Tomer Y, Barbesino G, Greenberg D A, Concepcion E, Davies T F
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
J Clin Endocrinol Metab. 1998 Dec;83(12):4321-7. doi: 10.1210/jcem.83.12.5343.
The autoimmune thyroid diseases [Graves' and Hashimoto's diseases (GD and HT)] develop in genetically susceptible individuals, but the genes responsible for this susceptibility remain unknown. To identify such genes, we have been testing candidate genes and chromosomal regions using highly polymorphic microsatellite markers. We recently reported evidence for the first locus linked to GD (GD-1) on chromosome 14q31 in a small group of families. We have now extended these studies and analyzed 53 multiplex families with GD and/or HT (323 individuals). Chromosome 14 was screened using 16 microsatellite markers spanning the entire chromosome. Three additional markers located inside candidate genes on chromosome 14 were also studied. Microsatellite markers were amplified using fluorescent-labeled primers and separated on an ABI-310 genetic analyzer. The data were analyzed using LIPED software for two-point logarithm of odds (LOD) score analysis and GeneHunter software for multipoint linkage analysis. No linkage of any marker was found to HT or autoimmune thyroid diseases (GD+HT). The previously identified GD-1 locus on 14q31 continued to show evidence of linkage to GD in this much larger set of families. The maximum LOD score was 2.1 obtained for marker D14S81 (theta=0.01), assuming a recessive mode of inheritance and a penetrance of 0.3. Multipoint analysis yielded a maximum LOD score of 2.5 between markers D14S81 and D14S1054. There was no evidence for heterogeneity in our sample. These data again suggest the presence of a major Graves' disease susceptibilitygene (GD-1) on chromosome 14q31. This locus is close to the recently identified multinodular goiter-1 locus.
自身免疫性甲状腺疾病（格雷夫斯病和桥本氏病，即GD和HT）在具有遗传易感性的个体中发病，但导致这种易感性的基因仍不清楚。为了鉴定此类基因，我们一直在使用高度多态性的微卫星标记来检测候选基因和染色体区域。我们最近报告了在一小部分家族中，位于14号染色体q31区域的第一个与GD相关的位点（GD-1）的证据。我们现在扩展了这些研究，并分析了53个患有GD和/或HT的多重家庭（323名个体）。使用跨越整个染色体的16个微卫星标记对14号染色体进行筛选。还研究了位于14号染色体上候选基因内部的另外三个标记。使用荧光标记引物扩增微卫星标记，并在ABI-310基因分析仪上进行分离。使用LIPED软件进行两点对数优势（LOD）评分分析，并使用GeneHunter软件进行多点连锁分析。未发现任何标记与HT或自身免疫性甲状腺疾病（GD+HT）存在连锁关系。在这组规模大得多的家族中，先前在14q31上鉴定出的GD-1位点继续显示出与GD存在连锁的证据。假设隐性遗传模式和外显率为0.3，标记D14S81（θ=0.01）获得的最大LOD评分为2.1。多点分析在标记D14S81和D14S1054之间产生的最大LOD评分为2.5。在我们的样本中没有异质性的证据。这些数据再次表明在14号染色体q31上存在一个主要的格雷夫斯病易感基因（GD-1）。该位点靠近最近鉴定出的多结节性甲状腺肿-1位点。
