Bayesian Reanalysis of a Multi-Site Gene-Mapping Study of Cleft Lip/Cleft Palate

唇裂/腭裂多位点基因图谱研究的贝叶斯再分析

• 批准号: 7261616
• 负责人: VERONICA J. VIELAND
• 金额: $ 14.4万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7261616
• 关键词: Bayesian; Reanalysis; Multi; Site; Gene

DESCRIPTION (provided by applicant): This application is in response to PAR-04-091. This goal of the project is to apply novel data analytic methods to an existing data set, in order to localize all genes of measurable effect underlying nonsyndromic cleft lip with or without cleft palate (CUP). CUP is a major structural birth defect, representing a significant public health burden. While a genetic role in etiology is certain, genome-wide linkage studies have been inconclusive. In an effort to achieve a comprehensive overview of the genetics of human CUP, we have undertaken the largest gene-mapping study to date by pooling together multiple independently collected sets of families manifesting CUP, drawn from 7 populations around the world. The Center for Inherited Disease Research has completed genotyping for an (approximate) 10 cM genome-screen on all families, and is currently completing genotyping based on a custom 1500 SNP panel. We now propose to analyze these data using a novel Bayesian approach to linkage and linkage disequilibrium mapping, specifically designed for the analysis of heterogeneous conditions based on multiple, genetically diverse samples. We will also conduct systematic comparisons of the performance of the Bayesian method with other commonly used statistics. This project will thus provide a comprehensive assessment, in both genomic and geographical terms, of the genetic architecture of CUP. It will also result in a set of recommendations regarding optimal data analytic methods for gene mapping studies of complex disorders based on multi-site designs .

描述（由申请人提供）：本申请是对PAR-04-091的回应。该项目的目标是将新的数据分析方法应用于现有的数据集，以定位所有非综合征性唇腭裂（CUP）相关的可测量效应基因。CUP是一种主要的结构性出生缺陷，是一个重大的公共卫生负担。虽然遗传在病因学中的作用是肯定的，但全基因组连锁研究尚未得出结论。为了全面概述人类CUP的遗传学，我们进行了迄今为止最大的基因图谱研究，将来自世界各地7个人群的多个独立收集的表现CUP的家庭集合汇集在一起。遗传疾病研究中心已经完成了对所有家庭的（大约）10 cM基因组筛选的基因分型，目前正在完成基于定制1500 SNP面板的基因分型。我们现在建议使用一种新的贝叶斯方法来分析这些数据的连锁和连锁不平衡映射，专门设计用于分析基于多个遗传多样性样本的异质性条件。我们还将系统地比较贝叶斯方法与其他常用统计方法的性能。因此，该项目将提供一个全面的评估，在基因组和地理方面，CUP的遗传结构。它还将导致在一组建议的最佳数据分析方法的基因定位研究的复杂疾病的基础上多站点设计。