Genetics and Cell Biology Section, National Cancer Center, 5-1-1 Tsukiji, Tokyo 104-0045, Japan
Function of orthologous genes within the human genome and model-animal genomes are divergent due to the protein evolution and the promoter evolution. Comprehensive characterization of genes within the human genome is the starting platform to elucidate the mechanism of human diseases and also to develop new therapeutics for human diseases.
Because WNT signaling molecules are implicated in carcinogenesis and embryogenesis, we engaged in the wet biology of WNT signaling molecules during 1996 - 2002. We have cloned and characterized more than 30 human genes encoding WNT signaling molecules, including 13 WNT family genes and 9 FZD family genes. Since 2003, we have been engaging in the dry biology of human protein-coding genes. We identified and characterized PRICKLE1, PRICKLE2, DACT1, DACT2, DAAM2 and BCL9L genes, encoding WNT signaling molecules.
Next to 'WNT-ome', we engaged in comprehensive characterization of Formin-ome, ARHGAP-ome, FOX-ome, etc. We identified and characterized FMNL1, FMNL2, FMNL3, DIAPH3, DAAM2, FMN1, FMN2, FHOD3, GRID2IP, FHDC1 genes encoding Formin-homology proteins, ARHGAP10, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP27, FNBP2 genes encoding Rho-like GTPase activator (RhoGAP), and also FOXK1, FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO2 (FOXO6) genes encoding Forkhead-box (FOX) transcription factors.
We also comprehensively characterized genes around recombination hotspots within the human genome. The 17q12-q21.1 region around PPP1R1B-STARD3-TCAP-PNMT-PERLD1-ERBB2-C17orf37-GRB7 amplicon and GSDML-GSDM locus was a recombination hotspot. We identified and characterized PERLD1, C17orf37, ZPBP2, GSDML and GSDM genes around the 17q12-q21.1 recombination hot spot. The 11q23.3 region around MLL amplicon and neuroblastoma deleted region was an oncogenomic recombination hotspot. We identified and characterized TMEM25, PHLDB1, BCL9L, FOXN5, TMEM24, RNF26 and MFRP genes around the 11q23.3 oncogenomic recombination hot spot. Oncogenes and tumor suppressor genes were clustered around oncogenomic hotspots within the human genome.
In conclusion, we have comprehensively identified and characterized the following human genes:  Genes implicated in signaling pathways (WNT-ome, Hedgehog-ome, etc);  Genes belonging to large families (Formin-ome, ARHGAP-ome, FOX-ome, KIF-ome, CLDN-ome, etc);  Genes located around oncogenomic recombination hotspots (chromosome 10q26, 11q13.3, 11q23.3, 17q12-q21.1, etc).
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