IMMUNOGENETICS OF TYPE 1 DIABETES IN A BEDOUIN FAMILY

描述：（改编自研究者摘要）：超过200万 美国人患有1型糖尿病，其中大多数是儿童和年轻人 成年人了除了每天注射胰岛素以维持生命的负担外， 糖尿病患者面临失明、肾衰竭、心脏病的高风险。 疾病中风和截肢更好地了解遗传原因 1型糖尿病的基因治疗应该导致新的基因疗法， 在儿科期间销毁或防止销毁 在已经受到疾病影响的患者中残留的β细胞。 此外，预测谁会患上这种疾病的能力取决于 测试被认为与之相关的多个基因中的每一个的能力。 这些高风险个体代表了测试的最佳目标人群 以最有效的方式进行实验性治疗和预防策略。 携带HLA-DR 3和/或DR 4的个体处于疾病的高风险中，但 人们普遍认为其他未知的基因也参与其中。但 很难识别非MHC基因，最有可能是由于遗传原因。 1型糖尿病的发病率有哪些？基于 一个有20个亲属的贝都因阿拉伯家庭的遗传连锁研究 受1型糖尿病影响，糖尿病易感基因座（IDDM 17） 定位于10号染色体长臂（10q25.1）。显著性（p=0.00004） 非参数连锁评分（NPLs）和参数LOD评分， 标记D10 S554也与IDDM 17连锁不平衡。D10S554 和侧翼标记映射到1，240 kb YAC。这家人以前研究过 由大约200名成员组成，他们是贝都因阿拉伯大部落的成员 大约有15,000名成员。值得注意的是，20名受影响的亲属中有8人 1990年至1999年确诊。部落的另一个密切相关的分支 1型糖尿病的发病率也很高。具体目标是 研究内容有：（1）确定预测1型糖尿病发展的能力 基于HLA基因型、10号染色体单倍型的糖尿病大家族 （2）鉴定胰岛细胞自身抗体的表达; 通过定位克隆得到IDDM 17对应的基因。

DESCRIPTION: (Adapted from the Investigator's abstract): Over 2 million Americans suffer from type 1 diabetes, most of the them children and young adults. In addition to the burden of daily insulin injection to sustain life, patients with diabetes face a high risk for blindness, kidney failure, heart disease, stroke, and amputations. A better understanding of the genetic causes of type 1 diabetes should lead to novel gene therapies for halting beta-cell destruction during the pediatric period or for preventing the destruction of residual beta -cells in patients who are already affected with the disease. Further, the ability to predict who will develop the disease depends on the ability to test for each of the multiple genes that are thought to be involved. These high-risk individuals represent the best target populations for testing experimental treatment and prevention strategies in the most efficient manner. Individuals carrying HLA-DR3 and/or DR4 are at high risk for disease, but there is general agreement that other, unknown genes are also involved. However, it has been difficult to identify non-MHC genes, most likely due to genetic heterogeneity of type 1 diabetes in the population under study. Based on genetic linkage studies in a remarkable Bedouin Arab family with 20 relatives affected with type 1 diabetes, a diabetes susceptibility locus (IDDM17) has been mapped to the long arm of chromosome 10 (10q25.1). Significant (p=0.00004) nonparametric linkage scores (NPLs) and parametric LOD scores were observed for marker D10S554, which was also in linkage disequilibrium with IDDM17. D10S554 and flanking markers map to a 1,240 kb YAC. The family previously studied consists of about 200 members, who are members of a large Bedouin Arab tribe with about 15,000 members. Remarkably, 8 of the 20 affected relatives were diagnosed between 1990 and 1999. Another, closely related branch of the tribe have a similarly high incidence of type 1 diabetes. The specific aims of this study are: (1) to determine the ability to predict the development of type 1 diabetes in the extended family based on HLA genotype, chromosome 10 haplotype (IDDM17), and the expression of islet-cell autoantibodies; and (2) identify the gene corresponding to IDDM17 by the position cloning.