A LINKAGE STUDY IN FAMILIAL PULMONARY FIBROSIS

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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.