Summary of Research Project Results under JSPS FY2004
"Research for the Future Program"

1. Research Institution   Keio University
2. Research Area Life Sciences
3. Research Field Genome Research
4. Term of Project FY 2000 - FY 2004
5. Project Number 00L01406
6. Title of Project Human Molecular Biology and Medicine Based on Genome Analysis

7. Project Leader

Name Institution, Department Title of Position
Nobuyoshi, Shimizu Keio University, School of Medicine Professor

8. Core Members

Names Institution, Department Title of Position
Shinsei, Minoshima Hamamatsu University School of Medicine, Photon Medical Research Center Professor

9. Summary of Research Results

In 2004, we as a member of the international consortium of human genome project (HGP) reported the completion of sequencing the entire human genome of 3 billion base pairs (Nature 431:931-945, 2004). The human genome contains at least 23,000 genes and each chromosome has many characteristic molecular features. We have contributed to the sequencing of several targeted regions of five chromosomes 22, 21, 8, 6 and 2. Comprehensive analysis of the sequence data with computer-aided annotation and experimental inspection enabled us to find over 2,000 genes that are associated with important biological functions and medical problems.
These important genes include the members of gene families such as Argonaute, YPEL and KAP (keratin-associated protein). The Argonaute family consists of 4 PIWI genes and 4 EIF2C genes and all the protein products interact with a DICER protein to participate in the new regulatory mechanism called RNA interference. The YPEL family consists of 5 similar but distinct genes whose protein products appear to be involved in the centrosome function. The KAP family consists of 93 genes whose protein products are essential for hair formation in association with the keratin intermediate filaments. Furthermore, we found TMPRSS3 gene for the causative gene for familial deafness DFNB8/10. We also proved that TBX1 gene in the DiGeorge syndrome (DGS) critical region of 22q11.2 is the main causative gene for DGS and conotruncal anomaly face syndrome (CAFS). Surprisingly, DGCR8 gene found in the same region is not only another candidate gene for those syndromes, but also a component of molecular apparatus for generation of miRNA. We also studied functions of several disease-responsible genes which we had previously found. These genes include PARKIN for autosomal recessive juvenile parkinsonism, AIRE for autoimmune disease APECED, and MYOCILIN for a glaucoma. Mutations in the genes found in this research project have been accumulated in our original database MutationView and made open to public via internet (

10. Key Words

( 1 ) Parkinson disease gene PARKIN ( 2 ) Glaucoma gene MYOC ( 3 ) Autoimmune regulator AIRE
( 4 ) deafness gene TMPRSS3 ( 5 ) DiGeorge syndrome gene TBX1 ( 6 ) BAC library
( 7 ) DNA microarray ( 8 ) KAONASHI gene ( 9 )KAP gene cluster