Worldwide genetic variation of the IGHV and TRBV immune receptor gene families in humans

Life Science Alliance
Shishi LuoYun S Song

Abstract

The immunoglobulin heavy variable (IGHV) and T cell beta variable (TRBV) loci are among the most complex and variable regions in the human genome. Generated through a process of gene duplication/deletion and diversification, these loci can vary extensively between individuals in copy number and contain genes that are highly similar, making their analysis technically challenging. Here, we present a comprehensive study of the functional gene segments in the IGHV and TRBV loci, quantifying their copy number and single-nucleotide variation in a globally diverse sample of 109 (IGHV) and 286 (TRBV) humans from over a 100 populations. We find that the IGHV and TRBV gene families exhibit starkly different patterns of variation. In addition to providing insight into the different evolutionary paths of the IGHV and TRBV loci, our results are also important to the adaptive immune repertoire sequencing community, where the lack of frequencies of common alleles and copy number variants is hampering existing analytical pipelines.

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Datasets Mentioned

BETA
PRJEB9586
EGAS00001001959

Methods Mentioned

BETA
genotyping
genetic modification

Software Mentioned

GATK
TimeTree
Bowtie2
Genepop
HaplotypeCaller
HapCUT2
ssw
Spades

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