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Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method
- Source :
- Cell Genomics, Vol 2, Iss 3, Pp 100101- (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- Summary: 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 (nreference = 689, imputation accuracy = 99.7%), apply it to biobank genotype (ntotal = 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 × 10−4). Our pipeline presents a broadly applicable framework to evaluate innate immunity in large-scale datasets.
Details
- Language :
- English
- ISSN :
- 2666979X
- Volume :
- 2
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Genomics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.90501fcf80d34f2380420ddb63a6f8b7
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.xgen.2022.100101