Limits...
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.

Show MeSH
The coverage of the reads mappable to the CYP2D6 and/or CYP2D7 genes is depicted in grey on the flanking regions of CYP2D8 (blue strip). Only two small 0.5 KB regions on the sides accept CYP2D6 and/or CYP2D7 reads
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4542776&req=5

btv232-F3: The coverage of the reads mappable to the CYP2D6 and/or CYP2D7 genes is depicted in grey on the flanking regions of CYP2D8 (blue strip). Only two small 0.5 KB regions on the sides accept CYP2D6 and/or CYP2D7 reads

Mentions: Although CYP2D8 is evolutionarily related to CYP2D6 and CYP2D7, its sequence composition is significantly different from that of the other two. In addition, there are no recombination events involving CYP2D6 and CYP2D8. As a result, we assume that CYP2D8 is always located downstream of CYP2D7 (considering 5’–3’ orientation in the human reference genome) and that, the vast majority of the reads originating from this gene are not mappable to the other two genes. However, there are two 0.5 kb flanking regions at CYP2D8 boundaries that can give rise to some reads mappable to CYP2D6 and/or CYP2D7 (Fig. 3Fig. 3.


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

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

The coverage of the reads mappable to the CYP2D6 and/or CYP2D7 genes is depicted in grey on the flanking regions of CYP2D8 (blue strip). Only two small 0.5 KB regions on the sides accept CYP2D6 and/or CYP2D7 reads
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542776&req=5

btv232-F3: The coverage of the reads mappable to the CYP2D6 and/or CYP2D7 genes is depicted in grey on the flanking regions of CYP2D8 (blue strip). Only two small 0.5 KB regions on the sides accept CYP2D6 and/or CYP2D7 reads
Mentions: Although CYP2D8 is evolutionarily related to CYP2D6 and CYP2D7, its sequence composition is significantly different from that of the other two. In addition, there are no recombination events involving CYP2D6 and CYP2D8. As a result, we assume that CYP2D8 is always located downstream of CYP2D7 (considering 5’–3’ orientation in the human reference genome) and that, the vast majority of the reads originating from this gene are not mappable to the other two genes. However, there are two 0.5 kb flanking regions at CYP2D8 boundaries that can give rise to some reads mappable to CYP2D6 and/or CYP2D7 (Fig. 3Fig. 3.

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.

Show MeSH