CHRONIC OBSTRUCTIVE PULMONARY DISEASE GENE LOCALIZATION

描述(申请人摘要)：慢性阻塞性肺疾病 慢性阻塞性肺疾病(COPD)是一种以呼吸道阻塞为特征的缓慢进展的疾病 这种情况至少会持续几个月。慢性阻塞性肺病的两个主要原因是 慢性支气管炎和肺气肿。这两种疾病中的任何一种都有可能发生，也可能没有 呼吸道阻塞，但呼吸道阻塞会导致肺功能损害 导致残疾和死亡。慢性阻塞性肺病是美国的一个主要健康问题 在美国和全世界，一直位居最常见的 美国的死因。吸烟是第一位的 增加COPD风险的环境因素，但其他环境因素 这些因素也牵连其中。然而，尽管这是一个公认的角色， 环境因素本身不会导致慢性阻塞性肺疾病。有症状的COPD发生在 只有10%-20%的重度吸烟者，可能是基因携带者 易感性，尽管常见的COPD易感基因尚未 已确认身份。 这个项目提出了一个单一的具体目标：在基因组内定位一个 COPD易感基因。建议的策略是应用统计联系 对家庭数据的分析。肺部测量数据已经收集在 16个家系的159名成员和支持COPD易感基因的证据 这些家系都是通过分离分析获得的。每人11,995人 已经在系谱成员上进行了基因分型的遗传标记将被 检测与推测的COPD易感基因相关联的证据。 与一个或多个遗传标记相关联的证据将识别基因组 COPD易感基因的定位。标记的高密度将允许 基因的精细定位。 成功完成这一基因定位项目是必要的 项目识别和表征COPD易感性的先决条件 吉恩。发现一种基因突变会增加慢性阻塞性肺疾病的风险 增加对肺功能的了解，以及允许基因携带者 被识别出来并让他们意识到自己的易感性。

DESCRIPTION (Applicant's Abstract): Chronic obstructive pulmonary disease (COPD) is a slowly progressive disorder characterized by airways obstruction that lasts for at least several months. The two major causes of COPD are chronic bronchitis and emphysema. Either disorder may occur with or without airways obstruction, but airways obstruction causes impairment of lung function leading to disability and death. COPD is a major health problem in the United States and throughout the world, consistently ranking among the most common causes of death in the United States. Cigarette smoking is the primary environmental factor that increases the risk of COPD, but other environmental factors have also been implicated. However, despite a well-established role, environmental factors alone do not cause COPD. Symptomatic COPD develops in only 10-20 percent of heavy cigarette smokers, probably those with a genetic susceptibility, although common COPD susceptibility genes have yet to be identified. This project proposes a single specific aim: to localize, within the genome, a COPD susceptibility gene. The strategy proposed is to apply statistical linkage analysis to family data. Pulmonary measurements have already been collected on 159 members of 16 pedigrees and evidence supporting a COPD susceptibility gene in these pedigrees has been obtained from segregation analysis. Each of 11,995 genetic markers, which have already been genotyped on pedigree members, will be tested for evidence of linkage to the inferred COPD susceptibility gene. Evidence of linkage to one or more genetic markers will identify genomic locations of COPD susceptibility genes. The high density of markers will allow fine-mapping of the gene. Successful completion of this gene localization project is the necessary prerequisite for a project to identify and characterize a COPD susceptibility gene. Identifying a gene that when mutated increases the risk of COPD may increase understanding of pulmonary function, as well as allowing gene-carriers to be identified and made aware of their susceptibility.