reirrac-noN cinegohtapenreirrac )VPGmreG( tnairavilMutation BRCA1BRCA2BRCA269DNA damageGastric epithelial cellDNA damageGPVBRCA1H.pyloriinfectionDNA repairCagAHomologous recombinationCagADNA damageError-prone repairCumulative lifetime(≤85 yr)risk of gastric cancer14.4%45.5%genome regulation by mapping regulatory elements and understanding of transcribed RNAs. The previous FANTOM projects showed that long non-coding RNAs (lncRNAs) play po-tentially important roles in health and diseases, however, lncRNA functional mechanisms are poorly understood.The finding that the majority of lncRNAs in the cell are lo-calized in the nucleus and a substantial fraction of them are chromatin-bound suggested some sort of gene regulation by lncRNAs. The FANTOM6 project, currently underway, focuses on RNA-chromatin interactome analysis and broadly maps regulation involving the transcriptome. The RNA-chromatin interactome sequencing data are generated by the RADICL-seq technology, which captures RNA-DNA interactions in a genome-cer, dementia, infection, and pharmacogenomics as priority areas for the implementation of genomic information in actual medical practice. To accomplish this goal, a combined 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 sequencing-based association studies. These include cancer (Momozawa & Nakagawa), pharmacogenomics (Mushiroda), car-diovascular diseases (Ito), autoimmune diseases (Yamamoto K), genome immunobiology (Parish), functional genetics (Ishigaki), and integrated analysis of all data and phenotypes (Terao). In ad-dition, we began to extract information about 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 sequencing approaches obtained by labo-ratories of the FANTOM and Human Cell Atlas projects. Finally, wide fashion, with various molecular biology techniques, such as full-length cDNAs, ssCAGE, Hi-CAP, and PARIS, among others, from ~15 cell types including time course analyses during the dif-ferentiation of iPSCs to neurons and THP1 monocyte activation to become a macrophage.In April 12-14 and October 2-3 2023, we organized the FAN-TOM6 on-site meetings in Milan, Italy to deepen our discussion and insights, involving many of the researchers from ~70 insti-tutes around the world (Figure). The FANTOM collaborators have been broadly generating invaluable complementary data and the analysis is identifying various dynamic patterns of RNA movements and interactions with chromosomes during differen-tiation.we have established collaborations with large Japanese cohorts including BioBank Japan (BBJ), Tohoku Medical Megabank and domestic and international universities.A key finding in 2023 is the accumulation of new evidence for disease management and the pathogenesis of gastric cancer. Based on large-scale genomic evaluation, we found nines genes associ-ated with gastric cancer risk. We also revealed a remarkable gene-environmental interaction between germline pathogenic variants in homologous recombination genes (ATM, BRCA1, BRCA2, and PALB2) and Helicobacter pylori infection (Figure). These findings are an example of “multihit” carcinogenesis, where two or more “hits” are essential for disease development, and pointed the way toward novel personalized disease prevention measures. Large-scale genomic evaluation allows for epidemiological assessment, leading to clinical management.Figure: The FANTOM6 meeting on October 2-3, 2023The FANTOM6 meetings were held at the Human Technopole in Milan, Italy on April 12-14 and October 2-3, 2023.Figure: Interaction between germline pathogenic variants in homologous recombination genes and Helicobacter pylori infection revealed from large-scale genomic evaluationATM, BRCA1, BRCA2, and PALB2 are homologous recombination genes. Germline pathogenic variants (GPV) in any of these four genes predisposed the carrier to a greatly increased lifetime risk of gastric cancer among individuals with Helicobacter pylori infection (carrier, 45.5% vs. non-carrier, 14.4%).FANTOMThe FANTOM project started in 2000 aiming to elucidate Human genome analysis In 2015, the Japanese government set rare hereditary diseases, can-
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