• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

As to the orgin of the disease-causing gene of the Japanese-type adenine phosphoribosyltransferase deficiency

Research Project

Project/Area Number 61480484
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内科学一般
Research InstitutionInstitute of Rheumatology, Tokyo Women's Medical College

Principal Investigator

KAMATANI Naoyuki  Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 助教授 (00114447)

Co-Investigator(Kenkyū-buntansha) WATANABE Tomihiro  Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 助手 (50182936)
KAWAI Kazuo  Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 助手 (60152899)
TERAI Chihiro  Institute of Rheumatology, Tokyo Women's Medical College, 医学部, 講師 (40188660)
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsgenetic disease / purine metabolism / urinary stone / urolithiasis / プリン代謝 / 核酸代謝 / ベプチド / 進化論 / 基質結合部位
Research Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disease characterized by reccurrent urolithiatic episodes and renal insufficiency. This disease is especially common among Japanese at least partially because Japanese, as an ethnical group, have a special type of the disease designated as "the Japanese-type APRT deficiency" as we havev previously clarified. The original aim of the present project to clarify the origin of the disease-causing gene of the Japanese-type APRT deficiency has almost completely achieved. Thus, we have identified the gene responsible for this disease (APRT*J), identidied a nucleotide substitution in this gene (in exon 5), and also identified an amino acid substitution in the Japanese-type APRT enzyme (Met to Thr at position 136). Furthermore, we confirmed that this nucleotide and amino acid substitution are present in all the separate families with the Japanese-type APRT deficiency. We have devised a new diagnostic method identifying the amono ac … More id substitution seen in the Japanese-type mutant enzyme. In addition to the mutation specific for the Japanese-type APRT deficiency, we found a nucleotide substitution in intron 2. Based on the data about this restriction fragment length polymorphism, we provided confidential evidence that the disease-causing genes in separate families with the Japanese-type APRT deficiency derived from a sngle ancestor gene which was created in an ancestor of Japanese. Besides the orginal aim of the present project, we have been able to obtain some valuable results. First, we have diagnosed more than half of all the patients with APRT deficiency in the world. Second, we found that as much as 80% of all the families with APRT deficiency in Japan were classified as the Japanese-type. Therefore, the fact that APRT deficiency is especially common among Japanese is, at least in part, explained by the wide distribution of this mutant gene (APRT*J) among Japanese (but not among Caucacians). Third, we found most of the patients with APRT deficiency had not been properly diagnosed, and our report as to this disease will be benificial to many patients with this disease. We confirm that the evidence for a common ancestor disease-causing gene for as much as 80% of all the patients with a single disease in an ethnical group will affect thories of evolution, and will be against the concept of eugenics that has affected even laws of many modern countries. Less

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kamatani, N;Yamanaka, H.;Nobori, T. et al.: Purine Metabolism in Man-V. 5. 39-46 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani, N;Yamanaka, H.;Nishioka, K. et al.: Purine Metabolism in Man-V. 5. 157-162 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Nobori, T.;Kamatani, N.;Mikanagi, K. et al.: Biochem. Biophys. Res. Commun.137-3. 998-1005 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani, N.;Terai, C.;Kuroshima, S. et al.: Hum. Genet.75. 163-168 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani, N.;Kuroshima, S.;Terai, C. et al.: Hum. Genet.76. 148-152 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hidaka, Y.;Tarle, S. A.;Fujumori, S.;Kamatani, N. et al.: J. Clin. Invest.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani, N.;Kuroshima, S.;Terai, C. et al.: J. Clin. Invest. submitted.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani,N., Yamanaka,H., Nobori,T., et al. jcommon altered characteristics of mutant enzymes from patients with Japanese type APRT deficiencies: Purine Metabolism in Man-V, Plenum, New York. 5. 39-46 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatami,N., Yamanaka,H., Nishioka,K., et al.: "Diagnosis of Lesch-nyhan heterozygotes by peripheral blood" Purine Metabolism in Man-V, Plemum, New York. 5. 157-162 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Nobori,T., Kamatani,N., Mikanagi,K., et al.: "Establishment and characterization of B cell lines from individuals with various types of adenine phosphoribosyltransferase deficiencies" Biochem. Biophys. Res. Commun.137. 998-1005 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani,N., Erai,C., Kuroshima,S., et al.: "Genetic and clinical studies on 19 families with adenine phosphoribosyl-transferase deficiencies" Hum. Genet.75. 163-168 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani,N., Kuroshima,S., Terai,C., et al.: "Selection of human cells having two different types of mutations in single cells (genetic/artificial mutants)" 76. 148-152 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hidaka,Y., Tarle,S.A., Fujimori,S., Kamatani,N., et al.: "Human adenine phosphoribosyltrnasferase (APRT) deficiency: Demonstration of a single mutant allele common to the Japanese" J. Clin. Invest.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani,N., Kuroshima,S., Terai,C., et al.: "Detection of an amino acid substitution in the mutant enzyme of the Japanese-type adenine phosphoribosyltransferase (APRT) deficiency patients by the sequence specific protein cleavage" J. Clin. Invest.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Kamatani,N;Yamanaka,H;Nobori,T.,et al.: Purine Metabolism in Man-【V】,Plenum,New York. 5. 39-46 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kamatani,N.;Yamanaka,H.;Nishioka,K.,et al.: Purine Metabolism in Man-【V】,Plenum,New York. 5. 157-162 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yamanaka,H.;Kamatani,N.;Nishida,Y.,et al.: Purine Metabolism in Man-【V】,Plenum,New York. 5. 281-285 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nobori,T.;Yamanaka,H.;Kamatani,N.,et al.: Purine Metabolism in Man-【V】,Plenum,New York. 5. 35-38 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yamanaka,H.;Kamatani,N.;Nobori,T.,et al.: Purine Metabolism in Man-【V】,Plenum,New York. 5. 583-588 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nobori,T;Kamatani,N.;Mikanagi,K.,et al.: Biochem.Biophys.Res.Commun.137:3. 998-1005 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kamatani,N.;Terai,C.;Kuroshima,S.,et al.: Hum.Genet.

    • Related Report
      1986 Annual Research Report
  • [Publications] Kamatani,N.;Kuroshima,S.;Terai,C.,et al.: Hum.Genet.

    • Related Report
      1986 Annual Research Report
  • [Publications] Kawai,K.;Kamatani,N.;Kuroshima,S.,et al.: Cancer Letters.

    • Related Report
      1986 Annual Research Report
  • [Publications] Fujimori,S.;Akaoka,I.;Takeuchi,F.;Kanayama,H.;Tatara,K.;Nishioka,K.;Kamatani,N.: Metabolism. 35:2. 187-192 (1986)

    • Related Report
      1986 Annual Research Report

URL: 

Published: 1987-03-31   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi