GENE LINKAGE STUDY OF IMMUNODEFICIENCY IN NAVAJO INDIANS

纳瓦霍印第安人免疫缺陷的基因连锁研究

• 批准号: 2593255
• 负责人: MORTON COWAN
• 金额: $ 20万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2593255
• 关键词: Native Americans; adult human (21+); alleles; autosomal recessive trait; biopsy; child (0-11); clinical chemistry; disease carrier state; family genetics; gene expression; gene frequency; genetic carriers; genetic markers; genetic polymorphism; human genetic material tag; human population study; immunogenetics; linkage mapping; nucleic acid probes; polymerase chain reaction; prenatal diagnosis; severe combined immunodeficiency; southern blotting

Severe Combined Immunodeficiency Disease (SCID) is an autosomal recessive mutation that occurs in Athabascan speaking Indians (Navajo and Apache) at a frequency of approximately 2%. The incidence of SCID in Navajo babies is 1:2000 live births. The specific aim of this study is to map the "Navajo SCID" recessive gene by using genetic linkage, looking for coinheritance of the SCID gene with a DNA marker of known chromosomal location. To accomplish this, we will use a collection of highly polymorphic DNA markers including CA repeat microsatellite markers throughout the human genome. To date, we have over 200 DNA markers, including 80+ variable number tandem repeats (VNTR) and 125 CA repeat microsatellite marker. To study inheritance, we have assembled a collection of DNA preparations from 16 different Navajo kindreds. This includes 17 affected children and a total of 78 family members. The affected sample population is growing at approximately two kindreds per year. The DNA samples will be typed using the DNA probes and microsatellite markers. These data will be analyzed to find linkage between a mapped probe and the SCID gene. We plan to use the linkage information for prenatal diagnosis of affected fetuses and carrier detection of unaffected relatives. Eventually, we plan to identify and characterize the gene which causes SCID in this native American population and understand its role in regulating immune function.

严重联合免疫缺陷病（SCID）是一种常染色体隐性遗传病， 发生在说阿萨巴斯卡语的印第安人（纳瓦霍人和阿帕奇人）中的突变 频率约为2%。 纳瓦霍人的SCID发病率 婴儿的比例是1：2000。 本研究的具体目的是绘制 “纳瓦霍SCID”隐性基因，利用遗传连锁，寻找 SCID基因与已知染色体的DNA标记的共遗传 位置. 为了实现这一点，我们将使用一个高度 多态性DNA标记，包括CA重复微卫星标记 整个人类基因组。 到目前为止，我们有超过200个DNA标记， 包括80+个可变数目串联重复序列（VNTR）和125个CA重复序列 微卫星标记 为了研究遗传，我们收集了一个 从16个不同的纳瓦霍部落收集DNA制品。 这 包括17名受影响的儿童和78名家庭成员。 的 受影响的样本数量以大约每千分之二的速度增长。 年 将使用DNA探针对DNA样本进行分型， 微卫星标记 这些数据将被分析以找出联系 和SCID基因之间的联系 我们计划使用链接 产前诊断受影响胎儿和携带者的信息 检测未受影响的亲属。 最终，我们计划识别和 在这位美国原住民身上发现了导致SCID的基因 并了解其在调节免疫功能中的作用。