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. 1995 Oct;40(4):361–367. doi: 10.1111/j.1365-2125.1995.tb04558.x

An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype.

S Panserat 1, C Mura 1, N Gérard 1, M Vincent-Viry 1, M M Galteau 1, E Jacoz-Aigrain 1, R Krishnamoorthy 1
PMCID: PMC1365155  PMID: 8554938

Abstract

1. The study of the CYP2D genotype and phenotype of a Caucasian family revealed that a XbaI-9 kb allele was associated with the poor metabolizer phenotype. 2. A Polymerase Chain Reaction (PCR)-based assay showed that the previously described mutations D6A and D6B are not associated with the XbaI-9 kb allele. 3. To explore the molecular basis of the poor metabolizer phenotype associated with the XbaI-9 kb allele, complete sequencing of the nine exons and intron-exon boundaries of the CYP2D6 gene was undertaken after amplification by PCR. 4. All the exons were successfully amplified using CYP2D6 gene-specific primers except exon 1 which required a combination of CYP2D7 gene-specific 5' primer and a CYP2D6 gene-specific 3' primer. 5. Sequence data derived from this amplified product revealed that the XbaI-9 kb allele corresponds to a novel rearrangement of the locus. This involved a deletion of an approximately 20 kilobase (kb) DNA segment generating a hybrid 5' CYP2D7/CYP2D6 3' gene. 6. The chimeric gene is non-functional presumably due to an insertion in exon 1 (characteristic of the exon 1 of the CYP2D7 gene) which causes a shift in the reading frame with premature termination of translation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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