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Molecular genetical analysis of the epitopes on Rh blood group antigen and establishment of genetic examination system in RH genes.

Research Project

Project/Area Number 11557036
Research Category

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

Allocation TypeSingle-year Grants
Section展開研究
Research Field Legal medicine
Research InstitutionJichi Medical School

Principal Investigator

KAJII Eiji  Jichi Medical School, Dept. of Medicine, Professor, 医学部, 教授 (40204391)

Co-Investigator(Kenkyū-buntansha) OMI Toshnori  Jichi Medical School, Dept. of Medicine, Assist. Professor, 医学部, 助手 (40296091)
OKUDA Hiroshi  Jichi Medical School, Dept. of Medicine, Assos. Professor, 医学部, 助教授 (50285772)
IWAMOTO Sadahiko  Jichi Medical School, Dept. of Medicine, Assos. Professor, 医学部, 助教授 (10232711)
KUMADA Maki  Jichi Medical School, Dept. of Medicine, Assist. Professor, 医学部, 助手 (40326830)
KAMESAKI Toyomi  Jichi Medical School, Dept. of Medicine, Assist. Professor, 医学部, 助手 (90316513)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥10,200,000 (Direct Cost: ¥10,200,000)
KeywordsRh blood system / RH gene / RHAG gene / promoter / enhancer / epitope / variant / genetic analysis
Research Abstract

