Mobile element variation contributes to population-specific genome diversification, gene regulation and disease risk.

Autor: Kojima S; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan. shohei.kojima@riken.jp., Koyama S; Laboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA., Ka M; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan.; Next-Generation Precision Medicine Development, Integrative Genomics Laboratory, Graduate School of Medicine, Department of Medical Science, The University of Tokyo, Tokyo, Japan., Saito Y; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan.; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan., Parrish EH; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan., Endo M; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Takata S; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Mizukoshi M; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Hikino K; Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Takeda A; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.; Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan., Gelinas AF; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan., Heaton SM; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan., Koide R; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan., Kamada AJ; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan.; Paleovirology Lab, Department of Biology, University of Oxford, Oxford, UK., Noguchi M; Cell Engineering Division, BioResource Research Center, RIKEN, Tsukuba, Japan., Hamada M; Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.; Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan., Kamatani Y; Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Murakawa Y; RIKEN-IFOM Joint Laboratory for Cancer Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan.; IFOM ETS - the AIRC Institute of Molecular Oncology, Milan, Italy., Ishigaki K; Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Nakamura Y; Cell Engineering Division, BioResource Research Center, RIKEN, Tsukuba, Japan., Ito K; Laboratory for Cardiovascular Genomics and Informatics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Terao C; Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.; The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan., Momozawa Y; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Parrish NF; Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan. nicholas.parrish@riken.jp.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2023 Jun; Vol. 55 (6), pp. 939-951. Date of Electronic Publication: 2023 May 11.
DOI: 10.1038/s41588-023-01390-2
Abstrakt: Mobile genetic elements (MEs) are heritable mutagens that recursively generate structural variants (SVs). ME variants (MEVs) are difficult to genotype and integrate in statistical genetics, obscuring their impact on genome diversification and traits. We developed a tool that accurately genotypes MEVs using short-read whole-genome sequencing (WGS) and applied it to global human populations. We find unexpected population-specific MEV differences, including an Alu insertion distribution distinguishing Japanese from other populations. Integrating MEVs with expression quantitative trait loci (eQTL) maps shows that MEV classes regulate tissue-specific gene expression by shared mechanisms, including creating or attenuating enhancers and recruiting post-transcriptional regulators, supporting class-wide interpretability. MEVs more often associate with gene expression changes than SNVs, thus plausibly impacting traits. Performing genome-wide association study (GWAS) with MEVs pinpoints potential causes of disease risk, including a LINE-1 insertion associated with keloid and fasciitis. This work implicates MEVs as drivers of human divergence and disease risk.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
Externí odkaz: