WO2016049878A1 - Procédé de test de filiation basé sur l'établissement de profils snp et application - Google Patents

Procédé de test de filiation basé sur l'établissement de profils snp et application Download PDF

Info

Publication number
WO2016049878A1
WO2016049878A1 PCT/CN2014/087988 CN2014087988W WO2016049878A1 WO 2016049878 A1 WO2016049878 A1 WO 2016049878A1 CN 2014087988 W CN2014087988 W CN 2014087988W WO 2016049878 A1 WO2016049878 A1 WO 2016049878A1
Authority
WO
WIPO (PCT)
Prior art keywords
base
snp
parent
ratio
sequencing
Prior art date
Application number
PCT/CN2014/087988
Other languages
English (en)
Chinese (zh)
Inventor
芦静
Original Assignee
深圳华大基因科技有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳华大基因科技有限公司 filed Critical 深圳华大基因科技有限公司
Priority to PCT/CN2014/087988 priority Critical patent/WO2016049878A1/fr
Priority to CN201480081788.1A priority patent/CN106715712B/zh
Priority to PCT/CN2014/095934 priority patent/WO2016049993A1/fr
Publication of WO2016049878A1 publication Critical patent/WO2016049878A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Definitions

  • the present invention relates to the field of biomedicine. More specifically, the present invention relates to a novel method of paternity testing.
  • Parent-child identification uses the theory of medicine, genetics and other disciplines and modern DNA detection technology to determine whether there is a blood relationship between controversial parents and children.
  • the means of paternity testing at home and abroad mainly include:
  • Blood type test that is, genetic polymorphism labeling test for various components in the blood.
  • the operation of this test method and the interpretation result depend on labor, and the operation is relatively complicated.
  • DNA polymorphism test It is currently the most internationally recognized method for paternity testing and individual identification.
  • sample used may be any tissue or organ of the human body such as blood, blood marks, saliva, hair, bones and the like.
  • DNA has individual uniqueness and group diversity, and no two individuals have identical DNA (except twins of identical twins). Therefore, the paternity test by DNA can achieve an accurate degree. Since the establishment of DNA fingerprinting technology by British geneticist Alec Jeffreys in 1985, new technologies and methods have emerged, and various genetic markers have been applied. Today's forensic DNA analysis technology has become the most effective method for personal identification and blood identification. .
  • STR locus and single nucleotide (SNP) locus detection are the core of second- and third-generation DNA analysis techniques, respectively, followed by RFLP (restriction fragment length polymorphism) and VNTR (variable Detection techniques developed by the study of quantitative tandem repeat polymorphisms.
  • RFLP restriction fragment length polymorphism
  • VNTR variable Detection techniques developed by the study of quantitative tandem repeat polymorphisms.
  • DNA analysis provides a scientific, reliable and fast means for forensic evidence testing, so that the identification of physical evidence can be transferred from individual exclusion to the level that can be used for the same identification.
  • DNA paternity testing can directly identify criminals and strong (violent) gestation in judicial criminals. The detection of major difficult cases such as the case provides an accurate and reliable basis.
  • the detection of DNA marker system will become an important means and means to solve the case. This method is very mature as a paternity test and is the best recognized method in the world.
  • STR is a second-generation molecular marker
  • SNP is a third-generation molecular marker technology that is future development.
  • STR is bound to be replaced by the third-generation molecular marker technology that was born in the late 1990s: a polymorphism (SNP) technique called mononucleoside.
  • SNP polymorphism
  • STR method is mainly detected by capillary sequencer.
  • SNP is only detected by gene chip or kit typing. Although these methods are highly accurate, the flux is small and the cost is high, which is not conducive to large scale. Identification of the sample.
  • the present invention provides a method for performing paternity testing based on SNP typing results of second-generation high-throughput sequencing, and provides a method for performing paternity testing based on the second-generation high-throughput sequencing SNP typing method.
  • the method includes the following steps:
  • the SNP meets the following criteria:
  • the length of the amplified product is from 150 bp to 250 bp, preferably from 180 to 220, particularly preferably 200 bp;
  • the SNP sites are in harmony with the Hardy-Weinberg equilibrium
  • the sample DNA from the progeny and the parent to be tested is amplified by the internal and external double primers, the internal primer is used to amplify the target product, and the external primer is amplified and added to the ligated adaptor so that the amplified product can be directly sequenced on the machine to achieve rapid Purpose of library construction (eg SEQ ID NO. 1 and SEQ ID NO. 2- [Barcode] - SEQ ID NO. 143);
  • the statistics in the parents and the children are statistically calculated.
  • the child and the parent are inconsistent with the number of sites n after the error rate, n is equal to 0, and is determined to be a parent-child relationship, otherwise there is 1-n *10 -8 viability confirms no parent-child relationship.
