title: Detecting non-allelic homologous recombination from high-throughput sequencing data.
abstract: Non-allelic homologous recombination (NAHR) is a common mechanism for generating genome rearrangements and is implicated in numerous genetic disorders, but its detection in high-throughput sequencing data poses a serious challenge. We present a probabilistic model of NAHR and demonstrate its ability to find NAHR in low-coverage sequencing data from 44 individuals. We identify NAHR-mediated deletions or duplications in 109 of 324 potential NAHR loci in at least one of the individuals. These calls segregate by ancestry, are more common in closely spaced repeats, often result in duplicated genes or pseudogenes, and affect highly studied genes such as GBA and CYP2E1.
authors.affiliation: Division of Applied Mathematics, Brown University, Providence, USA. matthew_parks@alumni.brown.edu.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Parks
authors.affiliation: Division of Applied Mathematics, Brown University, Providence, USA. charles_lawrence@brown.edu.|Center for Computational Molecular Biology, Brown University, Providence, USA. charles_lawrence@brown.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Lawrence
authors.affiliation: Center for Computational Molecular Biology, Brown University, Providence, USA. braphael@brown.edu.|Department of Computer Science, Brown University, Providence, USA. braphael@brown.edu.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005787:Gene Frequency; D015321:Gene Rearrangement; D056426:Genetic Loci; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011544:Pseudogenes; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA