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Further investigation on the Rh blood group system for the expression of the RH gene and the epitopes of the Rh antigens

Research Project

Project/Area Number 13557038
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) KAMESAKI Toyomi  Jichi Medical School, Dept.of Medicine, Lecturer, 医学部, 助手 (90316513)
OKUDA Hiroshi  Jichi Medical School, Dept.of Medicine, Assistant Professor, 医学部, 助教授 (50285772)
IWAMOTO Sadahiko  Jichi Medical School, Dept.of Medicine, Assistant Professor, 医学部, 助教授 (10232711)
KUMADA Maki  Jichi Medical School, Dept.of Medicine, Lecturer, 医学部, 助手 (40326830)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥9,400,000 (Direct Cost: ¥9,400,000)
KeywordsRh blood group / Rh variant / Partial D / Weak D / Molecular genetics / RHD gene / RHCE gene / Mouse genome / Rh式血液型 / Rh30遺伝子 / マウスオーソログ / weak D / エピトープ / 変異型 / Rhmod / 自己免疫性溶血性貧血
Research Abstract

The mouse genomic sequence of the region containing the gene Rhced, the orthologue to the human gene RH30, was entirely determined and compared with the corresponding human genomic region. Two genes Smpl and AK003528 (an orthologue of FLJ10747), flank Rhced. Neither sequences homologous to the characteristic nucleotide elements flanking the RHD gene in human (rhesus boxes) nor an additional Rh gene were found within the mouse region sequenced. This result demonstrate that this chromosomal region of the mouse comprises five genes (FLJ10474-RHCE-SMP1-NPD014-P29) that exhibit syntenic homology with the corresponding human region, which suggests that the RHD gene and rhesus boxes were inserted later.
The molecular characterization of weak D and partial D phenotypes was performed. The mutations - G212C (new weak D type), V270G (weak D type 1), and G358A (type 2) - in transmembranous regions had obvious effects on the D epitopes recognized by monoclonal anti-D antibodies. This result provide direct evidence that these mutations can account for weak D phenotypes. A novel partial D phenotype, termed DT1 was found. The DT1 phenotype affected the D polypeptide within the fourth external loop, resulting in a new RHD-CE (entire exon 5)-D hybrid gene. It is worth noting that P226, encoded by exon 5, is derived from E of RhCE in the DT1 polypeptide.
The screening system for detecting the autoantigens in autoimmune hemolytic anemia (AIHA) was constructed by using several recombinant Rh antigens or band 3 protein-expressing KU812 cells. The autoantigens in twenty patients with AIHA were Rh-related ones in 15 cases and band 3 protein in 7 cases.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] 亀崎豊実, 岩本禎彦, 奥田浩 他: "日本人Weak D 6例の分子遺伝学的解析"DNA多型. Vol.10. 186-190 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Kumada, S Iwamoto, T Kamesaki, H Okuda, E Kajii: "Entire sequence of a mouse chromosomal segment containing the gene Rhced and a comparative analysis of the homologous human sequence"Gene. 299. 165-172 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Kamesaki, S Iwamoto, E Kajii: "A new mutation detected in RhAG of a Japanese family with Rh(mod) syndrome may form a longer RhAG protein"Transfusion. 42. 383-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Omi, J Takahashi, T Seno, et al.: "Isotation, characterization, and family study of a novel partial D named DTI affecting the fourth external loop RhD polypeptides"Transfusion. 42. 481-489 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Kamesaki, M Kumada, T Omi, et al.: "A novel mutation in the RHD gene in Japanese individuals with weak D, encoding an amino acid change in the 11^<th> transmembranous domain of the RhD protein"Vox Sang. 84. 141 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwamoto S, Kamesaki T, Oyamada T, Okuda H, Kumada M, Omi T, Takahashi J, Tani Y, Omine M, Kajii E.: "Reactivity of autoantibodies of autoimmune hemolytic anemiawith recombinant rhesus blood group antigens or anion transporter band3"Am J Hematol.. 68. 106-114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamesaki T, Iwamoto S, Kumada M, Omi T, Okuda H, Tanaka M, Takahashi J, Obara K, Seno T, Tani Y, Kajii E: "Molecular characterization of weak D phenotypes by site-directed mutagenesis and expression of mutant Rh-green fluorescence protein fusions in K562 cells"Vox Sang. 81. 254-258 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka M, Yamashita N, Takahashi J, Hirayama F, Kajii E, Tani Y: "RHC/c genotyping based on polymorphisim in the promoter region of the RHCE gene"Legal Medicine. 3. 205-212 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamesaki T, Iwamoto S, Kajii E, Takahashi J, Kimura K, Nakade T, Tani Y.: "A new mutation detected in RhAG of a Japanese family with Rh(mod) syndrome may form a longer RhAG protein"Transfusion. 42. 383-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumada M, Iwamoto S, Kamesaki T, Okuda H, Kajii E.: "Entire sequence of a mouse chromosomal segment containing the gene Rhced and a comparative analysis of the homologous human sequence"Gene. 299. 165-172 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Omi T, Takahashi J, Seno T, Tanaka M, Hirayama F, Matsuo M, Ueda N, Ohar R, Okuda H, Iwamoto S, Tani T, Kajii E.: "Isolation, characterization, and family study of a novel partial D named DTI affecting the fourth external loop of the RhD polypeptides"Transfusion. 42. 481-489 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuda H, Kajii E.: "The evolution and formation of RH genes"Legal Medicine. 4. 139-155 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 亀崎豊実, 岩本禎彦, 奥田浩, 他: "日本人WeakD 6例の分子遺伝学的解析"DNA多型. Vol.10. 186-190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M Kumada, S Iwamoto, T Kamesaki, H Okuda, E Kajii: "Entire sequence of a mouse chromosomal segment containing the gene Rhced and a comparative analysis of the homologous human sequence"Transfusion. 42. 383-384 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T Omi, J Takahashi, T Seno, et al.: "Isolation, characterization, and family study of a novel partial D named DTI affecting the fourth external loop in the RhD polypeptides"Transfusion. 42. 481-489 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] T Kamesaki, M Kumada, T Omi, et al.: "A novel mutation in the RHD gene in Japanese individuals with weak D, encoding an amino acid change in the 11^<th> transmembranous domain of the RhD protein"Vox Sang. 84. 141 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwamoto S.: "Reactivity of autoantibodies of autoimmune hemolytic anemia with recombinan rhesus blood group antigens or anion transporter band3"Am J Hematol. 68. 106-114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kondo H.: "Direct-antiglobulin-test-negative immune haemolytic anaemia and thrombocytopenia in a patient with Hodgkin's disease"Acta Haematol. 105. 233-236 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kamesaki T.: "Molecular characterization of weak D phenotypes by site-directed mutagenesis an expression of mutant Rh-green fluorescence protein fusions in K562 cells"Vox Sang. 81. 254-258 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 奥田浩: "RH遺伝子の分子進化学的解析"DNA多型. 9. 220-225 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩本禎彦: "自己免疫と血液異常AIHAと自己抗体エピトープ解明へ向けての新戦略"臨床血液. 42. 167-169 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 梶井英治: "血液型遺伝子"臨床病理. 49. 19-28 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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