| Project/Area Number |
05670403
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Legal medicine
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| Research Institution | Osaka Medical College |
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Principal Investigator |
SUZUKI Koichi Osaka Medical College, Dept.of Legal Medicine, Associate Professor, 医学部, 助教授 (60171211)
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Kiyoshi Osaka Medical College, Dept.of Legal Medicine, Assistant, 医学部, 助手 (50247839)
TAMURA Akiyoshi Osaka Medical College, Dept.of Legal Medicine, Assistant, 医学部, 助手 (50207239)
ITO Shigenori Osaka Medical College, Dept.of Chemistry, Associate Professor, 医学部, 助教授 (90104281)
MIZOI Yasuhiko Osaka Medical College, Dept.of Legal Medicine, Professor, 医学部, 教授 (00030809)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | coagulation factor XIII / genetic polymorphism / base substitution / haplotype / rare variant / factor XIII deficiency / recombination hot-spot / 凝固第13因子 / 凝固因子 |
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| Research Abstract |
We demonstrated molecular basis of the genetic polymorphism of the coagulation factor XIII "a" subunit and novel sequence polymorphisms in five exons. Four F13A alleles were found to be defined by nucleotide substitutions at the three sites of exon 12 and exon 14. We developed PCR-RFLPs by which these substitutions can be detected at the genomic level. In addition to the three sites, we characterized novel polymorphic sites of exons 2,5,8,12 and 14 in Caucasian populations whereas these sites were non-polymorphic in Japanese except for the site of exon 2. These polymorphic sites were found to be transmitted as haplotypes. A total of 18 haplotypes out of theoretically 72 possible combinations were found to occur in the Caucasian populations, implying that frequent recombination events rather than reccurent point mutations lead to production of the haplotypes. Furthermore, we revealed sequence differences for 14 distinct variant alleles and one deficient allele by characterizing their complete sequences. Amino acid substitutions resulting from the nucleotide changes of the 14 variant alleles were consistent with mobility shift of their products in IEF gels. The deficient allele was found to result from abnormal splicing caused by a single nucleotide mutation at the splice-acceptor site in intron 5 of the F13A gene.
The data obtained in this study suggest that there are recombination hot-spots in the F13A gene region. We are now investigating the sequences of introns and 5'-and 3'-flanking regions.
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