70University ofPatras,Greece (304)United ArabEmiratesUniversity (100)DefenceServicesMedical ResearchCentre, Myanmar (100)Ministry of Health, Lao PDR (100)Vietnam NationalUniversity (100)Mahidol University,Thailand (100)University of thePhilippines (100)University of Malaya (105)YARSI University.Indonesia (562)cancer, dementia, infection, and pharmacogenomics as priori-ty areas for the implementation of genomic information for actual medical practice. To accomplish this goal, a combined analysis of germline variants with other information including somatic vari-ations, gene expression profiles and environmental factors would be key.IMS has analyzed various diseases and phenotypes by genome-wide association studies and/or targeted- and whole-genome se-quencing-based association studies, including cancer (Momozawa & Nakagawa), pharmacogenomics (Mushiroda), bone and joint diseases (Ikegawa), diabetes mellitus (Horikoshi), cardiovascular diseases (Ito), autoimmune diseases (Yamamoto K), genome im-munobiology (Parish), functional genetics (Ishigaki), and inte-grated analysis of all data and phenotypes (Terao). In addition, we began to extract information about somatic variations from DNA microarray data, which had previously been used only to call cogenomics Research Network (SEAPharm) together with five other Asian countries (Korea, Indonesia, Malaysia, Taiwan, and Thailand). Membership has been steadily increasing, with Singapore joining the team in 2014, Vietnam in 2016, Nepal, Laos and the Philippines in 2017, and Brunei and Myanmar in 2018. The aims of the collaboration are to identify genomic biomarkers associated with adverse drug reactions, such as severe cutaneous adverse drug reactions (cADRs), including Stevens-Johnson syn-drome (SJS), toxic epidermal necrolysis (TEN) and hepatic injury, to provide technical assistance and training of young researchers from the SEAPharm member countries, and to hold international seminars and workshops.germline variants. Further, to better understand disease biology, we integrated our results with knowledge of non-coding regions and single-cell sequencing approaches obtained by laboratories of the FANTOM and Human Cell Atlas projects. Finally, we have established collaborations with large Japanese cohorts including BioBank Japan (BBJ), Tohoku Medical Megabank and domestic and international universities.A key finding in 2021 was the discovery of a new hereditary bone disease, called “Ikegawa type craniotubular dysplasia”, and the identification of its causative gene, TMEM53, encoding a nuclear envelope protein. By comprehensive exome sequence analyses followed by in vitro and in vivo functional studies using gene knock-down and knock-out techniques, we elucidated the novel function of TMEM53 as a gatekeeper of the BMP/TGF-β signals controlling bone development and showed that bi-allelic loss of function of TMEM53 causes the disease.In 2018, SEAPharm started a new project involving next-gen-eration sequencing (NGS) of DNA samples to clarify the genetic diversity of 100 pharmacokinetics-related genes in individuals from 9 countries of Southeast Asia, the Middle East and Southern Europe. RIKEN IMS is responsible for the targeted sequencing using a PKSeq panel developed by RIKEN and reported substan-tial genetic variations in drug-metabolizing enzyme and drug transporter genes among Asian populations. These findings can account for interethnic variabilities in drug response phenotypes and are leading to the acceleration of further pharmacogenomic investigations and the implementation of genotype-guided drug therapies in clinical practice.Figure: Phenotype of the new disease, Ikegawa type craniotubular dysplasiaThe patients present characteristic radiographic features, including sclerosis of the skull and dysplasias of the spine and metaphyses of the long and short tubular bones.Figure: SEAPharm pharmacogenomic variation projectWe genotyped 1,571 genomic DNA samples collected by nine collaborative institutes (the number in parentheses in each country indicates the sample size) using the PKseq panel that targets the coding regions of 62 drug-metabolizing enzymes and 37 drug transporter genes. We were able to identify many previously unreported variants in 20 clinically important drug-metabolizing enzyme genes in the Japanese and SEAPharm populations.JapaneseSEAPharmNovelKnownHuman genome analysisIn 2015, the Japanese government set rare hereditary diseases, SEAPharm for establishment of stratified medicine in AsiaIn 2012, RIKEN established the South East Asian Pharma-
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