Multi-ethnic cytochrome-P450 copy number profiling: novel pharmacogenetic alleles and mechanism of copy number variation formation.
Pharmacogenomics J
; 13(6): 558-66, 2013 Dec.
Article
de En
| MEDLINE
| ID: mdl-23164804
ABSTRACT
To determine the role of CYP450 copy number variation (CNV) beyond CYP2D6, 11 CYP450 genes were interrogated by multiplex ligation-dependent probe amplification and quantitative PCR in 542 African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish individuals. The CYP2A6, CYP2B6 and CYP2E1 combined deletion/duplication allele frequencies ranged from 2 to 10% in these populations. High-resolution microarray-based comparative genomic hybridization (aCGH) localized CYP2A6, CYP2B6 and CYP2E1 breakpoints to directly oriented low-copy repeats. Sequencing localized the CYP2B6 breakpoint to a 529-bp intron 4 region with high homology to CYP2B7P1, resulting in the CYP2B6*29 partial deletion allele and the reciprocal, and novel, CYP2B6/2B7P1 duplicated fusion allele (CYP2B6*30). Together, these data identified novel CYP450 CNV alleles (CYP2B6*30 and CYP2E1*1Cx2) and indicate that common CYP450 CNV formation is likely mediated by non-allelic homologous recombination resulting in both full gene and gene-fusion copy number imbalances. Detection of these CNVs should be considered when interrogating these genes for pharmacogenetic drug selection and dosing.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pharmacogénétique
/
Ethnies
/
Cytochrome P-450 enzyme system
/
Variations de nombre de copies de segment d'ADN
Limites:
Humans
Langue:
En
Journal:
Pharmacogenomics J
Sujet du journal:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Année:
2013
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique