Elsevier

Genetics in Medicine

Volume 20, Issue 7, July 2018, Pages 697-707
Genetics in Medicine

Article
Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: implications for interpretation of structural variation in genomes and the future of clinical cytogenetics

https://doi.org/10.1038/gim.2017.170Get rights and content
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Abstract

Purpose

Recent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected.

Methods

The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold).

Results

With this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene.

Conclusion

Our study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.

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