【摘要】 目的　确定中国人Graves病 (GD)的染色体易感区。方法　采用 2 77个高度多态 (平均间距约为 13cM )的微卫星标记对 5 4个中国汉族GD多发家系的 3 2 2名个体做全基因组扫描研究。分别计算疾病在呈显性及隐性遗传的各外显率下 ,各微卫星的两点LOD值及多点LOD值 ,并计算多点非参数连锁(NPL)值。结果　参数法连锁分析显示染色体 5q3 1区的D5S43 6的两点LOD值与多点LOD值均最高 ,分别为 2 .8和 2 .3。为了进一步确定该区域在GD发生中的作用 ,在D5S43 6两侧又增加了 4个微卫星做基因分型和连锁分析 ,在D5S2 0 90处得到了最大两点LOD值 4.3 1和最大多点LOD值 4.12 (具有遗传异质性 ,α^ =0 .3 8)。多点非参数法连锁分析也显示D5S2 0 90的NPL值最高 ,为 2 .66(P =0 .0 0 1) ,同样支持该位点与GD相连锁。结论　GD的一个主要易感位点位于染色体 5 q3 1区 ;在GD中存在遗传异质性。更多还原

【Abstract】 Objective To identify chromosomal regions contributing to Graves′ disease (GD) in Chinese. Methods Using 277 highly polymorphic microsatellite markers with an average inter-marker spacing of 13 centimorgans, a genome-wide scan was conducted on 322 individuals from 54 Chiense Han multiplex GD pedigrees. Assuming both dominant and recessive models, two-point and multi-point LOD scores of various microsatellite markers were calculated under different levels of penetrance. Multipoint nonparametric linkage (NPL) score was also calculated. Results Parametric linkage analysis showed a strong evidence for linkage at D5S436 on chromosome 5q31 with a maximum two-point LOD score of 2.8 and a maximum multipoint LOD score of 2.3. To further assess the significance of this suggestive finding, four additional markers around D5S436 in this chromosome region were typed, and a maximum two-point LOD score of 4.31 and a maximum multipoint LOD score of 4.12 were obtained for marker D5S2090 (with heterogeneity, α^=0.38). Nonparametric multipoint analysis also showed the peak NPL score 2.66 at D5S2090 (P=0.001) , which also supports the evidence for linkage at this locus. Conclusion A susceptibility locus for GD locates in chromosome 5q31, which supports the existence of genetic heterogeneity in GD.更多还原