Browsing by Subject "Genotyping Techniques"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes
    (Springer Nature, 2018-02-26) Numanagić, Ibrahim; Malikić, Salem; Ford, Michael; Qin, Xiang; Toji, Lorraine; Radovich, Milan; Skaar, Todd C.; Pratt, Victoria M.; Berger, Bonnie; Scherer, Steve; Sahinalp, S. Cenk; Medicine, School of Medicine
    High-throughput sequencing provides the means to determine the allelic decomposition for any gene of interest-the number of copies and the exact sequence content of each copy of a gene. Although many clinically and functionally important genes are highly polymorphic and have undergone structural alterations, no high-throughput sequencing data analysis tool has yet been designed to effectively solve the full allelic decomposition problem. Here we introduce a combinatorial optimization framework that successfully resolves this challenging problem, including for genes with structural alterations. We provide an associated computational tool Aldy that performs allelic decomposition of highly polymorphic, multi-copy genes through using whole or targeted genome sequencing data. For a large diverse sequencing data set, Aldy identifies multiple rare and novel alleles for several important pharmacogenes, significantly improving upon the accuracy and utility of current genotyping assays. As more data sets become available, we expect Aldy to become an essential component of genotyping toolkits.
  • Thumbnail Image
    Item
    Tracheal Aspirate as an Alternative Biologic Sample for Pharmacogenomics Testing in Mechanically Ventilated Pediatric Patients
    (Wiley, 2021-03) Hargreaves, Katherine A.; Pratt, Victoria M.; Medeiros, Elizabeth B.; Lynnes, Ty C.; Granfield, Caitlin A.; Skaar, Todd C.; Iwata-Otsubo, Aiko; Tillman, Emma M.; Medical and Molecular Genetics, School of Medicine
    Patients in the pediatric intensive care unit are exposed to multiple medications and are at high risk for adverse drug reactions. Pharmacogenomic (PGx) testing could help decrease their risk of adverse reactions. Although whole blood is preferred for PGx testing, blood volume in this population is often limited. However, for patients on mechanical ventilation, tracheal secretions are abundant, frequently suctioned, and discarded. Thus, the aim of this pilot study was to determine if tracheal aspirates could be used as a source of human genomic DNA for PGx testing. We successfully extracted DNA from tracheal secretions of all 23 patients in the study. The samples were successfully genotyped for 10 clinically actionable single nucleotide variants across 3 cytochrome P450 genes (CYP2D6, CYP2C19, and CYP3A5). Using DNA from whole blood samples in 11 of the patients, we confirmed the accuracy of the genotyping with 100% concordance. Therefore, our results support the use of tracheal aspirates from mechanically ventilated children as an adequate biospecimen for clinical genetic testing.