Integrated view of genome structure and sequence of a single DNA molecule in a nanofluidic device.

Marie, Rodolphe; Pedersen, Jonas N; Bauer, David L V; Rasmussen, Kristian H; Yusuf, Mohammed; Volpi, Emanuela; Flyvbjerg, Henrik; Kristensen, Anders et al. · Proc Natl Acad Sci U S A · 2013

basic_science · Level V

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Abstract

We show how a bird's-eye view of genomic structure can be obtained at ∼1-kb resolution from long (∼2 Mb) DNA molecules extracted from whole chromosomes in a nanofluidic laboratory-on-a-chip. We use an improved single-molecule denaturation mapping approach to detect repetitive elements and known as well as unique structural variation. Following its mapping, a molecule of interest was rescued from the chip; amplified and localized to a chromosome by FISH; and interrogated down to 1-bp resolution with a commercial sequencer, thereby reconciling haplotype-phased chromosome substructure with sequence.

Medical subject headings