CN109423515A - One group of gene marker and its application for liver cancer detection - Google Patents

One group of gene marker and its application for liver cancer detection Download PDF

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CN109423515A
CN109423515A CN201710710566.7A CN201710710566A CN109423515A CN 109423515 A CN109423515 A CN 109423515A CN 201710710566 A CN201710710566 A CN 201710710566A CN 109423515 A CN109423515 A CN 109423515A
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liver cancer
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CN109423515B (en
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刘星
韩峻松
欧莹
杨超
袁箐
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SHANGHAI BIOCHIP CO Ltd
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Abstract

The gene marker and its application that the invention discloses one group for liver cancer detection, are particularly suitable for the detection of the detection of early liver cancer and/or the liver cancer of AFP negative, application field is bioscience: biology, biochemistry, biotechnology, medicine and medical technology.One group of hepatocarcinoma gene marker is made of EP400 gene, MAPK1IP1L gene, NUFIP2 gene, PHC3 gene, RPS6KB1 gene and STX7 gene.The invention has the advantages that gene marker of the invention, examination for liver cancer diagnoses, sensibility height, high specificity, it and due to being is detection sample with the peripheral blood that clinically most easily acquires, it is easy to detect, suitable for the early diagnosis of liver cancer, and the detection to AFP negative liver cancer patient, it has a extensive future.

Description

One group of gene marker and its application for liver cancer detection
Technical field
The gene marker and its application that the present invention relates to one group for liver cancer detection, are particularly suitable for the inspection of early liver cancer Survey and/or AFP negative liver cancer detection, application field is bioscience: biology, biochemistry, biotechnology, medicine and Medical technology.
Background technique
Liver cancer is to seriously affect one of the malignant tumour of China's national health.According to the national newest announcement of tumour Register " tumour registration annual report " data in 2014, disease incidence accounts for the 4th of all malignant tumours, and to account for all cancers dead for the death rate The 2nd died, is only second to lung cancer.Epidemiology statistics show that Chinese suffer from the high incidence age of liver cancer by pervious 40~60 years old 30~60 years old is advanceed to.Onset of liver cancer is in the trend of rejuvenation, serious to damage national population quality, social stability and each department Economic construction.
The Consensus of experts of 2009 " primary carcinoma of liver standardization diagnosis and treatment " is pointed out: primary carcinoma of liver is that the height in China is swelled Tumor, there are more difficult points for treatment；Therefore, it is necessary to pay attention to early detection and early diagnosis.The treatment means of liver cancer and prognosis and trouble The course of disease locating for person is closely related: to the course of disease, the treatment methods such as operation excision, liver transfer operation, 5 annual survival rates are can be used in patient earlier Up to 50~70%；And the means such as hepatic arteriochemotherapy, targeted therapy, 3 annual survival rates can only be taken to the later patient of the course of disease Only 10~40%.Early diagnosis liver cancer is to improve Resection Rate, reduces the death rate, extends life span, improves existence matter The Optimal action of amount.
Liver cancer is mainly applied in the world alpha-fetoprotein (AFP), ultrasound and the diagnostic techniques that combines of other iconographies into Row screening, but ultrasonic examination depends on the experience and equipment of operator, and other iconography means need high expense, liver Carcinogenesis early stage, imageological examination less than；And AFP sensibility is lower, surveys AFP and is not only difficult to use in early diagnosis, but also Be easy to cause disease fail to pinpoint a disease in diagnosis or mistaken diagnosis.Early diagnosis treatment delay, so that liver cancer patient more than 2/3rds is late It obtains medical treatment.China increases 38.76 ten thousand people of liver cancer patient newly every year at present, and wherein AFP negative liver cancer patient is about 11.6 ten thousand people, belongs to In easily because failing to pinpoint a disease in diagnosis, mistaken diagnosis due to be delayed the high-risk liver cancer patient group of best occasion for the treatment.
AFP negative liver cancer patient accounts for about the 30% of liver cancer patient sum, and small liver cancer (knurl≤3cm) is especially common and more For low differentiated liver cancer, prognosis is poor, and clinical cure rate can be improved in early diagnosis and early stage surgical excision.AFP negative liver cancer is suffered from Person's serum afp is normal (20 μ g/L of <), and clinical symptoms are relatively light and lack specificity, and clinical diagnosis depends on image more at present It learns and pathological examination, the AFP negative liver cancer particularly with tumour less than 3cm lacks valuable and practical diagnosis marker, Easily mistaken diagnosis is hepatic benign lesions, thus delay treatment.AFP negative liver cancer how is diagnosed, is merit attention the problem of. And joint-detection other tumor markers are a kind of methods that comparison is desirable to diagnosing liver cancer, especially AFP negative liver cancer.
Tumor biomarkers usually have drawn from tumor tissues sample or peripheral blood at present.Blood is a kind of in broad terms The connective tissue circulated contacts all organs of human body, includes the index for reacting body variation, participates in disease under pathological state Sick process；Compared with tumor tissue specimen sampling, the acquisition of marker is non-traumatic in blood circulation, have repeatable materials, The advantage of dynamic monitoring is the desired tissue for substituting pathogenic site biopsy, carrying out noninvasive Molecular Detection.Including mRNA (mRNA), the transcript profile level including Microrna (miRNA) and the nucleic acid mutation layer including Circulating tumor DNA (ctDNA) The research of the novel tumor markers in face is gradually taken seriously.Compared with traditional serum protein molecule marker, nucleic acid molecules mark Will object has clear superiority on stability, detection sensitivity and detection flux, is able to satisfy multi-tracer joint-detection more to mention The requirement of high diagnosis is the development trend of tumor markers research and development and detection.
Studies have shown that peripheral blood transcript profile can accurately show disease specific allelic expression, disease can be applied to The early diagnosis of disease and Index for diagnosis.Fluorescent quantitative PCR technique, Britain are combined on the basis of peripheral blood special gene expression profile Scientist detected in kidney 8 gene expression characteristics spectrum expression, as the early diagnosis index of clear-cell carcinoma, and with trouble Person's Overall survival is obviously related to progression free survival phase.Compared to miRNA, the research of tumour correlation mRNA express spectra is more thorough, inspection Survey method is more mature, as a result also more acurrate.The U.S. has been developed that the intestinal cancer Risk-warning peripheral blood base based on mRNA level in-site at present Because of diagnostic products, and introduce to the market.
Summary of the invention
The invention solves first technical problem be to provide one group and be effectively based on peripheral blood gene expression characteristic spectrum The new gene marker for liver cancer detection of system.
The invention solves another technical problem be to provide the application of said gene marker.
To achieve the above object, the invention adopts the following technical scheme:
The first aspect of the invention provides one group of hepatocarcinoma gene marker, by EP400 gene, MAPK1IP1L base Cause, NUFIP2 gene, PHC3 gene, RPS6KB1 gene and STX7 gene composition.Present invention research finds for the first time, these genes Expression is had differences in the peripheral blood of liver cancer patient (the especially liver cancer patient of AFP negative).
EP400 gene (Homo sapiens E1A binding protein p400, the source of people E1A binding protein It p400 is) polynucleotide sequence (NCBI number NM_015409) shown in sequence table SEQ ID NO:1, MAPK1IP1L gene (Homo sapiens mitogen-activated protein kinase 1interacting protein 1like, people 1 sample of source 1 interaction albumen of mitogen original activated protein kinase) it is polynucleotide sequence shown in sequence table SEQ ID NO:2 (NCBI number NM_144578), NUFIP2 gene (Homo sapiens NUFIP2, FMR1interacting protein 2, Source of people FMR1 interaction albumen 2) it is polynucleotide sequence (NCBI number NM_020772) shown in sequence table SEQ ID NO:3, PHC3 gene (Homo sapiens polyhomeotic homolog 3, the homologous homologue 3 of source of people poly) is sequence table SEQ Polynucleotide sequence shown in ID NO:4 (NCBI number NM_024947), RPS6KB1 gene (Homo sapiens Ribosomal protein S6kinase B1, source of people Ribosomal protein B1) it is shown in sequence table SEQ ID NO:5 Polynucleotide sequence (NCBI number NM_003161), STX7 gene (Homo sapiens syntaxin 7, melt by source of people cynapse Hop protein 7) it is polynucleotide sequence (NCBI number NM_003569) shown in sequence table SEQ ID NO:6.
The present invention is built upon on the basis of mankind's full genome express spectra quantitative analysis, passes through quantitative analysis peripheral blood total serum IgE Gene expression situation, compare the gene expression difference in liver cancer patient and Normal human peripheral's blood sample, then pass through supporting vector Machine (Support Vector Machine) method filters out 6 and differential expression (gene table occurs in Peripheral Blood of Patients with Hepatocellular Carcinoma Up to up-regulation or lower) gene signal.Then, fluorescence quantitative RT-RCR, chip gene expression profile or RNA sequencing technologies can be used The relative expression quantity of 6 gene markers in quantitative detection subject's peripheral blood, and then differentiate the probability that subject suffers from liver cancer.
The second aspect of the present invention provides the production for detecting the reagent of above-mentioned hepatocarcinoma gene marker in preparation detection liver cancer Purposes in product.
The product of the detection liver cancer includes but is not limited to real-time quantitative PCR kit, RNA sequencing kit or gene core Piece.
The reagent of the above-mentioned hepatocarcinoma gene marker of detection is the primer and/or probe for detecting above-mentioned liver cancer marker.
The primer is the primer of specific amplified SEQ ID NO:1~SEQ ID NO:6 gene order.Preferably, described Primer has sequence shown in sequence table SEQ ID NO:7~SEQ ID NO:18.
The probe is the probe that can hybridize with gene order shown in SEQ ID NO:1~SEQ ID NO:6.Preferably, The probe has sequence shown in sequence table SEQ ID NO:19~SEQ ID NO:24.
The third aspect of the present invention, provides a kind of kit for detecting liver cancer, is directed to SEQ ID NO:1 comprising specificity The primer and/or probe of gene order shown in~SEQ ID NO:6.
Preferably, the sequence of the primer is shown in SEQ ID NO:7~SEQ ID NO:18；The sequence of the probe is Shown in SEQ ID NO:19~SEQ ID NO:24.
The kit also includes for reference gene GAPDH (NM_002046.5, Homo sapiens Glyceraldehyde-3-phosphate dehydrogenase, source of people glyceraldehyde 3 phosphate dehydrogenase) primer and/or spy Needle.Forward primer sequence is ACCATGAGAAGTATGACAACAGCC (sequence table SEQ ID NO:25), and reverse primer sequences are CACGATACCAAAGTTGTCATGGA (sequence table SEQ ID NO:26), probe sequence TCAGCAATGCCTCCTGCACCACC (sequence table SEQ ID NO:27).GAPDH is an enzyme in glycolysis reaction, the cell being distributed widely in various tissues. The enzyme gene is house keeper (house keeping) gene, almost all high level expression in all organizations, is that common fluorescence is fixed Measure the standardization internal reference of PCR experiment operation.
The probe sequence have fluorescent marker, the end 5' fluorescent marker be FAM, HEX, TET, TAMRA, Cy5, Cy3, VIC, One of R0X and JOE, the end 3' fluorescent marker are one of TAMRA, BHQ, MGB, DABCYL and Elipse.
Using kit of the invention, can detecte in subject's peripheral blood shown in SEQ ID NO:1~SEQ ID NO:6 The expression of characterizing gene sequence, the information for then raising or lowering according to these gene expressions differentiate that subject suffers from liver cancer Probability, to realize the examination diagnosis of liver cancer.
All kits of the present invention may include that packaging appropriate and specification are used in method disclosed herein Middle use.Kit can further include buffer and polymerase appropriate, such as heat-resisting polymerase, such as Taq polymerase.It is this Kit also includes control primer and/or probe.
Detection kit of the present invention be kit for detecting nucleic acid, including peripheral blood total RNA extraction agent and PCR reaction system reagent, the PCR reaction system includes dNTP, MgCl2, Taq archaeal dna polymerase, PCR reaction buffer, draw Object and probe.
The fourth aspect of the present invention provides a kind of liver cancer detection method, measures this group of hepatocarcinoma gene biomarker In the presence of and/or level may include measurement encode the biomarker a kind of polynucleotides (such as a kind of biomarker genes Transcript) presence and/or level.This method comprises:
(1) presence and/or level of the hepatocarcinoma gene marker in the sample of subject are measured；And
(2) presence of hepatocarcinoma gene marker and/or level are compared with a kind of compare, wherein in the sample and this It compares a kind of different presence and/or level indicates liver cancer.
The sample includes blood, blood plasma, serum, urine, blood platelet, megacaryocyte (megakaryocytes) or excretion Object.
The fifth aspect of the present invention provides a kind for the treatment of method of liver cancer, this method comprises:
(1) diagnose or detect according to the method for the present invention liver cancer；And
(2) it gives or recommends a kind of for treating the therapeutic agent of liver cancer.
The peripheral blood gene marker that the present invention uses liver cancer to screen, examination of the marker for liver cancer diagnose, have Very high sensibility and specificity, and due to being detected using the peripheral blood clinically most easily acquired, detection process is easy, Diagnosis suitable for liver cancer early stage especially AFP negative liver cancer.Improve Current Diagnostic liver cancer mainly apply alpha-fetoprotein (AFP), The screening means that ultrasound and other iconographies combine reduce to reduce the missing inspection of AFP negative liver cancer and solve experience to operator With the dependence of equipment, a kind of new diagnostic method is provided for early diagnosis liver cancer.Research and development peripheral blood of patients with primary hepatocellular carcinoma molecular diagnosis product is answered To the developing direction and social demand of liver cancer clinic diagnosis, is conducive to further push the universal of Hepatocarcinoma screening, improves liver cancer and suffer from Person's recall rate and clinical treatment success rate save social capital and corresponding medical resource.
The invention has the advantages that gene marker of the invention, the examination for liver cancer is diagnosed, and sensibility is high, specific By force, easy to detect and due to being with the peripheral blood that clinically most easily acquires for detection sample, suitable for the early diagnosis of liver cancer, And the detection to AFP negative liver cancer patient, it has a extensive future.
Present invention will be further explained below with reference to specific examples.These embodiments are merely to illustrate the present invention and do not have to In limiting the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to normal condition or presses According to condition proposed by manufacturer.Unless otherwise defined, all professional and scientific terms as used herein and this field are ripe It is identical to practice meaning known to personnel.In addition, any method similar to or equal to what is recorded and material all can be applied to In the method for the present invention.The preferred methods and materials described herein are for illustrative purposes only.
Detailed description of the invention
Fig. 1 is the fluorescence intensity logarithm in embodiment 1 after 100 chip normalizeds.
Fig. 2 is that the embodiment of the present invention 3 is random to liver cancer and normal control sample using the hepatocarcinoma gene marker filtered out Sample the accuracy predicted, sensitivity and specificity distribution map.
Specific embodiment
Term " training set " or " control collection " refer to one group of sample of the correlation for establishing between two variables.For example, Training set is one group of clinical samples of the correlation for establishing between gene expression and the situation of patient.In background of the invention Under, training set be from liver cancer patient, hepatitis, normal person one group of sample, to its can get include clinical diagnosis, tumour The pathology relevant informations such as size, Serum AFP expression.Training set is used to set up expression overview and patient disease classification (including blood Clear AFP expression) between correlation.
Term " test set " refers to one group of sample for verifying the correlation for using training set to establish.For example, test set is One group of sample from all known patient of the situation to its gene expression and patient.The collection be used to verify true using training set Whether fixed correlation will be correctly predicted the situation of patient.In the context of the present invention, test set be from liver cancer patient and One group of sample of normal person can get patient disease classification (including Serum AFP expression) to it.Test set is for measuring Gene expression in overview and test actual patient disease classification whether with by prediction phase made by measurement gene expression Match.
The screening of 1 liver cancer characteristic gene marker of embodiment
One, material and method
(1) material
Inventor has collected a large amount of normal person, liver in July, -2013 in November, 2012 commission BeiJing University ShenZhen Hospital (sample for research is to collect the same period, sampling, packing, save to the peripheral blood sample of cancer patient and hepatic benign lesions patient Condition is uniform), by the arrangement to sample data, inventor has therefrom selected 81 patient's blood plasma (hepatitis B-liver cancer (including original Diagnosis and intrahepatic cholangiocarcinoma)) and 19 blood plasma with hospital and experimental group contemporaneity random collecting normal person, it keeps away as far as possible Exempt from the detection for taking the sample of the blood plasma of liver cancer family history people to carry out mRNA.
Hepatocellular carcinoma sample, which is included in, meets following two standards: 1., pathological diagnosis standard: Space occupation in liver lesion or The biopsy of extrahepatic metastases stove or group of tumor resection knit sample, are diagnosed as HCC through Histopathology and/or cytolgical examination, this is gold Standard.2., clinical criteria: it is required that meeting (1)+(2) a two or (1)+(2) b+ (3) three in the following conditions at the same time Xiang Shi may establish that the clinical diagnosis of HCC.(1) there is cirrhosis and HBV and/or HCV infection (HBV and/or HCV antigen sun Property) evidence；(2) typical HCC Features: the same period multiple rows of CT scan and/or Dynamic constrasted enhancement MRI check display liver Dirty occupy-place strengthens (arterial hypervascularity) in the quick heterogeneity blood vessel of arterial phase, and venous phase or period of delay Quickly elution (venous or delayed phase wash out).A: if Space occupation in liver diameter 2cm, CT and MRI two There is a display Space occupation in liver that there is the feature of above-mentioned liver cancer, i.e., diagnosable HCC in imageological examination；B: if Space occupation in liver is straight Diameter is 1~2cm, then needs two imageological examinations of CT and MRI all to show that Space occupation in liver has the feature of above-mentioned liver cancer, can examine Disconnected HCC, to reinforce the specificity of diagnosis.(3) 400 μ g/L of Serum AFP continues 1 month or 200 μ g/L to continue 2 months, and can arrange Except AFP caused by other reasons is increased, including gestation, system genitale embryo source property tumour, activity hepatopathy and secondary carcinoma of liver etc..
