Kazuyoshi Ishigaki

May 28, 2024 | nature.com | Jun Inamo |Mahoko Takahashi Ueda |Hiroshi Nishida |Tsutomu Takeuchi |Kazuyoshi Ishigaki |Yasushi Ishihama

AbstractAlternative splicing events are a major causal mechanism for complex traits, but they have been understudied due to the limitation of short-read sequencing. Here, we generate a full-length isoform annotation of human immune cells from an individual by long-read sequencing for 29 cell subsets. This contains a number of unannotated transcripts and isoforms such as a read-through transcript of TOMM40-APOE in the Alzheimer’s disease locus.

Feb 7, 2024 | nature.com | Hannah Park |Kazuyoshi Ishigaki |Aparna Nathan

AbstractAutoimmune disease heritability is enriched in T cell-specific regulatory regions of the genome. Modern-day T cell datasets now enable association studies between single nucleotide polymorphisms (SNPs) and a myriad of molecular phenotypes, including chromatin accessibility, gene expression, transcriptional programs, T cell antigen receptor (TCR) amino acid usage, and cell state abundances.

Oct 7, 2023 | nature.com | Kazuyoshi Ishigaki |Mark Anderson

AbstractPsoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs).

Jul 26, 2023 | nature.com | Saori Sakaue |Michelle Curtis |Yang Luo |Wanson Choi |Kazuyoshi Ishigaki |Aaron Deutsch | +2 more

AbstractThe human leukocyte antigen (HLA) locus is associated with more complex diseases than any other locus in the human genome. In many diseases, HLA explains more heritability than all other known loci combined. In silico HLA imputation methods enable rapid and accurate estimation of HLA alleles in the millions of individuals that are already genotyped on microarrays.

May 11, 2023 | nature.com | Shohei Kojima |Satoshi Koyama |Steven Heaton |Yoichiro Kamatani |Yasuhiro Murakawa |Kazuyoshi Ishigaki | +6 more

AbstractMobile 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.