123456789Non-synonymous variants of20 very important drug-metabolizing enzymes identified in the SEAPharmprojectMPLDNMT3AFOXP1/RYBPFHITTET2LossCN-LOHGainUndeterminedUntypedregionCentromereABCA1del(13q14)JAK2del(5q)13TRATNFAIP3PTEN10NEDD8/TINF2ATMMRE11NBN11ETV61214del(20q)15del(16p11.2)20DLK1TCL1ACTU216NF1TP531721CHEK218192266Myanmar–DefenceServicesMedical Research CentreThailand–Department of Medical Sciences, MahidolUniversity,KhonKaenUniversity,ChulalongkornUniversity,Thailand Center of Excellencefor Life Sciences (TCELS)Nepal –SwaconInternational HospitalTaiwan–Academia SinicaLaos–National Institute of Public HealthVietnam–Ho Chi Minh City International UniversityPhilippines–University of Philippines ManilaBrunei –UniversitiBrunei DarussalamSingapore –Genome Instituteof Singapore (GIS)Indonesia–YARSI University RIKEN Center forIntegrative Medical Sciences (IMS)Korea–InjeUniversityMalaysia–University of Malayacancer, dementia, infection, and pharmacogenomics as priori-ty areas for the implementation of genomic information for actual medical practice. To accomplish this goal, a combination analysis of germline variants with other information including somatic variations, 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 (Horikoshi), cardiovascular diseases (Ito), autoimmune diseases (Yamamoto K), and integrated analysis of all data and phenotypes (Terao). In addition, we began to extract information of somatic variations from DNA microarray data, which had previously been used only to call germline variants. Further, to better understand disease biology, we integrated our results with knowledge of non-coding regions and single cell se-quencing approaches by laboratories of the FANTOM and Human 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 (ADRs), 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.Recently, SEAPharm has started a new project involving next-generation sequencing (NGS) of about 2,000 genomic DNA samples from 12 countries to clarify the genetic diversity of 100 pharmacokinetics-related genes in individuals from Southeast Asia, Sothern Asia, Middle East and Southern Europe. RIKEN 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 2020 was elucidating the basics underlying mosaic chromosomal alterations (mCA), clonal hematopoiesis with somatic chromosomal alterations. We identified 33,250 mCAs in 179,417 BBJ participants and found that mCA seems inevitable with advancing age. Key differences in the genomic locations of mCA between Japanese and Europeans could help predict the relative rates of B-cell and T-cell leukemia between the populations.IMS is responsible for the targeted sequencing using a PKSeq panel developed by RIKEN and reported substantial genetic vari-ations in drug-metabolizing enzyme and drug transporter genes among Asian populations. These findings can account for inter-ethnic variabilities in drug response phenotypes, and are leading to acceleration of further pharmacogenomic investigations and genotype-guided drug therapies in clinical practice.Figure: Genomic locations of 33,250 autosomal mCAs detected in 27,910 unique BBJ participantsmCA events are plotted as blue, orange and red horizontal lines, according to their mCA classes. Events with undetermined copy numbers are plotted in grey. Commonly deleted regions are labelled in blue; loci associated with Copy Neutral - Loss of Heter-zygosity (CN-LOH) mutations in cis are labelled in orange.Figure: Members of the South East Asian Pharmacogenomics Research Network (SEAPharm)Please visit https://www.facebook.com/SEAPHARM/Human 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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