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The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus

The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (V H ) region locus was determined and 43 novel V H segments were identified. The region contains 123 V H segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 V H segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of V H region was calculated to be ∼6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional V H segments than in pseudogenes. Phylogenetic analysis of 114 V H segments clearly showed clustering of the V H segments of each family. However, an independent branch in the tree contained a single V H , V4-44.1P, sharing similar levels of homology to human V H families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region. immunoglobulin gene physical map antibody repertoire phylogenetic tree DNA duplication Footnotes F. Matsuda's current address is Centre National de Genotypage, BP191-2, rue Geston Cremieux, 91000 Evry Cedex, France. K. Ishii's current address is JST Laboratory, Kitasato University Faculty of Science, Kitasato 1-15-1, Sagamihara 228-8555, Japan. 1 Abbreviations used in this paper: Mb, megabase; ORF, open reading frame; RSS, recombination signal sequences; YAC, yeast artificial chromosome. Submitted: 20 August 1998 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus

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References (59)

Publisher
Rockefeller University Press
Copyright
© 1998 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.188.11.2151
Publisher site
See Article on Publisher Site

Abstract

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (V H ) region locus was determined and 43 novel V H segments were identified. The region contains 123 V H segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 V H segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of V H region was calculated to be ∼6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional V H segments than in pseudogenes. Phylogenetic analysis of 114 V H segments clearly showed clustering of the V H segments of each family. However, an independent branch in the tree contained a single V H , V4-44.1P, sharing similar levels of homology to human V H families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region. immunoglobulin gene physical map antibody repertoire phylogenetic tree DNA duplication Footnotes F. Matsuda's current address is Centre National de Genotypage, BP191-2, rue Geston Cremieux, 91000 Evry Cedex, France. K. Ishii's current address is JST Laboratory, Kitasato University Faculty of Science, Kitasato 1-15-1, Sagamihara 228-8555, Japan. 1 Abbreviations used in this paper: Mb, megabase; ORF, open reading frame; RSS, recombination signal sequences; YAC, yeast artificial chromosome. Submitted: 20 August 1998

Journal

The Journal of Experimental MedicineRockefeller University Press

Published: Dec 7, 1998

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