GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS

描述（改编自研究者摘要）：严重合并

DESCRIPTION (Adapted from investigator's abstract): Severe Combined Immunodeficiency Disease (SCID) is found with increased incidence among Athabascan-speaking (A-SCID), Navajo, Apache, and Dine' Native Americans. Cowan and his colleagues have recently mapped the A-SCID gene to a 2.5 cM interval of chromosome 10p by linkage, linkage disequilibrium, and haplotype analyses. They now propose to clone the A-SCID gene and identify its mutation. The long term goals of this research are to characterize the expression and function of the A-SCID gene and its mutation in animal models, correct the mutation by gene therapy and understand it's role in regulating immune function. The Specific Aims of this study are to: 1) Construct clone coverage spanning the candidate region and physically map the region; 2) Refine the candidate region using existing and new polymorphic microsatellite markers; 3) Identify the A-SCID gene and it's mutation. The hypothesis to be tested is that there is a novel gene and it's mutation. The hypothesis to be tested is that there is a novel gene located within the 2.5 cM candidate interval on chromosome 10p, a unique single mutation of which results in A-SCID. To clone this gene these investigators play to construct complete clone coverage of the region and further refine it using existing markers and newly generated polymorphic markers. They will evaluate genes and ESTs that they determine to be in the candidate region based on expression patterns and sequence. Upon identification of the disease gene, they will characterize its genomic structure, develop methods to detect the mutation in genomic DNA and establish a protocol with the Navajo, apache and Dine' Nations to survey the population for carriers. The results of this study will lead to better understanding of the maturation of T and B cell immunity and novel approaches to manipulating the immune system as well as more specific agents for treating certain malignancies.