Molecular Cytogenetics Guides Massively Parallel Sequencing of a Radiation-Induced Chromosome Translocation in Human Cells

Radiation Research
Michael N CornforthSusan M Bailey

Abstract

Chromosome rearrangements are large-scale structural variants that are recognized drivers of oncogenic events in cancers of all types. Cytogenetics allows for their rapid, genome-wide detection, but does not provide gene-level resolution. Massively parallel sequencing (MPS) promises DNA sequence-level characterization of the specific breakpoints involved, but is strongly influenced by bioinformatics filters that affect detection efficiency. We sought to characterize the breakpoint junctions of chromosomal translocations and inversions in the clonal derivatives of human cells exposed to ionizing radiation. Here, we describe the first successful use of DNA paired-end analysis to locate and sequence across the breakpoint junctions of a radiation-induced reciprocal translocation. The analyses employed, with varying degrees of success, several well-known bioinformatics algorithms, a task made difficult by the involvement of repetitive DNA sequences. As for underlying mechanisms, the results of Sanger sequencing suggested that the translocation in question was likely formed via microhomology-mediated non-homologous end joining (mmNHEJ). To our knowledge, this represents the first use of MPS to characterize the breakpoint junctions of...Continue Reading

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Citations

Oct 20, 2018·Radiation Research
Nov 9, 2018·Radiation Research·Michael N Cornforth, Bradford D Loucas

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Methods Mentioned

BETA
chromosomal aberrations
chromosomal aberration
mFISH
Assay
chip
PCR

Software Mentioned

Geometric Analysis of Structural Variants ( GASV )
Picard
Genome Analysis Toolkit ( GATK )
Array Designer
MetaVue
Genetic Information Research Institute ( GIRI )
BWA
CREST
mFISH
BLAST

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