title: High-throughput analysis of informative CYP2D6 compound haplotypes.
abstract: We describe a high-throughput protocol for detecting key polymorphisms in the drug-metabolizing enzyme gene CYP2D6 and a number of linked microsatellites that is both fast and relatively inexpensive to perform. This approach employs GeneScan technology to enable a researcher to determine rapidly the status of seven simple nucleotide polymorphisms in CYP2D6 and also to assay repeat number variation at five closely linked dinucleotide microsatellite loci. The method requires only three PCRs and two GeneScan runs per sample. We anticipate that this will be of value to researchers in three different ways: (1) rapid discrimination of common CYP2D6 alleles, (2) high-resolution haplotyping for association studies involving chromosome 22q13.1 using microsatellite variation, and (3) generation of compound haplotypes for investigating the evolution of CYP2D6 variation. We also report compound haplotype frequencies for an Ashkenazi Jewish and a British sample.
authors.affiliation: The Centre for Genetic Anthropology, Department of Biology and Department of Anthropology, University College London, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fletcher
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.forename: Amanda L R
authors.initials: AL
authors.lastname: Bradman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weale
authors.forename: Neil
authors.initials: N
authors.lastname: Bradman
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
mesh_terms: D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D006239:Haplotypes; D006801:Humans; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D019389:Cytochrome P-450 CYP2D6