Molecular diversity at the CYP2D6 locus in the Mediterranean region View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-11

AUTHORS

Silvia Fuselli, Isabelle Dupanloup, Elena Frigato, Fulvio Cruciani, Rosaria Scozzari, Pedro Moral, Johanna Sistonen, Antti Sajantila, Guido Barbujani

ABSTRACT

Despite the importance of cytochrome P450 in the metabolism of many drugs, several aspects of molecular variation at one of the main loci coding for it, CYP2D6, have never been analysed so far. Here we show that it is possible to rapidly and efficiently genotype the main European allelic variants at this locus by a SNaPshot method identifying chromosomal rearrangements and nine single-nucleotide polymorphisms. Haplotypes could be reconstructed from data on 494 chromosomes in six populations of the Mediterranean region. High levels of linkage disequilibrium were found within the chromosome region screened, suggesting that CYP2D6 may be part of a genomic recombination block, and hence that, aside from unequal crossingover that led to large chromosomal rearrangements, its haplotype diversity essentially originated through the accumulation of mutations. With the only, albeit statistically insignificant, exception of Syria, haplotype frequencies do not differ among the populations studied, despite the presence among them of three well-known genetic outliers, which could be the result of common selective pressures playing a role in shaping CYP2D6 variation over the area of Europe that we surveyed. More... »

PAGES

5201243

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.ejhg.5201243

DOI

http://dx.doi.org/10.1038/sj.ejhg.5201243

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020938987

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15340360


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