Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus
Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus
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DOI：
10.1007/s00439-005-0111-z
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Nickerson, DA
中科院分区：
文献类型：
--
作者：
Mackelprang, R;Livingston, RJ;Nickerson, DA
T细胞受体（TR）通过与主要组织相容性复合体的相互作用，在免疫应答和潜在的免疫相关疾病中发挥核心作用。我们对40名北方欧洲人、墨西哥人、非洲裔美国人和中国人后裔的人T细胞受体α和δ（TRA/TRD）基因座中的所有57个可变（V）基因进行了重新测序。鉴定出284种单核苷酸多态性（SNP）。V基因之间SNPs的分布是异质性的，每个基因平均有5个SNPs，范围为0到15。我们描述了这些新发现的SNP的连锁不平衡模式，并将这些模式与其他新兴的大规模数据集（例如Perlegen和HapMap项目）进行比较，将我们的研究结果纳入未来分析该位点基因型-表型关联的框架。此外，我们探讨了V基因之间的自然选择的签名。我们发现在这个位点的强定向选择的证据，证明了异常高的值Ft。
T cell receptors (TR), through their interaction with the major histocompatibility complex, play a central role in immune responsiveness and potentially immune-related disorders. We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent. Two hundred and eighty-four single nucleotide polymorphisms (SNPs) were identified. The distribution of SNPs between V genes was heterogeneous, with an average of five SNPs per gene and a range of zero to 15. We describe the patterns of linkage disequilibrium for these newly discovered SNPs and compare these patterns with other emerging large-scale datasets (e.g. Perlegen and HapMap projects) to place our findings into a framework for future analysis of genotype-phenotype associations across this locus. Furthermore, we explore signatures of natural selection across V genes. We find evidence of strong directional selection at this locus as evidenced by unusually high values of Ft.