Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4-Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here, we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.

主要组织相容性复合体（MHC，也称为HLA）中的基因在免疫应答中起关键作用，而扩展的4-Mb区域内的变异表明与许多疾病的主要风险相关。但是，很难解释这些关联的根本原因，因为MHC是基因组中具有复杂连锁不平衡结构的最多态的区域。在这里，我们从头组装的三重奏重建完整的MHC单倍型，而无需依赖参考基因组，并进行进化分析。我们报告了100个完整的MHC单倍型，并在该区域中调用了一大套结构变体，以供将来在GWAS数据中使用。