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: 6424379
• 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/6424379
• 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）是一个高度可变，但不可避免地致命的单基因 disorder.几条线索表明遗传背景 有助于CF表型的变异性。我们建议把CF发展为 模型的鉴定修饰基因的资本化， 受影响的双胞胎和兄弟姐妹的大量积极人群的可用性。 这项研究有四个目标： 1.通过双生子研究确定可遗传的CF表型。对内和对间 将确定选定CF表型的方差， 将进行相关性（MZ与DZ），以确定CF表型， 实质性遗传成分。 2.为了确定遗传和其他因素对 CF表型的变异性通过受影响的同胞分析。方差分量 方法将被用来评估CF表型似乎是遗传的 根据其他研究或目标1的结果。 3.鉴定与遗传CF表型相关的生物表型 通过对双胞胎和兄弟姐妹的临床研究。多变量分析将用于 发现与CF表型相关的生物表型。 4.确定遗传CF表型的修饰基因和位点 联系方式。血统认同与传递不平衡 方法将用于测试候选基因/位点之间的连锁， 遗传CF表型为了识别新的基因座，全基因组扫描将被用于 在选择的极端一致或不一致的同胞对上进行， 遗传特征