Introduction

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.

Publications

  1. Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library.
    Cite this
    Lam HY, Mu XJ, Stütz AM, Tanzer A, Cayting PD, Snyder M, Kim PM, Korbel JO, Gerstein MB, 2010-01-01 - Nature biotechnology

Credits

  1. Hugo Y K Lam
    Developer

    Program in Computational Biology and Bioinformatics, Yale University, United States of America

  2. Xinmeng Jasmine Mu
    Developer

  3. Adrian M Stütz
    Developer

  4. Andrea Tanzer
    Developer

  5. Philip D Cayting
    Developer

  6. Michael Snyder
    Developer

  7. Philip M Kim
    Developer

  8. Jan O Korbel
    Developer

  9. Mark B Gerstein
    Investigator

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Summary
AccessionBT000071
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByMark B Gerstein