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）：不孕不育是一个重大的公共卫生问题，影响着美国 10-15% 的夫妇（250 万）。该计划的目标是找到对自然双卵（DZ）双胞胎变异做出重大贡献的基因，以了解控制女性生育力的关键途径。这将在不孕不育的治疗中具有实际应用，并可能提供新的避孕方法。这项拟议的研究扩展了我们之前对人类和大型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。我们已经查明了 342 个有姐妹对的家庭，她们都自然生下了同卵双胞胎，另外还有 386 个有病例二父母三合会的家庭，并从姐妹的父母和其他兄弟姐妹那里收集了 DNA 样本。我们将利用双胞胎研究以及澳大利亚和荷兰双胞胎登记处的信息，收集来自澳大利亚和新西兰的另外 240 个受影响的姐妹对家庭以及来自荷兰的 418 个家庭。这些家庭的 DNA 样本将用于完成 1000 个家庭的 10cM 基因组扫描。我们将使用同胞对连锁分析来定位孪生 QTL。我们在动物模型中的候选定位克隆最近发现了来自卵巢内信号通路的两个基因（BMP15 和 BMPRIB）的突变，这些突变增加了双胞胎频率，并导致 BMP15 突变纯合携带者不孕。一个重要的问题是，人类双胞胎的自然变异是否是由这些新兴机制或其他途径控制的。我们将使用现有样本立即开始候选基因研究，通过突变筛选和对来自该途径的基因（BMP15、GDF9、BMPR1B）中的 SNP 标记进行打字，使用匹配的病例对照设计与来自我们现有家庭的病例和匹配的对照样本。将使用传递不平衡测试在其他病例及其父母中测试显着关联。

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

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

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

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