Parent-offspring trios - A resource to facilitate the identification of type 2 diabetes genes
Parent-offspring trios - A resource to facilitate the identification of type 2 diabetes genes
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DOI：
10.2337/diabetes.48.12.2475
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发表时间：
1999-12-01
期刊：
影响因子：
7.7
通讯作者：
Hattersley, AT
中科院分区：
文献类型：
--
作者：
Frayling, TM;Walker, M;Hattersley, AT
使用三人组（双亲受影响的先证者）进行的传播不平衡测试是评估基因变异在疾病中的作用的可靠方法，避免了可能混淆传统病例/对照研究的群体分层问题，并允许检测父母来源效应。三重奏在定义许多多基因疾病（包括 I 型糖尿病）的基因方面发挥了重要作用。我们评估了欧洲 2 型糖尿病三人组的患病率、临床特征以及定义 2 型易感基因的适用性。在英国的白人群体中，只有 2.5% 的 2 型患者的父母均健在。我们采用全国性策略，收集了 182 个按严格临床标准定义的三人组。免疫学和基因检测结果排除了 25 名三人组，原因包括潜在的自身免疫性糖尿病 (n = 13)、家庭关系不一致 (n = 7) 以及母系遗传的糖尿病和耳聋 (n = 5)。剩下的 157 名先证者与家族性 2 型糖尿病受试者具有相似的治疗要求，但发病年龄更小，更肥胖，并且更频繁地影响父母，利用这一资源， 我们尚未发现任何证据表明 2 型糖尿病与葡萄糖激酶基因标记 GCK1 和 GGK2 以及 20 号染色体标记 D20S197 之间存在连锁不平衡，我们得出结论，欧洲 2 型糖尿病三人组很难收集，但为剖析 2 型糖尿病的遗传学提供了一种重要的额外方法。
The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene variants in disease that avoids the problem of population stratification that may confound conventional case/control studies and allows the detection of parent-of-origin effects. Trios have played a major role in defining genes in a number of polygenic conditions, including type I diabetes. We assessed the prevalence, clinical characteristics, and suitability for defining type 2 susceptibility genes of European type 2 diabetes trios. In a Caucasian population in the U.K., only 2.5% of type 2 patients had both parents alive. Using a nationwide strategy, we collected 182 trios defined by strict clinical criteria. Immunological and genetic testing resulted in the exclusion of 25 trios as a result of latent autoimmune diabetes (n = 13), inconsistent family relationships (n = 7), and maternally inherited diabetes and deafness (n = 5), The 157 remaining probands had similar treatment requirements to familial type 2 diabetic subjects but presented at a younger age, were more obese, and more frequently had affected parents, Using this resource, we have not found any evidence for linkage disequilibrium between type 2 diabetes and the glucokinase gene markers GCK1 and GGK2 and the chromosome 20 marker D20S197, We conclude that European type 2 diabetes trios are difficult to collect but provide an important additional approach to dissecting the genetics of type 2 diabetes.