  • the selected SNP sites are the 70 SNP sites shown in Table 2. Randomly select 35 loci in these loci and use 11 samples for accuracy assessment
  • the 70 SNP loci shown in Table 2 are:
  • the primer that amplifies the SNP site is SEQ ID N 0.3-142, and each of the two primers sequentially amplifies the SNP site, as shown in Table 2.
  • the primer that amplifies the SNP site is SEQ ID NO. 3-72, and each of the two primers sequentially amplifies the SNP site, as shown in Table 2.
  • the library is built using the WaferGen platform.
  • the method of the invention can be applied to paternity identification or invasive paternity testing of triplet families.
  • nucleic acids can be extracted, and the second-generation sequencing platform (including the second-generation sequencing models such as Hiseq, Miseq, Proton, and PGM) is preferentially used for sample sequencing to perform paternity paternity testing.
  • the sample includes, but is not limited to, hair, oral cells, blood, urine, amniotic fluid, nails, cigarette butts, and the like.
  • base information including the base type and number of the tested SNP site is extracted, and if the number of primary base supports at the point is less than 50X, it is determined to be low coverage. The degree is not sufficient for accurate typing. When the number of major base supports is higher than 50X, it is determined as follows:
  • the ratio of the primary base to the second base is greater than 4/5 of all bases, the following heterozygous type is determined: if the ratio of the number of second bases to the number of third bases exceeds the threshold in Table 9. , giving a high tolerance to the heterozygous determination (the primary base to the second base ratio is within 15 times), and vice versa giving a medium latitude (the ratio of the primary base to the second base is 10 times Inside),
  • the method of the invention has high throughput, and up to 5184 loci in one amplification, only 70 SNP loci per sample, and 74 samples in a single amplification, suitable for large scale.
  • the sample identification analysis has low cost.
  • the identification cost of each family is less than 200 yuan.
  • the time is short.
  • the results can be reported within two days of single identification.
  • the genetic marker SNP has a lower mutation rate than STR, and the identification result is credible. Higher degrees.
  • the invention also provides a method for determining the parent-child relationship of SNP genotyping:
  • step 3 According to the genotype determined in step 2) and the threshold of the selected error rate, the number of statistically inconsistent sites in the triplet family is used to determine the parent-child relationship.
  • the relationship between the major base, the second base, and the third base number determines the genotype: if the ratio of the primary base to the second base is greater than all bases For 4/5, the following heterozygous type is determined:
  • the ratio of the primary base to the second base is not more than 4/5, the determination of the heterozygous type is given a low tolerance (the ratio of the primary base to the second base is within 2 times).
  • the error rate threshold selection range is: 3-6%, preferably 6%
  • the parent-child relationship determining method further comprises: counting, in the parent and the child, that the child and the parent exclude the number of sites n that are inconsistent after the experiment and the sequencing error, and if n is equal to 0, the parent-child relationship is determined, otherwise The feasibility of 1-n*10 -8 confirms that there is no parent-child relationship.
  • the method of the invention utilizes a second-generation sequencing platform, adopts a method of high-throughput site amplification and rapid database construction, and performs parent-child identification by large-scale sequencing method and typing results of SNP sites of sequencing data. set.
  • the method is flexible and simple, and can increase the site at random according to requirements. At the same time, the flux is high and the cost is low, and the identification of the parent and child can be effectively performed, and the credibility is higher than the STR paternity test.
  • the present inventors selected the third generation DNA molecular genetic marker SNP as a genetic marker for paternity identification, which has the advantages of small amplified fragments and low mutation rate, and selection of SNP sites and design of primers. , DNA extraction of the target, high-throughput PCR amplification, second-generation sequencing, SNP typing, paternity testing and other steps, can obtain more accurate typing results and paternity testing.
  • internal primer refers to a primer for a specific site to which a specific linker sequence is added, i.e., a specific common linker is added to 5' of the original common primers F and R.
  • the number of statistically inconsistent sites in the parental triplet is counted, and the parental judgment is performed according to the number of inconsistent sites.
  • the criterion for the determination is based on the number of sites after the exclusion experiment and the sequencing error. The number of loci that do not conform to the Mendelian inheritance law in the offspring and the parental family. If it is 0, it is judged as a parent-child relationship. If the number of loci is n (n>0), the probability of 1-n*10 -8 indicates that it is not a parent-child relationship. .
  • MAF refers to the Mionr Allele Frequency, the minimum allele frequency, which refers to the frequency of occurrence of unusual alleles in a given population.
  • TT TC
  • CC three genotypes
  • the frequency of C in the population is 0.36
  • the frequency of T is 0.64
  • Hardy-Weinberg balance refers to an infinite population in a group, and has the following conditions: random mating, no mutation without selection, no genetic drift, one position within the group The genotype frequency and gene frequency at the point will remain unchanged from generation to generation, in a genetic equilibrium state, which is called the Hardy-Weinberg equilibrium.
  • the determination of the typing threshold should be based on the effective depth of the sequencing data and the parameters should be adjusted.
  • the accuracy of the different thresholds is determined by comparison with the gold standard (sanger sequencing results), and the major alleles are based on the data of different depths.
  • the minor allele, the third allele sets different weights and thresholds, and uses the most accurate typing results as the basis for subsequent paternity testing.
  • step 6 is a statistic of the scored result of step 5).
  • the two alleles of the genotype of the offspring are from the parents, and all combinations of the genotypes of the parents are compared with the genotype of the child.
  • the parental genotype is not included in all combinations of the genotypes of the parents.
  • the method of using the third-generation molecular genetic marker combined with multi-site evidence for paternity testing in the method effectively improves the credibility of the paternity test, and the elimination rate is improved by at least four orders of magnitude.
  • high-throughput amplification and high-throughput sequencing individual SNP typing ensures that the work and efficiency of large sample sizes is improved, which can greatly reduce the cost of paternity testing.
  • the compatibility and scalability of the platform used can ensure the flexible and random increase of the site, which can further enhance the strength of paternity testing, ensure the accuracy of the results to the greatest extent, and at the same time maximize the genetic information of the family, and in the future. It can be used for the detection of family ancestors and the establishment of family maps.
  • the PCR Mix is prepared according to the following table system, shaken and mixed, placed on the ice box for use:
  • the chip Place the sample plate and chip into the corresponding positions of the spotter, select the 72 ⁇ 72 mode, 50nL volume, and start to spot. After the end of the sample for about 30 minutes, the chip was removed, and the chip was sealed with a specific sealing film and centrifuged. Remove the sample plate and seal the sealing film into a -20 ° C freezer for later use. Then put the primer plate and the centrifuged chip into the corresponding position of the spotter, select the 72 ⁇ 72 mode, 50nL volume, and start to spot. After about 30 minutes of sampling, the chip was removed, the parafilm was sealed, centrifuged, and ready for PCR amplification. Remove the primer plate and seal the sealing film into a -20 °C freezer for later use.
  • the SNP site is derived from the data of 90 inflammatory yellow data of the Yanhuang project and 1500 normal control individuals of the psoriasis project.
  • rs number which can also be called a reference SNP
  • specific information about the SNP including the sequence before and after, location information, distribution frequency, etc.
  • rs11239930 refers to a SNP site numbered rs11239930.
  • One skilled in the art can determine the specific location of the SNP site based on the number in the NCBI database.
  • This example was sequenced using the PGM platform, and the average depth of the data was 958X.
  • the data amounts of different depths correspond to different classification parameters, and the sample data amount in this embodiment is 958X, and the parameters used are as shown in the above table, and the parameters are empirical summaries, which can be compared. High accuracy.
  • the classification idea is to extract the base information (base type and number) of the tested SNP locus. If the number of main base supports at this point is lower than 50X, it is judged that the low coverage is not enough for accurate typing.
  • the number of base supports is higher than 50X, it is determined as follows: If the ratio of the main base to the second base is greater than 4/5 of all bases, the following heterozygous type is determined [if the number of second bases and The ratio of the number of three bases exceeds the threshold in the above table, giving a high tolerance to the heterozygous determination (the primary base to the second base ratio is within 15 times), and vice versa giving a medium tolerance (mainly The base to the second base ratio is within 10 times)], if the main base and the second base are A ratio of no more than 4/5 gives a low tolerance to the determination of the heterozygous type (the ratio of the major base to the second base is within 2 times).
  • the multi-site combined high-throughput parent-child method has an effective improvement in the accuracy of identification relative to the conventional paternity test method. Especially after adding more sites and reducing the tolerance, the reliability of the exclusion has been further improved.
  • This example is only intended to explain a conventional embodiment of the method and is not intended to limit the invention. All such changes, modifications, improvements, etc., made within the spirit and scope of the invention are intended to be included within the scope of the appended claims.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

