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 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.

HLA imputation in an admixed population: An assessment of the 1000 Genomes data as a training set

“…It has proven a valuable resource through its potential to enrich the degree of information about HLA polymorphism in association studies [1–4]. …”

“…specific predisposing HLA alleles which are already known). Imputation can even provide, with a high reliability, the variant an individual carries at a specific amino-acid position, and this can be included in models testing for association between genotypes and disease phenotypes [2–4]. …”

The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex

“…Furthermore, HLA imputation methods are only able to resolve HLA genotypes at the two field resolution level and may not be used to infer any associations between synonymous variations or variations within noncoding regions of HLA alleles. However, despite these limitations, HLA genotype imputation has proven to be a valuable tool in associating specific HLA alleles with various traits from large‐scale SNP genotyping data in the absence of targeted HLA sequencing data (Sanchez‐Mazas & Meyer, ).…”

Nasopharyngeal Carcinoma (NPC) Related Human Leukocyte Antigen (HLA) Haplotype Sharing among Southern East Asian Population

“…1 East Asian population is consistently reported to have two population groups division that are Southern and Northern groups used for studies using various genetic markers such as Y chromosome, 2,3 mtDNA, 4 and HLA. [5][6][7] The genetic studies of human diversity in East Asian and the migration routes of ancestral populations also have been investigated, emphasizing the history of East Asian and the North-South differentiation in Chinese population. 3,8 Southern China and Southeast Asia have been reported to be endemic regions of NPC, one of the most common cancers in Asians but it is rare in Caucasians.…”