Rapid, Paralog-Sensitive CNV Analysis of 2457 Human Genomes Using QuicK-mer2.

TitleRapid, Paralog-Sensitive CNV Analysis of 2457 Human Genomes Using QuicK-mer2.
Publication TypeJournal Article
Year of Publication2020
AuthorsShen, F, Kidd, JM
JournalGenes (Basel)
Date Published2020 01 29

Gene duplication is a major mechanism for the evolution of gene novelty, and copy-number variation makes a major contribution to inter-individual genetic diversity. However, most approaches for studying copy-number variation rely upon uniquely mapping reads to a genome reference and are unable to distinguish among duplicated sequences. Specialized approaches to interrogate specific paralogs are comparatively slow and have a high degree of computational complexity, limiting their effective application to emerging population-scale data sets. We present QuicK-mer2, a self-contained, mapping-free approach that enables the rapid construction of paralog-specific copy-number maps from short-read sequence data. This approach is based on the tabulation of unique k-mer sequences from short-read data sets, and is able to analyze a 20X coverage human genome in approximately 20 min. We applied our approach to newly released sequence data from the 1000 Genomes Project, constructed paralog-specific copy-number maps from 2457 unrelated individuals, and uncovered copy-number variation of paralogous genes. We identify nine genes where none of the analyzed samples have a copy number of two, 92 genes where the majority of samples have a copy number other than two, and describe rare copy number variation effecting multiple genes at the APOBEC3 locus.

Alternate JournalGenes (Basel)
PubMed ID32013076
PubMed Central IDPMC7073954
Grant ListR01 GM103961 / GM / NIGMS NIH HHS / United States
DP5 OD009154 / OD / NIH HHS / United States
UM1 HG008901 / HG / NHGRI NIH HHS / United States