La présente invention est un procédé de test de filiation basé sur le résultat d'établissement de profils de PNU d'un séquençage à haut débit de seconde génération. La présente invention sélectionne un PNU marqueur génétique moléculaire d'acide nucléique de troisième génération pour servir de marqueur génétique dans un test de filiation et, à l'aide de plusieurs étapes telles que la sélection de loci PNU, la conception d'amorce, l'extraction d'acide nucléique cible, l'amplification PCR à haut débit, le séquençage de seconde génération SNP, l'établissement de profils de PNU et d'un test de filiation, produit des résultats d'établissement de profils et un test de filiation d'une précision accrue.
PCT/CN2014/087988 2014-09-30 2014-09-30 Procédé de test de filiation basé sur l'établissement de profils snp et application WO2016049878A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/CN2014/087988 WO2016049878A1 (fr) 2014-09-30 2014-09-30 Procédé de test de filiation basé sur l'établissement de profils snp et application
CN201480081788.1A CN106715712B (zh) 2014-09-30 2014-12-31 用于鉴定多个生物样本之间身份关系的方法和系统
PCT/CN2014/095934 WO2016049993A1 (fr) 2014-09-30 2014-12-31 Procédé et système d'analyse de relations d'identité parmi de multiples échantillons biologiques

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2014/087988 WO2016049878A1 (fr) 2014-09-30 2014-09-30 Procédé de test de filiation basé sur l'établissement de profils snp et application

Publications (1)

Publication Number Publication Date
WO2016049878A1 true WO2016049878A1 (fr) 2016-04-07

Family

ID=55629305

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/CN2014/087988 WO2016049878A1 (fr) 2014-09-30 2014-09-30 Procédé de test de filiation basé sur l'établissement de profils snp et application
PCT/CN2014/095934 WO2016049993A1 (fr) 2014-09-30 2014-12-31 Procédé et système d'analyse de relations d'identité parmi de multiples échantillons biologiques

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/095934 WO2016049993A1 (fr) 2014-09-30 2014-12-31 Procédé et système d'analyse de relations d'identité parmi de multiples échantillons biologiques

Country Status (2)

