A LINKAGE STUDY IN FAMILIAL PULMONARY FIBROSIS

描述：（改编自研究者摘要） 该项目旨在研究遗传因素，这些遗传因素在 肺纤维化的发展。这项调查的总体假设是 是遗传因素使个体易患肺部疾病， 纤维化这项研究的目的是确定一组遗传位点 在家族性肺纤维化的发展中发挥作用。整体 以下观察结果支持这一假设：家族性肺动脉高压 纤维化在病理学上与特发性肺纤维化难以区分 并且似乎是作为常染色体显性性状遗传的， 肺纤维化与多效性遗传有关 疾病，如Hermansky-Pudlak综合征、神经纤维瘤病、结节性 硬化症、Neimann-Pick病、Gaucher病和家族性低钙尿症 高钙血症;肺纤维化经常在自身免疫性疾病中观察到， 包括类风湿性关节炎和系统性硬化症; 据报道，在职业暴露于 类似浓度的纤维化粉尘;和近交系小鼠不同 对纤维化粉尘的敏感性结合指数 人类分子遗传学的发展，研究人员指出，这些临床 观察表明，一个组织良好的方法来定义遗传 肺纤维化的决定因素在科学上是可行和合理的。 本项目建议使用标准遗传学方法（连锁分析）， 调查匿名遗传标记多态性在 有家族性肺纤维化的家族调查人员表示， 使用标准遗传标记进行全面的全基因组研究， 他们来鉴定随后可能被证明含有新基因的基因座， 在肺纤维化的发病机制中起作用。一旦基因位点 在家族性肺纤维化中定义，候选基因可以在 位置和功能标准的基础。此外，他们指出， 该方法将提供关于高优先级基因座的基本信息， 适用于快速进化的密集人类转录本图谱， 在有两个或两个以上肺纤维化病例的家庭中，

DESCRIPTION: (Adapted from Investigator's Abstract) The overall goal of this project is to investigate inherited genetic factors that play a role in the development of pulmonary fibrosis. The overall hypothesis of this investigation is that inherited genetic factors predispose individuals to develop pulmonary fibrosis. The goal of this investigation is to identify a group of genetic loci that play a role in the development of familial pulmonary fibrosis. The overall hypothesis is supported by the following observations: familial pulmonary fibrosis is indistinguishable pathologically from idiopathic pulmonary fibrosis and appears to be inherited as an autosomal dominant trait with variable penetrance; pulmonary fibrosis is associated with pleiotropic genetic disorders, such as Hermansky-Pudlak syndrome, neuofibromatosis, tuberous sclerosis, Neimann-Pick disease, Gaucher's disease, and familial hypocalciuric hypercalcemia; pulmonary fibrosis is frequently observed in autoimmune disease, including rheumatoid arthritis and systemic sclerosis; variable susceptibility is evident among workers who are reported to be exposed occupationally to similar concentrations of fibrogenic dusts; and inbred strains of mice differ in their susceptibility to fibrogenic dust. In conjunction with the exponential growth of human molecular genetics, the investigators state that these clinical observations suggest that a well organized approach to define the genetic determinants of pulmonary fibrosis is scientifically feasible and justified. This project proposes to use standard genetic methodology (linkage analysis) to investigate the distribution of polymorphisms for anonymous genetic markers in families with familial pulmonary fibrosis. The investigators state that their comprehensive genome-wide study, using standard genetic markers, will allow them to identify loci which subsequently may prove to contain novel genes that play a role in the pathogenesis of pulmonary fibrosis. Once genetic loci are defined in familial pulmonary fibrosis, candidate genes can be identified on the basis of both positional and functional criteria. Moreover, they note that this approach will provide basic information on high priority loci that will be applicable to the rapidly evolving dense human transcript map for pulmonary fibrosis in families with two or more cases of pulmonary fibrosis.