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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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 |
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author | 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 |
author_facet | 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 |
author_sort | Sakaue, Saori |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9903714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99037142023-02-10 Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method 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 Cell Genom Article 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. Elsevier 2022-03-09 /pmc/articles/PMC9903714/ /pubmed/36777335 http://dx.doi.org/10.1016/j.xgen.2022.100101 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article 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 Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title | Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title_full | Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title_fullStr | Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title_full_unstemmed | Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title_short | Decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
title_sort | decoding the diversity of killer immunoglobulin-like receptors by deep sequencing and a high-resolution imputation method |
topic | Article |
url | 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 |
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