| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2000: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Research Abstract |
To establish a system for DNA diagnosis of skeletal dysplasias, genetic disorders of bone and cartilage, and gain insight for their pathogenesis, I performed genetic analysis of skeletal dysplasias and obtained the following results.
1. Isolation of a candidate gene for Shwachman syndrome
I analyzed a de novo reciprocal translocation, (t(6 ; 12)(q16.2 ; q21.2)) associated with Shwachman syndrome. I cloned the translocation breakpoints and determined the DNA sequences. I identified a gene that is disrupted by the breakpoint, a candidate gene for Shwachman syndrome.
2. Isolation of novel candidate genes
Through in silico cloning, I cloned novel candidate genes for skeletal dysplasias, ASH2L (ash2-like), PROSC (proline synthetase co-transcribed), C8orf2, CILP (cartilage intermediate layer protein), PRG4 (proteoglycan 4). I determined genomic structure and chromosomal localization of the genes, and analyzed their expression.
3. Identification of a candidate gene for Engelamnn disease
In collaboration with Prof.Niikawa's group by a positional candidate gene approach, I found the disease gene for Engelmann disease is TGF-beta1.
4. Mutation analysis of EBP gene in X-linked dominant chondrodysplasia punctata
I identified 5 novel mutations of the EBP (emopamil-binding protein) gene in X-linked dominant chondrodysplasia punctata ; three of them were nonsense and two missense mutations. I found the enzyme activity of EBP in the patients correlated well with the genotype.
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