MATERNAL, FETAL & ENVIRONMENTAL CAUSES OF BIRTH DEFECTS

描述：(根据申请者的描述改编)当前建议书 是基于这样一个前提，即对遗传结构的充分理解 因为许多先天缺陷只有在以下情况下才会出现： 基因-环境(GxE)互作、基因-基因(GXG)互作与母体 基因型别效应的评估与更传统的 流行病学和遗传风险因素。此外，最近在这方面的进展 分子和统计遗传学提供了建立在其上的基础 解决高阶效应的作用的研究，当这种效应 根据目前对一种疾病的病因学的理解而提出的。调查人员 建议评估GxE交互作用、GXG交互作用和 神经管在两组出生缺陷病因中的母体效应 畸形和颅骨异常，包括颅缝融合和不融合 后部斜头畸形(CSINSPP)。这些条件选自其他条件 潜在的候选人，因为目前对其病因的理解支持 关于高阶效应的多种假说。因此，对于这些 特别是在条件允许的情况下，现在开始建设一个多层次的 他们基因结构的维度蓝图。他们将使用状态- 最先进的基因分型方法，包括高通量阵列技术，以及 使用最先进的统计方法评估更高级别的 脊柱裂与CS/NSPP病因学的顺序效应

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.