Country Link
CN (1) CN106715712B (fr)
WO (2) WO2016049878A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106599612A (zh) * 2016-10-28 2017-04-26 上海阅尔基因技术有限公司 一种基于高通量测序数据的指纹识别方法
CN108694304A (zh) * 2018-05-21 2018-10-23 广州金域医学检验中心有限公司 一种身份关系鉴定方法、装置、设备及存储介质
WO2018214010A1 (fr) * 2017-05-23 2018-11-29 深圳华大基因研究院 Procédé, dispositif, et support d'informations pour détecter la mutation sur la base des données de séquençage
CN108998507A (zh) * 2018-07-24 2018-12-14 陈梦麟 一种应用于人群复杂亲缘关系鉴定的无创高通量检测方法

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106399535A (zh) * 2016-10-19 2017-02-15 江苏苏博生物医学股份有限公司 一种高通量测序检测无创亲子鉴定的方法
WO2019047083A1 (fr) * 2017-09-06 2019-03-14 深圳华大生命科学研究院 Procédé et dispositif pour déterminer un ensemble de loci snp et applications associées
SG11202001715YA (en) * 2017-09-07 2020-03-30 Regeneron Pharma Systems and methods for leveraging relatedness in genomic data analysis
CN110211631B (zh) * 2018-02-07 2024-02-09 深圳先进技术研究院 一种全基因组关联分析方法、系统及电子设备
CN108647495B (zh) * 2018-05-21 2020-04-10 广州金域医学检验中心有限公司 身份关系鉴定方法、装置、设备及存储介质
CN110846310B (zh) * 2018-08-21 2024-03-22 深圳华大法医科技有限公司 Snp位点集及胚胎核酸样本进行亲缘鉴定的方法和用途
CN110942806A (zh) * 2018-09-25 2020-03-31 深圳华大法医科技有限公司 一种血型基因分型方法和装置及存储介质
CN114496081A (zh) * 2020-10-27 2022-05-13 深圳华大基因股份有限公司 构建突变集合的方法及其应用
CN113470744B (zh) * 2021-06-04 2024-05-24 中国农业大学 基于snp位点数据的系谱推断方法、装置及电子设备
CN115125314A (zh) * 2022-06-01 2022-09-30 四川大学华西医院 一种异质性耐药细菌中碱基杂合的检测方法
CN117423382B (zh) * 2023-10-21 2024-05-10 云准医药科技(广州)有限公司 一种基于SNP多态性的单细胞barcode身份识别方法
CN118240948B (zh) * 2024-05-29 2024-09-03 中国科学院海洋研究所 基于靶向测序分型的凡纳滨对虾亲缘关系的鉴定方法和应用
CN118335195B (zh) * 2024-06-13 2024-09-20 浙江省标准化研究院(金砖国家标准化(浙江)研究中心、浙江省物品编码中心) 一种基于高通量测序数据的str分型方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102978286A (zh) * 2012-12-08 2013-03-20 上海迪道科技有限公司 利用特定snp组合进行亲子鉴定的方法
CN103608466A (zh) * 2010-12-22 2014-02-26 纳特拉公司 非侵入性产前亲子鉴定方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102952855B (zh) * 2011-08-26 2015-05-20 深圳华大基因科技服务有限公司 遗传图谱构建方法和装置、单体型分析方法和装置
CN103173557A (zh) * 2013-04-08 2013-06-26 上海邃志生物科技有限公司 一组用于人类亲子鉴定的多重pcr引物组合及检测方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103608466A (zh) * 2010-12-22 2014-02-26 纳特拉公司 非侵入性产前亲子鉴定方法
CN102978286A (zh) * 2012-12-08 2013-03-20 上海迪道科技有限公司 利用特定snp组合进行亲子鉴定的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HWAN YOUNG LEE ET AL.: "Selection of twenty-four highly informative SNP markers for human identification and paternity analysis in Korean s", FORENSIC SCIENCE INTERNATIONAL, vol. 148, 31 December 2005 (2005-12-31), pages 107 - 112 *
LI, LI ET AL.: "SNP Genotyping by Multiplex Amplification and Microarrays Assay and Forensic Application", JOURNAL OF FORENSIC MEDICINE, vol. 21, no. 2, 31 May 2005 (2005-05-31), pages 90 - 95 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106599612A (zh) * 2016-10-28 2017-04-26 上海阅尔基因技术有限公司 一种基于高通量测序数据的指纹识别方法
WO2018214010A1 (fr) * 2017-05-23 2018-11-29 深圳华大基因研究院 Procédé, dispositif, et support d'informations pour détecter la mutation sur la base des données de séquençage
CN108694304A (zh) * 2018-05-21 2018-10-23 广州金域医学检验中心有限公司 一种身份关系鉴定方法、装置、设备及存储介质
CN108694304B (zh) * 2018-05-21 2020-03-24 广州金域医学检验中心有限公司 一种身份关系鉴定方法、装置、设备及存储介质
CN108998507A (zh) * 2018-07-24 2018-12-14 陈梦麟 一种应用于人群复杂亲缘关系鉴定的无创高通量检测方法

Also Published As

Publication number Publication date
CN106715712A (zh) 2017-05-24
WO2016049993A1 (fr) 2016-04-07
CN106715712B (zh) 2021-02-19

Similar Documents

Publication Publication Date Title
WO2016049878A1 (fr) Procédé de test de filiation basé sur l'établissement de profils snp et application
JP6760917B2 (ja) 多型カウントを用いたゲノム画分の分析
KR102028375B1 (ko) 희귀 돌연변이 및 카피수 변이를 검출하기 위한 시스템 및 방법
CN103874767B (zh) 对核酸样本中预定区域进行基因分型的方法和系统
CN107771221B (zh) 用于癌症筛查和胎儿分析的突变检测
JP6161607B2 (ja) サンプルにおける異なる異数性の有無を決定する方法
CN106591441B (zh) 基于全基因捕获测序的α和/或β-地中海贫血突变的检测探针、方法、芯片及应用
JP2015534807A (ja) 胎児の染色体異数性を検出するための非侵襲的方法
CN110800063A (zh) 使用无细胞dna片段大小检测肿瘤相关变体
WO2018184495A1 (fr) Procédé de construction d'une bibliothèque d'amplicons à travers un procédé à étape unique
WO2016071369A1 (fr) Procédé de détermination de la présence d'un état biologique par détermination des quantités totales et relatives de deux acides nucléiques différents
CN112955958A (zh) 用于确定短串联重复区域中的变化的基于序列图的工具
CN111748628B (zh) 一种用于检测甲状腺癌预后相关基因变异的引物及试剂盒
CN109686404B (zh) 检测样本混淆的方法及装置
CN109207600A (zh) 鉴定生物样本间亲缘关系的方法和系统
CN114015749A (zh) 一种基于高通量测序的线粒体基因组测序文库的构建方法及扩增引物
CN110819710A (zh) 髓系肿瘤的高通量测序检测
CN111850116A (zh) 一组nk/t细胞淋巴瘤的基因突变位点群、靶向测序试剂盒及应用
CN110993025B (zh) 胎儿浓度定量的方法和装置及胎儿基因分型的方法和装置
AU2018201992A1 (en) Sequencing methods and compositions for prenatal diagnoses
CN105648044A (zh) 确定胎儿目标区域单体型的方法和装置
CN111020710A (zh) 造血及淋巴组织肿瘤的ctDNA高通量检测
CN110846310B (zh) Snp位点集及胚胎核酸样本进行亲缘鉴定的方法和用途
WO2020119626A1 (fr) Procédé de test prénatal non invasif de fœtus pour maladie génétique
CN109280697B (zh) 利用孕妇血浆游离dna进行胎儿基因型鉴定的方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14903017

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14903017

Country of ref document: EP

Kind code of ref document: A1