Genetic Modifiers of Cystic Fibrosis: Sibling Study

囊性纤维化的基因修饰：兄弟姐妹研究

• 批准号: 6946801
• 负责人: Garry R Cutting
• 金额: $ 100.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946801
• 关键词: biotechnology; chloride channels; clinical research; cystic fibrosis; data collection methodology /evaluation; family genetics; gene expression; gene mutation; genetic polymorphism; genetic registry /resource /referral center; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; linkage disequilibriums; linkage mapping; longitudinal human study; patient /disease registry; phenotype; siblings; twin /multiplet

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is a highly variable but inevitably fatal single gene disorder. Several lines of evidence suggest that genetic background contributes to the variability of CF phenotypes. We propose to develop CF as a model for the identification of modifier genes by capitalizing on the availability of a large motivated population of affected twins and siblings. The study has four aims: 1. To identify heritable CF phenotypes by twin study. Intrapair and interpair variance will be determined for selected CF phenotypes, and interclass correlations (MZ vs DZ) will be performed to identify CF phenotypes with a substantial heritable component. 2. To determine the contribution of genetic and other factors to the variability of CF phenotypes by analysis of affected sibs. Variance component methods will be used to evaluate the CF phenotypes that appear to be heritable based upon other studies or the results of aim 1. 3. To identify biologic phenotypes that correlate with heritable CF phenotypes by clinical study of twins and sibs. Multivariate analysis will be used to find biologic phenotypes associated with CF phenotypes. 4. To identify modifier genes and loci responsible for heritable CF phenotypes by linkage approaches. Identity by descent and transmission disequilibrium methods will be used to test linkage between candidate genes/loci and heritable CF phenotypes. To identify novel loci, genome-wide scans will be performed upon sib pairs selected for extreme concordance or discordance for heritable traits.

描述（由申请人提供）： 囊性纤维化（CF）是高度可变但不可避免的致命单基因 紊乱。几条证据表明遗传背景 有助于CF表型的变异性。我们建议将CF作为一个 通过资本化识别修饰符基因的模型 大量受影响的双胞胎和兄弟姐妹的动机人口的可用性。 该研究有四个目标： 1。通过双研究确定可遗传的CF表型。内部和插入 将确定针对选定的CF表型和阶级间的方差 将执行相关性（MZ与DZ），以识别具有A的CF表型 实质性的遗传组成部分。 2。确定遗传和其他因素对 通过分析受影响的SIB的CF表型的变异性。方差组件 方法将用于评估似乎是可遗传的CF表型 基于其他研究或目标1的结果。 3。确定与可遗传CF表型相关的生物学表型 通过双胞胎和SIBS的临床研究。多变量分析将用于 查找与CF表型相关的生物学表型。 4。识别负责遗传CF表型的修饰符基因和基因座 通过链接方法。下降和传播不平衡的身份 方法将用于测试候选基因/基因座和 可遗传的CF表型。为了识别新的基因座，全基因组扫描将是 根据SIB对进行的，以进行极端的一致性或不一致 可遗传的特质。