Strong association between microsatellites and an HLA-B, DR haplotype (B18-DR3): Implication for microsatellite evolution
Strong association between microsatellites and an HLA-B, DR haplotype (B18-DR3): Implication for microsatellite evolution
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DOI：
10.1007/bf02440992
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发表时间：
1996-01-01
期刊：
影响因子：
3.2
通讯作者：
CambonThomsen, A
中科院分区：
文献类型：
--
作者：
CrouauRoy, B;Bouzekri, N;CambonThomsen, A
HLA单倍型B18-DR 3具有广泛的地理分布，但在南欧的频率最高，可能是该地区最早人群的遗迹，特别是在巴斯克和撒丁岛。该单倍型具有医学意义，是胰岛素依赖型糖尿病中最有牵连的风险因素。在这项研究中，在肿瘤坏死因子（TNF）基因的区域中紧密连锁的微卫星标记（TNF α，B，c）已被用于尝试在两个人群和/或在健康和糖尿病人群中对该单倍型进行分型。共分析了79个HLA-BI 8-DR 3单倍型：巴斯克人54个（12个来自健康个体，42个来自糖尿病患者或其一级亲属），撒丁岛人25个（13个来自健康个体，12个来自糖尿病个体）。TNF单倍型al-b5-c2在两个群体中与B18-DR 3完全相关。在两个种族纯群体中B18-DR 3单倍型的同质性意味着进化的稳定性，这表明这些微卫星标记的突变率必须低于通常假设的（即，类似于每代每个位点5 × 10（-4））。这些标记应该是研究遗传漂变和种群混合的有力工具，但这种稳定性是否是NW单倍型中所有微卫星的规则，或者是否仅限于某些微卫星和/或某些HLA单倍型，仍有待确定。与HLA B18-DR 3相关的那些微卫星的群体遗传学也在巴斯克人群的随机样本中进行了研究。
The HLA haplotype B18-DR3 has a widespread geographical distribution, but has its greatest frequencies in Southern Europe, probably vestigial of the earliest populations of this region, particularly in the Pays Basque and Sardinia. This haplotype is of medical significance, being that most implicated as a factor of risk in insulin-dependent diabetes mellitus. In this study, the closely linked microsatellite markers (TNFa,b,c) in the region of the tumor necrosis factor (TNF) genes have been used in an attempt to subtype this haplotype in the two populations and/or in healthy and diabetic populations. A total of 79 HLA-BI8-DR3 haplotypes were analyzed: 54 in Basques (12 from healthy individuals and 42 from diabetics or their first-degree relatives) and 25 in Sardinians (13 from healthy and 12 from diabetic individuals). The TNF haplotype al-b5-c2 is completely associated with B18-DR3 in both populations. The homogeneity of the B18-DR3 haplotype in two ethnically pure populations implies stability in evolution, which suggests that the mutation rate of these microsatellite markers must be less than is usually assumed (i.e., similar to 5 x 10(-4) per site per generation). Such markers should be powerful tools for studying genetic drift and admixture of populations, but it remains to be established whether this stability is a rule for all microsatellites in NW haplotypes or whether it is restricted to some microsatellites and/or some HLA haplotypes. The population genetics of those microsatellites associated with HLA B18-DR3 was also studied in a random sample of the Basque population.