1996 Fiscal Year Final Research Report Summary
Human genetic analysis on the regulation of Duffy gene expression.
| Project/Area Number |
07672451
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | Jichi Medical School |
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Principal Investigator |
IWAMOTO Sadahiko Jichi Medical School, Dept.of Medicine, Assis.Proff., 医学部, 助教授 (10232711)
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| Co-Investigator(Kenkyū-buntansha) |
KAJII Eiji Jichi Medical School, Dept.of Medicine, Proffessor, 医学部, 教授 (40204391)
OKUDA Hiroshi Jichi Medical School, Dept.of Medicine, Assis.Lect., 医学部, 助手 (50285772)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Duffy blood group / Regulation of gene expression / Molecular evolution of gene |
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| Research Abstract |
The genomic structure of Duffy gene has been shown not to be split by introns, even in its 5' and 3' untranslated regions. The genes of IL-8 receptors, which are the highly homologous genes of Duffy gene, are not split by introns within the coding regions but are split in the 5' untranslated regions. Then we reanalyzed the transcriptional start position by 5'-rapid amplification of cDNA ends (5'-RACE), and identified a novel first exon and spliced form mRNA that was predominant transcript in both erythroid and postcapillary venule endothelium. The 5' flanking region of the novel first exon was regarded as the transcription controlling unit for both tissues. However, the transcriptional start position in endotherium was 48 bases upstream from that of the erythroid cells. And the 48 bases included an inverted consensus binding site for the GATA transcription factor. We found homozygous one base substitution at the GATA motif in black individuals with Fy (a-b-) phenotype. The Fy (a-b-) in
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dividuals have been shown not to produce Duffy mRNA in the bone marrow, but to produce it in endothelial cells. The tissue-specific lacking of expression in Fy (a-b-) indicates that the transcription control of Duffy gene is under tight tissue-specific regulation. The 5' flanking region of the novel first exon was inserted in the upstream of CAT reporter gene and was analyzed the transcription controlling efficiency. The promotor sequence of Duffy positives efficiently transcribed the reporter gene in both erythroid and endothelial cells. When one base substitution of Duffy negatives was introduced in the GATA motif, the promotor activity in erythroid cells was completely diminished. These data clearly explain the erythroid specific disruption of Duffy gene expression in black type Fy (a-b-). The selective pressure other than Plasmodium vivax have to be studied in the future on the saving of Duffy glycoprotein along endothelial cells in Fy (a-b-) individuals and the fixing the phenotype in West Africa. Less
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