The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus
Project/Area Number |
09670335
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Immunology
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Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
TASHIRO Kei (1998) Kyoto University, Center for Molecular Biology and Genetics Associate Professor, 遺伝子実験施設, 助教授 (10263097)
松田 文彦 (1997) 京都大学, 医学研究科, 助手 (50212220)
|
Co-Investigator(Kenkyū-buntansha) |
田代 啓 京都大学, 遺伝子実験施設, 助手 (10263097)
|
Project Period (FY) |
1997 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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Keywords | Immunoglobulin / V_HRegion / nucleotide sequence / gene / pseudogene / antibody / Molecular Evolution / chromosome 14 / 免疫グロブリン遺伝子 / 可変部領域 / 酵母人工染色体 / 物理地図 |
Research 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.
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Report
(3 results)
Research Products
(3 results)