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Cited by 774Genomic variations and chromosomal abnormalitiesGenome Rearrangement AlgorithmsDNA Repair Mechanisms

Mechanisms underlying structural variant formation in genomic disorders

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Carvalho, Claudia M. B., Lupski, James R.·2016·Nature Reviews Genetics
DOI 10.1038/nrg.2015.25PMC PMC4827625
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Abstract

With the recent burst of technological developments in genomics, and the clinical implementation of genome-wide assays, our understanding of the molecular basis of genomic disorders, specifically the contribution of structural variation to disease burden, is evolving quickly. Ongoing studies have revealed a ubiquitous role for genome architecture in the formation of structural variants at a given locus, both in DNA recombination-based processes and in replication-based processes. These reports showcase the influence of repeat sequences on genomic stability and structural variant complexity and also highlight the tremendous plasticity and dynamic nature of our genome in evolution, health and disease susceptibility.

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  • SVs and CNVs represent a significant portion of the genetic variation responsible for clinical phenotypes such as cancer and rare genetic disorders.

    “Over the past decade, we and others have highlighted that not only SNVs and indels but also SVs and CNVs represent a significant portion of the genetic variation responsible for clinical phenotypes70,71, such as cancer and rare genetic disorders.”

    From Comprehensive genome analysis and variant detection at scale using DRAGEN (2025) · cites this paper as [70]

    The Abstract (page unavailable) describes disease-causing structural variants, including CNVs, and gives examples involving rare genomic disorders. The section ‘RBMs show a high mutational rate’ links genomic rearrangements to some cancers, but does not establish that SVs and CNVs account for a significant portion of the genetic variation responsible for cancer phenotypes. (LLM, conf=0.79)

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Cited by

Sorted by citations

Authors
Carvalho, C. M. B., & Lupski, J. R.
Affiliations
Baylor College of Medicine (US)
Corresponding author
Lupski, James R.
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2016-02-29
Volume
17
Issue
4
Pages
224-238
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/nrg.2015.25
PMC
PMC4827625
OpenAlex
W2289509647
Cited by
774
References
6
Citations by year
2026: 60 · 2025: 91 · 2024: 88 · 2023: 89 · 2022: 56 · 2021: 71 · 2020: 70 · 2019: 67 · 2018: 100 · 2017: 59 · 2016: 23
FWCI
11.10
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion)
Funders
  • National Human Genome Research Institute (U54HG006542, UM1HG006542)
  • National Institute of General Medical Sciences (R01GM106373)
  • National Institute of Neurological Disorders and Stroke (R01NS058529)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
structural variants, genomic disorders, genome organization, DNA recombination, DNA replication, repetitive DNA, genome stability, genome plasticity, disease susceptibility
MeSH terms
Humans, Models, Genetic, Mutation, Repetitive Sequences, Nucleic Acid, Genetic Variation, Gene Rearrangement, Genome, Human, Genetic Predisposition to Disease, Genetic Diseases, Inborn, Genomic Instability, Homologous Recombination

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