Collaborative Study of Genetics of Dizygotic Twinning

异卵双胞胎遗传学的合作研究

• 批准号: 7114898
• 负责人: GRANT W MONTGOMERY
• 金额: $ 39.56万
• 依托单位: QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114898
• 关键词: Australia; Europe; clinical research; dizygotic twins; endocrinology; epidemiology; family genetics; female; fertility; follicle stimulating hormone; gene mutation; genetic polymorphism; genetic regulation; genetic screening; genetic susceptibility; genome; genotype; human subject; interdisciplinary collaboration; linkage mapping; molecular genetics; nucleic acid sequence; ovulation; quantitative trait loci; single nucleotide polymorphism; transforming growth factors

DESCRIPTION (provided by applicant): Infertility is a major public health problem that affects 10-15% of couples (2.5 million) in the US. The goal of this program is to locate genes that make substantial contributions to variation in natural dizygotic (DZ) twinning to understand critical pathways controlling female fertility. This will have practical application in treatment of infertility and may provide new approaches to contraception. The proposed study extends our previous studies of the endocrinology, epidemiology, and molecular genetics of twinning in humans and in large animal models. We have ascertained 342 families with sister pairs who have both given birth to spontaneous DZ twins and a further 386 families with case-two parent triads and have collected DNA samples from the sisters' parents and other siblings. We shall use information from our twin studies and the Australian and Netherlands Twin Registries to collect an additional 240 affected sister pair families from Australia and New Zealand and 418 families from the Netherlands. DNA samples from these families will be used to complete a 10cM genome scan in 1000 families. We will use sib pair linkage analysis to locate QTLs for twinning. Our candidate positional cloning in animal models recently identified mutations in two genes (BMP15 and BMPRIB) from intra-ovarian signaling pathways that increase twinning frequency, and cause infertility in homozygous carriers of the BMP15 mutations. One important question is whether natural variation in human twinning is controlled by these emerging mechanisms or through other pathways. We will use available samples to immediately begin candidate gene studies by mutational screening and typing SNP markers in genes from this pathway (BMP15, GDF9, BMPR1B) using a matched case-control design with cases from our existing families and matched control samples. Significant associations will be tested in additional cases and their parents using the transmission disequilibrium test.

描述（由申请人提供）：不育是一个主要的公共卫生问题，在美国影响10-15％的夫妇（250万）。该程序的目的是定位对自然二叶植物（DZ）孪生变异做出重大贡献的基因，以了解控制女性生育能力的关键途径。这将在治疗不孕症治疗中具有实际应用，并可能提供新的避孕方法。拟议的研究扩展了我们先前关于人类和大动物模型中双胞胎的内分泌学，流行病学和分子遗传学的研究。我们已经确定了342个有姐妹对的家庭，他们既生育自发的DZ双胞胎，又有386个带有案例两个父母三合会的家庭，并从姐妹的父母和其他兄弟姐妹那里收集了DNA样本。我们将使用我们的双胞胎研究和澳大利亚和荷兰双胞胎登记处的信息来收集来自澳大利亚和新西兰的240个受影响的姊妹家庭，以及来自荷兰的418个家庭。这些家族的DNA样品将用于完成1000个家庭中的10厘米基因组扫描。我们将使用SIB对链接分析来定位QTL用于孪生。我们在动物模型中的候选位置克隆最近鉴定出来自卵巢内信号传导途径的两个基因（BMP15和BMPRIB）的突变，这些突变会增加孪晶频率，并在BMP15突变的纯合子中引起不育。一个重要的问题是，人双胞胎的自然变化是由这些新兴机制或其他途径控制的。我们将使用可用的样品立即通过使用匹配的病例对照设计的设计与现有家族的病例和匹配的控制样品的案例设计，并在该途径（BMP15，GDF9，BMPR1B）的基因（BMP15，GDF9，BMPR1B）中立即开始候选基因研究。在其他情况下，将使用传输不平衡测试对其他情况进行重大关联。

项目成果

Genetics of dizygotic twinning: a feasibility study for a biobank.

双卵双胞胎的遗传学：生物库的可行性研究。

• DOI: 10.1375/1369052042663751
• 发表时间: 2004
• 期刊: Twin research : the official journal of the International Society for Twin Studies
• 作者: Hoekstra,Chantal;Meijer,Piet;Kluft,Cornelis;Heutink,Peter;Smit,Guus;deGeus,Eco;Smit,JanH;vanBruggen,Angelique;Montgomery,GrantW;Boomsma,DorretI
• 通讯作者: Boomsma,DorretI

Dizygotic twinning is not associated with methylenetetrahydrofolate reductase haplotypes.

异卵双胞胎与亚甲基四氢叶酸还原酶单倍型无关。

• DOI: 10.1093/humrep/deg441
• 发表时间: 2003
• 期刊: Human reproduction (Oxford, England)
• 作者: Montgomery,GrantW;Zhao,ZhenZhen;Morley,KatherineI;Marsh,AnnaJ;Boomsma,DorretI;Martin,NicholasG;Duffy,DavidL
• 通讯作者: Duffy,DavidL

Variation in bone morphogenetic protein 15 is not associated with spontaneous human dizygotic twinning.

骨形态发生蛋白 15 的变异与自发的人类异卵双胞胎无关。

• DOI: 10.1093/humrep/den268
• 发表时间: 2008
• 期刊: Human reproduction (Oxford, England)
• 作者: Zhao,ZhenZhen;Painter,JodieN;Palmer,JamesS;Webb,PenelopeM;Hayward,NicholasK;Whiteman,DavidC;Boomsma,DorretI;Martin,NicholasG;Duffy,DavidL;Montgomery,GrantW
• 通讯作者: Montgomery,GrantW

Genome-Wide DNA Methylation Profiles in Whole-Blood and Buccal Samples-Cross-Sectional, Longitudinal, and across Platforms.

• DOI: 10.3390/ijms241914640
• 发表时间: 2023-09-27
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Van Asselt AJ;Beck JJ;Finnicum CT;Johnson BN;Kallsen N;Hottenga JJ;de Geus EJC;Bios Consortium;Boomsma DI;Ehli EA;van Dongen J
• 通讯作者: van Dongen J

Effects of smoking on genome-wide DNA methylation profiles: A study of discordant and concordant monozygotic twin pairs.

• DOI: 10.7554/elife.83286
• 发表时间: 2023-08-10
• 期刊: eLife
• 影响因子: 7.7
• 作者: van Dongen J;Willemsen G;BIOS Consortium;de Geus EJC;Boomsma DI;Neale MC
• 通讯作者: Neale MC