GENETIC BASIS OF ABDOMINAL AORTIC ANEURYSM

描述：(改编自《调查者摘要》)腹主动脉 动脉瘤(Aaa)是腹主动脉的扩张，如果 未被发现，会导致破裂。与腹主动脉破裂相关的死亡率 估计为90%，而选择性修复的死亡风险为 大约6%。腹主动脉破裂是老年人死亡的主要原因。 美国人。AAA风险标记物的识别可能导致 预防性干预。AAA在家庭中的聚集度和分离 分析表明，AAA的家族风险最好地解释为 一对常染色体隐性主基因的分离 继承。 这个项目的目标是确定遗传(主效基因)和 AAA显著聚集的环境因素 在受影响个人的亲属中。这一目标将通过以下方式实现 满足以下具体目标：1)收集至少180个 带有AAA和NO的受影响的亲属对(主要是兄弟对) 有结缔组织疾病家族史的证据，并 对这些个体进行150个高信息量微卫星的基因分型 常染色体基因组的20厘米分辨率的多态标记；2) 使用稳健受影响的方法测试AAA和这些座位之间的连锁 鉴定基因组区域的系谱成员方法 易患AAA的基因；3)确认 易感基因(S)的存在及其定位 明确的搜索策略，以更高的分辨率进行基因分型， 以及对家庭资料的重新分析；以及4)确定易感基因 通过饱和图谱和分子分析相结合的方法 候选基因座；5)研究AAA与 环境措施，以确定估计风险的方程式 AAA患者的亲属基于环境措施和 基因分型。基于数量和结构的功率计算 已经收集的家庭证明了识别的可行性 使用这种策略易患AAA的基因，即使在存在 与所涉及的基因座有关的显著异质性。在……里面 除了通过连锁识别AAA所必需的基因外 分析，将对联想进行一系列分析，以 确定既不必要也不必要的真实易感基因 足以导致疾病，但这会改变个人患上 发展AAA。

DESCRIPTION: (Adapted from Investigator's Abstract) Abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta which can, if undetected, lead to rupture. The mortality associated with ruptured AAA is estimated to be 90%, while elective repair has a mortality risk of approximately 6%. Ruptured AAA is a leading cause of death among older Americans. The identification of markers of AAA risk could lead to preventive intervention. AAA aggregates in families, and segregation analysis shows that familial risk of AAA is best explained by the segregation of a major gene with an autosomal recessive mode of inheritance. The goal of this project is to identify the genetic (major genes) and environmental factors responsible for the significant aggregation of AAA among relatives of affected individuals. This goal will be achieved by satisfying the following specific aims: 1) to collect a minimum of 180 affected relative pairs (primarily sibling pairs) with AAA and no evidence of a family history of a connective tissue disorder, and to genotype these individuals for 150 highly informative microsatellite polymorphisms marking the autosomal genome at a resolution of 20 cM; 2) to test for linkage between AAA and these loci using robust affected pedigree member methods to identify genomic regions which may contain genes that predispose individuals to develop AAA; 3) to confirm the existence of predisposing gene(s) and refine their location using a defined search strategy, genotyping at increasing levels of resolution, and re-analysis of family data; and 4) to identify the predisposing gene by a combination of saturation mapping and molecular analysis of candidate loci; and 5) to investigate the association of AAA with environmental measures to determine an equation for estimating risk for relatives of AAA patients based upon environmental measures and genotype. Power calculations based upon the number and structure of families already collected demonstrate the feasibility of identifying genes that predispose to AAA using this strategy, even in presence of significant heterogeneity with respect to the loci involved. In addition to identifying genes that are necessary for AAA by linkage analysis, a series of analyses of association will be undertaken to identify true susceptibility genes that are neither necessary nor sufficient to cause disease, but which modify an individual's risk of developing AAA.