CN113689914B - 一种单基因遗传病扩展性携带者筛查方法及芯片 - Google Patents

一种单基因遗传病扩展性携带者筛查方法及芯片 Download PDF

Info

Publication number
CN113689914B
CN113689914B CN202011494818.5A CN202011494818A CN113689914B CN 113689914 B CN113689914 B CN 113689914B CN 202011494818 A CN202011494818 A CN 202011494818A CN 113689914 B CN113689914 B CN 113689914B
Authority
CN
China
Prior art keywords
screening
mutation
gene
pathogenic
genes
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN202011494818.5A
Other languages
English (en)
Other versions
CN113689914A (zh
Inventor
毛良伟
柯雅娟
姚辉
卢飞
吴丰盛
谭刚
项慰
吴超男
周媛
杨帆
袁林玲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wuhan Liangpei Medical Laboratory Co ltd
Original Assignee
Wuhan Liangpei Medical Laboratory Co ltd
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 Wuhan Liangpei Medical Laboratory Co ltd filed Critical Wuhan Liangpei Medical Laboratory Co ltd
Priority to CN202011494818.5A priority Critical patent/CN113689914B/zh
Publication of CN113689914A publication Critical patent/CN113689914A/zh
Application granted granted Critical
Publication of CN113689914B publication Critical patent/CN113689914B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B50/00—ICT programming tools or database systems specially adapted for bioinformatics
    • 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
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/50—Mutagenesis
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Landscapes

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

Abstract

本发明公开了一种单基因遗传病扩展性携带者筛查方法及芯片。所述的筛查方法包括：(1)预估所有遗传疾病基因的致病突变携带率；(2)基于步骤(1)所得致病突变携带率、计算相应基因的携带率(GCR)；(3)基于步骤(2)所得GCR，计算基因筛查等级分数(GSR)。整合变异与疾病表型数据库、gnomAD东亚人群频率数据库及大规模中国女性群体变异频率数据库分别计算东亚男性、东亚女性和中国女性各基因的筛查等级分数，可作为常染色体和性染色体隐性遗传病筛选策略构建适合东亚人群或者中国女性人群遗传背景的扩展性携带者筛查疾病列表。

Description

一种单基因遗传病扩展性携带者筛查方法及芯片
技术领域
本发明属于生物遗传领域，具体涉及一种单基因遗传病扩展性携带者筛查方法及芯片，特别是东亚、中国人群单基因遗传病扩展性携带者筛查方法。
背景技术
单基因遗传病是指受一对等位基因控制的遗传病，如遗传性耳聋、进行性假肥大性肌营养不良、脊髓性肌肉萎缩症、地中海贫血等。单基因遗传病种类多，目前已发现8000多种，综合发病率高达1/100。总体来看，单基因遗传病是婴儿死亡和儿童住院的重要原因之一[1,2]。多数单基因遗传病对人类健康造成严重损伤(致死、致残或致畸)，然而却缺乏有效的诊治手段，目前仅5％的疾病有有效的治疗药物，且治疗费用昂贵。单基因遗传病不仅对患者的健康造成严重危害，也给家庭和社会带来了沉重的精神和经济负担。
根据临床基因组数据库(https://research.nhgri.nih.gov/CGD/)的数据显示[3]，约有1875个基因与隐性疾病相关，常染色体隐性疾病和x连锁疾病是其主要的疾病负担。在过去50年中，随着植入前遗传学诊断技术的不断提升和遗传学知识的推广普及，常染色体隐性疾病和x连锁疾病引起了广泛的重视[4]。此外，快速且成本低廉的全基因组和全外显子组测序技术的应用和推广加上基因组变异数据库的完善以及新的致病基因和突变的不断认知逐步拓宽了对人类基因组探索的视野。这些进展都为成功筛查不同人群中所有导致严重疾病的常染色体隐性疾病和x连锁疾病的突变携带状态提供了机会，从而减轻这一重要的疾病负担。
国外权威学术机构相继发布关于扩展性携带者筛查的临床应用指南规范。2013年，ACMG出台相应声明以规范孕/产前扩大化携带者筛查[5]。2015年，ACMG、ACOG联合NSGC(美国遗传咨询学会)、Perinatal Quality Foundation(围产期质量基金会)及SMFM(美国母胎医学会)发表了针对扩展性携带者筛查在生殖领域应用的联合声明，建议对于育龄期女性，携带者筛查最好在妊娠前进行。配子供者在进行其他筛查检测之前，也应进行携带者筛查[6]。ACOG在2017年3月发布了两个委员会意见(NO.690，NO.691)[7,8]，在先前指南基础上进行更具体的ECS指导，并指出每一名孕妇都应该被告知携带者筛查项目。
在我国，每年的出生缺陷婴儿数量约占全世界的20％，据原卫生部发布的《中国出生缺陷防治报告(2012)》显示，目前我国出生缺陷总发生率约为5.6％，每年新增出生缺陷高达90万例。这其中，单基因遗传病占据了相当的比例。有鉴于此，开展单基因病的携带者筛查不仅能够加强出生缺陷防控网络，而且还有助于提升一部分单基因病的预防级别。
考虑到ECS panel临床效用最大化的重要性，亟需一种方法用于评估针对东亚人群的疾病纳入标准。
发明内容
本发明所要解决的技术问题是为克服现有技术中缺乏一种用于评估针对东亚人群的疾病纳入标准的方法的缺陷，提供一种单基因遗传病扩展性携带者筛查方法及芯片。
在本发明中，通过整合突变数据库和人群频率数据库计算基因致病突变携带率，并综合考虑每个基因对于突变的容忍度进一步量化，最终筛选出适合东亚人群的扩展性携带者筛查基因。使其最大限度地在我国发挥临床效用，产生重要的社会和经济价值。
本发明的技术方案之一为：一种单基因遗传病扩展性携带者的筛查方法，其包括如下步骤：
(1)预估所有遗传疾病基因的致病突变携带率；利用如下公式计算每种致病突变或可能致病突变的携带率(VCR)：
其中：AC是该致病突变个体计数，HOM是该突变纯合子个体计数，AN是该基因座个体总计数；
(2)基于步骤(1)所得致病突变携带率、通过如下公式计算相应基因的携带率(GCR)：
其中：VCRi是突变i的携带率，v是基因g中致病或可能致病的突变数量；
(3)基于步骤(2)所得GCR、通过如下公式计算基因筛查等级分数(GSR)：
GSRg＝GCRg×GeVIRg
其中：GCRg为基因g的突变携带率，GeVIRg则为基因g的不耐受等级virlof_ar_enrichment参数分数。
较佳地，步骤(1)中所用数据库为变异与疾病表型数据库(ClinVar)和基因组突变频率数据库(gnomAD)。
基于如上所述方法，所筛查到的东亚男性各基因的筛查等级分数见下表：
所筛查到的东亚女性各基因的筛查等级分数较佳地如下表所列：
/>
/>
所筛查到的中国女性各基因的筛查等级分数较佳地见下表所列：
/>
/>
/>
本发明的技术方案之二为一种芯片，其包含如上所定义表格中的基因的全部转录本的外显子坐标，且每个外显子区两边分别扩充10bp，每个基因的每个转录本数据来源于https://genome.ucsc.edu/cgi-bin/hgTables。
在符合本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于：
整合变异与疾病表型数据库、gnomAD东亚人群频率数据库及大规模中国女性群体变异频率数据库分别计算东亚男性、东亚女性和中国女性各基因的筛查等级分数，可作为常染色体和性染色体隐性遗传病筛选策略构建适合东亚人群或者中国女性人群遗传背景的扩展性携带者筛查疾病列表。
附图说明
图1为东亚男性的基因分布绘制图。
图2为东亚女性的基因分布绘制图。
图3为中国女性的基因分布绘制图。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
实施例1
(1)遗传病致病基因筛选策略
通过变异与疾病表型数据库(ClinVar)和基因组突变频率数据库(gnomAD)估计所有遗传疾病基因的致病突变携带率。
致病突变携带率计算的主要步骤如下：首先，获得ClinVar数据库(https://www.ncbi.nlm.nih.gov/clinvar/)中标记为likely pathogenic或者pathogenic的突变信息。然后，利用gnomAD v2.1.1(https://gnomad.broadinstitute.org/)东亚人群数据库中男性与女性的突变频率对上述突变进行注释。在注释的过程中可以获得每个致病或者疑似致病突变的个体计数(Allele Count)，基因座个体总计数(Allele Number)和纯合子个体数量(Number of Homozygotes)。
首先计算每种致病突变或可能致病突变的携带率(VCR)，公式如下：
这里，AC是该致病突变个体计数，HOM是该突变纯合子个体计数，AN是该基因座个体总计数。
然后可以通过突变的携带率计算相应基因的携带率(GCR)：
在此，VCRi是突变i的携带率，v是基因g中致病或可能致病的突变数量。
(2)根据基因突变容忍性排序对筛选基因进行排序
对于基因突变耐受能力的度量同样有助于疾病致病基因的优先排序。通过基因变异不耐受等级(GeVIR，gene variation intolerance rank)对上述基因排序进一步矫正。GeVIR可用于优先选择错义突变不耐受的候选基因，校正基于virlof_ar_enrichment参数，因为它可用于评估基于变异的基因约束项的最佳性能。因此，基因筛查等级分数(GSR)公式如下：
GSRg＝GCRg×GeVIRg
其中，GCRg为基因g的突变携带率，GeVIRg则为基因g的不耐受等级virlof_ar_enrichment参数分数。
东亚男性各基因的筛查等级分数见表1和图1，东亚女性各基因的筛查等级分数见表2和图2。
表1
/>
/>
/>
/>
/>
/>
/>
/>
/>
表2
/>
/>
/>
/>
/>
/>
/>
/>
/>
(3)根据中国女性群体变异频率数据库对筛选基因进行排序
CMDB(http://cmdb.bgi.com/)是唯一一个提供大规模中国女性群体变异频率数据库。同样地，我们通过变异与疾病表型数据库(ClinVar)和CMDB估计所有遗传疾病基因的致病突变携带率。致病突变携带率计算的主要步骤如下：首先，获得ClinVar数据库(https://www.ncbi.nlm.nih.gov/clinvar/)中标记为likely pathogenic或者pathogenic的突变信息。然后，利用CMDB中女性的突变频率对上述突变进行注释。因数据库中并没有纯合子个体数量，因此，我们直接根据每个突变的频率计算基因的携带率(GCR)，公式如下：
其中，VCRi是突变i的频率，v是基因g中致病或可能致病的突变数量。
同样地，最后基于基因变异不耐受等级(GeVIR，gene variation intolerancerank)对上述基因排序进一步矫正得到中国女性各基因的筛查等级分数。
所得结果见表3和图3。
表3
/>
/>
/>
/>
/>
/>
参考文献：
1.Langlois S,Benn P,Wilkins-Haug L:Current controversies in prenataldiagnosis 4:pre-conception expanded carrier screening should replace allcurrent prenatal screening for specific single gene disorders.Prenat Diagn2015,35(1):23-28.
2.Kingsmore S:Comprehensive carrier screening and moleculardiagnostic testing for recessive childhood diseases.PLoS Curr 2012:e4f9877ab9878ffa9879.
3.Solomon BD,Nguyen AD,Bear KA,Wolfsberg TG:Clinical genomicdatabase.Proc Natl Acad Sci U S A 2013,110(24):9851-9855.
4.Antonarakis SE:Carrier screening for recessive disorders.Nat RevGenet 2019,20(9):549-561.
5.Grody WW,Thompson BH,Gregg AR,Bean LH,Monaghan KG,Schneider A,LeboRV:ACMG position statement on prenatal/preconception expanded carrierscreening.Genet Med 2013,15(6):482-483.
6.Edwards JG,Feldman G,Goldberg J,Gregg AR,Norton ME,Rose NC,Schneider A,Stoll K,Wapner R,Watson MS:Expanded carrier screening inreproductive medicine-points to consider:a joint statement of the AmericanCollege of Medical Genetics and Genomics,American College of Obstetriciansand Gynecologists,National Society of Genetic Counselors,Perinatal QualityFoundation,and Society for Maternal-Fetal Medicine.Obstet Gynecol 2015,125(3):653-662.
7.Committee on G:Committee Opinion No.690:Carrier Screening in theAge of Genomic Medicine.Obstet Gynecol 2017,129(3):e35-e40.
8.Committee on G:Committee Opinion No.691:Carrier Screening forGenetic Conditions.Obstet Gynecol 2017,129(3):e41-e55.

Claims (6)

1.一种单基因遗传病扩展性携带者的筛查方法，其包括如下步骤：
(1)预估所有遗传疾病基因的致病突变携带率；利用如下公式计算每种致病突变或可能致病突变的携带率：
其中：AC是该致病突变个体计数，HOM是该突变纯合子个体计数，AN是基因座个体总计数；
(2)基于步骤(1)所得致病突变携带率、通过如下公式计算相应基因的携带率：
其中：VCRi是突变i的携带率，v是基因g中致病或可能致病的突变数量；
(3)基于步骤(2)所得GCR、通过如下公式计算基因筛查等级分数：
GSRg＝GCRg×GeVIRg
其中：GCRg为基因g的突变携带率，GeVIRg则为基因g的不耐受等级virlof_ar_enrichment参数分数；
所述筛查方法为非诊断目的的。
2.如权利要求1所述的筛查方法，其特征在于，步骤(1)中所用数据库为变异与疾病表型数据库和基因组突变频率数据库。
3.如权利要求2所述的筛查方法，其特征在于，所筛查到的东亚男性各基因的筛查等级分数见下表：
4.如权利要求2所述的筛查方法，其特征在于，所筛查到的东亚女性各基因的筛查等级份数见下表：
/>
/>
。
5.如权利要求2所述的方法，其特征在于，所筛查到的中国女性各基因的筛查等级分数见下表：
/>
/>
/>
6.一种芯片，其特征在于，其包含如权利要求3～5中任一项中所定义表格中的基因的全部转录本的外显子坐标，且每个外显子区两边分别扩充10bp，每个基因的每个转录本数据来源于https://genome.ucsc.edu/cgi-bin/hgTables。
CN202011494818.5A 2020-12-17 2020-12-17 一种单基因遗传病扩展性携带者筛查方法及芯片 Active CN113689914B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011494818.5A CN113689914B (zh) 2020-12-17 2020-12-17 一种单基因遗传病扩展性携带者筛查方法及芯片

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011494818.5A CN113689914B (zh) 2020-12-17 2020-12-17 一种单基因遗传病扩展性携带者筛查方法及芯片

Publications (2)

Publication Number Publication Date
CN113689914A CN113689914A (zh) 2021-11-23
CN113689914B true CN113689914B (zh) 2024-02-20

Family

ID=78576167

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011494818.5A Active CN113689914B (zh) 2020-12-17 2020-12-17 一种单基因遗传病扩展性携带者筛查方法及芯片

Country Status (1)

Country Link
CN (1) CN113689914B (zh)

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITPD20070415A1 (it) * 2007-12-19 2009-06-20 Istituto Di Ricovero E Cura A Metodo ed apparato per la rilevazione dello stato di portatore sano della mutazione genetica 35delg sul gene gjb2 come fattore di rischio di ipoacusie
WO2014052909A2 (en) * 2012-09-27 2014-04-03 The Children's Mercy Hospital System for genome analysis and genetic disease diagnosis
WO2015127853A1 (zh) * 2014-02-25 2015-09-03 林巍 家族特异性遗传病关联等位基因单体型变异标签确认方法
CN106011224A (zh) * 2015-12-24 2016-10-12 晶能生物技术（上海）有限公司 神经系统遗传性疾病基因联合筛查方法、试剂盒及其制备方法
KR20170093511A (ko) * 2016-02-05 2017-08-16 사회복지법인 삼성생명공익재단 추정 자손의 유전질환 발병 위험성을 예측하는 방법 및 시스템
WO2018096308A1 (en) * 2016-11-23 2018-05-31 Logical Medical Systems Limited Non-invasive prenatal screening method
CN110364226A (zh) * 2019-08-16 2019-10-22 复旦大学 一种用于辅助生殖供精策略的遗传风险预警方法和系统
WO2019204632A1 (en) * 2018-04-18 2019-10-24 Rady Chidren's Hospital Research Center Method and system for rapid genetic analysis
CN110648722A (zh) * 2019-09-19 2020-01-03 北京市儿科研究所 新生儿遗传病患病风险评估的装置
CN111139291A (zh) * 2020-01-14 2020-05-12 首都医科大学附属北京安贞医院 一种单基因遗传性疾病高通量测序分析方法
CN111883210A (zh) * 2020-06-08 2020-11-03 国家卫生健康委科学技术研究所 基于临床特征和序列变异的单基因病名称推荐方法及系统
CN111961713A (zh) * 2020-07-24 2020-11-20 天津华大医学检验所有限公司 用于遗传病致病基因携带者筛查的探针组合物、试剂盒及其制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030082606A1 (en) * 2001-09-04 2003-05-01 Lebo Roger V. Optimizing genome-wide mutation analysis of chromosomes and genes

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITPD20070415A1 (it) * 2007-12-19 2009-06-20 Istituto Di Ricovero E Cura A Metodo ed apparato per la rilevazione dello stato di portatore sano della mutazione genetica 35delg sul gene gjb2 come fattore di rischio di ipoacusie
WO2014052909A2 (en) * 2012-09-27 2014-04-03 The Children's Mercy Hospital System for genome analysis and genetic disease diagnosis
WO2015127853A1 (zh) * 2014-02-25 2015-09-03 林巍 家族特异性遗传病关联等位基因单体型变异标签确认方法
CN106011224A (zh) * 2015-12-24 2016-10-12 晶能生物技术（上海）有限公司 神经系统遗传性疾病基因联合筛查方法、试剂盒及其制备方法
KR20170093511A (ko) * 2016-02-05 2017-08-16 사회복지법인 삼성생명공익재단 추정 자손의 유전질환 발병 위험성을 예측하는 방법 및 시스템
WO2018096308A1 (en) * 2016-11-23 2018-05-31 Logical Medical Systems Limited Non-invasive prenatal screening method
WO2019204632A1 (en) * 2018-04-18 2019-10-24 Rady Chidren's Hospital Research Center Method and system for rapid genetic analysis
CN110364226A (zh) * 2019-08-16 2019-10-22 复旦大学 一种用于辅助生殖供精策略的遗传风险预警方法和系统
CN110648722A (zh) * 2019-09-19 2020-01-03 北京市儿科研究所 新生儿遗传病患病风险评估的装置
CN111139291A (zh) * 2020-01-14 2020-05-12 首都医科大学附属北京安贞医院 一种单基因遗传性疾病高通量测序分析方法
CN111883210A (zh) * 2020-06-08 2020-11-03 国家卫生健康委科学技术研究所 基于临床特征和序列变异的单基因病名称推荐方法及系统
CN111961713A (zh) * 2020-07-24 2020-11-20 天津华大医学检验所有限公司 用于遗传病致病基因携带者筛查的探针组合物、试剂盒及其制备方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China;He, J，等;GENETICS IN MEDICINE;第19卷(第9期);第1022-1031页 *
Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy;Bao, JR，等;CHINESE MEDICAL JOURNAL;第126卷(第22期);第4238-4241页 *
单基因病扩展性携带者筛查的发展与挑战;杨锴，等;中国计划生育学杂志(第11期);第1131-1134页 *
单基因病的携带者筛查;蒋宇林，等;中国产前诊断杂志;第11卷(第2期);第12-15页 *

Also Published As

Publication number Publication date
CN113689914A (zh) 2021-11-23

Similar Documents

Publication Publication Date Title
Pös et al. Recent trends in prenatal genetic screening and testing
Zhang et al. Genetic analysis of first‐trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH
Lee et al. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies
Faas et al. Identification of clinically significant, submicroscopic chromosome alterations and UPD in fetuses with ultrasound anomalies using genome-wide 250k SNP array analysis
Sheth et al. Chromosomal abnormalities in couples with repeated fetal loss: An Indian retrospective study
Han et al. Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: benefit for prenatal counseling and pregnancy management
de Lima et al. Cytokine gene polymorphisms in preeclampsia and eclampsia
Cheng et al. Chromosomal polymorphisms are associated with female infertility and adverse reproductive outcomes after infertility treatment: a 7-year retrospective study
Dai et al. Effect of maternal age on spontaneous abortion during the first trimester in Northeast China
Zhang et al. Maternal common variant rs2305957 spanning PLK4 is associated with blastocyst formation and early recurrent miscarriage
Chang et al. A novel method for noninvasive diagnosis of monogenic diseases from circulating fetal cells
Hosseini Teshnizi et al. Influence of forkhead box protein 3 polymorphisms (rs2232365, rs3761548) with the outcome of pregnancy: a meta‐analysis
Lin et al. Intrauterine phenotypic features associated with 16p11. 2 recurrent microdeletions
Messaoudi et al. Interleukin-18 promoter polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population
Leme Galvão et al. Analysis of association of clinical aspects and IL1B tagSNPs with severe preeclampsia
Gou et al. Clinical utilization of chromosomal microarray analysis for the genetic analysis in subgroups of pregnancy loss
Brennan et al. Identification of a myometrial molecular profile for dystocic labor
CN113689914B (zh) 一种单基因遗传病扩展性携带者筛查方法及芯片
Meng et al. Changes in and efficacies of indications for invasive prenatal diagnosis of cytogenomic abnormalities: 13 years of experience in a single center
Milunsky et al. Prenatal molecular diagnosis of tuberous sclerosis complex
Zou et al. Unusual twinning: additional findings during prenatal diagnosis of twin zygosity by single nucleotide polymorphism (SNP) array
Wu et al. Prenatal diagnosis of Pallister‐Killian syndrome and literature review
Cheng et al. Should prenatal chromosomal microarray analysis be offered for isolated ventricular septal defect? A single-center retrospective study from China
Ye et al. Preimplantational genetic diagnosis and mutation detection in a family with duplication mutation of DMD gene
Wadt et al. Fetal ventriculomegaly due to familial submicroscopic terminal 6q deletions

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant