MATERNAL, FETAL & ENVIRONMENTAL CAUSES OF BIRTH DEFECTS

母体、胎儿

• 批准号: 6786633
• 负责人: LAURA E. MITCHELL
• 金额: $ 45.47万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786633
• 关键词: clinical research; congenital oral /facial /cranial defect; craniosynostosis; disease /disorder etiology; disease /disorder proneness /risk; embryo /fetus toxicology; environmental exposure; environmental toxicology; family genetics; gene environment interaction; gene interaction; genetic susceptibility; genotype; high throughput technology; human subject; microarray technology; spina bifida

DESCRIPTION: (Adapted from the Applicant's Description) The current proposal is based on the premise that a full understanding of the genetic architecture for many birth defects will only be obtained if "higher-order" effects such as gene-environment (GxE) interactions, gene-gene (GxG) interactions and maternal genotypic effects are evaluated in concert with more traditional epidemiological and genetic risk factors. Moreover, recent advances in molecular and statistical genetics provide a foundation upon which to build studies that address the role of higher-order effects, when such effects are suggested by current understanding of a disease's etiology. The investigators propose to evaluate the role of GxE interactions, GxG interactions and maternal effects in the etiology of two groups of birth defects: neural tube defects and cranial abnormalities including craniosynostosis and nonsynostotic posterior plagiocephaly (CSINSPP). These conditions were selected from other potential candidates because current understanding of their etiologies support multiple hypotheses regarding higher-order effects. Hence, for these conditions in particular, it is now feasible to begin to construct a multi- dimensional blueprint of their genetic architecture. They will use state-of- the-art genotyping methods, including high-throughput array technologies, and employ state-of-the-art statistical approaches to evaluate the role of higher- order effects in the etiology of spina bifida and CS/NSPP.

描述：（根据申请人的描述改编）当前提案 是基于对遗传结构的充分理解的前提 对于许多出生缺陷，只有在“高阶”效应（例如 基因环境（GXE）相互作用，基因基因（GXG）相互作用和母体 基因型效应是与更传统的 流行病学和遗传危险因素。此外，最近的进步 分子和统计遗传学为建立的基础提供了基础 解决高阶效应作用的研究，当这种影响是 通过当前对疾病病因的理解提出。调查人员 建议评估GXE相互作用，GXG相互作用和 两组出生缺陷的病因中的母体影响：神经管 缺陷和颅异常，包括颅突变和非脑词 后颅后畸形（CSINSPP）。这些条件是从其他条件中选择的 潜在的候选人，因为当前对其病因支持的理解 关于高阶效应的多个假设。因此，为此 特别是条件，现在可以开始构建多个 其遗传结构的维蓝图。他们将使用最新 ART基因分型方法，包括高通量阵列技术和 采用最先进的统计方法来评估高等的作用 脊柱裂和CS/NSPP病因的顺序效应。

项目成果

Association between the NAT1 1095C > A polymorphism and homocysteine concentration.

NAT1 1095C > A 多态性与同型半胱氨酸浓度之间的关联。

• DOI: 10.1002/ajmg.a.31475
• 发表时间: 2006
• 期刊: American journal of medical genetics. Part A
• 作者: Stanisławska-Sachadyn,Anna;Jensen,LiselotteE;Kealey,Carmel;Woodside,JayneV;Young,IanS;Scott,JohnM;Murray,Liam;Boreham,ColinA;McNulty,Helene;Strain,JJ;Whitehead,AlexanderS
• 通讯作者: Whitehead,AlexanderS

Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida.

• DOI: 10.1002/bdra.23163
• 发表时间: 2013-09
• 期刊: Birth defects research. Part A, Clinical and molecular teratology
• 作者: Agopian AJ;Bhalla AD;Boerwinkle E;Finnell RH;Grove ML;Hixson JE;Shimmin LC;Sewda A;Stuart C;Zhong Y;Zhu H;Mitchell LE
• 通讯作者: Mitchell LE

Spina bifida.

• DOI: 10.1038/nrdp.2015.7
• 发表时间: 2015-04-30
• 期刊: Nature reviews. Disease primers
• 作者: Copp AJ;Adzick NS;Chitty LS;Fletcher JM;Holmbeck GN;Shaw GM
• 通讯作者: Shaw GM