从三个东南亚人群的高分辨率单核苷酸多态性数据预测人类白细胞抗原等位基因。
Predicting HLA alleles from high-resolution SNP data in three Southeast Asian populations.
作者信息
Pillai Nisha Esakimuthu, Okada Yukinori, Saw Woei-Yuh, Ong Rick Twee-Hee, Wang Xu, Tantoso Erwin, Xu Wenting, Peterson Trevor A, Bielawny Thomas, Ali Mohammad, Tay Koon-Yong, Poh Wan-Ting, Tan Linda Wei-Lin, Koo Seok-Hwee, Lim Wei-Yen, Soong Richie, Wenk Markus, Raychaudhuri Soumya, Little Peter, Plummer Francis A, Lee Edmund J D, Chia Kee-Seng, Luo Ma, De Bakker Paul I W, Teo Yik-Ying
机构信息
Saw Swee Hock School of Public Health.
Division of Rheumatology, Immunology, and Allergy, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
出版信息
Hum Mol Genet. 2014 Aug 15;23(16):4443-51. doi: 10.1093/hmg/ddu149. Epub 2014 Apr 3.
The major histocompatibility complex (MHC) containing the classical human leukocyte antigen (HLA) Class I and Class II genes is among the most polymorphic and diverse regions in the human genome. Despite the clinical importance of identifying the HLA types, very few databases jointly characterize densely genotyped single nucleotide polymorphisms (SNPs) and HLA alleles in the same samples. To date, the HapMap presents the only public resource that provides a SNP reference panel for predicting HLA alleles, constructed with four collections of individuals of north-western European, northern Han Chinese, cosmopolitan Japanese and Yoruba Nigerian ancestry. Owing to complex patterns of linkage disequilibrium in this region, it is unclear whether the HapMap reference panels can be appropriately utilized for other populations. Here, we describe a public resource for the Singapore Genome Variation Project with: (i) dense genotyping across ∼ 9000 SNPs in the MHC; (ii) four-digit HLA typing for eight Class I and Class II loci, in 96 southern Han Chinese, 89 Southeast Asian Malays and 83 Tamil Indians. This resource provides population estimates of the frequencies of HLA alleles at these eight loci in the three population groups, particularly for HLA-DPA1 and HLA-DPB1 that were not assayed in HapMap. Comparing between population-specific reference panels and a cosmopolitan panel created from all four HapMap populations, we demonstrate that more accurate imputation is obtained with population-specific panels than with the cosmopolitan panel, especially for the Malays and Indians but even when imputing between northern and southern Han Chinese. As with SNP imputation, common HLA alleles were imputed with greater accuracy than low-frequency variants.
包含经典人类白细胞抗原(HLA)I类和II类基因的主要组织相容性复合体(MHC)是人类基因组中多态性最高、最具多样性的区域之一。尽管确定HLA类型具有临床重要性,但很少有数据库能在同一样本中联合表征高密度基因分型的单核苷酸多态性(SNP)和HLA等位基因。迄今为止,HapMap是唯一的公共资源,它提供了一个用于预测HLA等位基因的SNP参考面板,该面板由来自西北欧、中国北方汉族、日本人和尼日利亚约鲁巴族的四个个体集合构建而成。由于该区域连锁不平衡模式复杂,尚不清楚HapMap参考面板是否能适用于其他人群。在此,我们描述了新加坡基因组变异项目的一个公共资源,该资源具有:(i)对MHC中约9000个SNP进行高密度基因分型;(ii)对96名中国南方汉族、89名东南亚马来人和83名印度泰米尔人的8个I类和II类基因座进行四位数字的HLA分型。该资源提供了这三个群体中这八个基因座HLA等位基因频率的群体估计值,特别是对于HapMap中未检测的HLA - DPA1和HLA - DPB1。通过比较群体特异性参考面板和由所有四个HapMap群体创建的一个世界性面板,我们证明,与世界性面板相比,群体特异性面板能获得更准确的推断,尤其是对于马来人和印度人,甚至在对中国北方汉族和南方汉族之间进行推断时也是如此。与SNP推断一样,常见HLA等位基因的推断比低频变异更准确。