| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The mitochondrial genome contains two ribosomal RNA genes, 22 transfer RNA (tRNA) genes, and 13 genes for proteins of the oxidative phosphorylation system. The nucleotide sequence of mitochondrial DNA (mtDNA) evolves at a rate 5-10 times higher than that of nuclear DNA. Thus, the differences in maternally transmitted mtSNPs are proposed to be more functionally significant than those of SNPs in the nuclear genome. To test the hypothesis that certain mitochondrial single nucleotide polymorphisms (mtSNPs) might be associated with obesity, type-2 diabetes or trainability, we determined the entire sequences of the mitochondrial genomes. Moreover, In order to identify genes whose expression is altered as a result of the presence of mtDNA mutations, DNA microarray analysis was performed using human 143B osteosarcoma cells harboring 3243A > G [tRNA-Leu (UUR)] and 8993T > G [ATPase6 Leu156Arg] mtDNA mutations associated with MELAS and NARP syndromes (2SD and NARP3-1 cybrid cells), respectively. The following results were obtained. (1), Haplogroup A was found in many marathon and ekiden runners. (2), Haplogroup M7b2 was observed in obese people, not non-obese. (3), The presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively.
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