Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes.

TitleAllelic decomposition and exact genotyping of highly polymorphic and structurally variant genes.
Publication TypeJournal Article
Year of Publication2018
AuthorsNumanagić, I, Malikić, S, Ford, M, Qin, X, Toji, L, Radovich, M, Skaar, TC, Pratt, VM, Berger, B, Scherer, S, S Sahinalp, C
JournalNat Commun
Date Published2018 Feb 26
KeywordsAlleles, Chromosome Mapping, Cytochrome P-450 CYP2D6, DNA Copy Number Variations, Genome, Human, Genotype, Genotyping Techniques, High-Throughput Nucleotide Sequencing, Humans, Isoenzymes, Phenotype, Polymorphism, Genetic, Sequence Analysis, DNA, Software

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.

Alternate JournalNat Commun
PubMed ID29483503
PubMed Central IDPMC5826927
Grant ListR01 GM108348 / GM / NIGMS NIH HHS / United States
U01 HG007762 / HG / NHGRI NIH HHS / United States
U19 GM061388 / GM / NIGMS NIH HHS / United States

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