Balanced Chromosomal Rearrangement Detection by Low-Pass Whole-Genome Sequencing

Curr Protoc Hum Genet. 2018 Jan 24;96:8.18.1-8.18.16. doi: 10.1002/cphg.51.


Balanced chromosomal rearrangements (or balanced chromosome abnormalities, BCAs) are common chromosomal structural variants. Emerging studies have demonstrated the feasibility of using whole-genome sequencing (WGS) for detection of BCA-associated breakpoints, but the requirement for a priori knowledge of the rearranged regions from G-banded chromosome analysis limits its application. The protocols described here are based on low-pass WGS for detecting BCA events independent from chromosome analysis, and has been validated using genomic data from the 1000 Genomes Project. This approach adopts non-size-selected mate-pair library (3∼8 kb) with 2∼3 μg DNA as input, and requires only 30 million read-pairs (50 bp, equivalent to 1-fold base-coverage) for each sample. The complete procedure takes 13 days and the total cost is estimated to be less than $600 (USD) per sample. © 2018 by John Wiley & Sons, Inc.

Keywords: balanced translocations; chromosomal structural rearrangements; inversions; low-pass whole-genome sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / pathology
  • Chromosome Mapping
  • Genome, Human / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Translocation, Genetic
  • Whole Genome Sequencing*