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Cypiripi: exact genotyping of CYP2D6 using high-throughput sequencing data.

Numanagić I, Malikić S, Pratt VM, Skaar TC, Flockhart DA, Sahinalp SC - Bioinformatics (2015)

Bottom Line: CYP2D6 genotyping is recommended prior to treatment decisions involving one or more of the numerous drugs sensitive to CYP2D6 allelic composition.In this context, high-throughput sequencing (HTS) technologies provide a promising time-efficient and cost-effective alternative to currently used genotyping techniques.To achieve accurate interpretation of HTS data, however, one needs to overcome several obstacles such as high sequence similarity and genetic recombinations between CYP2D6 and evolutionarily related pseudogenes CYP2D7 and CYP2D8, high copy number variation among individuals and short read lengths generated by HTS technologies.

View Article: PubMed Central - PubMed

Affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.

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Five known CYP2D6 gene arrangements. The reference strand of human genome was used in all cases. Various number, including zero, of CYP2D6 copies is allowed within the parenthesis. (a) CYP2D6 non-duplicated arrangement consisting one copy of each of CYP2D6, CYP2D7 and CYP2D8. Purple rectangle represents CYP2D6 untranslated region. This region contains several variations important for the detection of some CYP2D6 alleles; (b) typical CYP2D6 duplication arrangement; (c) the deletion arrangement, indicating the absence of CYP2D6 (denoted as *5 allele); (d) CYP2D6/2D7 fusions (*13 family of alleles) lacking CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles; (e) CYP2D7/2D6 fusion cases with presence of CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles in this case as well
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btv232-F1: Five known CYP2D6 gene arrangements. The reference strand of human genome was used in all cases. Various number, including zero, of CYP2D6 copies is allowed within the parenthesis. (a) CYP2D6 non-duplicated arrangement consisting one copy of each of CYP2D6, CYP2D7 and CYP2D8. Purple rectangle represents CYP2D6 untranslated region. This region contains several variations important for the detection of some CYP2D6 alleles; (b) typical CYP2D6 duplication arrangement; (c) the deletion arrangement, indicating the absence of CYP2D6 (denoted as *5 allele); (d) CYP2D6/2D7 fusions (*13 family of alleles) lacking CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles; (e) CYP2D7/2D6 fusion cases with presence of CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles in this case as well

Mentions: Most of the known CYP2D6 variants are characterized by single-nucleotide polymorphisms (SNPs) and short insertions/deletions (indels). However, in addition to CYP2D6, the human CYP2D locus contains two pseudogenes CYP2D7 and CYP2D8, closely located and evolutionarily related to CYP2D6 (Kimura et al., 1989). The presence of highly homologous gene units in CYP2D6 and CYP2D7 facilitates crossing-over and formation of large gene conversions, deletions, duplications and multiplications (Kramer et al., 2009). Figure 1Fig. 1.


Cypiripi: exact genotyping of CYP2D6 using high-throughput sequencing data.

Numanagić I, Malikić S, Pratt VM, Skaar TC, Flockhart DA, Sahinalp SC - Bioinformatics (2015)

Five known CYP2D6 gene arrangements. The reference strand of human genome was used in all cases. Various number, including zero, of CYP2D6 copies is allowed within the parenthesis. (a) CYP2D6 non-duplicated arrangement consisting one copy of each of CYP2D6, CYP2D7 and CYP2D8. Purple rectangle represents CYP2D6 untranslated region. This region contains several variations important for the detection of some CYP2D6 alleles; (b) typical CYP2D6 duplication arrangement; (c) the deletion arrangement, indicating the absence of CYP2D6 (denoted as *5 allele); (d) CYP2D6/2D7 fusions (*13 family of alleles) lacking CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles; (e) CYP2D7/2D6 fusion cases with presence of CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles in this case as well
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4542776&req=5

btv232-F1: Five known CYP2D6 gene arrangements. The reference strand of human genome was used in all cases. Various number, including zero, of CYP2D6 copies is allowed within the parenthesis. (a) CYP2D6 non-duplicated arrangement consisting one copy of each of CYP2D6, CYP2D7 and CYP2D8. Purple rectangle represents CYP2D6 untranslated region. This region contains several variations important for the detection of some CYP2D6 alleles; (b) typical CYP2D6 duplication arrangement; (c) the deletion arrangement, indicating the absence of CYP2D6 (denoted as *5 allele); (d) CYP2D6/2D7 fusions (*13 family of alleles) lacking CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles; (e) CYP2D7/2D6 fusion cases with presence of CYP2D7. Variable number of copies of CYP2D6 gene might precede fusion alleles in this case as well
Mentions: Most of the known CYP2D6 variants are characterized by single-nucleotide polymorphisms (SNPs) and short insertions/deletions (indels). However, in addition to CYP2D6, the human CYP2D locus contains two pseudogenes CYP2D7 and CYP2D8, closely located and evolutionarily related to CYP2D6 (Kimura et al., 1989). The presence of highly homologous gene units in CYP2D6 and CYP2D7 facilitates crossing-over and formation of large gene conversions, deletions, duplications and multiplications (Kramer et al., 2009). Figure 1Fig. 1.

Bottom Line: CYP2D6 genotyping is recommended prior to treatment decisions involving one or more of the numerous drugs sensitive to CYP2D6 allelic composition.In this context, high-throughput sequencing (HTS) technologies provide a promising time-efficient and cost-effective alternative to currently used genotyping techniques.To achieve accurate interpretation of HTS data, however, one needs to overcome several obstacles such as high sequence similarity and genetic recombinations between CYP2D6 and evolutionarily related pseudogenes CYP2D7 and CYP2D8, high copy number variation among individuals and short read lengths generated by HTS technologies.

View Article: PubMed Central - PubMed

Affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.

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Related in: MedlinePlus