We determined the entire nucleotide sequences of both RHD and RHCE genes. Based on the data of these nucleotide sequences, we analyzed the genomic structure of both RH genes in detail. Various short tandem repeats (STRs) and many interspersed nuclear elements, for instance, Alu sequences were identified in both genes. By the alignment analysis of both RH genes, we confirmed multiple recombinations within 2〜3kb in introns 1 and 2. It was speculated that intron 2 in the RHCE (C) gene was produced by two recombinations between RHCE (c) and RHD genes and the following insertion of Alu-Sx.
It was supported that Rh50 glycoprotein, which constituted the core of the Rh complex along with Rh polypeptide, showed the erythroid-specific expression. For the purpose of explaining the mechanism of the regulation for the expression in the RHAG gene, we identified and cloned an erythroid specific major DNaseI hypersensitive site (HS). HS located about 10kb upstream from the translation start site of the RHAG gene. A short core enhancer sequence of 195bp that corresponded with the major HS and possessed position- and orientation-independent enhancer activity in K562 cells. Homology plot analysis indicated that the enhancer region was conserved in human and mouse. The GATA motifs bound GATA-1 and mutagenesis analysis revealed that the proximal one is critical for the enhancing activity.
In Rh blood system, molecular genetical analysis of various Rh variants smoothly developed. As for partial D variant, we were able to identify new type. Furthermore we proved that weak D variant possessed the qualitative and quantitative change of the RhD antigen.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Iwamoto S,Suganuma H,Kamesaki T,Omi T,Okuda H,Kajii E.: "Cloning and characterization of erythroid-specific DNase I-hypersensitive site in human rhesus-associated glycoprotein gene."J Biol Chem. 275. 27324-27331 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuda H,Fujiwara H,Omi T,Iwamoto S,Kawano M,Ishida T,Nomura S,Fukuhara S,Nagai A,Ohya I.Kajii E.: "A Japanese propositus with D-phenotype characterized by the deletion of both the RHCE gene and D1S80 locus situated in chromosome 1p and the existence of a new CE-D-CE hybrid gene."J Hum Genet. 45. 142-153 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuda H,Suganuma H,Kamesaki T,Kumada M,Tsudo N,Omi T,Iwamoto S,Kajii E.: "The analysis of nucleotide substitutions, gaps, and recombination events between RHD and RHCE genes through complete sequencing."Biochem Biophys Res Commun. 274. 670-683 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Omi T,Okuda H,Iwamoto S,Takahashi J,Tanaka M,Tani Y,Fraser RH,Seno T,Kajii E.: "Detection of Rh23 in the partial D phenotype associated with the D (Va) category."Transfusion. 40. 256-258 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 近江俊徳,高橋順子,瀬尾たい子,田中光信,亀崎豊実,奥田浩,岩本禎彦,谷慶彦,梶井英治: "DVa(Partial D)表現型のエピトープマッピング"DNA多型. 8. 203-206 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 梶井英治: "蛋白系赤血球型の新知見"医学のあゆみ. 195(4). 266-267 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 梶井英治: "血液型.(池田久實監修,霜山龍志編:輸血学 理論と展望)"北海道大学図書刊行会. 21-36 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuda H, Suganuma H, Tsudo N, Omi T, Iwamoto S, Kajii E.: "Sequence Analysis of the Spacer Region between the RHD and RHCE Genes."Biochem Biophys Res Commun. 263(2). 378-383 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Omi T, Takahashi J, Tsudo N, Okuda H, Iwamoto S, Tanaka M, Seno T, Tani Y, Kajii E.: "The genomic organization of the partial D category DVa : the presence of a new partial D associated with the DVa phenotype."Biochem Biophys Res Commun. 254(3). 786-94 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiwara H, Okuda H, Omi T, Iwamoto S, Tanaka Y, Takahashi J, Tani Y, Minakami H, Araki S, Sato I, Kajii E.: "The STR polymorphisms in intron 8 may provide information about the molecular evolution of RH haplotypes."Hum Genet. 104. 301-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwamoto S, Suganuma H, Kamesaki T, Omi T, Okuda H, Kajii E.: "Cloning and characterization of erythroid-specific DNase I-hypersensitive site in human rhesus-associated glycoprotein gene."J Biol Chem. 275. 27324-27331 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuda H, Fujiwara H, Omi T, Iwamoto S, Kawano M, Ishida T, Nomura S, Fukuhara S, Nagai A, Ohya I.and Kajii E.: "A Japanese propositus with D--phenotype characterized by the deletion of both the RHCE gene and D1S80 locus situated in chromosome 1p and the existence of a new CE-D-CE hybrid gene."J Hum Genet. 45. 142-153 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Omi T, Okuda H, Iwamoto S Takahashi J, Tanaka M, Tani Y, Fraser RH, Seno T, Kajii E.: "Detection of Rh23 in the partial D phenotypd associated with the D (Va) category."Transfusion. 40. 256-258 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Iwamoto S,Suganuma H,Kamesaki T,Omi T,Okuda H,Kajii E.: "Cloning and characterization of erythroid-specific DNase I-hypersensitive site in human rhesus-associtated glycoprotein gene."J Biol Chem. 275. 27324-27331 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okuda H,Fujiwara H,Omi T,Iwamoto S,Kawano M,Ishida T,Nomura S,Fukuhara S,Nagai A,Ohya I.Kajii E.: "A Japanese propositus with D-phenotype characterized by the deletion of both the RHCE gene and D1S80 locus situated in chromosome 1p and the existence of a new CE-D-CE hybrid gene."J Hum Genet. 45. 142-153 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okuda H,Suganuma H,Kamesaki T,Kumada M,Tsudo N,Omi T,Iwamoto S,Kajii E.: "The analysis of nucleotide substitutions, gaps, and recombination events between RHD and RHCE genes through complete sequencing."Biochem Biophys Res Commun. 274. 670-683 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Omi T,Okuda H,Iwamoto S,Takahashi J,Tanaka M,Tani Y,Fraser RH,Seno T,Kajii E.: "Detection of Rh23 in the partial D phenotype associated with the D (Va) category."Transfusion. 40. 256-258 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 近江俊徳,高橋順子,瀬尾たい子,田中光信,亀崎豊実,奥田浩,岩本禎彦,谷慶彦,梶井英治: "DVa(Partial D)表現型のエピトープマッピング"DNA多型. 8. 203-206 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 梶井英治: "蛋白系赤血球型の新知見"医学のあゆみ. 195(4). 266-267 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 梶井英治: "血液型.(池田久實監修,霜山龍志編:輸血学 理論と展望)"北海道大学図書刊行会. 21-36 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 梶井英治: "赤血球の分子生物学"日本輸血学会誌. 45. 497-501 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okuda,H.,Suganum,H.,Tsudo,N.,Omi,T.,Iwamoto,S.,Kajii,E.: "Sequence Analysis of the Spacer Region between the RHD and RHCE Genes"Biochem Biophys Res Commun. 263(2). 378-383 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Omi,T.,Takahashi,J.,Tsudo,N.,et al.: "The genomic organization of the partial D category Dva : the presence of a new partial D associated with the DVa phenotype"Biochem Biophys Res Commun. 254(3). 786-794 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Omi T,T,Okuda H,Iwamoto S,Kajii E,et al.: "Detection of Rh23 in the partial D phenotype associated with the D(Va) category"Transfusion. 40(2). 256-257 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujiwara H,Okuda H,Omi t,et al.: "The STR polymorphisms in intron 8 may provide information about the molecular evolution of RH haplotypes"Hum Genet. 104(4). 301-306 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okuda,H.,Fujiwara,H.,Omi,T.,et al.: "A Japanese propositus with D--phenotype characterized by the deletion of both the RHCE gene and D1S80 locus situated in chromosome 1p and the existance of a new CE-D-CE hybrid gene"J Hum Genet. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 梶井英治: "Annual Review血液1999(高久史麿,宮崎澄雄,斎藤英彦,溝口秀昭,坂田洋 一編)温式自己免疫性溶血性貧血の自己抗原"中外医学社. 5 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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