It is passed through discussion through Hospital Ethical Committee, after patient's signature informed consent form, collects patient peripheral's blood sample.
(2) method
1. being used in combination using the total serum IgE in the PAXgeneBlood RNA Kit extraction purification peripheral blood of QIAGEN company The total serum IgE fragment integrity and yield that the identification of 2100 type microelectrophoresis analyzer of Agilent BioAnalyzer is extracted；
2. complete using Affymetrix Gene Expression Using Affymetrix 2.0 mankind of U133Plus Chip gene expression profile (Affymetrix, Inc.Santa Clara, Calif.) makes a definite diagnosis patient's (packet to 54 primarys carcinoma of liver Containing 25 AFP negative liver cancer and 29 AFP masculine liver cancers), that 9 intrahepatic cholangiocarcinomas (AFP negative) make a definite diagnosis patient, 18 hepatitis is true Diagnose a disease people's (comprising 12 AFP negative hepatitis and 6 AFP positive hepatitis), 19 normal persons peripheral blood mRNA carry out gene table Up to the detection of spectrum；
3. chip data pre-processes: carrying out the background correction of intensity of probe using MAS5 method first, carry out 100 chips Normalized.Fig. 1 is the fluorescence intensity logarithm after 100 chip normalizeds.
4. rejecting probe collection (Probeset) signal that expression signal is excessively high and too low in total serum IgE, select in training set institute There is the probe collection signal for having appropriate expression (between fluorescence signal value 100-10000) in 100 samples to carry out subsequent analysis；
5. selecting liver cancer and hepatitis, normal person's difference expression gene using the T method of inspection, screening conditions are that multiple changes FC >1.2 times, the probe collection signal of significance P<0.05 obtains 248 groups of satisfactory probe collection；
6. concentrating screening liver cancer from above-mentioned 248 probes with support vector machine method (Support Vector Machine) Characterizing gene, according to SFFS (Sequential Forward Floating Selection) screening strategy, two classification number of building Model is learned, random sampling is carried out to training set sample using LOOCV (leave-one-out cross validation) method And the sample cluster generated to sampling carries out classification prediction, picks out have highest prediction accuracy (accuracy) to liver cancer 6 A gene establishes liver cancer and the examination diagnostic model of normal person as liver cancer candidate feature gene.
Two, result:
Analysis comparison is carried out by the gene expression profile to different type sample, using correlation analysis, most can be filtered out Distinguish the characterizing gene express spectra of AFP negative liver cancer and check sample.One group of liver cancer characteristic gene marker is obtained, is AFP yin Property liver cancer characteristic expressing gene catalogue (gene panel), by EP400 gene, MAPK1IP1L gene, NUFIP2 gene, PHC3 Gene, RPS6KB1 gene and STX7 gene composition.
The 6 genes composition of the AFP negative liver cancer characteristic marker that the present invention obtains as shown in Table 1.
The sequence of 1 liver cancer characteristic gene marker of table
Serial number Liver cancer characteristic Gene Name Sequence table numbering
1 EP400 gene SEQ ID NO:1
2 MAPK1IP1L gene SEQ ID NO:2
3 NUFIP2 gene SEQ ID NO:3
4 PHC3 gene SEQ ID NO:4
5 RPS6KB1 gene SEQ ID NO:5
6 STX7 gene SEQ ID NO:6
The fluorescence quantitative RT-PCR kit of the detection liver cancer of embodiment 2
One, kit forms:
1. detecting the specific primer of 6 liver cancer characteristic gene markers (shown in table 1):
Reagent 1:EP400 gene forward primer: 5'GGATCTTGTCAGTGACGTTGT 3'(SEQ ID NO:7)
Reagent 2:EP400 gene reverse primer: 5'GTAGCGATTCCGGCACTGT 3'(SEQ ID NO:8)
Reagent 3:MAPK1IP1L gene forward primer: 5'ACCTGAGGCAGCTCTTTTGC 3'(SEQ ID NO:9)
Reagent 4:MAPK1IP1L gene reverse primer: 5'GGATGTGTGTGCTCCTTCTAAAGAA3'(SEQ ID NO: 10)
Reagent 5:NUFIP2 gene forward primer: 5'TTTCTCTCAAAGGACTACGAGAT 3'(SEQ ID NO:11)
Reagent 6:NUFIP2 gene reverse primer: 5'AGCAGCCCTCAGGTCAAA 3'(SEQ ID NO:12)
Reagent 7:PHC3 gene forward primer: 5'CAGTTCTACCAGCGGCAGTA 3'(SEQ ID NO:13)
Reagent 8:PHC3 gene reverse primer: 5'GGTAGCGGGTGTGAAAATCA 3'(SEQ ID NO:14)
Reagent 9:RPS6KB1 gene forward primer: 5'CCGAACTCTGGGCCATACA 3'(SEQ ID NO:15)
Reagent 10:RPS6KB1 gene reverse primer: 5'TTGCAGGATGCTCACACATCTC 3'(SEQ ID NO:16)
Reagent 11:STX7 gene forward primer: 5'CTCTTTTGTGAGTGAGTGATTGGAA 3'(SEQ ID NO:17)
Reagent 12:STX7 gene reverse primer: 5'CCCTGCATTGTCCATTCTGTT 3'(SEQ ID NO:18)
2. detecting the quantitative fluorescent PCR probe sequence of 6 liver cancer characteristic gene markers (shown in table 1), 6 target gene Probe label be the end 5' be FAM mark, the end 3' be MGB mark:
Reagent 13:EP400 gene probe sequence: 5'AACTCCTGTAGCCGAATCTACCGCTC 3'(SEQ ID NO: 19)
Reagent 14:MAPK1IP1L gene probe sequence: 5'TAGCCACCCCCACCCCACTTGC 3'(SEQ ID NO: 20)
Reagent 15:NUFIP2 gene probe sequence: 5'TCAAAATCCTCTGGCCTCTCCTACGAAC3'(SEQ ID NO: 21)
Reagent 16:PHC3 gene probe sequence: 5'CCCCTACCCTAACGGCAAGCCA3'(SEQ ID NO:22)
Reagent 17:RPS6KB1 gene probe sequence: 5'CAAACGGCCAGAGCACCTGCGT3'(SEQ ID NO:23)
Reagent 18:STX7 gene probe sequence: 5'ACTCCTGTTGCCAGAATCAGACTGCCCTA 3'(SEQ ID NO: 24)
Crt gene 3. (SEQ ID NO:28) detection reagent
Reagent 19:GAPDH gene forward primer: ACCATGAGAAGTATGACAACAGCC (SEQ ID NO:25)
Reagent 20:GAPDH gene reverse primer: CACGATACCAAAGTTGTCATGGA (SEQ ID NO:26)
Reagent 21:GAPDH gene probe sequence: TCAGCAATGCCTCCTGCACCACC (SEQ ID NO:27) GAPDH's Probe label is the end 5' for VIC label, and the end 3' is MGB label.
Two, application methods
The above reagent is the core reagent for forming liver cancer detection kit of the present invention, and each reagent is independently packed.Herein On the basis of, other reagents can also be increased, such as total RNA extracts reagent, PCR reaction solution, Taq enzyme system, packing material etc., For this field conventional reagent.
Each primer and probe is 10 μM using concentration, and the application method of kit is referring to embodiment 3.
Embodiment 3 carries out examination diagnosis to normal person using the liver cancer characteristic gene marker filtered out
One, method and step
1. the collection of sample peripheral blood sample to be detected: being collected using the BD PAXgeneRNA heparin tube of QIAGEN company Patient's peripheral blood sample.Sample source is the same as embodiment 1.
2. the extraction purification of total serum IgE in sample peripheral blood sample to be detected: using the PAXgeneBlood of QIAGEN company Total serum IgE in RNA Kit extraction purification peripheral blood, and reflected with Agilent BioAnalyzer2100 type microelectrophoresis analyzer Surely the total serum IgE fragment integrity and yield extracted；
3. reverse transcription reaction: using the High-Capacity cDNA Reverse of Life Techonolgy company Transcription kit reverse transcription reagent box is template using total serum IgE, using Random Primes as reverse transcriptase primer, into Row reverse transcription reaction synthesizes cDNA；
Table 2: reaction system
Reactive component Volume (μ l)
10×RT Buffer 2
25×dNTP mix 0.8
10×RT Random Primers 2
MultiScribeTM Reverse Transcriptase 1
RNase Inhibitor 1
mRNA Volume comprising 1 μ g mRNA
Nuclease-free H2O It is supplemented to 20 μ l of total volume
Table 3: reaction condition
Setting Step 1 Step 2 Step 3 Step 4
Temperature 25℃ 37℃ 85℃ 4℃
Time 10 minutes 120 minutes 5 minutes ∞
4. fluorescence quantitative RT-RCR detects:
According to 6 liver cancer characteristic gene EP400 genes, MAPK1IP1L gene, NUFIP2 gene, PHC3 gene, RPS6KB1 gene and STX7 gene (SEQ ID NO:1~SEQ ID NO:6) and reference gene GAPDH (SEQ ID NO:28) Correlated series, with specific primer SEQ ID NO:7~SEQ ID NO:18, the SEQ ID NO:25, SEQ ID of embodiment 2 NO:26 is primer, using specific probe SEQ ID NO:19~SEQ ID NO:24, SEQ ID NO:27 as probe, using anti- The cDNA that transcription obtains carries out real-time fluorescence quantitative RT-PCR reaction, obtains 6 gene markers outside as amplification template MRNA relative amount in all blood samples.Table 4 is the composition of PCR reaction premixed liquid (Master Mix), wherein forward primer, anti- Refer to EP400 gene, MAPK1IP1L gene, NUFIP2 gene, PHC3 gene, RPS6KB1 gene and STX7 to primer and probe Forward primer, reverse primer and the probe of the independent gene of each of gene.System when fluorescence quantitative PCR detection is single mesh Gene and internal reference GAPDH primed probe mixing, form a double PCR system, each target gene detection is primary.
Table 4: the reaction system by taking Taqman sonde method as an example
Composition ×1(μl)
PCR reaction premixed liquid (2 ×) 10
Forward primer (10 μM) 1.8
Reverse primer (10 μM) 1.8
Probe (10 μM) 0.5
GAPDH forward primer (10 μM) 1.8
GAPDH reverse primer (10 μM) 1.8
GAPDH probe (10 μM) 0.5
Blood sample cDNA (20ng/ μ l) 1
H2O 0.8
Table 5: reaction condition
5. the diagnosis of sample donor result to be detected: according to 6 gene markers in fluorescence quantitative RT-RCR in peripheral blood MRNA relative amount in sample differentiates to whether subject suffers from liver cancer.
Two, interpretations of result
Detection data file is saved after reaction.According to the Start value, End value of image adjustment Baseline after analysis And (user can voluntarily adjust Threshold value according to the actual situation, and start value can be in 5- in I-10, stop value 20, Threshold value can be selected in 5K-50K range), reach the canonical plotting under " Standard curve " window Most preferably, i.e. R2 value (correlation numerical value) 0.97.It finally arrives register instrument under " Report " window and automatically analyzes and calculate The copy number (E2A-PBX1-Qty) of the non-key sample of E2A-PBX1, which is exported.Again it is arranged the 4 of TBP by corresponding sequence A positive qualitative reference product, step is the same, and the copy number (TBP-Qty) of the non-key sample of TBP is exported.
Three, result judgements
If the not S-type curve of growth curve or Ct value are blank, sentence gene expression amount detected and be less than detection limit Degree.
If value < 37 Ct of the S-type curve of growth curve and sample calculate separately each target gene in sample first The expression quantity (Δ Ct) of opposite internal reference: Δ Ct=Ct(target gene)-Ct(reference gene), then the logic for using following equation to calculate the sample Regressand value: Logit=4.2715* Δ Ct(MAPK1IP1L)+1.1987*ΔCt(RPS6KB1)-1.2091*ΔCt(NUFIP2)+0.2748* ΔCt(PHC3)+1.9441*ΔCt(STX7)+0.4728*ΔCt(EP400)+18.1326。
When the Logit value of sample to be tested > 2.30873, determine the sample properties for liver cancer；As the Logit of sample to be tested When value < -1.67951, determine that the sample properties are normal；When value >=-1.67951 Logit and≤2.30873 of sample to be tested When, then the sample properties can not be determined using this method.
53 liver cancer, which are had detected, with fluorescence quantitative RT-RCR makes a definite diagnosis patient (comprising 24 AFP negative liver cancer and 29 AFP sun Property liver cancer), 6 hepatocarcinoma gene marker relative expression quantities in 19 normal human peripheral bloods, utilize liver cancer to screen diagnostic model pair Above-mentioned example sample (including training set (Training set) and test set sample (Test set)) carries out classification prediction, will predict As a result compared with the clinical diagnosis testing result of liver cancer, obtain 6 hepatocarcinoma gene markers of the invention to liver cancer (comprising AFP yin Property liver cancer) sensitivity (Sensitivity), specific (Specificity) and the accuracy (Accuracy) of screening diagnosis, have Body testing result is shown in Fig. 2 and table 6.
Table 6: the sensitivity of detection, specificity, accuracy are screened to liver cancer, normal person
Embodiments of the present invention above described embodiment only expresses, the description thereof is more specific and detailed, but can not Therefore limitations on the scope of the patent of the present invention are interpreted as.It should be pointed out that for those of ordinary skill in the art, Without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection model of the invention It encloses.
Sequence table
<110>Shanghai Biochip Co., Ltd
<120>one groups of gene markers and its application for liver cancer detection
<130>
<160> 28
<170> PatentIn version 3.5
<210> 1
<211> 12317
<212> DNA
<213>Genus Homo, ethnic group, Homo sapiens (human)
<400> 1
gtagcagccg cgccgccgct tcctcccgcc ggggccccgg atgcactgag cggctgcggc 60
gcggcttcca tcctcccgcc ctcctgacgc ggccggagcg cagccctgag gcccagggag 120
aacgacacat tggatacaga agggaggtga tcatgcacca tggcactggc ccccagaacg 180
tccagcatca gctgcagagg tccagggcct gccctggcag cgagggtgag gagcagccgg 240
cccaccccaa cccacccccg tcccccgcag ctcccttcgc tccctcagca agcccgtcgg 300
caccccagtc tcccagttat caaatacagc agctgatgaa taggagccct gcaaccgggc 360
agaacgtgaa catcaccctg cagagcgtgg gccctgtcgt cgggggaaac cagcagatca 420
cactggcccc actgccgctc cccagcccca cctctccagg cttccagttc agcgctcagc 480
ctcggcggtt tgagcatggg tctccatcat acattcaggt cacgtccccc ttgtcccagc 540
aggtccagac ccagagtccc acgcagccca gtccggggcc ggggcaggcc ttgcagaatg 600
tgcgtgcagg tgcccctggc cctgggctgg gcctctgcag cagcagccct acagggggct 660
tcgtggatgc cagcgtgctg gtgaggcaga tcagcttgag cccctccagt ggtggacact 720
ttgtgtttca ggatgggtca gggctcaccc agatcgccca gggagcccag gttcagctcc 780
agcacccggg tacgcccatc acagtccgag agcggagacc ctcccagccc cacacacagt 840
cagggggcac catccaccac ctgggacccc agagccctgc agccgcgggt ggggccggcc 900
tgcagcccct ggccagccca agccacatca ccacggctaa cttgccaccg cagatcagca 960
gcatcatcca gggccagctg gttcagcagc agcaggtgct gcaggggccg ccgctgcccc 1020
ggcccctggg cttcgagagg acacccggcg tgctgctccc cggggctggg ggcgcagcgg 1080
ggtttgggat gacgtcccca cccccgccca ccagcccttc caggactgcc gtgcccccag 1140
gcctttccag cctcccactc acgtctgtgg ggaacacggg aatgaagaag gttcccaaga 1200
agttagagga gattccccca gcctctccgg agatggcaca gatgaggaag cagtgcctgg 1260
actatcatta ccaggagatg caggctctga aggaggtctt caaggagtat ttgattgaac 1320
tgtttttctt gcaacacttt caagggaaca tgatggattt cttagctttc aagaagaaac 1380
attatgcccc attacaagca tatcttaggc agaatgattt ggacattgaa gaagaggagg 1440
aggaggagga agaggaggaa gaaaaatctg aggttatcaa tgacgagcag caagccctcg 1500
cagggagcct ggtagcaggg gccggaagca cagtagagac ggacctgttt aagaggcagc 1560
aggcgatgcc ctccacaggt atggcagagc agtctaagag gcctcgcctt gaagtgggtc 1620
accaaggggt agttttccag cacccagggg cggacgcagg cgttcctctc cagcaactaa 1680
tgccgaccgc acaaggagga atgcccccca cgccgcaggc cgcgcagctc gctggacaga 1740
ggcagagtca gcagcagtat gacccctcca cggggcctcc cgtgcagaac gctgccagct 1800
tgcacacccc actgccgcag ctgcccggga ggctgccccc agccggtgtt cccactgcag 1860
ccctctcctc tgcgctgcag tttgcacagc agccgcaagt ggtagaggcc cagacacagc 1920
tccaaatccc ggtgaagact cagcagccca atgttcccat ccctgcaccg cccagcagcc 1980
aactccccat ccctccctcg cagcctgcac agctggccct ccacgttccc acacctggaa 2040
aggtgcaggt gcaggcctct cagctttcct ccctgccaca gatggtagca tcgacaaggc 2100
tccctgtgga ccctgccccg ccctgcccac ggcctctgcc cacctcttct acctcgtccc 2160
tcgcgcctgt gagtggctcc ggcccaggac cctcccctgc tcgatcctct ccagtaaata 2220
gaccttcctc agccaccaat aaggcactat ctccagtcac ttcccggacc ccaggggtgg 2280
tggcatctgc ccccaccaaa ccacagagtc ctgctcagaa tgccacctcg tcccaagaca 2340
gttctcagga tacgctgaca gaacaaataa ctctggagaa ccaggtgcat cagcgcattg 2400
cggagctgag gaaagcaggt ctgtggtccc agaggcgtct gccaaagctg caggaggccc 2460
cacgccccaa gtcccactgg gactatctgc tggaggagat gcagtggatg gccacagact 2520
ttgcccagga gaggaggtgg aaggtggctg ctgcgaagaa gctcgttaga actgtggtgc 2580
gccatcacga ggagaagcag ctccgtgaag aaagggggaa gaaggaagag cagagcagac 2640
tgaggcggat agccgcctcc acggcccggg agatagagtg cttttggtcg aatattgaac 2700
aggttgtgga aataaaacta cgagtagaat tagaagaaaa aaggaagaag gccttaaatt 2760
tacagaaagt ttccaggaga gggaaagaat tgagacctaa aggatttgac gcattacagg 2820
aaagttctct ggattcagga atgtctggaa gaaaaagaaa agctagcata tctttgactg 2880
atgacgaagt ggacgatgaa gaggaaacaa ttgaagagga ggaagcaaat gaaggcgttg 2940
tggaccacca aacagaactt tctaatttag ccaaggaagc tgagctgccc ctcctggacc 3000
tgatgaagct gtacgaaggc gccttcctgc cgagttctca gtggccccgg ccgaagcctg 3060
atggggagga cacaagcgga gaggaagatg cagatgactg tccaggcgac agggagagtc 3120
gcaaggactt ggttctcatc gactcgcttt tcatcatgga tcagttcaaa gctgccgaga 3180
ggatgaatat cgggaagcca aacgccaagg acattgcgga cgtcactgcg gtggctgaag 3240
ccatcctgcc gaagggcagt gctcgggtca caacctcggt caagtttaat gctccatctt 3300
tgttgtatgg ggctctcaga gattatcaga agattggcct ggactggctg gccaaacttt 3360
acaggaagaa tctcaatggc atattggcag atgaagctgg gctgggtaaa acagtgcaga 3420
tcattgcttt ttttgcccac ctagcttgta acgaaggtaa ttggggcccc catcttgttg 3480
ttgtgagaag ttgtaacata ctcaagtggg agcttgaatt gaaacgttgg tgtcccggac 3540
tcaaaatcct ctcatatatt ggcagccaca gagaactcaa agcaaagaga caggagtggg 3600
ccgaacccaa cagcttccac gtctgcatca cgtcctacac tcagttcttc cggggcctca 3660
ccgccttcac acgagtgcgc tggaagtgcc tggtcattga tgagatgcag cgcgtgaagg 3720
gcatgaccga gaggcactgg gaagcggttt tcaccctgca gagccaacaa cgtctgcttc 3780
tgatcgactc gccgctgcac aataccttcc tggagctctg gaccatggtg cacttcctgg 3840
tcccagggat ctccaggccc tacctgagct cccctctgag ggcccccagt gaagagagcc 3900
aggattacta ccataaagtg gtcataaggt tacacagggt gacacagcca tttattttga 3960
ggagaactaa gagagatgtg gaaaagcaac taacaaagaa atatgagcat gttttgaagt 4020
gtcgcctttc taaccgacaa aaagccttat acgaggacgt tatcctgcaa cctggcactc 4080
aggaggcctt gaagagcggg cactttgtca acgtcctgag catccttgtg cggctgcagc 4140
gcatctgcaa ccaccctggg ctcgtcgagc cccggcaccc aggctcttcc tacgtggcgg 4200
ggccactgga gtatccgtcc gcatctctaa tcctgaaggc actggagaga gatttctgga 4260
aggaagcaga tctttctatg tttgatctca tcggcttaga aaataaaatc actcgtcacg 4320
aggcagagtt gctgtctaag aaaaagatac cgcggaaact catggaggaa atctccactt 4380
cagcagcccc agcagcccga ccagcagcag caaagctgaa ggccagcagg ttgtttcagc 4440
ctgtgcagta tggccagaag cccgagggtc gcaccgtggc tttccccagc actcacccgc 4500
cccggacggc agcccccacc acggcctctg ctgctccaca gggcccgctt cgaggacggc 4560
cgcccatcgc cacgttctct gccaatccgg aggcaaaagc agcagcagcc ccgtttcaga 4620
cctctcaggc ttccgccagt gctccacgac accagcccgc ctcggcctcc agcacagccg 4680
ctagcccggc ccatcctgcg aaactgcggg cccagaccac agcacaggcc tccaccccag 4740
gccagccccc gccccagccc caggccccct cgcacgcggc cgggcagagc gcgctgcctc 4800
agaggctggt gctcccctcg caggcccagg cccgcttgcc cagtggagag gtagtgaaaa 4860
tagctcagct ggcatccatc acaggaccac agagccgcgt ggctcagcca gagacgccgg 4920
tgacactgca gttccagggc agcaagttca ccctgtcaca cagccagctc cggcagctca 4980
cagcgggcca gccgctgcag ctgcaaggca gcgtcctcca gatcgtgtcc gcccccgggc 5040
agccctacct tcgagcccct ggccctgtgg tgatgcagac cgtgtctcag gcgggcgctg 5100
tgcacggcgc cctgggaagc aagcccccgg ccggcggtcc cagccctgca cccttgaccc 5160
cacaagttgg cgttccgggc cgcgtggcgg tgaatgcctt ggctgtagga gaacccggaa 5220
cggcctccaa accagcttct cccattggag ggccgaccca ggaggaaaag accagactct 5280
tgaaagagcg cctggatcag atttatttag tcaacgagcg gcgctgttct caagctccag 5340
tctatggcag agacttgcta aggatttgtg ccctgcctag ccatggaagg gtacagtggc 5400
gtgggtccct ggatggccgt cgtgggaagg aggccgggcc agcgcacagt tacacttcat 5460
cctcagaaag tccaagtgag ctgatgttga cgctttgtcg gtgtggagag tctctgcagg 5520
atgttattga cagggtggcc tttgtgattc ctccggtggt ggcagcaccc ccgtccctac 5580
gggtgccgcg gccgccaccc ctgtacagcc acagaatgag gatcttgagg cagggcctga 5640
gagagcacgc tgcgccgtac ttccagcagc tgcggcagac cacggctcca cgcctgctgc 5700
agttccctga gctgaggctg gtgcagttcg actcagggaa gttggaagct ttagctatct 5760
tgcttcagaa attgaaatct gaaggacgtc gggtgctgat tttatcacag atgattctta 5820
tgttggacat tttagagatg ttcttgaact tccattacct cacctatgta agaatcgatg 5880
aaaatgccag cagtgagcaa cggcaggaac tgatgaggag tttcaacaga gacaggcgga 5940
ttttttgtgc cattctctcc actcacagcc gtaccacagg tataaacctt gtagaggcgg 6000
acaccgtcgt gttttatgac aatgacctga atccagtgat ggatgccaaa gctcaggagt 6060
ggtgcgatag gatcgggaga tgcaaagaca tccacatata caggcttgtg agtggcaatt 6120
ccattgaaga gaaattgttg aaaaatggaa ctaaagatct gatccgagaa gtggctgctc 6180
agggaaatga ctactccatg gctttcttaa ctcagcgaac catccaggag ctgtttgaag 6240
tttattctcc catggatgat gctggcttcc cggtcaaagc tgaggagttt gtggtgcttt 6300
ctcaggaacc ttctgtcacg gaaaccattg cacccaaaat tgcaagacct ttcatagagg 6360
ccctcaagag tattgagtat ctggaggagg atgcccagaa gtccgcacag gagggggtgc 6420
tgggaccaca cactgatgct ctgtcatcag actctgagaa catgccgtgt gatgaagaac 6480
catcccaatt agaggagcta gctgacttca tggagcagct tacaccaatt gaaaaatatg 6540
ctttaaatta cctggaatta ttccatactt ctattgagca agaaaaggag agaaacagtg 6600
aggacgcagt gatgactgca gtgagggcat gggagttctg gaacctgaag accctgcagg 6660
agagggaggc ccggctgcgg ctggagcagg aggaggcgga gctcctgacc tacacgcgag 6720
aggatgccta cagcatggag tatgtctacg aagatgtcga tgggcagaca gaagtcatgc 6780
cgctctggac cccacccacc ccgccgcagg acgacagcga catctacctc gactcggtca 6840
tgtgtctcat gtatgaagcc actcccatcc cagaggctaa gctgccccct gtgtacgtga 6900
ggaaggagcg gaagcgacac aaaacagacc cctcagctgc aggcaggaag aagaagcagc 6960
gtcacgggga ggcggtcgtc cctcctcggt ccctgtttga ccgcgcaaca ccaggacttc 7020
tgaaaattcg cagagagggc aaggagcaga agaagaatat tctgctgaag cagcaggtgc 7080
cattcgccaa gcccctgcca acttttgcca aacccacagc tgagcctggt caagacaacc 7140
ccgagtggct catcagtgag gactgggcgc tgctgcaggc tgtaaagcag ttactggagc 7200
tgcctttgaa cctcacaatc gtgtcacctg ctcacacacc taattgggat cttgtcagtg 7260
acgttgttaa ctcctgtagc cgaatctacc gctcttccaa acagtgccgg aatcgctacg 7320
agaatgtcat cattccacga gaggagggga agagtaaaaa caaccgtcct ctccgtacga 7380
gccagatcta tgcccaggat gagaatgcca cacacaccca gctgtacacg agccactttg 7440
acttaatgaa aatgactgct ggcaagagga gtcccccaat caaacctctg cttggcatga 7500
atccctttca gaagaacccc aagcacgcgt ctgtgttggc agaaagtgga atcaactatg 7560
acaagccgct gcctcccatc caggtggcat ctctccgtgc agagcgaatc gcaaaagaga 7620
aaaaggctct ggctgatcag cagaaggcac agcagccggc cgtggcccag ccacccccgc 7680
cccagccgca gcccccacca cccccgcagc agccaccgcc accgctgcca caaccacagg 7740
cagcgggcag ccagccgcca gcagggccac cagctgtcca gccccaaccc cagccacagc 7800
cccagaccca gccacagcct gtgcaggccc cagcgaaggc gcagcccgca atcacgacgg 7860
ggggcagtgc agccgtactg gcaggaacca ttaaaacatc agttactggg acgagcatgc 7920
ccactggtgc cgtgagtgga aatgtgatcg tgaacaccat cgcaggggtc ccagctgcca 7980
ccttccagtc catcaacaag cgcctggcgt cgccagtggc tcctggggcc ttgactacgc 8040
cgggaggctc tgctcccgcc caggtggtgc acacccagcc cccgccacgg gcagtcggct 8100
ccccagccac ggcgacccct gacctggtgt ccatggcaac gactcagggt gttcgagcgg 8160
tcacttctgt gacagcctcg gccgtggtca ctaccaacct gaccccagtg cagaccccgg 8220
cacggtcttt ggtgccccaa gtgtcccaag ccacaggagt tcagctccct ggaaaaacca 8280
tcacacctgc acatttccag cttctcaggc agcagcagca gcagcagcaa caacagcagc 8340
agcagcagca gcagcagcag cagcagcagc agcagcaaca gcagcagcag caacagacga 8400
cgacgacctc tcaggtgcaa gttccacaga tccagggcca ggcccagtcc ccagcacaga 8460
tcaaagctgt gggcaagctg acgccggaac acctcatcaa aatgcagaag cagaaactgc 8520
agatgccccc gcagccccca ccgccacagg cccagtctgc gcccccgcag ccaacagccc 8580
aagtgcaagt gcagacctcg cagccgccgc agcagcagag cccccagctc acgacggtca 8640
cggccccaag gcctggtgcc ctgctgacgg gcaccaccgt ggccaacctc caggtggccc 8700
ggctcacccg ggttcccact tctcagctgc aggcgcaagg gcagatgcag acccaggcac 8760
cccagccagc ccaggtggcc ttggcgaagc ctccggtggt gtccgtcccg gcagctgtgg 8820
tctcctcacc gggagtcacc accctgccca tgaacgtcgc ggggatcagc gtggcgatcg 8880
gtcagccaca gaaggcagca ggacagaccg tggtggccca gcccgtgcac atgcagcagc 8940
tgctgaagct gaagcagcag gccgtccagc agcagaaggc catccagccc caggctgcac 9000
agggcccggc agccgtccag cagaagatca ccgcacagca gatcaccacc cctggcgcgc 9060
agcagaaggt tgcctacgcc gcgcagccgg cccttaagac ccagtttctt accacaccca 9120
tctcccaggc ccagaaactg gccggggccc agcaagtgca gacccagatc caggttgcaa 9180
aacttcctca agttgttcaa cagcaaacac ccgtggccag catccagcaa gttgcctctg 9240
cttcccagca ggcttctcca cagactgtgg cgctcacgca ggcgacggcg gccgggcagc 9300
aggtgcagat gatccctgca gtgaccgcga ctgcccaggt ggttcagcag aaactcattc 9360
agcagcaggt ggtgaccacg gcgtcggccc cgctccagac tccaggcgct cccaacccag 9420
cccaggtgcc cgccagctcc gacagcccaa gccagcagcc caagttacag atgagggtcc 9480
ctgctgtcag gctaaagaca cctactaagc ctccgtgcca gtagtcaggg cagcagggct 9540
gcctctcatc taaagcaaaa ctaccttcct cacagaaaac gctttattag tgaaccttgg 9600
gaccatgtca cgcaagagat tcagcactgg gaaagatata attgaaacaa aatagtgtaa 9660
tcattttatt aaaatgcatc ccacactgca ggacaaatgg tccttatgga gtgccgcgtt 9720
ctctgtacta cgtggctcat ggaaaaagtg acaacatggc ttcctctaaa tcatttcacc 9780
tttcagtccc cacccgcacc cgtcccctag agccatagta ctgtgttctg aaagccattt 9840
agaatttctt tgtgagcatg tagtgctttg cacgccacag aagccgtctg ccgtgtgtga 9900
ggagcataca atggactttc taaagataag gcgtgggctt ccacagtgtc tgccagagtt 9960
tagttcttta taccttactg aaaaatgcct cgtggtcttc gcagagggga aggcctgtct 10020
aaagtcaatc atccgagatg ggttttccat tccaaagaaa ggcaatatgg ttccttcctt 10080
ccctcctaaa atatgactta acttttaaga gaaatgttct gacacccacc taaacacaca 10140
aggcacgttc ctggcctgtg ttcaagggaa atgatcagtc attgcattgt tattccaaag 10200
agcagccaac agtggcctcc cccaggccct accctgcaat gggattcgct ttcatttaat 10260
ggaaacttct gggactgatg cccaactcag tgcactcaag acgcatctcc agttttcggg 10320
ggaagctggt atttgacata gtgtgttaaa cagctcctga gaacctttgg gacactctgc 10380
catggctggc gtgaggccca gaggaccacg cagaggcaat ggtagtacag atgtcacagc 10440
tgagggtacg atgaggcctg ggctcagtga gccaggacga atgtgacaga caccccttgc 10500
tgccacagtc agccctttga cgaaggtggg ctggtgattc tggaagtatt ggctatagcg 10560
gtgggcccag tcaactcttc cttgtggact tacgacagca gattttctct aggataagct 10620
tgtgtggttc tgccagtgaa gcagagaacc acctgtgctg ttgtggaagg cgtgccgttg 10680
agggggaaaa cgaagcccag tatttgctac tgtttttcct ttttttacta tgacaggaaa 10740
ataaatgcaa ttttagtgga attgattgac agtgtctcct tactttgaag ttttcaccaa 10800
agcaaaaagg tccatatcca atagtatcct ttgtgctgtg gcttgatttt ggcctatttt 10860
acattatttg gtccaggaaa ttaggttata ttaggttttt tgtatactaa aaatcagtta 10920
tggcacaata aagattttct gtttttaaat tgtatttcat ctgcttcctc cccattctct 10980
cactttaagt gacattgagg aaggtattct gtcccacagg tttctgtgga cagcgataca 11040
gcaggagtca gtgaaatcaa ctggggagct cacttgagct cttgataaga aatgtggaga 11100
aaagtaaaaa ccaagctttg aagaaacaga agaaattaat cttttagtta gttgaacata 11160
ccaaagcaga ggactggaat ctgtttgttc taaccaaccc gttctccctg gcttggcacg 11220
tgccgtgaga gcgcagcttg ccggagggag ggccgctgtg tgcgcctcac atctggctcc 11280
cagtggaaac ttttactcct cctcatccgc agatgtgata gaactgaagt atctaggaat 11340
tctgcctttg tcatttgttt taatttgtgt gccctgttca ttttttttgt ctttcccaaa 11400
tcttggtagt ctccttatag ttgaagataa aatgttgagt gcacttattt tagaatatcc 11460
tagacataac tgtctaagta aaagcgctct attaatctaa aacactacaa gagaatttaa 11520
caccatctct caaatgcttt tttggagagc ttaatgggat tctgaatatt tgcaatgtgg 11580
agtttccgcc ccgatctcac gtcagtgagg gtctcctgtc tctcaagtgt gtttcctttg 11640
gctgttccct aatacaaaac acggacatat ttttactcgt agcactcaat ttagtaactt 11700
ctagatgcta ccgttgacct gagttaaatt catttagtcg tgtacgtaaa aactctcctt 11760
ttagtgtgtt attttcttgg ccttcccttt taaaggttaa agtttctaac ctaagaatta 11820
agtacgcgtt caggaagctg ttgtctaggc cttccccttg tgaatctggg ttcattccaa 11880
tacggcaagt aagagttgga aactttgaga acacagacta taaaggcagc agcccgaaca 11940
ctgtcagact ctaattggcg accctgggaa acagttgccc tgctattctt taaagaaaga 12000
cgtttattct gatgataaaa acagttagcc agactgtttt taaagcacct ggcgggaagc 12060
agaaggttgg atccaagccc ttgttcagat ttggtgcctg ataagacagg ggtttctctt 12120
tttgtgacct ttattattat tattttgtta actgttgtaa ccagttagct gttgtgtttt 12180
aagatagaaa ggaacaagac taaaattgta aatactttgt aaacatcagc atttgtactt 12240
gaatagtagg attttaaagg gcattgatag cataccaaac aaaaggcaaa ataaagtgac 12300
ctttttatat atttttt 12317
<210> 2
<211> 6469
<212> DNA
<213>Genus Homo, ethnic group, Homo sapiens (human)
<400> 2
ggcgcttcct gttccggcgc caggaggagc cgcgcgctgc tggtgctgtt gccgccgctg 60
ctctagctgc cgtcagtcag gctgcgcccg cgtcttcagg gcccagtccc tcggacccat 120
cgccgcttct agaccctact gcggtctcgg atattgccgg gaaaatgtct gatgaatttt 180
cgttggcaga tgcactacct gaacactccc ctgccaaaac ctctgctgtg agcaatacaa 240
aacctggcca acctcctcaa ggctggccag gctccaaccc ttggaataat ccgagtgctc 300
catcttcagt gccatctgga ctcccaccaa gtgcaacacc ctccactgtg ccttttggac 360
cagcaccaac aggaatgtat ccctccgtgc ctcccaccgg accacctcca ggacccccag 420
caccctttcc tccttccgga ccatcatgtc ccccacctgg tggtccttat ccagccccaa 480
ctgtgccggg ccctggcccc acagggccat atcctacacc aaatatgccc tttccagagc 540
tacccagacc atatggtgca cccacagatc cagctgcagc tggtccttta ggtccatggg 600
gatccatgtc ttctggacct tgggcgccag gaatgggagg gcagtatcct acccctaata 660
tgccatatcc atctccaggc ccatatcccg ctcctcctcc tccccaagcc cctggggcag 720
caccacctgt tccatggggc accgttccac caggagcctg gggaccacca gcaccatatc 780
ctgcccctac aggatcgtat cccacaccag gactctatcc tactcccagt aatcctttcc 840
aagtgccttc aggaccttct ggtgctccac caatgcctgg tggcccccat tcttaccatt 900
aagttaacaa tggacgaaga gatgacgctt tgctttttga agtacatgta tatgcacatg 960
aatgcatata taaaaattgc tggtttcact attagagggc attcatgaaa gaacaactct 1020
tgcacctctc agagaagata actgcctctt gtacttggat gcgtagtaca tcatatgtat 1080
acaatcagat aaaagcatag aagtaaatca ttcggatgtg atttttattt ggttttcatg 1140
gaaagttaaa gtgataaagt atattgaata gttctttgac agaatttgtt taaactatga 1200
aactacacac ttaaaaatct aagatgtgga ttattgttag aatctgcaac ttcattggca 1260
aattatttca agtatttttc tataatcact ttccccttct aaataaataa acttcgagaa 1320
taacccatca taatccaaac aaatgatgcc tcaacatttt gagctgctct gtcggacaaa 1380
taaacctggt cctcttgagg ttatattttg gatatacatt tttaaactgt cagtaattat 1440
tgtcagatgt ggagttcaat agccagccag tgttcatttt tatccttgag cttttagtaa 1500
aaacttcctg gttttatttt tagtcattgg gtcatacagc actaaagtct gctatttatg 1560
gaaactaact tttttgtttt taatccaggc caacatgtat gtaaattaaa tttttagata 1620
attgattatc tctttgtact acttgagatt tgattatgag atgtgcatat tgctttggga 1680
agagctcgag gaaggaaata attctctcct ttgttttgaa cctcaaacta gataaaccct 1740
aggaattgct taactgcaac aagtaatttt cattcccaca aaaacctgag gcagctcttt 1800
tgcccagagc gttccctgta gccaccccca ccccacttgc ccttggttct ttagaaggag 1860
cacacacatc ccttgattcc tccctgatgt ggtaaactgg cacactccag gggtctaaaa 1920
cataaaacag ttgtgtttag ggaaccttaa gtcatgcaga catgactgtt ctctttgtac 1980
aagtgtgaat caaaatatgt atctcttttt cagagtctgg ttaagctatg tcattgtcta 2040
ctgcatagtt tcctgagtct gtttgtaaag tgcttatggc taacagttca gttctgtatt 2100
tgttgacagg taaataagtg gagttgagtg ccatctttga aaaaattacc ctctagctct 2160
aacactgaaa ataataataa attgtagatc tctgcaacta agtttaaagc agtgtgactg 2220
tgttgcttaa atatcaagta ttgtttataa ccaccaaaaa aaaaaagccc tggtagtttt 2280
ttggcacctt atgtttaaat cagattctta gatttggagt agacctgacc ttgttattta 2340
ttagataaca ttttgaatgt atccattgga tttctaaaat gtattgtgaa tttctcagac 2400
aaacaggatt tatgctggag ctctgttttg cttagaaata aaatatttag tagtttattt 2460
ctgctctaat taaaatgtca agaatgccaa atgctgccag ttttttggtt tgatagctac 2520
ctccttctaa gaaagcaaaa tggttacctt tgagaggaac attcagtgtt taatcatccc 2580
ttatgttaac tagatgatag attcaagctt ttagaaatga gaaagtagaa actaatttgt 2640
taagatattt tcagactgcg gaatgttgtt agctttttct ttcacttctc ttcaaggaca 2700
ggtgttagct gtctacaata ctgttgaact ctgttgtcaa agtagccccc ttagtctaca 2760
aggcaggtag ccttggcttg aattatcaat atcaaaatgt cagttaacca tggagggata 2820
aagtaatgtg aaaagtgaga tggctgcaaa gatagctctc cttacagtta ttttggctgt 2880
cctacattgg gataagctga caaattagca gtatttagtt taacactgga gcaaatataa 2940
tttgagtagg aagaagagat agcaggtttg ggaatctata attatgaagt ccattgattt 3000
tgggagaaaa tctgttgcta aaggatttga agggccatga acacaatttg ggattattac 3060
tccctataag tataataatt ttgctagtga cccatactgt ccagtgtgcc ctaaatcata 3120
ctgctattgt actccctttg ttttcaagga ctttgcaact ggtatttggg ggagattttt 3180
tttttttttt gagacggagt ctcgctctgt cgcccatgct ggagtgcagt ggtgctatct 3240
tggttcactg caagctccat ctcccaggtt cacaccattc tcctgcctca gcctcccaag 3300
cagctgggac tacaggtgcc cgccaccatg cccggctaat tttttttttt tttttttttt 3360
agtagagatg gggtttcact gtgttagcca ggatggtctc gatctcctga cctcgtgatc 3420
tgcccgcctt ggcttcccaa agtgctggga ttacaggcgt gagccaccac gtccggccga 3480
tttttttttt tttttttaat gtaagaatgg agataaaagg gataatataa tttgctttta 3540
tattgttatt tttgtaaagc atcttttctt caattcttgt tggcattctg ggccaaaata 3600
tttcaggttg gttcggtgtg gagttaagaa aagcaggcgt tttagtggag aaatggggaa 3660
cagcatcaag aaaggctttt ttcctttttt cttttttttt tggagacaga gtcttgccct 3720
gtcacccagg ctggagtgca atggcgtgat cttggctcgc tgcaacctct gcctccaggt 3780
tcaaacgatt cttctgcctc agcctcccaa gtagctggga ttacaggtgc ccgccaccac 3840
acccattttt gtatttttag tagagacggg ggtttcacca tgttggccag ggtggtctga 3900
aactcctgac ctcgtgatcc gcctgcctca gcctcccaaa gtgctgagat tacaggcgtg 3960
agccaccatg cgtgaccttt ttttcttttt aaaagggaac aatgttgctt tcaaaacaag 4020
acatgctagg ctgaaactga tttatggaaa agactgcttg ttagcaagta tatttggtct 4080
tgagggggat acagattata gaatatgctg acatttgggc ttcagaggaa gaattttcaa 4140
atctaatgga aatagttgag gtgttcagga atgctgtttc ttggagttgg aagcttaggt 4200
tttgaaatgt tgaaaccaaa aagacaaaaa ttaaaacata gaccttaggt cgtcattcac 4260
acccggttct caagaatcaa gtggagcact tcaaagacct tggcttgtct gtcccatcct 4320
gccactttct catcttttca tgcttttgaa gacaccattt acagctctga ctcagcccta 4380
ttttgtgtaa agtaatatat tgattattca gaaatagaca atacattttt taattaccca 4440
aggactgact gttttgtgca ttttactgtt ggttgtcttc agtagagaat agtaataggg 4500
cagagaaaag tatatatttt gcctcagtca gtcccaccac cacaatggac tattgggata 4560
ttttctaaaa aaccaatcaa tttgcccatg attacctcac aaataattag tgctacctgg 4620
ggtactctca aatatacagc ttttgaaact gtagatgaaa aaagctctac tcagagtttt 4680
tgtcaagact gtgcctgggt tgaatatcag tcaattgcct acacttctaa acaataagtg 4740
ccaatgtctc aattttctca ccctgaatga tagaagctag ctttatcaaa tgccaaggtt 4800
agaaagcctg gaaataaaac ttaagcacag acattcaagt ttttgaaaag cataagccta 4860
aattcagata aatcacactg atatattgta ctatgcatag aaagttgtag gtggcgttca 4920
gggaagactt tgattttaat aaagcaatat ttagtattga agacaaacac tttttatttt 4980
cagatttctg ccaagtaaaa cagaaattgc caataaaata atcagtattt tgtaaatggc 5040
aggcaagctt ctggctgtcg aaaacatctg agtcatttat tcagtagaca atatgtcctt 5100
gatccaggtt ctttgccagc tataagggaa tccctgtcct tgagaggctc atagtctata 5160
agtaacatta cagaatttgt tagcataccc attcattatt agttttacct aaacgtgtta 5220
ggatcactac tggtggaaat tgtaaccagc ctttgggcat cttaaagggt gacatgtggc 5280
atgccttttt ttttttttaa gaatttaatg tttttcaaga ttgtagtgtt gatcagcgca 5340
acaattcaag tgtgcaaagt aacaggatag tttgcctctt cactttaccc ctggataaag 5400
gcactttcac tgcctgtcac tgatcagcag atactgactt gttgccatta agtgaacttg 5460
acttcttatg tgtgctctat gagtttgttg taattttctt cttgaaattg tgatttttca 5520
ctgacagtaa tgacaaattt aatgtatgta attgtctatg cattttaagt taaactgcct 5580
aaaatgtgat ttgagacata tacatatgtt tgtattataa attgtaagca atcagtttga 5640
gatactaggt tttatcacct gctgctgtat ttgtaaacaa agacaaatgt tgctttaaga 5700
agtaattata attaggaata ggctatggat gtgatacttg gtatttttta agataaactt 5760
gtttgctttt gtgtattata cctggaaact ttttttaaaa aatgtatttt catggtttca 5820
cagatttttc atgttatttt attctttagg cccaattctg ggcttctctg agcaagtcca 5880
gagcctaatt aactgtaaat ttgttgtcaa aaaggaagaa aaaagggcct gagatacctc 5940
tttgcatgtg acctgcattc actaaggata tctggaaacc acccttcctc cgcaaaccct 6000
ctcagcaaca tggtgtccat tgtggtgatt ttctcttctt ttaaggctag gctactcttg 6060
gtaaccagat tatccgtata tatgataata tgaagtcagg gaactttctc tgtctgtccc 6120
tactcccctc actcccccac tttctgttat gaaagatagt tctactttta tcattaactg 6180
ctacgcattt agtgagggtc acattattaa acttggagtt taccattttc ccacaggaga 6240
tttcgctggc attccttgga actcccaatt tcagtagggc aatgaatgaa tgaatacttt 6300
gcagtgctac ttttggaagg aatttctgct ttttgcctta tgattggaca aaatgcagct 6360
gtaaaatttt aaattgtttt tgatatgtta ttcaatatcc catgaaagta ttcacctaaa 6420
gtggagttat gaaatggatg gtgaaataat aagaccattc tggagcagg 6469
<210> 3
<211> 10897
<212> DNA
<213>Genus Homo, ethnic group, Homo sapiens (human)
<400> 3
agatatactg agtgagccct gagaagcagt ctcagatcct gacggtgcag cagcccgcag 60
cctcagccag ggagtcccag ccgctttcaa tggaggagaa gcccggccag ccacagcctc 120
agcaccatca cagccaccac catccgcacc atcaccctca gcagcagcag cagcagccgc 180
accaccacca ccattattat ttctacaacc acagccacaa ccaccaccac caccatcatc 240
accagcagcc tcaccaatac ctgcagcatg gagccgaggg cagccccaag gcccagccaa 300
agccgctgaa acatgagcag aaacacaccc tccagcagca ccaggaaacg ccgaagaaga 360
aaacaggcta tggtgaacta aacggtaatg ctggagaaag agaaatatct ttaaagaacc 420
tgagttctga tgaagccacc aaccctattt ccagggtcct caatggcaac cagcaagttg 480
tagacactag cctgaagcag actgtaaagg ccaacacctt tgggaaagca ggaattaaaa 540
ccaagaattt cattcagaaa aacagtatgg acaaaaagaa tgggaagtct tatgaaaata 600
aatctggaga gaatcagtct gtagataagt ctgatactat accaattcca aatggtgtgg 660
taacaaataa ttctggttat attactaatg gttatatggg taaaggagca gataatgatg 720
gtagtggatc tgagagcgga tatacaactc ctaaaaaaag gaaagctagg cgcaatagtg 780
ccaagggttg tgaaaacctt aatatagtgc aggacaaaat aatgcaacaa gagaccagtg 840
tcccaacctt aaaacaggga cttgaaactt tcaagcctga ctatagtgaa caaaagggaa 900
atcgagtaga tggttcgaag cccatttgga agtatgaaac tgggcctgga ggaacaagtc 960
gaggaaaacc tgctgtgggt gatatgcttc ggaaaagctc agatagtaaa cctggtgtga 1020
gcagcaaaaa gtttgatgat cggcccaaag gaaagcatgc ttcagctgtt gcctccaaag 1080
aggactcgtg gaccctattt aaaccacccc cagtttttcc agtggacaat agcagtgcta 1140
aaatagttcc taaaataagt tatgcaagca aagttaagga aaacctcaac aaaactatac 1200
agaactcttc tgtgtcacca acttcatctt catcatcttc atcatctacc ggggaaactc 1260
agacccaatc atcaagtcgc ttatcccagg tccctatgtc agcgctgaaa tctgttactt 1320
ctgccaactt ttctaatggg cctgttttag cagggactga tggaaatgtt tatcctccag 1380
ggggtcagcc actgctaact actgctgcta atactctaac acccatctct tctgggacag 1440
attcagttct ccaggacatg agtctaactt cagcagctgt tgaacaaatt aagactagcc 1500
tttttatcta tccttcaaat atgcaaacta tgctgttgag cacagcacaa gtggatctgc 1560
cctctcagac agatcagcaa aacctggggg atatcttcca gaatcagtgg ggtttatcat 1620
ttataaatga gcccagtgct ggccctgaga ctgttactgg gaagtcatca gagcataaag 1680
tgatggaggt gacatttcaa ggagaatatc ctgctacttt ggtttcacag ggtgctgaaa 1740
taattccctc aggaactgag catcctgtgt ttcccaaggc ttacgagctg gagaaacgga 1800
ctagtcctca agttctgggt agcattctaa aatctgggac tactagtgag agtggagcct 1860
tatccttgga acccagtcat ataggtgacc tgcagaaagc agacaccagt agtcaaggtg 1920
ctttagtgtt tctctcaaag gactacgaga tagaaagtca aaatcctctg gcctctccta 1980
cgaacacttt gttaggctct gccaaagaac agagatacca gagaggccta gaaaggaatg 2040
atagctgggg ttcttttgac ctgagggctg ctattgtata tcacactaaa gaaatggaat 2100
ctatttggaa tttgcagaag caagatccca aaaggataat cacttacaat gaagccatgg 2160
atagtccaga tcaatgaagg accagactgc ctattcgtaa cctttctgca gcattagagc 2220
catcgttcat gggggacaca aggcttttat gctcctagat cttcaacgca gcagaggaac 2280
cataagtaga atcacaggat aatatataca aatatatata tatacatata tatatatata 2340
gttatttaaa aaaggcaact gaaagtaatt agacttctta aggaatcaaa tttatttcaa 2400
gagactacac atggttattt aatctccggt actgaatagg ttttttttct tctgttagtt 2460
tttgttttta agtgtgaatg caagtgatta atgaatacag acttaacaag tgtggttcta 2520
aagttcctgc tgtcatcaac ttgggcaaca aatgacccac tggaaaggca aatccactta 2580
aaagatctct gtatcttgtt ctgtgactga agtgatacac taatcacggg gaacccagaa 2640
tgattcaaca ttttcccccc actcctccct tgatcttttt ggttttactt taattaagcc 2700
ctgcgagaat gctggataaa tgccttgaag ttagcagggt gtattttttt agcgaatatg 2760
atttgcatgt cttgccagga gttaagcggc ctctggggtg ttggggaaat actttatttc 2820
tttccattta ttttttgtgg ggcggggata ggggagggca ttgaagttct acaattctgg 2880
aatagttagt tgatggtaca tagttaactt ggcttcggtt acatattgga ctttaacaac 2940
tgaagaatct atgcgtgtca tttaaagaaa agttgcagaa caagcaattg gcttagatat 3000
acaatctgga aaaatattcc tgtgcccata ttttaatgta attgtataac tgggagcaaa 3060
aatatattct gcttttcaac tgtaggtgct ccagacttgc tctccgtcac taacactaaa 3120
tgtgctgttt tccttgtttt tcatcaaaca tttaagacaa acttagacct ttctgtaaat 3180
tatcttttaa tttctcagca aaatctaaaa ggggaagaaa aaagtccatg aaaactaaaa 3240
cttttcatgt ttttagccag tgagaagata ataaaccctg actgtagaag gtgtgttttc 3300
atgcaaacta tacttctgag cttgttagct tctaattata tcttaataaa tatattttat 3360
tactagagca agatgggttt ttaaggaaaa taatgtgaaa ttctggaaat tttctttggg 3420
gcagagaaga gcattagccc tgtcttatca ttacattgcc atcctgttgc actgcagctt 3480
gtgtatagca tgctaaaata aatttttgtg tgtgtgtgca gaaattaagg gtccaattga 3540
gattgggtga tgttagtaac ataataacaa gttgtctggc ctgacacagc atcacatcac 3600
acacacagaa attagtatat ccatgtatgt caaatacagg ttaaaatatc agggcattta 3660
tataaagagt tgtagtcttc tgataaaagt agactggatc ccctggggta tttggggaga 3720
aagtaactac tttggctcta cccctagaaa tgtccagttt tgagtgactg tagtatggat 3780
gggttttctt gttttgttga ttatttgagg cttttaaaac aagtagttca tgaaagaagc 3840
tgttggactc aacatagagt agagtaacta tctttttagt ctggatttct gccctgctta 3900
gattttaaaa gtataagcat ggattgccaa ttccacttga tgtaaacaaa actttttttt 3960
atacataata tatatatata tatataaaat aacttattgt atcagtccag gttcagaaac 4020
ttgtggtagg ccagttccag atagtttcat ttcacctgta aactgtatca ctttgactga 4080
tattgtaatt ttcaaatgta taatatgttt acagatgtgc cctgcattta gtctgccttg 4140
ttcctatttt gatttttgtt gagtctcctg cctgcttgcc aaaagctagg atgcttcagg 4200
cccatgtaca attgaaagca gaggcatcct tgagctttaa agcattgaac aaactggaaa 4260
atgcaacata ccacataact gaagtgaaaa aagtctgtgt ttttgtgttt ttttaaataa 4320
aaattttcaa aaagttaaaa aaaaagacat ataaggttga ttaaagggaa aaaaggctcc 4380
agtttgtttt acaggtttta aagttctgct gtgtgttcaa ttgccttgtg taaccacttg 4440
tcgccttagg gccagattcc cctctctagt cccctttttt aaatgtccat tttgcttgcc 4500
tggaatttta aagttcttcc gtctcacaac tcacaagaaa ctttctgggt ttgtgacata 4560
cagaggttga attgagtata tatttgaaaa ggaaaaaaca aaaaacaaac ccagacccca 4620
cctgaattgg gctttttaac ttagaagcaa cacttgatta aacatcttta gaaagctatt 4680
gcttttctaa tttccttcca tatccctcag gcctcagtgt tcagagaagc caaaaagaat 4740
gtatcacttc tctgtctgtc caaaggtttt tgagagtctc acttctaaat gaaacaatgc 4800
aacatttcac tttgatttct ccactgaaat ttccttgatt atatggttag aggtatgtag 4860
ttaggaatgt ctgttaactt tctgagaacc ctagtgcccc atcatattaa ctgtcagtat 4920
tttgggggca ttaggttaat agacttaatt gcctaggtac aagcaggact ttgggacaaa 4980
tctctttgtg ctgtttggta acacttaact ctatttgttg caatctttct ccttaggtcc 5040
tcacacaatt ccttacagag cacttattaa aaaaaaatct taagagttga tctgttttct 5100
gattattttg tgtaagcttc taaacaaact tcagctgtga ttaatttagc acatttaaat 5160
aacgtgttat tgtttggtat aaagaatttt ccttcaactc agagtattag tactgtagca 5220
taaaccaaat acagtctaga ggggattttt aacatccctc cattataaag actgaaaaag 5280
gggtgtgtgt gtgtgtgtgt gtttatgtat gtatgtatgt gtgtgtgagg aaaagatgga 5340
gatattaaaa attagtaaat gaatgtgtat aagacattag tattcagaga atgaacttgt 5400
atttattttg tgccatttgt tttcattaca cagaaaaaag tcaggtggtt taaatcctta 5460
aaagggtagt attgaaaaat ggcactaaga atgaaattat gacctatttt tttaatagct 5520
atgaagatac taattatggg tgaagatttc tttttaaatc tgttttgatt attgtaggct 5580
tctgtgtcac ataccactct tgtaggtgtc ctcaataatc cccttttccc acaaaataca 5640
cagggtgtat tatctttctc tttattcacc cccactttgc tgaactgaag ttaattacat 5700
agcctttctt ctaacctcct tagtaatgaa ccttcacata aagtgtattt acagcgtctg 5760
tggtagccag cccttcctcc tctactttct aggaggggat agccaataac taggaattta 5820
atgacagatt tttttttctt tgaaataaat ggccagagtt tctccatttt agaattttgt 5880
tgtcctcctt aatcatctgc ttacctagtc attactcaat ctgcagaaac ttcataaagg 5940
aaaagtgctg cattgttttt acaaataaca gtttgtaggg aaaatatgac aaacctcaac 6000
tatgggagtt gtccacaata caaaattttg aaaaaacatt acatagtgat aatatcatac 6060
ttggttgtta ggcttgttgc ttccccacat cagaggcatc taatgattta tcttttgtaa 6120
ttgctgtgaa cttttttaaa taagccattt agtgtgaaat tgtcatgtat caaatggcta 6180
ttggaaatgg actttactca attttaattc cactgtaaat aaggacggag tcattcctac 6240
aaggctctct tcagagaaat agattaaaag tccaatttcc aggtattatt agtatagtta 6300
tgccgctggg ccacatcctc aacaacagct gatccctctt gtataaatat gttaactgtg 6360
cagaacagtt atgttatggg acaaatataa tggtcattat ggtcagattg gttgatgcca 6420
caccagtcaa ggtagagtct gatagggcag tatcttaata accctaccca tgacttaact 6480
gttggatttg aaaggaaaac gtaggatttg ctcttgtccc cttacccgcc acaaaatttt 6540
gataatttgt ttaaaaggga gaggcagagg aaaagactag aagcataaat agctgcttta 6600
ggtttgccag aggcacatag cttaacatta gttcttaata tcgatgttat ttttactaat 6660
gtaattaatc aacagagcac caagattctt tcatggtgaa aagggtgggc ttctgttttg 6720
gtatcttaaa atgtttcttt taaaatatac atcacctgtg tgagaaccag gaccacctgg 6780
gagagtgatg aatcattggc tccactcaaa agcattgctt tactgagttt taaatttcac 6840
actgttttgc cgctcaagaa aggtcttaaa gtagttaaag gatgccagca atagtgcgaa 6900
tagaattttc ggttgtctgc ataataaaaa cacccattgc agcatgattg gtatgttgct 6960
cttgcattat tgggaatggt aaatcagtta tgggctagaa actatggaat ggccgtcctc 7020
atatgtgatg ggattgctga ttcagacttc cctattttcc atacaatttt gttatgtgca 7080
gagttctaaa gccattttat aatactgcag tatccccccc ccccccacct tttttttttt 7140
gagacggact gtctgttgcc caggctggag tacagtggcg caatcttggc tcactgcaac 7200
ctccacctcc ctggttcaag caattcccct gcctcagcct cccatgtagc tgggattacg 7260
ggcgcacacc accacacctg gctaatttgt attcttagta gagacggggt ttcaccatgt 7320
tgaccagact ggtctcgaac tcctgacctc aggcaatctg cccgcctcag cctcccaaag 7380
tgctggaatt acaggtgtga gccaccgtgc ccggccaagt atctcttttc tacagcctta 7440
ttaaactaac tacaaacatt tattttccaa tttagtttta ctttcagtgc atatcaaagt 7500
tgttgtactc ttcagaccaa caaattaact tgagggcaaa ttacatagct ttccatgtac 7560
ccttttttcc tcaggtgcta atcaaaggct ctgaaaatgg atactgcttt agtgatgtct 7620
gctttattct taaaatgctt atttcttttg ctagatgtaa agatttggtg ttaacaaaag 7680
tggttttaat atgtaaatat gaatgaatgc ctttagttta ccctgtttgt ctattattaa 7740
tctgttttca tttatccttc atagaggagg atcctttcat gatcttgaat acatttcatt 7800
agatattgtt gcattttaag aatgaaaata caactgtttt ctgtcttaga ttaatcctgc 7860
tgctatgaga aactgaaaat caagaatgtg atgcactttt tacattacta tataccatac 7920
atataccata ggttgctttg atacctttcc tgtagcacag ccactaacaa gagtgaatga 7980
attataaaat tctttttggg agggaatcaa tacaagtaac taattcttag ctgatattgt 8040
cctatgaagg acaataactt aggaatataa gaattctgtt aatagtacac tttttggcct 8100
taaatgtctt ctactactga aaatagttta aatcttagct ttgtttctat tattccctct 8160
ctctgcctca gaaagaggaa ttgggaagaa tggcttaaag gacgtggtgt cattgatttg 8220
ttgctgatct tttagaaaac atttgtctat gtaagctggg gacttatttt ttgtttgtat 8280
atagagggga aatagtgctg ccctgaacca atcagattta gtttaaatca aatcaatcaa 8340
aactccagct gtttctcttg tctttttact tagcaaagga aaactttagt gaatgctact 8400
tgacaagaag aaaagtcatt tctcaagcac atacccaaac ttgaaggtga ttgaacccaa 8460
aataatgggt gggaaacacc aaatgaggtg gaggaatgag aaagatgtgt gggccaaagc 8520
tatctggtta tattttgatg ttgccaatat cgcaaagcca aaattttaat ttgcttattt 8580
aatatatttg ttggccagag atctattttt atatcaatgt gccttgcatg tatattaaaa 8640
aaaaaaaatt ggaaacgcca tgtagtaatg cctgagatag tcgatggttc ttaccacctc 8700
actaattttt atgcagtatg aaatgctcat tctattgccc aactggtgct ctctgtttaa 8760
agttacagat cttgcgaaac tggaactatt ttataagctg gggaagtgat ttactttttt 8820
tgttgtatct tttttgttct tagtctgtta gtggctgtcc tgtagtggga aatagtaaaa 8880
ggattcttca ctcccttctc ccctcagcac cttcttcaag taaacatttc ttgtgtgctt 8940
tgaaaaaagt ttcagcttgc tgtctctttt agtgttttaa agaagtgtta tacaaagcat 9000
tgtttgcaaa atatagggag ataatggagt ccactttaat ttggaattct gtgtgagcta 9060
tgatccaagt tatcagctct ttccaacttt aaaaattttg ttaaaagcac cttgcttaga 9120
aaattttaaa tatttatgtc tgcaacaatt gtctcaaaat aataaactgt gcaattcttg 9180
tcattaaaaa aaaaaaagat ctgaattttc cctaatgtga cttgttagtt tctctctgta 9240
tttcctgcca gtgtaaatgt gaaagctttg cttgcattac gttttagaaa tgcattttgc 9300
acactcgaat tttgccgaag ctccgtgaaa aggttagatc taagtagatg aataaagcta 9360
tgcacatgtt ttgaaagttt aatttgtgtg tcattaccaa aagtgaccga tttgtcctta 9420
ctactttgct gttgttagct ttaccatctt tggaaacttg gctcaaagtt acatagttct 9480
gggctagctc atcagtggaa ctaggagaga ggaaaactgg cacctatttt aataaagttc 9540
aatttaaacg agagcttgac ttgtatctat taaagagctt ttcttgaaac agggcagttt 9600
tatcagcttt acaaatcatt ggatgctctt ccttagtaat attttggttt atttgatcaa 9660
atagaaatgg aaagtaattc aaactgaaag accctttttt gtcatatgga acttggtgac 9720
gattttttgt cttaaagctg gtttaaaggt aggataggct tttaccttta ttgctttagc 9780
ataaatttgg tttactgaat tgactggctt gagattagaa ttattcagtt gtttgtaaga 9840
tcaaagcact ggttgtttta aagataacgt gtatctttta aaaaattgcc caagctgatt 9900
agaacaagtt taggagttgg gtacatttgg ttcaagtgct gcaatctgta tgtactaaat 9960
agctttactt tgtgtatgtg tacttataat gtgtagatgt actactaccc aggttttgtc 10020
aaatcatctt ttttaaagtt tttttttttt taattggttc aggacctttg taggagaggc 10080
taatatgttt aagtagaaga tattactgat agcattttcc ccatgctcct acataaaaaa 10140
taaatatttc cattttatag ctttttcaat atacagaaga gggttacttc ttcatcaagt 10200
atattgttgc ctttgaggac acagcaaaac ccttctatat gtatcttcat tgatagtggc 10260
agttaaaaac taagttatcc agttaagact taaaaggtga cccatattaa ttgcatggcc 10320
ttaaaaggca gaaatgcagg agtgtagcaa gcatcatttt agatggctat ggttcctctt 10380
ccgcatctgt cagtagttca cttatgttca gtcttagaac ctactggagg agtgaagtaa 10440
tttctctgtc tcgtgcagag gcactaagga gctgagttac ctcttaatct gggggaatgg 10500
ataataagtg gagtacagtt atgttaaagg atgttccccc cgctcaaaaa aaagtttcaa 10560
tgtttgtttt gcccagtcaa aaatataggt cttttctaca tataagaaca gtcaccagaa 10620
attttccctt ttgctaaatg cttaggtatt tgctatagct gtttctgatg tcatggattc 10680
tgaggaagtg tcatttacgt gatgatcttc ctttattgat gtcttcatca tgttcagtgt 10740
tttaaaaata taaattacaa acactctaca accataccca gatttactta ttttatcaga 10800
aaaaaaactt gagaaatttg tagatcaaat tgagagacaa taagtgtaca ttgttgaata 10860
aaaaatttta aagtttctga aaaaaaaaaa aaaaaaa 10897
<210> 4
<211> 12687
<212> DNA
<213>Genus Homo, ethnic group, homo sapiens (human)
<400> 4
atgcgcagcc catgttagtg atggaggaga gaagatggcg gaagcggaat ttaaggacca 60
tagtacagct atggatactg aaccaaaccc gggaacatct tctgtgtcaa caacaaccag 120
cagtaccacc accaccacca tcaccacttc ctcctctcga atgcagcagc cacagatctc 180
tgtctacagt ggttcagacc gacatgctgt acaggtaatt caacaggcat tgcatcggcc 240
ccccagctca gctgctcagt accttcagca aatgtatgca gcccaacaac agcacttgat 300
gctgcatact gcagctcttc agcagcagca tttaagcagc tcccagcttc agagccttgc 360
tgctgttcag gcaagtttgt ccagtggaag accatctaca tctcccacag gaagtgtcac 420
acagcagtca agtatgtccc aaacgtctat caacctctcc acttctccta cacctgcaca 480
gttaataagc cgttcccagg cttccagttc taccagcggc agtattaccc aacagactat 540
gttactaggg agtacttccc ctaccctaac ggcaagccaa gctcaaatgt atctccgagc 600
tcaaatgctg attttcacac ccgctaccac tgtggctgct gtacagtctg acattcctgt 660
tgtctcgtcg tcatcgtcat cttcctgtca gtctgcagct actcaggttc agaatttaac 720
attacgcagc cagaagttgg gtgtattatc tagctcacag aatggtccac caaaaagcac 780
tagtcaaact cagtcattga caatttgtca taacaaaaca acagtgacca gttctaaaat 840
cagccaacga gatccttctc cagaaagtaa taagaaagga gagagcccaa gcctggaatc 900
acgaagcaca gctgtcaccc ggacatcaag tattcaccag ttaatagcac cagcttcata 960
ttctccaatt cagcctcatt ctctaataaa acatcagcag attcctcttc attcaccacc 1020
ttccaaagtt tcccatcatc agctgatatt acaacagcag caacagcaaa ttcagccaat 1080
cacacttcag aattcaactc aagacccacc cccatcccag cactgtatac cactccagaa 1140
ccatggcctt cctccagctc ccagtaatgc ccagtcacag cattgttcac cgattcagag 1200
tcatccctct cctttaacag tgtctcctaa tcagtcacag tcagcacagc agtctgtagt 1260
ggtgtctcct ccaccacctc attcaccaag tcagtctcct actataatta ttcatccaca 1320
agcacttatt cagccacacc ctcttgtgtc atcagctctc cagccagggc caaatttgca 1380
gcagtccact gctaatcagg tgcaagctac agcacagttg aatcttccat cccatcttcc 1440
acttccagct tcccctgttg tacacattgg cccagttcag cagtctgcct tggtatcccc 1500
aggccagcag attgtctctc catcacacca gcaatattca tccctgcagt cctctccaat 1560
cccaattgca agtcctccac agatgtcgac atctcctcca gctcagattc caccactgcc 1620
cttgcagtct atgcagtctt tacaagtgca gcctgaaatt ctgtcccagg gccaggtttt 1680
ggtgcagaat gctttggtgt cagaagagga acttccagct gcagaagctt tggtccagtt 1740
gccatttcag actcttcctc ctccacagac tgttgcggta aacctacaag tgcaaccacc 1800
agcacctgtt gatccaccag tggtttatca ggtagaagat gtgtgtgaag aagaaatgcc 1860
agaagagtca gatgaatgtg tccggatgga tagaacccca ccaccaccca ctttgtctcc 1920
agcagctata acagtgggga gaggagaaga tttgacttct gaacatcctt tgttagagca 1980
agtggaatta cctgctgtgg catcagtcag tgcttcagta attaaatctc catcagatcc 2040
ctcacatgtt tctgttccac cacctccatt gttacttcca gctgccacca caaggagtaa 2100
cagtacatct atgcacagta gcattcccag tatagagaac aaacctccac aggctattgt 2160
taaaccacag atcctaaccc atgttattga aggctttgtg attcaggagg gattggagcc 2220
atttcctgtg agtcgttcct ctttgctaat agaacagcct gtgaaaaaac ggcctctttt 2280
ggataatcag gtgataaatt cagtgtgtgt tcagccagag ctacagaata atacaaaaca 2340
tgcggataat tcatctgaca cagagatgga agacatgatt gctgaagaga cattagaaga 2400
aatggacagt gagttgctca agtgtgaatt ctgtgggaaa atgggatatg ctaatgaatt 2460
tttgcggtca aaacgattct gcactatgtc atgtgccaaa aggtacaatg ttagctgttc 2520
taaaaaattt gcacttagtc gttggaatcg taagcctgat aatcaaagtc ttgggcatcg 2580
tggccgtcgt ccaagtggcc ctgatggggc agcgagagaa catatcctta ggcagcttcc 2640
aattacttat ccatctgcag aagaagactt ggcttctcat gaagattctg tgccatctgc 2700
tatgacaact cgtctgcgca ggcagagcga gcgggaaaga gaacgtgagc ttcgggatgt 2760
gagaattcgg aaaatgcctg agaacagtga cttgctacca gttgcacaaa cagagccatc 2820
tatatggaca gttgatgatg tctgggcctt catccattct ttgcctggct gccaggatat 2880
cgcagatgaa ttcagagcac aggagattga tggacaggcc cttctcttgc tgaaagaaga 2940
ccatctcatg agtgcaatga atatcaagct aggcccagcc ctgaagatct gtgcacgcat 3000
caactctctg aaggaatctt aacaggaaca tgaagccttg ataaaacagc agttttactt 3060
ttctcacaaa aacttgtaag gtaaaggcct aacttggtct agaatatgac acttattgtg 3120
gtggatagcc aagcacattg ggatctccac atcaaatact gacatttctt ctacaggtat 3180
aataattcat catgcatttt cataattaat aaacattggt aaaattaatt ttacaggtta 3240
catgaaacat tgaaagactt gttacagagg gccatgatat ttttcaaaga aatgtgttat 3300
actagataat ttttttaaag gtgatgttta tcattaatat aaagaatcct tttaaaagta 3360
atttaatgat ttacatttct cctcttttga ttcaattttc ttatacattt tttctaccct 3420
attagttttc taaaggttgt catgagaggt atattatgga ataatttagt agtccagtga 3480
cagaatcgta tgaaatcagt gtacatttta aaaaacatgt cttttagaca tatgctttat 3540
ctataaaaaa ggaattgtgt tctagtatga acaatactga tctggaagtg agaagagtta 3600
gtttctattc caaacttgac caagaatttg gtttgactga gaacgttttc ctctcagttt 3660
ttgtacattt atttagagca gtggttctca gtggaggtca gttttgatcg ccaggggaca 3720
tctggcaatg ttgagacatt ttggttgtca cagcttgggg gtgggttcag gggagggttg 3780
ctactggtgt ctagtagtta gaagccagag atgtttctaa acatcttata atgcacagga 3840
cagcacccct ccactgtaaa gaattattgg ttcaaaaata tcggtactgc caaggttgag 3900
aaactctgat atagaaggag tgataaatat tgttttcacc caaaggaata cttttaaagg 3960
atgaagctta ctaaacatat atgatggaag tattattcag ataacattaa tattctgctg 4020
aataattttt tctagtttaa tcatactaga aaaagaaaaa aaatctacaa attgtcctat 4080
aaaataagga caaacatgca aataatttaa ctctcagaaa gtactaattc attctgatta 4140
tctttcatac ctctgtgctc ctctgcactg acgaagacat aatatgatta tacctatgaa 4200
ctagtgcaca gccttttctg gcaagaaaat agtttgtagc agatacgtgg ttgctctttg 4260
gatttttttc tattgttgaa catgctggga ctagctagaa tgcacattcc tacttccttt 4320
accaaacgtt tgcatgcttc ctgcaaagca cttaccaagt gatttctctt gaaccatcgg 4380
atataatttt gtatgtacat gtttgaggaa aaaaatgtaa agcaaaacct tttactgaac 4440
agtgttctat agaattatga cactaaaaca aaattgtttg tggaagccct gaaagcttta 4500
tagtcctgga catcaaaaat tttatttgag atgatgaatg ttttgttttc atcttttctt 4560
atattaccac aattgagata ttttagtaat tgaaggaaca tacacagata tttggcagaa 4620
gtcgagtaag gaggggaaaa aaagagtccg tgagtttcag tcattttcac tgctcttttc 4680
aaaaagattg tgttgagctg gtagaagact aaagatgtca ctgaagacat cacagatact 4740
atatttatct tttggctttg tgtacattag agaatgttga ttatttttat acaaaaatac 4800
agcgggtaat ttttttaatc tttagatgcc tcttgtttga atgtatgctt tgtggaattc 4860
tttgtgtagt aatgttttaa aaaaagatgt ttactgatag ttacatgtag gattagaata 4920
tgtaatataa tataaggctc atgttccaga cctacgatag cttgtagtct atgttacgta 4980
tttctttata tcacattttt aatcattgga ttaaagtatc aaggaaagct aggtactcta 5040
taatgagttt tcatttatta gcagttaatc atcatgacag aattgtcata tgcttgactt 5100
ttccctcttc ttggaatttc agaacacaaa tacaggctaa gcattagtaa gagatggccc 5160
acagtatgag agagagaggt gcaacggaaa atctcgcctg gaattaaaac ttttcataga 5220
ttatccacgg ttaatacaaa atttattata tggggataga ctgctccagc aataatgatt 5280
acatcctata actgtattac ctatggcctt taaggtatca attttgaact gtgttgtagg 5340
ctctcctttt atttgttctc tttcctaata gcagccattc tgtacttatt gaaagcccct 5400
gtgcctactg ctgtcttaag tattcaggag gggcttacaa gagggttttc tattggagaa 5460
taccgtataa tcttaaatct agtccagatc tctgttgtcc ccactcaaaa catacacaaa 5520
atatgcactt gcttttttca agtgagtttt tatttaaaaa tggcttgttt gctatcacat 5580
tggtgcagct gtttctttca agatgagtta atcatcttaa tttcaaagct tcagctatat 5640
ataatggata tatagacaac actgagcatc cacctctctc ctgagcttta aagcagagtt 5700
tcagtatgat ataggtgggg agagtaaatt gttttcatat cctttcatac tactactaat 5760
agttttagga ttttgactgg ggagagataa tgacaaacag aaagggaaca tggaggttct 5820
tcctactttt gctacctaag tttgcatttt ctgacttcct tgcagtgttg cactctttgt 5880
cccattggga taaaaagcat aagtttgaaa ttttgcttta agccttgtgt tcctggggaa 5940
gttaaacaac taagagagct gatttgtaaa aattattttt tatatgacat taatattcat 6000
caagccttgt gtaggcatgt gtaagacaca gctatgcagc tttgagtagt caatatagta 6060
tgagatagag tgttgtccca aatcctcctg tcacttttta agtagcatat tatttccctg 6120
atggtcctgt tactttgctg ttgaatgctc taaacagaac tttttaaaag gtgtgtttta 6180
agagcagtca cctaggagta gacaaggtgg aatgggagga gagaaatggt aatgcaaaag 6240
cttgagcatg ggaagagtca gaggaggagg ccatcatcct tgttagctta gcctacttca 6300
acactgagca catttctgca cttttgaagt gaaattcatg ttttacttag aagaaataat 6360
tttctttcat tagggatccc agttgatttt tgtttcctgg tgtatcaaaa tacttagaac 6420
tatgaaacaa gtattattgt gatcatgcct ttgaataatt tttgacgtag cttatcttca 6480
tgtatcaagt ataaaattat aatgagacat ctattcacaa atacaagtct tagattgaat 6540
tgaaatgtgt tatagtgccc tgtctcccac tgacttgttc agttaaatgt cttaaagtac 6600
attatgtaca tcttcaggct tttggtacca caatggcaca agtatggtag ggaggcaata 6660
tagtcttagg ctatatgcct atattaagtg tgtataaaca atttttgaaa gaatacacta 6720
ttatagatgt atgtgagtga tgctgacctg acagccatat ccagtggatg aaactgactg 6780
gacacactgt taaaatgttt taaagatgta ttttcagcca gaacagcctg gttatagttt 6840
gtggttttca ccttggtgga ttgcaggaac acatgcagcc tactggcatt gagcattagc 6900
taatggcatg aaagggcctc atctcactac ctctctaagg cctctagctc caagaaaacc 6960
atgaaaactt ctttcttgga gagatctttg tctcagaatc cttagagagg atttcgtatg 7020
ggggctaact ttaggaaggg aggcagctgg ggcaggactt tctgatacct gacagtcatg 7080
ttccagagca acctttgggc agtggaaact ggcgcatcta tgcaaaatga ttgctcaatc 7140
tctatcttgt gtactacata tgtaactagc tgggccctaa ggaaggtttt ctagggggaa 7200
ggatagggaa gtagaggagg agacaagtag gaggaacaaa gcattctaga cccaagagga 7260
tagaagatat ttaggataga tatggctttc atccatagtt caaaataatg cgttttgtta 7320
gatgccagtt atagcagtaa ataggttata gtttttatat gtcaagattt acctgtaatc 7380
agactcattc tttcactctc tatacccact gtctccatgc ttgggagcat ggatattaat 7440
agttccagtg atgtagaagt tagtgatttt tgatttctga aaaaggtgag aaccttttat 7500
tacagttgga gaatatttgt caaaaattca aaggttgttg taattgagtt gccagaatta 7560
cagagtttcc attttcagat atcacagttg aatcacctct gtagattgtt ataaagagag 7620
gcattttaag atagtatttt atttgctagg ttgtgtctca gtctaagaat tgggaaaaga 7680
agagctatag gtttctcttt cctagtctgg atttcagtaa acacaagcct acctctgctt 7740
ctttggttca cagcagtgtg gatcatgaaa tgaactgttt acccacattc atcaatattg 7800
gtattttaca aatctacttg gagcatttaa tttcatctca aagattgtga tccactttag 7860
ataagcacaa atacagtatt aggaaaagta aatatgcaat cttactaaaa tttcaacttg 7920
ttaagctgta tatcttaaaa gaaattattt ggggctgggc atggtggctc acacctgtaa 7980
tcccagcact ttgggaggct gaggtgggta gatcacctga ggtcaggagt tcgagaccag 8040
cctgaccaat atggtgaaac cctatctcta ctaaaaacac aaaaattagc tgggtgtggt 8100
ggcatgcacc tgtaattcca gctacttggg aggctgagac aggagaattg cttgaaccca 8160
ggtggtggag gttgcagtga gccaagatca cacccctgca ctccagcctg ggtgacagag 8220
cgagactcca tctcaaaaaa acaaaacaaa aaattatttg ggaagatacg tcctctttta 8280
ttagaagttc ataaaatgta tcatatagtt ttgttcacag tagttatata agctttcttc 8340
aaataaattt aaaattagat taccttcttt ggaaaaagaa tttcctaaat ttttaagaat 8400
tttcaaagtt ttacatatta gtttttagaa cctaatccgt tttaaaattg tactatgaga 8460
aagctttttt ttgaaagttg taaagcatta atacaaataa tacaaatata attattacca 8520
tcacattcca gagaatatgg ctttttctaa actttcaatt tagaaaacat acattaaggg 8580
agaatctctg ccctcctttt cagctctgaa gatcagcttt tctactcaga cacatgcaca 8640
caccccttcc aagtgtcatg tttatgggaa catttgggaa atgttttcca gatgttttat 8700
tttttccctt ttatagtttg ttgacattta attttactta aagatgacaa ttttaatcgg 8760
aaatgttaga ggtacaacat agtgaggttc tagctagctt tatacttttg aaaaatattt 8820
ttgtttctac tgctttttac aagtactagt cctctcagtg atactggtgg tgttcagtat 8880
gaatccatag aaagaaaaca aaatttgttg tttaaaaaaa gcagagtaat gaatgaattt 8940
cagttttgaa aacaacataa tttgaaaaca ctgttatact aacatggcaa ggtgttaatt 9000
aaatataaga gtaaggtagt aagttctttt agagcacctg tttaaattta ctccagtaat 9060
catcttaagg attgatagtc accatcactt attggcttaa aagttatatt tcatggaata 9120
ttatcagtgt taaatccaag ctttgtggag ctttaagtga tggtggtgaa aaagttggtg 9180
tttatgagag agtggtgggg tgtctagtca ttagtgaagt taaacatcaa cctgttttag 9240
aaagaatttt ttagtcttgc ctaaagtaaa ccagaagtgt ctagtgttta aatctttatt 9300
tagaatgctt ctcttaaaag tattttttgt tttgggtagt attaaataat cagtaaataa 9360
tctatttcag tagtaaataa tgaattaaga tgatgatgaa tgaggattaa cacactggtc 9420
tggagactgg ggttttattt cagtgggtta gctgtgtgtg acatgttggg caattactca 9480
gctgttttaa cagcttccag atatgcagta tggtgcctgt actactcaaa agttgatttt 9540
ggtttaattc atctttaagg tacctcccag ctctaaaact atgattctag gctgtgtaat 9600
ggggttattc ctactttatt ctctttcctt ttttaagggt tcattttata cttaataagc 9660
atccatttct tgggtcacct acagtctttg ttctcctaag gattaaaata gaaaattcat 9720
acataacaag caaatgatga cattttccta aatgctcctt attggttaac cactgaatat 9780
atgaacacat atgaatattg tcattcatgt acttaaattc atttagcaaa ctatttgaac 9840
acttacatgt gcagtgtttg gtgaacatga catgaggaac tagtagtaag taaaatcttc 9900
cccccaaaat tcattgtggc ttaaataaat atgaacataa tcattactac ttaatatact 9960
gagagggaat cttaataaac ttggaactgg gagggaatat ttgtatacat tgggtaaagg 10020
gttaggctag atgacatcta aggggtctga gtgaatcata tcataatttt tataacacat 10080
ttcacatact aaacatcagt tggccccata cctgattaag ttacaaaatt taggagactt 10140
aacattaagg acttacaggt tgagacagcc cgtatttcac aacattattt tgacacttga 10200
ctctattcca gagttgttgc tatacaaggc atgtggcaga acaaaaaaaa agctggtgtt 10260
gatataagag ctttttaccc agtattgaca gtgagcaact ttctttcttt tttttttttt 10320
ttcttttttt tttttttgag atgggttcgc tctgttgccc aggctggtgt gcagtggtgc 10380
gatctcagct cactgcaacc tccacctccc gggttgaagc gattgtcttg cctcagcctt 10440
ccaagtagct ggaattacag gtgcccgccg ccacacctgg ctaatttttg tatttttagt 10500
agagacgggg cttcaccatg ttggccaggc tagtctcgaa ctcttgacct caagtgatcc 10560
acctgccttg gcctccctaa gtgctgggat tacaggcatg agccaccaca cctgtccgac 10620
agtgtagcaa ctttctaaaa ctgaaaaatc tcaaaggaga tcattggaac tgacttgttc 10680
atttattttt tgtttttaaa ttaagaaaga ttacacaaaa taagtgttac tgtactttaa 10740
gctattacaa atatccaact tttaaagata tgtaagaatc agtaatattc tagaaagcac 10800
atatatagta aaagggcatc ctttaaatgt agaacgggta aacatgaaac agttccatgc 10860
ttgaattgtt aagtatctag ggggtaaaca ttgaatggga gaatcattta ttgggttaag 10920
gtcccttcct tgtcattctg ggatctgtga atcacattgt aattcctgtt gacaaagctt 10980
tacttgttaa catcagttga tactgacatt ctccataaag atatagaatg aaaatatcta 11040
ttaaaaatag tttatcattg ttttagcttt tttgttttgt ttgttttgag acagagtctc 11100
actgtcaccc aggcttgagt gcagcggtgt gatcttggct caatgcaacc tccacctccc 11160
aggttcaata gattctccca ccttggcctc ccaagtagct gggattactg gcatgcacca 11220
ctatgcctgg ccagtttttt gtatttttag tagagatggg gtttcaccat gttggccagg 11280
ctggactcga actcctgacc tcaagtgatc cgcccacctc agcctcccaa agtgccggga 11340
ttataggcat gagccactgc gcctagcctg ttgcagcttt ttaaagcagg aaaatatcca 11400
tataaactgt tgggttagaa tctatattag aatctttcaa actaattgaa aacaggaaga 11460
ctatcatcta agtagccaga taatctgggt ttcaaaaagt tattccatgg tactggttta 11520
aaaaatactt ttcaagtgtt ttaattttta aagtgtaact aattcttcaa atatgttatg 11580
ctgttaaaat atgtattcca taagtacttt ttgtatatgt attcttaaat tttaaaaagt 11640
caactgaatg cgcaaagatg atataatttt ggatgtagac atttaaacta gattcccagt 11700
cctctccttc aaaagcttgg tctttgtttt tcctataggg aaaaaagtca aaataagttc 11760
caaaaactat cctcaaagta gtattgtgct tgtagtaaat gaaggttgga tggatggata 11820
ctgacaatgg tggcaggcat ttcaagcctt ttaaattagt actttttgtc gtcttgctta 11880
ttaaaatttt gttaatttta gcaaagacca attgttgtga taaactggtg ttttttggat 11940
gcttcaagca cacgttaacc aattttttaa ttcccctttt ggttcctccc attgttctaa 12000
aataggactt tcatattatt aaaacctcaa aagatgatcc acccaggatg aacaaagatc 12060
accaagggga aagaaaacat tttttatctt tacagaaaac atgttaagat tatatataga 12120
tgtattcttt acattggata ttgtattaga gtcctcctta caagaaatga aatagttttt 12180
agcactctta gcattagagt tcctagattg gtgttgatag ctacagtttt aaaatgtata 12240
acctgaaaat gaaggttaat tttgcattgt aagagcacat ttgatctatg taaaaagtgt 12300
ccatttggtg tattttttta aaaaagagaa agcactttca tattaagtag catgtgtatg 12360
aatttagatt ttcatatttg ttgtgtctgt attcagtgaa gtaaattgag catttaaatg 12420
tttgttgatg gcaacattaa ctattaaatt aaagcacctt atactctgct gcttaacttg 12480
cttgtaattg cacctttgtt acctgcacat tttcatatag aatattgttg taacattgct 12540
tcatgtgggt ctggatggaa gattagtggg cctacaggat catttattta tattgtttat 12600
attacaataa tatattgtag atcagttgta agttcatttc tttacaaata aaagcctctt 12660
ccatttgact ggaaaaaaaa aaaaaaa 12687
<210> 5
<211> 5368
<212> DNA
<213>Genus Homo, ethnic group, homo sapiens (human)
<400> 5
gtttggcttc acggaaccct gtacgcatgc tcctacgctg aactttagga gccagtctaa 60
ggcctaggcg cagacgcact gagcctaagc agccggtgat ggcggcagcg gctgtggtgg 120
ctgcggcggg tccgggccca tgaggcgacg aaggaggcgg gacggctttt acccagcccc 180
ggacttccga gacagggaag ctgaggacat ggcaggagtg tttgacatag acctggacca 240
gccagaggac gcgggctctg aggatgagct ggaggagggg ggtcagttaa atgaaagcat 300
ggaccatggg ggagttggac catatgaact tggcatggaa cattgtgaga aatttgaaat 360
ctcagaaact agtgtgaaca gagggccaga aaaaatcaga ccagaatgtt ttgagctact 420
tcgggtactt ggtaaagggg gctatggaaa ggtttttcaa gtacgaaaag taacaggagc 480
aaatactggg aaaatatttg ccatgaaggt gcttaaaaag gcaatgatag taagaaatgc 540
taaagataca gctcatacaa aagcagaacg gaatattctg gaggaagtaa agcatccctt 600
catcgtggat ttaatttatg cctttcagac tggtggaaaa ctctacctca tccttgagta 660
tctcagtgga ggagaactat ttatgcagtt agaaagagag ggaatattta tggaagacac 720
tgcctgcttt tacttggcag aaatctccat ggctttgggg catttacatc aaaaggggat 780
catctacaga gacctgaagc cggagaatat catgcttaat caccaaggtc atgtgaaact 840
aacagacttt ggactatgca aagaatctat tcatgatgga acagtcacac acacattttg 900
tggaacaata gaatacatgg cccctgaaat cttgatgaga agtggccaca atcgtgctgt 960
ggattggtgg agtttgggag cattaatgta tgacatgctg actggagcac ccccattcac 1020
tggggagaat agaaagaaaa caattgacaa aatcctcaaa tgtaaactca atttgcctcc 1080
ctacctcaca caagaagcca gagatctgct taaaaagctg ctgaaaagaa atgctgcttc 1140
tcgtctggga gctggtcctg gggacgctgg agaagttcaa gctcatccat tctttagaca 1200
cattaactgg gaagaacttc tggctcgaaa ggtggagccc ccctttaaac ctctgttgca 1260
atctgaagag gatgtaagtc agtttgattc caagtttaca cgtcagacac ctgtcgacag 1320
cccagatgac tcaactctca gtgaaagtgc caatcaggtc tttctgggtt ttacatatgt 1380
ggctccatct gtacttgaaa gtgtgaaaga aaagttttcc tttgaaccaa aaatccgatc 1440
acctcgaaga tttattggca gcccacgaac acctgtcagc ccagtcaaat tttctcctgg 1500
ggatttctgg ggaagaggtg cttcggccag cacagcaaat cctcagacac ctgtggaata 1560
cccaatggaa acaagtggca tagagcagat ggatgtgaca atgagtgggg aagcatcggc 1620
accacttcca atacgacagc cgaactctgg gccatacaaa aaacaagctt ttcccatgat 1680
ctccaaacgg ccagagcacc tgcgtatgaa tctatgacag agcaatgctt ttaatgaatt 1740
taaggcaaaa aaggtggaga gggagatgtg tgagcatcct gcaaggtgaa acgactcaaa 1800
atgacagttt cagagagtca atgtcattac atagaacact tcagacacag gaaaaataaa 1860
cgtggatttt aaaaaatcaa tcaatggtgc aaaaaaaaac ttaaagcaaa atagtattgc 1920
tgaactctta ggcacatcaa ttaattgatt cctcgcgaca tcttctcaac cttatcaagg 1980
attttcatgt tgatgactcg aaactgacag tattaagggt aggatgttgc ttctgaatca 2040
ctgttgagtt ctgattgtgt tgaagaaggg ttatcctttc attaggcaaa gtacaaaatt 2100
gcctataata cttgcaacta aggacaaatt agcatgcaag cttggtcaaa ctttttccag 2160
caaaatggaa gcaaagacaa aagaaactta ccaattgatg ttttacgtgc aaacaacctg 2220
aatctttttt ttatataaat atatattttt caaatagatt tttgattcag ctcattatga 2280
aaaacatccc aaactttaaa atgcgaaatt attggttggt gtgaagaaag ccagacaact 2340
tctgtttctt ctcttggtga aataataaaa tgcaaatgaa tcattgttaa ccacagctgt 2400
ggctcgtttg agggattggg gtggacctgg ggtttatttt cagtaaccca gctgcaatac 2460
ctgtctgtaa tatgagaaaa aaaaaatgaa tctatttaat catttctact tgcagtactg 2520
ctatgtgcta agcttaactg gaagccttgg aatgggcata agttgtatgt cctacatttc 2580
atcattgtcc cgggcctgca ttgcactgga aaaaaaaatc gccacctgtt cttacaccag 2640
tatttggttc aagacaccaa atgtcttcag cccatggctg aagaacaaca gaagagagtc 2700
aggataaaaa atacatactg tggtcggcaa ggtgagggag atagggatat ccaggggaag 2760
agggtgttgc tgtggcccac tctctgtcta atctctttac agcaaattgg taagattttc 2820
agttttactt ctttctactg tttctgctgt ctaccttcct tatatttttt tcctcaacag 2880
ttttaaaaag aaaaaaaggt ctattttttt ttctcctata cttgggctac attttttgat 2940
tgtaaaaata tttgatggcc ttttgatgaa tgtcttccac agtaaagaaa acttagtggc 3000
ttaatttagg aaacatgtta acaggacact atgtttttga aattgtaaca aaatctacat 3060
aaatgattta caggttaaaa gaataaaaat aaaggtaact ttacctttct taaatatttc 3120
ctgccttaaa gagagcattt ccatgacttt agctggtgaa agggtttaat atctgcagag 3180
ctttataaaa atatatttca gtgcatactg gtataataga tgatcatgca gttgcagttg 3240
agttgtatca ccttttttgt ttgtctttta taatgtcttc agtctgagtg tgcaaagtca 3300
atttgtaata ttttgcaacc ctaggatttt tttaaataga tgctgcttgc tatgttttca 3360
aacctttttg agccatagga tccaagccat aaaattcttt atgcatgttg aattcagtca 3420
gaaaagagca aggctttgct ttttgaaatt gcaactcaaa tgagatggga tgaaatccta 3480
tgacagtaag caaaaacaga accatgaaaa atgattggac atacaccttt tcaattgtgg 3540
caataattga aagaatcgat aaaagttcat ctttggacag aaagccttta aaaaaaaaat 3600
cactccctct tccccctcct cccttattgc agcagcctac tgagaacttt gactgttgct 3660
ggtaaattag aagctacaat aataattaag ggcagaaatt atacttaaaa agtgcagatc 3720
cttgttcttt gacaatttgt gatgtctgaa aaaacagaac ccgaaaagct atggtgatat 3780
gtacaggcat tatttcagac tgtaaatggc ttgtgatact cttgatactt gttttcaaat 3840
atgtttacta actgtagtgt tgactgcctg accaaattcc agtgaaactt atacaccaaa 3900
atattcttcc taggtcctat ttgctagtaa catgagcact gtgattggct ggctataacc 3960
accccagtta aaccattttc ataattagta gtgccagcaa tagtggcaaa cactgcaact 4020
tttctgcata aaaagcatta attgcacagc taccatccac acaaatacat agtttttctg 4080
acttcacatt tattaagtga aatttatttc ccatgctgtg gaaagtttat tgagaacttg 4140
tttcataaat ggatatccct actatgactg tgaaaacatg tcaagtgtca cattagtgtc 4200
acagacagaa agcacacacc tatgcaatat ggcttatcta tatttatttg taaaaatcca 4260
agcatagttt aaaatatgat gtcgatatta ctagtcttga gtttctaaga gggttcttta 4320
tgttatacca ggtaagtgta taaaagagat taagtgcttt tttttcatca cttgattatt 4380
ttctttaaaa tcagctatta caggatattt ttttatttta tacatgctgt tttttaatta 4440
aaatataatc actgaagttt actaatttga ttttataagg tttgtagcat tacagaataa 4500
ctaaactggg atttataaac cagctgtgat taacaatgta aagtattaat tattgaactt 4560
tgaaccagat ttttaggaaa attatgttct ttttccccct ttatggtctt aactaatttg 4620
aatccttcaa gaaggatttt tccatactat tttttaagat agaagataat ttgtgggcag 4680
gggtggagga tgcatgtatg atactccata aattcaacat tctttactat aggtaatgaa 4740
tgattataaa caagatgcat cttagatagt attaatatac tgagccttgg attatatatt 4800
taatatagga cctattttga atattcagtt aatcatatgg ttcctagctt acaagggcta 4860
gatctaagat tattcccatg agaaatgttg aatttatgaa gaatagattt taaggctttg 4920
aaaatggtta atttctcaaa aacatcaatg tccaaacatc tacctttttt cataggagta 4980
gacactagca agctggacaa actatcacaa aagtatttgt cacacataac ctgtggtctg 5040
ttgctgatta atacagtact ttttcttgtg tgattcttaa cattatagca caagtattat 5100
ctcagtggat tatccggaat aacatctgaa agatgggttc atctatgttt gtgtttgctc 5160
tttaaactat tgtttctcct atcccaagtt cgctttgcat ctatcagtaa ataaaattct 5220
tcagctgcct tattaggagt gctatgaggg taacacctgt tctgcttttc atcttgtatt 5280
tagttgactg tattatttga tttcggattg aatgaatgta aatagaaatt aaatgcaaat 5340
ttgaatgaac ataaaaaaaa aaaaaaaa 5368
<210> 6
<211> 4270
<212> DNA
<213>Genus Homo, ethnic group, Homo sapiens (human)
<400> 6
gagggccgct gtcactcagc cccgcgggcc aatagaaaag gggtgaaccc cgccttcttc 60
ctgagttgtg ctgcgggcat gcgcactggg cgtccccacg ccaccgccca tcagctgaga 120
attgcagctg agggctccgg ggtaggtggg tgacggcggt cggaggtgta ggagggagcc 180
gtggaggtcc aggtgactgc ttagaaaact gcacagcatc tgatgaaatt agcgaataag 240
aacatcaacc atgtcttaca ctccaggagt tggtggtgac cccgcccagt tggcccagag 300
gatctcttct aacatccaga agatcacaca gtgttctgtg gaaatacaaa gaactctgaa 360
tcaacttgga acacctcaag attcacctga attgaggcaa cagttgcaac agaagcagca 420
gtatactaac cagcttgcca aagaaacaga taagtacatt aaagagtttg gatctctgcc 480
caccaccccc agtgaacagc gtcaaaggaa aatacagaag gatcgcttag tggcagagtt 540
cacaacatca ctgacaaact tccagaaggt ccagaggcag gctgctgagc gagagaaaga 600
gtttgttgct cgagtaagag ccagttccag agtgtctggc agttttcctg aggacagctc 660
aaaagaaagg aatcttgtat cctgggaaag ccaaactcaa cctcaagtgc aggtgcagga 720
tgaagaaatt acagaggatg acctccgtct tattcatgag agagaatctt ctatcaggca 780
acttgaagct gatattatgg atattaatga aatatttaaa gatttgggaa tgatgattca 840
tgaacaagga gatgtaatag atagcataga agccaatgtg gaaaatgcag aggtgcacgt 900
tcagcaagca aatcagcagc tgtcaagggc agcagattat cagcgcaaat ccagaaaaac 960
cctgtgcatc atcattctta tccttgtcat tggagttgcg attatcagtc tcatcatatg 1020
gggattgaac cactgaagtt ataaaggagc acactgtcgc actacattgt ctaaattatg 1080
taggaagatt cctgtaatca tgttttttta attattattt taaagctatt gtataaagga 1140
tggttcccat actttgttat ttttattggg ggggttgggg tggttccttt ggattaaatc 1200
tgatattttc taatactgaa agattttcta aatgtcactg ctgacataac tcccttggtc 1260
ttcaatttaa tagttgttaa gtttttgccc acattgcata tgcctttcat ttataattta 1320
tttaccctgc ttgacttagt tttgggaatt cgtaaattta aaggtgtgtg tattctgttt 1380
gcatctccct gtcactgtga cacacctaga tgtgtgttac ttcaattaaa attctcaaat 1440
ttaattttga tttgcttcag cagggaaaat attctcaata atgtaaaata attaaggtct 1500
atacatgggt tgtatttttc tggttcacaa cagcacaaag tgtctttcat ttttttgttg 1560
gttttctttt aagatctttt ttaccctgaa gtcggtgaat acttttctag tttatttgat 1620
actctttctg tgtatatatt aagcttttgc tgtagattgc ctagtaaaat tactaaggat 1680
aggttgtttt tacatatggt ctatttaagt ctgatgttta cgggggaaag tgtagttact 1740
aaaaatgttt aacataattt ggaagaagag tatgaacaac caataccaat acctattgcg 1800
tttggattct taagacccca gtttgttatt ccactaaact agttatctta accatatcat 1860
ctggttttgt gggccattat ttaccttccc ttatgtctta tagaataatg gttaatattt 1920
ttaggtcaaa attacttttg gaaagtaact ttcccacaat taactgtttt tgagcacctg 1980
acaaaattta gtgtttacct tgcgtgccat tttgtgtcat ccttcattaa aaaagcaatt 2040
ggaggtttgc cagttatctc acttcccttt ttaaatcaat gttgttttaa tgcactaatc 2100
tgaattctgt aaagaggatt atcttagttt atactttgta ttttataatg ttcttgtata 2160
gcagctcggt actgaaggcg gtgtttaact tggcaagctc tgagacttca aatgggaaca 2220
aatagtaagt agctaagtaa accacatctt tgcaaccaaa ataaagatga gttaaaaggt 2280
atctggttag gcctatttca tgaggactat gctctggtgg gaccacaggt cacctgatac 2340
ttagtgctgt gctgcctgaa acctcagcat ggagacatca ccacatgcac tgtggccatt 2400
cagcatcttt ctggagcacc agttcactcc aggtttttat tttagggtgt catcgatttt 2460
acctactttg tcagactggt agaagttgct ttgcatatca gaaaaactcc atttttttcc 2520
acaaaaggga ttacagaaaa ctcttttgtg agtgagtgat tggaacttag agactcctgt 2580
tgccagaatc agactgccct agaacagaat ggacaatgca gggaggagaa ttcacacaaa 2640
cagcacctgt tctgaggcct gtgccagccc accaggcctg ctcaaatgtg gtctttactt 2700
caagtgcaca gaggcacatg aggtttctgg tgataaacca gcgtcttacc gctgttttaa 2760
agtcccatcc ccatggcttt cacaatcagt tccgtttttt ttgctgtact tgataaaatg 2820
tttattctca tacaggtcaa gtacatttac ttctattcac agtgagtacc caataacaac 2880
aaaagcgctt acaaatttgg ggggcgtgat tttagtacct ttatttgaag tgtaatcatt 2940
ttaaattatt attattttaa ctggggcagt tatcagtggt ttaaacagga actttagtgg 3000
cttcaatttg tttaagaaac atattaagtt tgagggaaaa atttcccatg aaatatttgg 3060
aacgtaagag tagtattgat tagagaaaat taaataagaa acatagtatg gtagccaaat 3120
tttttaaaaa atcttgaact tttctgtagg tcagttttag aactgctgtg aaaagtgaag 3180
gttgccctgt ggagattaaa attagagttg ttttcataac tgacagcatg gtgaatccat 3240
ttgagtcaaa gtgaagaatt tcctcatcaa gtgactatac atttgttttt gtgtgctcaa 3300
aagaaatact caaacacaga ctgatattaa ccagccaggt aaattgaacg acaatgtggc 3360
attaggtatt tggctgttta ttggtcgtta aatactatgg ttttgcaata tgattgatgg 3420
taaaagagtg atgtcatatt gatactagag tagcttgttt ttttagtagg tgtgggacca 3480
tctcttttac aagtgcaact cagtctagga cagccatgga tgcagtgtct ggagttggac 3540
cctctgagcc cgctggctgc cccagtagca tctgcattgg tgaccaagga cactgcactt 3600
tgaagaggtc gccactgggt tatttagtgt cttcactgct tttgttaaaa attgtaaaat 3660
tttgtacaca aaaagttgtg tttttgaata tcaattgttt agacacacct acaatgataa 3720
ataagtgcct ttaaaggccc ctctttccat gaaatacatc tgtggtttag caaggaaagt 3780
acaaaatagt ttatgtagtt ggtataattt ttatttgtgt cttcatgtag aaaaaatgaa 3840
tgtcataata aaatataaaa cttacgtaaa gaaaataaag tcattgtcca ccttaatagc 3900
taaggtccac aagggtaact tatgcagcat ttattttttt tgaaagtcaa aattgaattt 3960
atttctttca catggctggt ttgctgcaat atgaagtttc agaatgggct gaagtaagtt 4020
gattgaggga tttgagttga atgacatttt caagttcatt taaatatgat aaaaattcat 4080
tggtggtaaa taacatctgt ctttcctgga aaaaaaaaag ttgtgtattt tcatgattca 4140
gttaaaacaa aaaatgagcc tgtgaatccc aggccttttt agtcctccat aacatttgaa 4200
cagtttgact tgtcagcaaa gaaatacact tatcaaattt taaaccaatg ggagcctgaa 4260
agtgttacag 4270
GAPDH sequence
gcctcaagac cttgggctgg gactggctga gcctggcggg aggcggggtc cgagtcaccg 60
cctgccgccg cgcccccggt ttctataaat tgagcccgca gcctcccgct tcgctctctg 120
ctcctcctgt tcgacagtca gccgcatctt cttttgcgtc gccagccgag ccacatcgct 180
cagacaccat ggggaaggtg aaggtcggag tcaacggatt tggtcgtatt gggcgcctgg 240
tcaccagggc tgcttttaac tctggtaaag tggatattgt tgccatcaat gaccccttca 300
ttgacctcaa ctacatggtt tacatgttcc aatatgattc cacccatggc aaattccatg 360
gcaccgtcaa ggctgagaac gggaagcttg tcatcaatgg aaatcccatc accatcttcc 420
aggagcgaga tccctccaaa atcaagtggg gcgatgctgg cgctgagtac gtcgtggagt 480
ccactggcgt cttcaccacc atggagaagg ctggggctca tttgcagggg ggagccaaaa 540
gggtcatcat ctctgccccc tctgctgatg cccccatgtt cgtcatgggt gtgaaccatg 600
agaagtatga caacagcctc aagatcatca gcaatgcctc ctgcaccacc aactgcttag 660
cacccctggc caaggtcatc catgacaact ttggtatcgt ggaaggactc atgaccacag 720
tccatgccat cactgccacc cagaagactg tggatggccc ctccgggaaa ctgtggcgtg 780
atggccgcgg ggctctccag aacatcatcc ctgcctctac tggcgctgcc aaggctgtgg 840
gcaaggtcat ccctgagctg aacgggaagc tcactggcat ggccttccgt gtccccactg 900
ccaacgtgtc agtggtggac ctgacctgcc gtctagaaaa acctgccaaa tatgatgaca 960
tcaagaaggt ggtgaagcag gcgtcggagg gccccctcaa gggcatcctg ggctacactg 1020
agcaccaggt ggtctcctct gacttcaaca gcgacaccca ctcctccacc tttgacgctg 1080
gggctggcat tgccctcaac gaccactttg tcaagctcat ttcctggtat gacaacgaat 1140
ttggctacag caacagggtg gtggacctca tggcccacat ggcctccaag gagtaagacc 1200
cctggaccac cagccccagc aagagcacaa gaggaagaga gagaccctca ctgctgggga 1260
gtccctgcca cactcagtcc cccaccacac tgaatctccc ctcctcacag ttgccatgta 1320
gaccccttga agaggggagg ggcctaggga gccgcacctt gtcatgtacc atcaataaag 1380
taccctgtgc tcaaccagtt aaaaaaaaaa aaaaaaaaaa a 1421
<210> 7
<211> 21
<212> DNA
<213>artificial sequence
<400> 7
ggatcttgtc agtgacgttg t 21
<210> 8
<211> 19
<212> DNA
<213>artificial sequence
<400> 8
gtagcgattc cggcactgt 19
<210> 9
<211> 20
<212> DNA
<213>artificial sequence
<400> 9
acctgaggca gctcttttgc 20
<210> 10
<211> 25
<212> DNA
<213>artificial sequence
<400> 10
ggatgtgtgt gctccttcta aagaa 25
<210> 11
<211> 23
<212> DNA
<213>artificial sequence
<400> 11
tttctctcaa aggactacga gat 23
<210> 12
<211> 18
<212> DNA
<213>artificial sequence
<400> 12
agcagccctc aggtcaaa 18
<210> 13
<211> 20
<212> DNA
<213>artificial sequence
<400> 13
cagttctacc agcggcagta 20
<210> 14
<211> 20
<212> DNA
<213>artificial sequence
<400> 14
ggtagcgggt gtgaaaatca 20
<210> 15
<211> 19
<212> DNA
<213>artificial sequence
<400> 15
ccgaactctg ggccataca 19
<210> 16
<211> 22
<212> DNA
<213>artificial sequence
<400> 16
ttgcaggatg ctcacacatc tc 22
<210> 17
<211> 25
<212> DNA
<213>artificial sequence
<400> 17
ctcttttgtg agtgagtgat tggaa 25
<210> 18
<211> 21
<212> DNA
<213>artificial sequence
<400> 18
ccctgcattg tccattctgt t 21
<210> 19
<211> 26
<212> DNA
<213>artificial sequence
<400> 19
aactcctgta gccgaatcta ccgctc 26
<210> 20
<211> 22
<212> DNA
<213>artificial sequence
<400> 20
tagccacccc caccccactt gc 22
<210> 21
<211> 28
<212> DNA
<213>artificial sequence
<400> 21
tcaaaatcct ctggcctctc ctacgaac 28
<210> 22
<211> 22
<212> DNA
<213>artificial sequence
<400> 22
cccctaccct aacggcaagc ca 22
<210> 23
<211> 22
<212> DNA
<213>artificial sequence
<400> 23
caaacggcca gagcacctgc gt 22
<210> 24
<211> 29
<212> DNA
<213>artificial sequence
<400> 24
actcctgttg ccagaatcag actgcccta 29
<210> 25
<211> 24
<212> DNA
<213>artificial sequence
<400> 25
accatgagaa gtatgacaac agcc 24
<210> 26
<211> 23
<212> DNA
<213>artificial sequence
<400> 26
cacgatacca aagttgtcat gga 23
<210> 27
<211> 23
<212> DNA
<213>artificial sequence
<400> 27
tcagcaatgc ctcctgcacc acc 23
<210> 28
<211> 1421
<212> DNA
<213>Genus Homo, ethnic group, Homo sapiens (human)
<400> 28
gcctcaagac cttgggctgg gactggctga gcctggcggg aggcggggtc cgagtcaccg 60
cctgccgccg cgcccccggt ttctataaat tgagcccgca gcctcccgct tcgctctctg 120
ctcctcctgt tcgacagtca gccgcatctt cttttgcgtc gccagccgag ccacatcgct 180
cagacaccat ggggaaggtg aaggtcggag tcaacggatt tggtcgtatt gggcgcctgg 240
tcaccagggc tgcttttaac tctggtaaag tggatattgt tgccatcaat gaccccttca 300
ttgacctcaa ctacatggtt tacatgttcc aatatgattc cacccatggc aaattccatg 360
gcaccgtcaa ggctgagaac gggaagcttg tcatcaatgg aaatcccatc accatcttcc 420
aggagcgaga tccctccaaa atcaagtggg gcgatgctgg cgctgagtac gtcgtggagt 480
ccactggcgt cttcaccacc atggagaagg ctggggctca tttgcagggg ggagccaaaa 540
gggtcatcat ctctgccccc tctgctgatg cccccatgtt cgtcatgggt gtgaaccatg 600
agaagtatga caacagcctc aagatcatca gcaatgcctc ctgcaccacc aactgcttag 660
cacccctggc caaggtcatc catgacaact ttggtatcgt ggaaggactc atgaccacag 720
tccatgccat cactgccacc cagaagactg tggatggccc ctccgggaaa ctgtggcgtg 780
atggccgcgg ggctctccag aacatcatcc ctgcctctac tggcgctgcc aaggctgtgg 840
gcaaggtcat ccctgagctg aacgggaagc tcactggcat ggccttccgt gtccccactg 900
ccaacgtgtc agtggtggac ctgacctgcc gtctagaaaa acctgccaaa tatgatgaca 960
tcaagaaggt ggtgaagcag gcgtcggagg gccccctcaa gggcatcctg ggctacactg 1020
agcaccaggt ggtctcctct gacttcaaca gcgacaccca ctcctccacc tttgacgctg 1080
gggctggcat tgccctcaac gaccactttg tcaagctcat ttcctggtat gacaacgaat 1140
ttggctacag caacagggtg gtggacctca tggcccacat ggcctccaag gagtaagacc 1200
cctggaccac cagccccagc aagagcacaa gaggaagaga gagaccctca ctgctgggga 1260
gtccctgcca cactcagtcc cccaccacac tgaatctccc ctcctcacag ttgccatgta 1320
gaccccttga agaggggagg ggcctaggga gccgcacctt gtcatgtacc atcaataaag 1380
taccctgtgc tcaaccagtt aaaaaaaaaa aaaaaaaaaa a 1421

Claims (15)

1. one group of hepatocarcinoma gene marker, it is characterised in that: by EP400 gene, MAPK1IP1L gene, NUFIP2 gene, PHC3 Gene, RPS6KB1 gene and STX7 gene composition.
2. one group of hepatocarcinoma gene marker according to claim 1, it is characterised in that: the EP400 gene is sequence table Polynucleotide sequence shown in SEQ ID NO:1 (NCBI number NM_015409), MAPK1IP1L gene are sequence table SEQ ID Polynucleotide sequence shown in NO:2 (NCBI number NM_144578), NUFIP2 gene are shown in sequence table SEQ ID NO:3 Polynucleotide sequence (NCBI number NM_020772), PHC3 gene are polynucleotide sequence shown in sequence table SEQ ID NO:4 (NCBI number NM_024947), RPS6KB1 gene are (the NCBI number of polynucleotide sequence shown in sequence table SEQ ID NO:5 NM_003161), STX7 gene is polynucleotide sequence (NCBI number NM_003569) shown in sequence table SEQ ID NO:6.
3. purposes of the reagent of hepatocarcinoma gene marker described in detection as claimed in claim 1 or 22 in the product of preparation detection liver cancer.
4. purposes according to claim 3, it is characterised in that: the product of the detection liver cancer is real-time quantitative PCR reagent Box, RNA sequencing kit or genetic chip.
5. purposes according to claim 3, it is characterised in that: the reagent of the above-mentioned hepatocarcinoma gene marker of detection is inspection Survey the primer and/or probe of hepatocarcinoma gene marker.
6. purposes according to claim 5, it is characterised in that: the primer is specific amplified SEQ ID NO:1~SEQ The primer of ID NO:6 gene order；The probe is that can hybridize with gene order shown in SEQ ID NO:1~SEQ ID NO:6 Probe.
7. purposes according to claim 6, it is characterised in that: the primer has sequence table SEQ ID NO:7~SEQ Sequence shown in ID NO:18；The probe has sequence shown in sequence table SEQ ID NO:19~SEQ ID NO:24.
8. a kind of kit for detecting liver cancer, it is characterised in that: be directed to SEQ ID NO:1~SEQ ID NO:6 comprising specificity Shown in hepatocarcinoma gene marker primer and/or probe.
9. kit according to claim 8, it is characterised in that: the sequence of the primer is SEQ ID NO:7~SEQ Shown in ID NO:18；The sequence of the probe is shown in SEQ ID NO:19~SEQ ID NO:24.
10. kit according to claim 8 or claim 9, it is characterised in that: the kit also includes for reference gene The primer and/or probe of GAPDH；Primer is sequence shown in sequence table SEQ ID NO:25 and sequence table SEQ ID NO:26, is visited Needle is sequence shown in sequence table SEQ ID NO:27.
11. kit according to claim 10, it is characterised in that: the probe sequence has fluorescent marker, and the end 5' is glimmering Cursor is denoted as one of FAM, HEX, TET, TAMRA, Cy5, Cy3, VIC, R0X and JOE, the end 3' fluorescent marker be TAMRA, One of BHQ, MGB, DABCYL and Elipse.
12. a kind of liver cancer detection method measures presence and/or the water of hepatocarcinoma gene biomarker of any of claims 1 or 2 Flat may include a kind of depositing for polynucleotides (such as a kind of biomarker genes transcript) that measurement encodes the biomarker And/or it is horizontal.
13. detection method according to claim 12, which is characterized in that this method comprises:
(1) presence and/or level of the hepatocarcinoma gene marker in the sample of subject are measured；And
(2) presence of hepatocarcinoma gene marker and/or level are compared with a kind of compare, are wherein compareed in the sample with this A kind of different presence and/or level indicate liver cancer.
14. detection method according to claim 12 or 13, it is characterised in that: the described sample includes blood, blood plasma, blood Clearly, urine, blood platelet, megacaryocyte or excreta.
15. a kind for the treatment of method of liver cancer, this method comprises:
(1) 2 to 14 method diagnosis or detection liver cancer according to claim 1；And
(2) it gives or recommends a kind of for treating the therapeutic agent of liver cancer.
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CN110241220A (en) * 2019-07-31 2019-09-17 华夏帮服科技有限公司 For the peripheral blood open gene marker of breast cancer detection and its application
CN110241220B (en) * 2019-07-31 2022-11-01 青岛解码医学检验有限公司 Peripheral blood transcriptional gene marker for breast cancer detection and application thereof
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CN110904225B (en) * 2019-11-19 2022-04-12 中国医学科学院肿瘤医院 Combined marker for liver cancer detection and application thereof
CN111413498A (en) * 2020-04-08 2020-07-14 复旦大学附属中山医院 Autoantibody 7-AAb detection panel for hepatocellular carcinoma and application thereof
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CN112626198A (en) * 2020-12-25 2021-04-09 杭州师范大学附属医院 Molecular marker for liver disease severe treatment and application thereof
CN113555118A (en) * 2021-07-26 2021-10-26 内蒙古自治区人民医院 Method and device for predicting disease degree, electronic equipment and storage medium
CN113555118B (en) * 2021-07-26 2023-03-31 内蒙古自治区人民医院 Method and device for predicting disease degree, electronic equipment and storage medium
CN115717167A (en) * 2021-11-30 2023-02-28 杭州翱锐基因科技有限公司 Novel marker combination and kit for early detection of multi-target liver cancer
CN115717167B (en) * 2021-11-30 2023-09-05 杭州翱锐基因科技有限公司 Novel marker combination and kit for early detection of multi-target liver cancer

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