We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Gene copy number variations: it is important to determine which allele is affected

    Anuradha Ramamoorthy

    Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, Baltimore, MD, USA

    and
    Todd C Skaar

    † Author for correspondence

    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

    Published Online:https://doi.org/10.2217/pgs.11.5
    Free first page

    Bibliography

    • Sebat J, Lakshmi B, Troge J et al.: Large-scale copy number polymorphism in the human genome. Science305(5683),525–528 (2004).
    • Redon R, Ishikawa S, Fitch KR et al.: Global variation in copy number in the human genome. Nature444(7118),444–454 (2006).
    • Iafrate AJ, Feuk L, Rivera MN et al.: Detection of large-scale variation in the human genome. Nat. Genet.36(9),949–951 (2004).
    • Shrestha S, Tang J, Kaslow RA: Gene copy number: learning to count past two. Nat. Med.15(10),1127–1129 (2009).
    • Wain LV, Armour JA, Tobin MD: Genomic copy number variation, human health, and disease. Lancet374(9686),340–350 (2009).
    • Mccarroll SA, Hadnott TN, Perry GH et al.: Common deletion polymorphisms in the human genome. Nat. Genet.38(1),86–92 (2006).
    • Hebbring SJ, Adjei AA, Baer JL et al.: Human SULT1A1 gene: copy number differences and functional implications. Hum. Mol. Genet.16(5),463–470 (2007).
    • Bolt HM, Thier R: Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr. Drug Metab.7(6),613–628 (2006).
    • Yokoi T, Kamataki T: Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and CYP2A6 genes in Japanese. Pharm. Res.15(4),517–524 (1998).
    • 10  Bradford LD: CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics3(2),229–243 (2002).
    • 11  Ingelman-Sundberg M: Genetic polymorphisms of CYP450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J.5(1),6–13 (2005).
    • 12  Aklillu E, Persson I, Bertilsson L, Johansson I, Rodrigues F, Ingelman-Sundberg M: Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J. Pharmacol. Exp. Ther.278(1),441–446 (1996).
    • 13  Ishiguro A, Kubota T, Ishikawa H, Iga T: Metabolic activity of dextromethorphan O-demethylation in healthy Japanese volunteers carrying duplicated CYP2D6 genes: duplicated allele of CYP2D6*10 does not increase CYP2D6 metabolic activity. Clin. Chim. Acta344(1–2),201–204 (2004).
    • 14  Kiyotani K, Shimizu M, Kumai T, Kamataki T, Kobayashi S, Yamazaki H: Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population. Eur. J. Clin. Pharmacol.66(10),1065–1068 (2010).
    • 15  Meijerman I, Sanderson LM, Smits PH, Beijnen JH, Schellens JH: Pharmacogenetic screening of the gene deletion and duplications of CYP2D6. Drug Metab. Rev.39(1),45–60 (2007).
    • 16  Schaeffeler E, Schwab M, Eichelbaum M, Zanger UM: CYP2D6 genotyping strategy based on gene copy number determination by TaqMan real-time PCR. Hum. Mutat.22(6),476–485 (2003).
    • 17  Hosono N, Kato M, Kiyotani K et al.: CYP2D6 genotyping for functional-gene dosage analysis by allele copy number detection. Clin. Chem.55(8),1546–1554 (2009).
    • 18  Strobietto HL, Leeder JS, Gaedigk A: Simultaneous detection of CYP2D6, SULT1A1 and UGT2B17 copy number variation (CNV) by multiplex PCR. Presented at: American Society of Clinical Pharmacology and Therapeutics. Atlanta, GA, USA, March 17–20, 2010.
    • 19  Ramamoorthy A, Flockhart DA, Hosono N, Kubo M, Nakamura Y, Skaar TC: Differential quantification of CYP2D6 gene copy number by four different quantitative real-time PCR assays. Pharmacogenet. Genomics20(7),451–454 (2010).
    • 20  Craddock N, Hurles ME, Cardin N et al.: Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature464(7289),713–720 (2010).
    • 101  Indiana University; Division of Clinical Pharmacology: P450 Drug Interaction Table http://medicine.iupui.edu/clinpharm/ddis/table.asp
    • 102  CYP2D6 allele nomenclature www.cypalleles.ki.se/cyp2d6.htm