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: 6794626
• 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 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6794626
• 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）是一种高度可变但不可避免致命的单基因 紊乱。多项证据表明遗传背景 导致CF表型的变异性。我们建议将 CF 开发为 利用模型识别修饰基因 受影响的双胞胎和兄弟姐妹中有大量积极的群体。 该研究有四个目标： 1. 通过双胞胎研究鉴定可遗传的CF表型。内对和间对 将确定选定的 CF 表型和类间差异 将执行相关性（MZ 与 DZ）来识别具有以下特征的 CF 表型： 实质性的遗传成分。 2. 确定遗传和其他因素对 通过对受影响同胞的分析来了解 CF 表型的变异性。方差分量 方法将用于评估看似可遗传的 CF 表型 基于其他研究或目标 1 的结果。 3. 鉴定与可遗传的CF表型相关的生物表型 通过双胞胎和同胞的临床研究。多变量分析将用于 寻找与 CF 表型相关的生物表型。 4. 鉴定导致可遗传 CF 表型的修饰基因和基因座 通过联动方式。血统同一性和传递不平衡 方法将用于测试候选基因/位点和 可遗传的CF表型。为了识别新的位点，将进行全基因组扫描 对因极端一致性或不一致而选择的同胞对进行 可遗传的特征。