Nucleotide-resolution Analysis of Structural Variants Using BreakSeq and a Breakpoint Library

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2009 Dec 29

PMID 20037582

Citations 106

Authors

Hugo Y K Lam

Xinmeng Jasmine Mu

Adrian M Stutz

Andrea Tanzer

Philip D Cayting

Michael Snyder

Philip M Kim

Jan O Korbel

Mark B Gerstein

Affiliations

Soon will be listed here.

Abstract

Structural variants (SVs) are a major source of human genomic variation; however, characterizing them at nucleotide resolution remains challenging. Here we assemble a library of breakpoints at nucleotide resolution from collating and standardizing ~2,000 published SVs. For each breakpoint, we infer its ancestral state (through comparison to primate genomes) and its mechanism of formation (e.g., nonallelic homologous recombination, NAHR). We characterize breakpoint sequences with respect to genomic landmarks, chromosomal location, sequence motifs and physical properties, finding that the occurrence of insertions and deletions is more balanced than previously reported and that NAHR-formed breakpoints are associated with relatively rigid, stable DNA helices. Finally, we demonstrate an approach, BreakSeq, for scanning the reads from short-read sequenced genomes against our breakpoint library to accurately identify previously overlooked SVs, which we then validate by PCR. As new data become available, we expect our BreakSeq approach will become more sensitive and facilitate rapid SV genotyping of personal genomes.

Citing Articles

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Small polymorphisms are a source of ancestral bias in structural variant breakpoint placement.

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