IMMUNOGENETICS OF TYPE 1 DIABETES IN A BEDOUIN FAMILY

描述：(改编自《调查者摘要》)：超过200万 美国人患有1型糖尿病，大多数是儿童和年轻人 成年人。除了每天注射胰岛素维持生命的负担外， 糖尿病患者面临失明、肾功能衰竭、心脏病的高风险 疾病、中风和截肢。更好地理解遗传原因 1型糖尿病的研究应该导致阻止β细胞的新基因疗法 在儿科期间销毁或防止销毁 已经感染这种疾病的患者体内残留的β细胞。 此外，预测谁会患上这种疾病的能力取决于 能够对被认为涉及的多个基因中的每一个进行测试。 这些高危个体代表了检测的最佳目标人群 以最有效的方式进行实验性治疗和预防战略。 携带HLA-DR3和/或DR4的个体患疾病的风险很高，但 人们普遍认为，其他未知的基因也参与其中。然而，它 很难识别非MHC基因，很可能是由于遗传 接受研究的人群中1型糖尿病的异质性。基于 一个有20个亲戚的贝都因阿拉伯家族的遗传连锁研究 受1型糖尿病影响，一个糖尿病易感基因(IDDM17)有 被定位于10号染色体的长臂(10q25.1)。显著(p=0.00004) 观察两组患者的非参数连锁评分(NPLS)和参数LOD评分 标记D10S554，也与IDDM17连锁不平衡。D10S554 侧翼标记映射到1240 kb的YAC。之前研究过的家族 由大约200名成员组成，他们是一个庞大的贝都因阿拉伯部落的成员 大约有15,000名会员。值得注意的是，20名受影响的亲属中有8人是 在1990至1999年间确诊。部落的另一个密切相关的分支 也有同样高发病率的1型糖尿病。这样做的具体目的是 研究内容有：(1)确定预测1型儿童发展的能力 基于人类白细胞抗原10号染色体单倍型的糖尿病大家族 (IDDM17)和胰岛细胞自身抗体的表达；以及(2)鉴定 通过定位克隆得到与IDDM17相对应的基因。

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.