GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS

描述（改编自研究者摘要）：重度合并 免疫缺陷病（SCID）的发病率增加， 阿萨巴斯卡语（A-SCID）、纳瓦霍语、阿帕奇语和Dine' Native 美国人科万和他的同事最近绘制了A-SCID基因的图谱 染色体10 p的2.5cM间隔， 不平衡和单体型分析。他们现在建议克隆 A-SCID基因并鉴定其突变。这一长期目标 研究的目的是表征A-SCID的表达和功能， 基因及其突变的动物模型，通过基因纠正突变 了解它在调节免疫功能中的作用。的 本研究的具体目的是：1）构建覆盖范围为 候选区域并物理映射该区域; 2）细化 使用现有和新的多态性微卫星的候选区域 3）鉴定A-SCID基因及其突变。的假设 有一个新的基因和它的突变。的 有待检验的假设是，有一个新的基因位于 2.5染色体10 p上的cM候选间隔，一个独特的单突变 其中一个导致了A-SCID。为了克隆这个基因， 构建该区域的完整克隆覆盖， 它使用现有的标记和新产生的多态性标记。他们 将评估他们确定的候选人中的基因和EST 基于表达模式和序列的区域。一旦识别 他们将描述其基因组结构， 开发检测基因组DNA突变的方法， 与纳瓦霍人，阿帕奇人和Dine' Nations的协议， 携带者的人口。这项研究的结果将导致更好的 了解T和B细胞免疫的成熟， 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剂。

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.