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1995 Fiscal Year Final Research Report Summary

Structural analysis of the human immunoglobulin H-chain locus

Research Project

Project/Area Number 06670349
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

MATSUDA Fumihiko  Kyoto University, Center for Molecular Biology and Genetics, Assistant Professor, 遺伝子実験施設, 助手 (50212220)

Project Period (FY) 1994 – 1995
KeywordsImmunoglobulin gene / Physical map / Multigene family / YAC / Nucleotide sequence / Translocation / Gene conversion
Research Abstract

The human immunoglobulin V_H region genes are clustered at the distal end of chromosome 14 (14q32.33). The human V_H segments are classified into 7 families and members of different families are highly interspersed. In order to elucidate the organization of the V _H locus, we set out to construct its physical map by isolation of YAC and P1 clones. Physical mapping and sequencing analysis allowed us to conclude the following :
1. We analyzed the entire human V_H locus by isolation of YAC and P1 clones. Altogether 81 V_H segments belonging to 7 different families were identified within the 1.0-Mb region. The total number of the V_H segments is calculated to be 81, with additional 7, or more, polymorphic V_H segments.
2.A phylogenetic tree of 33 potentially functional V_H segments clearly supported the previous classification of human V_H segments into 7 families. Unidirectional transfer of segmental sequences was identified within the V_H-3 and V_H-4 families, providing clear examples of germline gene conversion.
3. Nucleotide sequence analysis of the entire locus is in progress. A Primer walking method was employed to avoid possible confusion in assembly of the sequences due to the repetitive nature of the locus. To date, we have determined the nucleotide sequence of approximately 600-kb DNAs.
4. The translocated V_H region on 16p11 consists of 7 V_H segments. The D_5 locus was mapped to 15q11-12. The putative ancestor of these regions was found within the V_H locus on chromosome 14. Comparison of V_H sequences suggested that the two orphon loci might have been translocated simultaneously about 20 Myr ago.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Haino, M. 他: "Comparison and evolution of human immunoglobulin V_H segments located in the 3′0.8-megabase region" J. Biol. Chem.269. 2619-2626 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin, E. K. 他: "Variable-regions of immumoglobuhin heasry-chain genes encoding anti-thyrotropin receptor mtibodies of patients with Guaues disease" J. Immunol.152. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniwaki, M. 他: "Detection of 14q32 translocation in B-cell malignancies by in-situ hyleridization with yeast artificial cheomosome clones contaiming the human 1gH gene locus." Blood. 83. 2962-2969 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagaoka, H. 他: "Recant translocation of variable and diversity(D) segment of the human immuroglobulin heasry chain fiom unromosome 14 to ohromssomes 15 and 16." Genomies. 22. 189-197 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Li, H. 他: "Isolation of Zpstein-Barr virus-trnsformed lymphoaytes producing IgG class monoclonal antibodies using a magnetic cell separator(MACS)" Biophys. Biochem. Res. Commum.207. 985-993 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda, Y. 他: "Tumor-speafic rearrangements of the immumoglobulim heaery-chain gene in B-cell Non-Hodgkin′s lymphoma detected by in situ hybridigation" Blood. 87. 292-298 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuda, F. and Honjo, T.: "Advances in immunology(印刷中)" Academic press, San Diego U. S. A., (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Honjo, T. and Matsuda, F.: "Immunoglobulin Genes 2nd edition" Academic press, London U. K., 443 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Haino, M.et al.: "Comparison and evolution of human immunoglobulin V_H segments located in the 3' 0.8-megabase region : evidence for unidirectional transfer of segmental gene sequences" J.Biol.Chem.269. 2619-2626 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin, E.K.et al.: "Variable-regions of immunoglobulin heavy-chain genes encoding anti-thyrotropin (TSH) receptor antibodies of patients with Graves' disease." J.Immunol.152. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniwaki, M.et al.: "Detection of 14q32 translocations in B-cell malignancies by in situ hybridization with yeast artificial chromosome clones containing the human IgH gene locus." Blood. 83. 2962-2969 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagaoka, H.et al.: "Recent translocation of variable and diversity (D) segment of the human immunoglobulin heavy chain from chromosome 14 to chromosomes 15 and 16" Genomics. 22. 189-197 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Li, H.et al.: "Isolation of Epstein-Barr virus-transformed lymphocytes producing IgG class monoclonal antibodies using a Magnetic Cell Separator (MACS) : Preparation of thyroid-stimulating IgG antibodies from patients with Graves' disease." Biochem.Biophys.Res.Commun.207. 985-993 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Honjo, T.and Matsuda, F.: "Immunoglobulin heavy chain loci of mouse and man" in "Immunoglobulin Genes" (T.Honjo and F.W.Alt, eds.) Academic Press, London, U.K.145-171 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueda, Y.et al.: "Tumor-specific rearrangements of the immunoglobulin heavy-chain gene in B-cell Non-Hodgkin's lymphoma detected by in situ hybridization." Blood.87. 292-298 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda, F.and Honjo, T.: "Organization of the Human Immunoglobulin Heavy-chain Locus." in "Advances in Immunology" (F.Dixon, ed.) Academic Press, San Diego, U.S.A.(in the press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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