Genetic Modifiers of Cystic Fibrosis: Sibling Study

描述(由申请人提供)： 囊性纤维化是一种高度可变但不可避免的致命性单基因 无序。多条证据表明，遗传背景 导致了Cf表型的多样性。我们建议将CF作为一种 利用大写字母识别修饰基因的模型 有大量受影响的受影响双胞胎和兄弟姐妹的动机人口。 这项研究有四个目标： 1.通过双生子研究鉴定可遗传的CF表型。内部对和内部对 将为选定的Cf表型和类间确定方差 将进行相关(MZ与DZ)，以识别具有 大量的可遗传成分。 2.确定遗传因素和其他因素对 通过对受影响同胞的分析发现Cf表型的变异性。方差分量 方法将用于评估看起来可遗传的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 通过对双胞胎和同胞的临床研究。将使用多变量分析来 寻找与CF表型相关的生物表型。 4.确定可遗传的CF表型的修饰基因和基因座 通过联动的方法。世系同一性与传承不平衡 将使用各种方法来测试候选基因/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 对为极端一致或不一致而选择的兄弟姐妹对执行 可遗传的特征。

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.