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

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...

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Detalles Bibliográficos
Autores principales: Sakaue, Saori, Hosomichi, Kazuyoshi, Hirata, Jun, Nakaoka, Hirofumi, Yamazaki, Keiko, Yawata, Makoto, Yawata, Nobuyo, Naito, Tatsuhiko, Umeno, Junji, Kawaguchi, Takaaki, Matsui, Toshiyuki, Motoya, Satoshi, Suzuki, Yasuo, Inoko, Hidetoshi, Tajima, Atsushi, Morisaki, Takayuki, Matsuda, Koichi, Kamatani, Yoichiro, Yamamoto, Kazuhiko, Inoue, Ituro, Okada, Yukinori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903714/
https://www.ncbi.nlm.nih.gov/pubmed/36777335
http://dx.doi.org/10.1016/j.xgen.2022.100101
Descripción
Sumario: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(reference) = 689, imputation accuracy = 99.7%), apply it to biobank genotype (n(total) = 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.