Homologous Unequal Cross-Over within the Human CYP2A Gene Cluster as a Mechanism for the Deletion of the Entire CYP2A6 Gene Associated with the Poor Metabolizer Phenotype
To clarify the molecular mechanisms involved in the generation of the CYP2A6 gene deletion (E-type variant), we analyzed the CYP2A7 gene, which is located in the 5‘-flanking region of the CYP2A6 gene, from individuals with the E-type variant and compared it with the sequences of wild type CYP2A7 and...
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Published in | Journal of biochemistry (Tokyo) Vol. 126; no. 2; pp. 402 - 407 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.08.1999
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Subjects | |
Online Access | Get full text |
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Summary: | To clarify the molecular mechanisms involved in the generation of the CYP2A6 gene deletion (E-type variant), we analyzed the CYP2A7 gene, which is located in the 5‘-flanking region of the CYP2A6 gene, from individuals with the E-type variant and compared it with the sequences of wild type CYP2A7 and CYP2A6 genes. The 3’-downstream sequence (up to 324 bp from the Sad site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A7 gene. However, the 3‘-downstream sequence (starting from 325 bp from the SacI site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A6 gene, indicating that the 3’-downstream region of CYP2A7 and the 3‘-downstream region of CYP2A6 linked directly eliminating the whole CYP2A6 gene. PCR analysis using primers specific to the CYP2A7 gene and the CYP2A6 and CYP2A7 genes confirmed that all DNA samples obtained from 7 individuals carrying the E-type variant possessed the same break points. These results indicate that the breakpoint of the CYP2A6 gene deletion lies in the 3’-downstream region of the CYP2A7 and CYP2A6 genes. |
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Bibliography: | 1This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan, and also from the Ministry of Health and Welfare for the second-term Comprehensive 10-Year Strategy for Cancer Control. istex:F007EAAE08E145B5F1FB893AD867C2405C3EE2F8 ark:/67375/HXZ-2GG47V07-W ArticleID:126.2.402 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-924X 1756-2651 |
DOI: | 10.1093/oxfordjournals.jbchem.a022464 |