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Journal Article
Review
The MHC in the era of next-generation sequencing: Implications for bridging structure with function.
Human Immunology 2019 January
The MHC continues to have the most disease-associations compared to other regions of the human genome, even in the genome-wide association study (GWAS) and single nucleotide polymorphism (SNP) era. Analysis of non-coding variation and their impact on the level of expression of HLA allotypes has shed new light on the potential mechanisms underlying HLA disease associations and alloreactivity in transplantation. Next-generation sequencing (NGS) technology has the capability of delineating the phase of variants in the HLA antigen-recognition site (ARS) with non-coding regulatory polymorphisms. These relationships are critical for understanding the qualitative and quantitative implications of HLA gene diversity. This article summarizes current understanding of non-coding region variation of HLA loci, the consequences of regulatory variation on HLA expression, the role for evolution in shaping lineage-specific expression, and the impact of HLA expression on disease susceptibility and transplantation outcomes. A role for phased sequencing methods for the MHC, and perspectives for future directions in basic and applied immunogenetic studies of the MHC are presented.
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