Immunogenetics of HLA‐B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds
Immunogenetics of HLA‐B: SNP, allele, and haplotype diversity in populations from different continents and ancestry backgrounds
复制标题
HLA-B 的免疫遗传学：来自不同大陆和祖先背景的人群中的 SNP、等位基因和单倍型多样性
作者：
Nayane S B Silva;A. Souza;H. S. Andrade;Raphael N. Pereira;C. F. B. Castro;N. Vince;Sophie Limou;M. Naslavsky;M. Zatz;Y. Duarte;C. Mendes;E. Castelli
HLA B是人类基因组中变异最大的基因之一。该基因编码抗原呈递给CD 8 + T淋巴细胞和NK细胞调节的关键分子。尽管有无数的研究评估其编码区（重点是外显子2和3），很少有研究评估内含子和调控序列在真实的人口样本。因此，HLA B变异性可能被低估了。我们对来自80个不同人群的5347个样本（其中包括1000多名混合巴西人）应用了针对HLA基因量身定制的生物信息学管道，以评估外显子、内含子和调控区的HLA B变异性（SNP、indels、MNP、等位基因和单倍型）。我们在整个HLA B中观察到610个变异位点;最常见的变异是全世界共有的。然而，单倍型分布是地理结构。我们检测到920个全长单倍型（外显子，内含子和非翻译区）编码239个不同的蛋白质序列。B基因多样性在混合人群和欧洲人中较高，而在非洲血统个体中较低。每个B等位基因组与特定的启动子序列相关。这种HLA B变异资源可能会提高HLA填补的准确性和疾病相关性研究，并提供有关人类群体中HLA B遗传多样性的进化见解。
HLA‐B is among the most variable gene in the human genome. This gene encodes a key molecule for antigen presentation to CD8+ T lymphocytes and NK cell modulation. Despite the myriad of studies evaluating its coding region (with an emphasis on exons 2 and 3), few studies evaluated introns and regulatory sequences in real population samples. Thus, HLA‐B variability is probably underestimated. We applied a bioinformatics pipeline tailored for HLA genes on 5347 samples from 80 different populations, which includes more than 1000 admixed Brazilians, to evaluate the HLA‐B variability (SNPs, indels, MNPs, alleles, and haplotypes) in exons, introns, and regulatory regions. We observed 610 variable sites throughout HLA‐B; the most frequent variants are shared worldwide. However, the haplotype distribution is geographically structured. We detected 920 full‐length haplotypes (exons, introns, and untranslated regions) encoding 239 different protein sequences. HLA‐B gene diversity is higher in admixed populations and Europeans while lower in African ancestry individuals. Each HLA‐B allele group is associated with specific promoter sequences. This HLA‐B variation resource may improve HLA imputation accuracy and disease‐association studies and provide evolutionary insights regarding HLA‐B genetic diversity in human populations.
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影响因子：
158.5
作者：
Gao, XJ;Nelson, GW;Carrington, M
通讯作者：
Carrington, M
DOI：
10.2741/a298
发表时间：
1998-05
期刊：
Frontiers in bioscience : a journal and virtual library
影响因子：
--
作者：
A. Hughes;M. Yeager
通讯作者：
A. Hughes;M. Yeager
影响因子：
2.7
作者：
Noble, JA;Valdes, AM;Erlich, HA
通讯作者：
Erlich, HA
影响因子：
7
作者：
McKenna, Aaron;Hanna, Matthew;DePristo, Mark A.
通讯作者：
DePristo, Mark A.