The inter-regional distribution of HLA class II haplotypes indicates the suitability of the Sardinian population for case-control association studies in complex diseases
The inter-regional distribution of HLA class II haplotypes indicates the suitability of the Sardinian population for case-control association studies in complex diseases
复制标题
HLA II 类单倍型的区域间分布表明撒丁岛人群适合复杂疾病的病例对照关联研究
DOI：
10.1093/hmg/9.20.2959
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发表时间：
2000-12-12
影响因子：
3.5
通讯作者：
Cucca, F
中科院分区：
文献类型：
--
作者：
Lampis, R;Morelli, L;Cucca, F
我们分析了撒丁岛人口的HLA II类基因为基础的子结构，以评估可能的影响，这个参数在常见疾病位点的映射使用关联方法。我们首先研究了来自该岛7个不同地区的631名新生儿的HLA-DRB 1-DQA 1-DQB 1单倍型的分布，发现最常见的单倍型均匀分布在所有地区，但在撒丁岛特有的频率。在其他白色欧洲人群中常见的其他单倍型在整个岛屿上一直很罕见或不存在。分子方差分析（AMOVA）表明，沿海地区，多年来遭受反复入侵之间的遗传分化程度很低，最内部和孤立的岛屿的一部分。这表明，在过去的3000年里，入侵该岛的各种人群几乎没有遗传流，撒丁岛是一个相对同质的人群。这些无关对照HLA单倍型频率的有效性和我们的同质性声明是通过证明来自撒丁岛的243个1型糖尿病和495个多发性硬化症家族与无关对照的受影响的基于家族的对照（AFBAC）HLA单倍型频率的接近同一性而建立的。这些结果表明，稳健的病例对照研究可以在撒丁岛进行，提供一定的家庭为基础的设计的成本效益。
We have analysed HLA class II gene-based substructure of the Sardinian population in order to evaluate the possible influence of this parameter in the mapping of common disease loci using association methods. We first examined the distribution of the HLA-DRB1-DQA1-DQB1 haplotypes in 631 newborns from seven different regions of the island, and found that the most frequent haplotypes were uniformly distributed in all regions, but at frequencies unique to Sardinia. Other haplotypes, common in other white European populations, are consistently rare or absent across the whole island. Analysis of molecular variance (AMOVA) showed a very low degree of genetic differentiation between the coastal regions, which have suffered repeated invasions over many years, and the most internal and isolated part of the island. This suggests that there has been little genetic flow from the various populations that have invaded the island during the last 3000 years and that Sardinia is a relatively homogeneous population. The validity of these unrelated control HLA haplotype frequencies and our claim of homogeneity were established by demonstrating the near identity of the affected family-based control (AFBAC) HLA haplotype frequencies in 243 type 1 diabetes and 495 multiple sclerosis families from Sardinia and those of the unrelated controls. These results indicate that robust case-control studies can be carried out in Sardinia offering cost efficiency over certain family-based designs.