Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method.

Cell genomics
Authors
Keywords
Abstract

The killer cell immunoglobulin-like receptor (KIR) recognizes human leukocyte antigen (HLA) class I molecules and modulates the function of natural killer cells. Despite its role in immunity, the complex genomic structure has limited a deep understanding of the KIR genomic landscape. Here we conduct deep sequencing of 16 KIR genes in 1,173 individuals. We devise a bioinformatics pipeline incorporating copy number estimation and insertion or deletion (indel) calling for high-resolution KIR genotyping. We define 118 alleles in 13 genes and demonstrate a linkage disequilibrium structure within and across KIR centromeric and telomeric regions. We construct a KIR imputation reference panel (n = 689, imputation accuracy = 99.7%), apply it to biobank genotype (n = 169,907), and perform phenome-wide association studies of 85 traits. We observe a dearth of genome-wide significant associations, even in immune traits implicated previously to be associated with KIR (the smallest p = 1.5 Ã— 10). Our pipeline presents a broadly applicable framework to evaluate innate immunity in large-scale datasets.

Year of Publication
2022
Journal
Cell genomics
Volume
2
Issue
3
Pages
100101
Date Published
03/2022
ISSN
2666-979X
DOI
10.1016/j.xgen.2022.100101
PubMed ID
36777335
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