Resolving genomic disorder-associated breakpoints within segmental DNA duplications using massively parallel sequencing.

ABSTRACT: The most common recurrent copy-number variants associated with autism, developmental delay and epilepsy are flanked by segmental duplications. Complete genetic characterization of these events is challenging because their breakpoints often occur within high-identity, copy-number polymorphic paralogous sequences that cannot be specifically assayed using hybridization-based methods. Here we provide a protocol for breakpoint resolution with sequence-level precision. Massively parallel sequencing is performed on libraries generated from haplotype-resolved chromosomes, genomic DNA or molecular inversion probe (MIP)-captured breakpoint-informative regions harboring paralog-distinguishing variants. Quantification of sequencing depth over informative sites enables breakpoint localization, typicall

SUBMITTER: Nuttle X 

PROVIDER: S-EPMC4114152 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature