Complex genomic rearrangements: an underestimated cause of rare diseases

Complex genomic rearrangements (CGRs) are known contributors to disease but are often missed during routine genetic screening. Identifying CGRs requires (i) identifying copy number variants (CNVs) concurrently with inversions, (ii) phasing multiple breakpoint junctions incis, as well as (iii) detect...

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Bibliographic Details
Published inTrends in genetics Vol. 38; no. 11; pp. 1134 - 1146
Main Authors Schuy, Jakob, Grochowski, Christopher M, Carvalho, Claudia M B, Lindstrand, Anna
Format Journal Article
LanguageEnglish
Published England 01.11.2022
Subjects
DNA Copy Number Variations - genetics
Gene Rearrangement - genetics
Genome, Human - genetics
Genomics - methods
Humans
Medicin och hälsovetenskap
Rare Diseases - genetics
structural variation
chromosomal abnormalities
clinical diagnostics
genomic disorders
constitutional diseases
whole-genome sequencing
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Summary:Complex genomic rearrangements (CGRs) are known contributors to disease but are often missed during routine genetic screening. Identifying CGRs requires (i) identifying copy number variants (CNVs) concurrently with inversions, (ii) phasing multiple breakpoint junctions incis, as well as (iii) detecting and resolving structural variants (SVs) within repeats. We demonstrate how combining cytogenetics and new sequencing methodologies is being successfully applied to gain insights into the genomic architecture of CGRs. In addition, we review CGR patterns and molecular features revealed by studying constitutional genomic disorders. These data offer invaluable lessons to individuals interested in investigating CGRs, evaluating their clinical relevance and frequency, as well as assessing their impact(s) on rare genetic diseases.
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ISSN:0168-9525
DOI:10.1016/j.tig.2022.06.003