The Relevance ofHLASequencing in Population Genetics Studies

Abstract

Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method forHLApolymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of theHLAgenes 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 ofHLAsequence data will be available in the next years for different populations, with the potential to change our understanding ofHLAvariation in humans. In this review, we first explain howHLAsequencing allows a better assessment of theHLAdiversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzingHLAsequence 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 bothHLAand genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of theHLAmolecular diversity observed today.