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Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for  HLA  polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the  HLA  genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of  HLA  sequence data will be available in the next years for different populations, with the potential to change our understanding of  HLA  variation in humans. In this review, we first explain how  HLA  sequencing allows a better assessment of the  HLA  diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing  HLA  sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both  HLA  and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the  HLA  molecular diversity observed today.

The Relevance ofHLASequencing in Population Genetics Studies