A LINKAGE STUDY IN FAMILIAL PULMONARY FIBROSIS

描述：(改编自《调查人员摘要》)这项工作的总体目标 该项目的目的是调查遗传遗传因素，这些遗传因素在 肺纤维化的发展。这项调查的总体假设 是遗传遗传因素使个体容易患上肺病 纤维化症。这项调查的目标是确定一组遗传基因座 在家族性肺纤维化的发生发展中起一定作用。整体而言 以下观察结果支持这一假说：家族性肺 纤维化在病理学上与特发性肺纤维化难以区分 并表现为常染色体显性遗传，具有可变性 外显性；肺纤维化与多效性遗传相关 疾病，如Hermansky-Pudlak综合征、神经纤维瘤病、结节 硬化症、Neimann-Pick病、高谢病和家族性低钙尿症 高钙血症；肺纤维化常见于自身免疫性疾病， 包括类风湿性关节炎和系统性硬化症；易感性可变 在据报道在职业上暴露于 相似浓度的致纤维化粉尘；近亲交配的小鼠不同 他们对纤维性粉尘的易感性。与指数相结合 人类分子遗传学的发展，研究人员指出，这些临床 观察表明，一种组织良好的方法来定义基因 肺纤维化的决定因素在科学上是可行和合理的。 该项目建议使用标准遗传方法(连锁分析)来 调查中国人群匿名遗传标记的多态分布 家族性肺纤维化家族。调查人员表示，他们的 全面的全基因组研究，使用标准遗传标记，将允许 以确定随后可能被证明包含新基因的基因座 在肺纤维化的发病机制中起一定作用。一旦遗传基因座被 在家族性肺纤维化中定义的候选基因可以在 位置标准和功能标准的基础。此外，他们指出， 这种方法将提供有关高优先级位置的基本信息，这些位置将 适用于快速进化的高密度人肺组织基因转录图谱 有两个或两个以上肺纤维化病例的家庭中的纤维化。

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.