises: and SEQ ID NO:1 to SEQ ID NO:10, or a fragment thereof.

8. A kit for detecting breast cancer is characterized in that specific primers and/or probes for detecting breast cancer are provided in the kit, the specific primers and/or probes are specific primers and/or probes for specifically detecting a combination of peripheral blood transcriptional gene markers which are differentially expressed in peripheral blood cells of a population with normal age distribution and breast cancer, and the sequence of the peripheral blood transcriptional gene markers is SEQ ID NO:1 to SEQ ID NO: shown at 10.

9. The kit of claim 8, wherein the primer has the sequence of SEQ ID NO:11 to SEQ ID NO:30 under stringent conditions.

10. The kit of claim 8, wherein the sequence of the probe is SEQ ID NO: 31-SEQ ID NO:40, or a nucleotide sequence shown in the specification.

11. A gene chip for detecting breast cancer is characterized in that an oligonucleotide hybridization probe for detecting breast cancer on the gene chip is a hybridization probe for specifically detecting the combination of peripheral blood transcription gene markers which are differentially expressed in peripheral blood cells of a population with normal distribution in the same age, and the peripheral blood transcription gene markers are SEQ ID NO:1 to SEQ ID NO: shown at 10.

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