Yale Web supplement accompanying:

Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library
Hugo Y. K. Lam*, Xinmeng Jasmine Mu*, Adrian M. Stütz, Andrea Tanzer, Philip D. Cayting, Michael Snyder, Philip M. Kim, Jan O. Korbel*,#,§, Mark B. Gerstein#,§
 Collaborations
Nature Biotechnology. Epub: 2009 Dec 27

Introduction
Structural Variants (SVs) are a major source of genomic variation. However, the resolution of most SV maps published to date has been insufficient for accurate breakpoint assignment. This has limited further analyses such as inferring SV ancestral states and formation mechanisms (e.g. NAHR, non-allelic homologous recombination). To this end, we collected ~2,000 SVs with breakpoints at nucleotide resolution and standardized their description in a library. We demonstrate how rapidly scanning the reads from personal genomes against this allows accurate identification of previously overlooked SVs, which we demonstrate by extensive PCR validations. Next, we characterize each breakpoint by inferring its ancestral state (through comparison against primates) and by classifying its formation mechanism. Finally, we analyze the breakpoint sequences with respect to genomic landmarks, chromosomal location, sequence motifs, and physical properties. We find, for example, that the occurrence of insertions and deletions is more balanced than previously reported and that NAHR-formed breakpoints are associated with relatively rigid and stable DNA helices.

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References
Library Compilation:

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  • Kim, P.M. et al. Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history. Genome Res 18, 1865-1874 (2008).



* These authors contributed equally to this work
# These authors co-directed this work 
§ To whom correspondence should be addressed