CHRONIC OBSTRUCTIVE PULMONARY DISEASE GENE LOCALIZATION

描述（申请人摘要）：慢性阻塞性肺病 慢性阻塞性肺病（COPD）是一种以气道阻塞为特征的缓慢进行性疾病 至少会持续几个月COPD的两个主要原因是 慢性支气管炎和肺气肿。任何一种疾病都可能发生， 气道阻塞，但气道阻塞导致肺功能受损 导致残疾和死亡。COPD是美国的一个主要健康问题， 国家和世界各地，一直是最常见的 美国的死亡原因。吸烟是主要的 增加COPD风险的环境因素，但其他环境因素 因素也有牵连。然而，尽管有一个既定的作用， 环境因素本身并不引起COPD。症状性COPD发生于 只有10%-20%的重度吸烟者，可能是那些有遗传缺陷的人。 易感性，尽管常见的COPD易感基因尚未被发现。 鉴定 该项目提出了一个单一的具体目标：在基因组内定位一个 COPD易感基因拟议的战略是应用统计联系 家庭数据分析。已经收集了肺部测量结果， 16个家系的159名成员和支持COPD易感基因的证据 在这些家系中，已获得分离分析。11995人 遗传标记，已经在系谱成员上进行了基因分型，将被 检测与推断的COPD易感基因的关联证据。 与一个或多个遗传标记连锁的证据将鉴定基因组 COPD易感基因的位置。标记的高密度将允许 基因的精细定位 成功地完成这个基因定位项目是必要的 识别和表征COPD易感性项目的先决条件 基因确定一个基因，当突变时，会增加患COPD的风险， 增加对肺功能的了解，以及允许基因携带者 来识别和了解他们的易感性。

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.