CYP2D6: novel genomic structures and alleles.
OBJECTIVE
CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today.


METHODS
Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure.


RESULTS
Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles.


CONCLUSIONS
Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis.
Kramer
Whitney E
WE
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Walker
Denise L
DL
O'Kane
Dennis J
DJ
Mrazek
David A
DA
Fisher
Pamela K
PK
Dukek
Brian A
BA
Bruflat
Jamie K
JK
Black
John L
JL
D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D020440:Gene Duplication; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D011110:Polymorphism, Genetic
D019389:Cytochrome P-450 CYP2D6