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Molecular studies on genomic imprinting at APRT locus

Research Project

Project/Area Number 07457127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionTokyo Women's Medical College

Principal Investigator

KAMATANI Naoyuki  Tokyo Women's Medical College, 医学部, 教授 (00114447)

Co-Investigator(Kenkyū-buntansha) HAKODA Masayuki  Tokyo Women's Medical College, 医学部, 講師 (70208429)
YAMANAKA Hisashi  Tokyo Women's Medical College, 医学部, 講師 (10166754)
TERAI Chihiro  Tokyo Women's Medical College, 医学部, 助教授 (40188660)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥3,200,000 (Direct Cost: ¥3,200,000)
Keywordssomatic mutation / purine metabolism / loss of heterozygosity / tumor suppressing gene / gene therapy / familial tumor / adenine phosphoribosyltransferase / プリント代謝 / 体細胞遺伝子 / ジャームライン遺伝子 / 突然変異率 / クローン生物 / Loss of heterozygosity / プリン代謝 / ゲノムインプリント / LOH / APRT欠損症 / Lesch-Nyhan症候群 / HPRT欠損症
Research Abstract

Studies on in vivo somatic mutations at the adenine phosphoribosyltransferase (APRT) locus have disclosed that human somatic cells have mutations at surprisingly high frequencies. Most of the mutations are of the loss of heterozygosity (LOH) type. However, in 3 heterozygotes for APRT deficiency, LOH was not observed suggesting the genomic imprinting at this region. Precise analyzes, however, clarified that the genomic imprinting was not observed in this area, but the 3 persons had a unique deletion mutation which suppressed the occurrence of LOH.By the techniques of selective PCR and inverse PCR,the germline mutation suppressing LOH phenomenon was analyzed. This mutation gene (APRT^<**>del) had a deletion from the intron 4 and was ligated to an unknown gene. The determination of the sequence of the recombination site disclosed that the deletion encompassed at least 2,000 bp and an important gene (tentatively named LSG : LOH-supporter gene) was missing. Thus, when a LSG gene is damaged in the germline as a heterozygous state, then the LOH of the homologous area on the other chromosome is suppressed. The discovery of the new phenomenon for the mechanisms of the suppression of LOH is likely to be applied to various areas. Thus, when a tumor suppressing gene is damaged, a gene therapy destroying a nearby LSG on the same chromosome may successfully suppress the LOH of the other intact chromosome. Such a gene therapy may be useful to treat families with high incidence of cancers. Furthermore, the present type of gene changes may explain the mechanisms of low incidence of tumors in some families.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Terai C,et al: "Adenine phosphoribosyltransferase deficiency identified by urinary sediment analysis : cellular and molecular confirmation" Clin.Genet.48. 246-250 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al: "Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase(HPRT)in Lesch-Nyhan heterozygotes occarsat the level of multipotent stemce" Hum.Genet. 96. 674-680 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kamatani N.et al: "Origin of the most common mutation of adenine phosphoribosyltransferase among Japanese gces back to prehistoric era." Hum.Genet.98. 596-600 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al.: "Similarity of in vivo somatic mutations at an autosomal adenine phosphoribosyltransferase locus between T and B cells in human periphera blood" Mutat.Res.357. 107-113 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al: "Intervension of somatic mutational events in vivo by a germline defect at adenine phosphoribosyltransferase locus." Hum.Genet.99. 164-170 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taniguchi A.et al: "Agermline mutation abolishing the original stop codon of human adenine phosphoribosyltransferase (APRT) gene leads to the complete loss of the enzyme protein" Submitted for publication.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Terai C.et al: "Adenine phosphoribosyltransferase deficiency indentified by urinary sediment analysis : cellular and molecular confirmation." Clin.Genet.48. 246-250 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al: "Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells." Hum.Genet.96. 674-680 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kamatani N.et al: "Origin of the most common mutation of adenine phosphoribosyltransferase among Japanese goes back to prehistoric era." Hum.Genet.98. 596-600 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al: "Similarity of in vivo somatic mutations at an autosomal adenine phosphoribosyltransferase locus between T and B cells in human peripheral blood." Mutat.Res.357. 107-113 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda M.et al: "Intervention of somatic mutational events in vivo by a germline defect at adenine phosphoribosyltransferase locus." Hum.Genet.99. 164-170 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taniguchi A.et al: "A germline mutation abolishing the original stop codon of human adenine phosphoribosyltransferase (APRT) gene leads to the complete loss of the enzyme protein." (Submitted for publication).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hakoda,M et al: "Intervention of somatic mutational events in vivo by a germline defect at adenine phosphoribosyl transferase locus" Hum.Genet.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Hakoda, M., et al: "Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells." Hum. Genet.96. 674-680 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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