HLA diversity in the 1000 genomes dataset.
HLA diversity in the 1000 genomes dataset.
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DOI：
10.1371/journal.pone.0097282
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Oksenberg J
中科院分区：
文献类型：
--
作者：
Gourraud PA;Khankhanian P;Cereb N;Yang SY;Feolo M;Maiers M;Rioux JD;Hauser S;Oksenberg J
千人基因组计划旨在通过测序对人类基因组序列变异进行深入表征，测序水平应允许在全基因组范围内检测频率低至1%的大多数变异。然而，在主要组织相容性复合体（MHC）中，只有前10个最常见的单倍型在1%的频率范围内，而数以千计的单倍型以较低的频率存在。考虑到由1000个基因组计划产生的序列的覆盖范围和读取长度的限制，定义HLA等位基因的高度可变的位置可能难以鉴定。我们使用经典的桑格测序技术对现有的1000个基因组样本中的HLA-A、HLA-B、HLA-C、HLA-DRB 1和HLA-DQB 1基因进行分型，并将结果与1000个基因组计划分型的MHC区域中的103，310个变体相结合。利用个体间的逐代身份距离和主成分分析，我们建立了祖先和MHC区域遗传多样性之间的关系。正如预期的那样，MHC变体和HLA表型都可以识别主要的祖先谱系，主要由最常见的HLA单倍型告知。在某种程度上，具有相似遗传或相似重组率的基因组区域具有相似的特性。以MHC为中心的分析强调了MHC的祖先背景与全基因组图像之间的偏离。我们的连锁不平衡（LD）衰减在这些样本中的分析表明，高估成对LD发生由于有限的采样的MHC多样性。这些HLA特异性MHC变体的集合，可在dbMHC门户网站上获得，是未来分析MHC在人口和疾病研究中作用的宝贵资源。
The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC), only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD) decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.
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影响因子：
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作者：
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通讯作者：
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