Tomer Y, Barbesino G, Greenberg D A, Concepcion E, Davies T F
Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai School of Medicine, New York, USA.
Am J Hum Genet. 1998 Dec;63(6):1749-56. doi: 10.1086/302146.
The autoimmune thyroid diseases (AITDs) include two related disorders, Graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDs are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of.3. The maximum nonparametric LOD score was 2.4 (P=.00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD-susceptibility gene on chromosome 20q11.2.
自身免疫性甲状腺疾病（AITDs）包括两种相关病症，格雷夫斯病（GD）和桥本甲状腺炎，其中免疫调节紊乱导致对甲状腺的免疫攻击。AITDs是多因素的，在遗传易感性个体中发生。然而，导致这种易感性的基因仍然未知。最近，我们启动了一项AITD患者的全基因组连锁研究，以确定他们的易感基因。我们使用高度多态且间隔密集的微卫星标记（标记间距离<10 cM）研究了53个多重、多代AITD家族（323人）的数据集。通过两点和多点参数方法（经典LOD评分分析）进行连锁分析。在研究20号染色体时，我们在20q11.2染色体上发现了一个与GD紧密连锁的位点。假设隐性遗传模式和外显率为0.3，在标记D20S195处获得的最大两点LOD评分为3.2。最大非参数LOD评分为2.4（P = 0.00043）；该评分也在标记D20S195处获得。多点连锁分析在标记D20S195和D20S107之间的6 cM区间产生了最大LOD评分为3.5。在我们的样本中没有异质性的证据。我们认为，这些结果表明有很强的连锁证据，并提示在20q11.2染色体上存在一个主要的GD易感基因。
