GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS

描述(改编自调查人员摘要)：严重合并 免疫缺陷疾病(SCID)的发病率在以下人群中增加 阿萨巴斯加语(A-SCID)、纳瓦霍语、阿帕契语和Dine‘Native 美国人。考恩和他的同事们最近绘制了A-SCID基因的图谱 通过连锁，连锁到染色体10p的2.5 cM间隔 不平衡和单倍型分析。他们现在提议克隆 A-SCID基因，并鉴定其突变。这样做的长期目标是 研究A-SCID的表达和功能 基因及其突变在动物模型中的应用，用基因纠正突变 治疗并了解它在调节免疫功能中的作用。这个 这项研究的具体目的是：1)构建跨越 候选区域并物理映射该区域；2)细化 利用现有和新的多态微卫星的候选区域 3)鉴定A-SCID基因及其突变。假说 要检测的是，有一种新的基因，它是突变的。这个 有待检验的假设是，存在一种新的基因位于 染色体10p上的2.5 cM候选间隔，一种独特的单一突变 这导致了A-SCID。为了克隆这种基因，这些研究人员扮演了 构建该地区的完整克隆覆盖并进一步完善 它利用了现有的标记和新产生的多态标记。他们 将评估他们确定在候选中的基因和EST 基于表达模式和序列的区域。一旦被识别 对于疾病基因，他们将描述其基因组结构， 开发检测基因组DNA突变的方法并建立 与纳瓦霍人、阿帕奇人和用餐民族签订协议，调查 航空母舰的人口。这项研究的结果将导致更好的 对T、B细胞免疫成熟的认识与创新 操纵免疫系统的方法以及更具体的 用于治疗某些恶性肿瘤的药物。

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.