ArticleAmerican journal of human genetics2015
Paired-Duplication Signatures Mark Cryptic Inversions and Other Complex Structural Variation.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Exploring the size limits of Bionano optical genome mapping to resolve alternative structures of linked interspersed chromosomal duplications.Genome medicine · 2025Article
- Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.medRxiv : the preprint server for health sciences · 2025Article
- International Society for Prenatal Diagnosis 2024 Debate 3-Cytogenetics Is a Dinosaur and Should Be Replaced by Molecular Technologies.Prenatal diagnosis · 2025Review
- Diversity and consequences of structural variation in the human genome.Nature reviews. Genetics · 2025Review
- The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.American journal of human genetics · 2024Article
- The Chlamydomonas Genome Project, version 6: Reference assemblies for mating-type plus and minus strains reveal extensive structural mutation in the laboratory.The Plant cell · 2023Article
- Complex genomic rearrangements: an underestimated cause of rare diseases.Trends in genetics : TIG · 2022Review
- Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript.The Journal of experimental medicine · 2021Article
- De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families.American journal of human genetics · 2021Article
- Complex Variant Discovery Using Discordant Cluster Normalization.Journal of computational biology : a journal of computational molecular cell biology · 2021Article
- Cytogenetically visible inversions are formed by multiple molecular mechanisms.Human mutation · 2020Article
- Article
- A Balanced Translocation in Kallmann Syndrome Implicates a Long Noncoding RNA, RMST, as a GnRH Neuronal Regulator.The Journal of clinical endocrinology and metabolism · 2020Article
- Structural variant identification and characterization.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2020Article
- Structural variation in the sequencing era.Nature reviews. Genetics · 2020Review
- Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants.Genome medicine · 2019Article
- Discovery of tandem and interspersed segmental duplications using high-throughput sequencing.Bioinformatics (Oxford, England) · 2019Article
- Complex structural variants in Mendelian disorders: identification and breakpoint resolution using short- and long-read genome sequencing.Genome medicine · 2018Article
- Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization.PLoS genetics · 2018Article
- A RAB27A 5' untranslated region structural variant associated with late-onset hemophagocytic lymphohistiocytosis and normal pigmentation.The Journal of allergy and clinical immunology · 2018Article
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15 authors.
Funding
Abstract
Copy-number variants (CNVs) have been the predominant focus of genetic studies of structural variation, and chromosomal microarray (CMA) for genome-wide CNV detection is the recommended first-tier genetic diagnostic screen in neurodevelopmental disorders. We compared CNVs observed by CMA to the structural variation detected by whole-genome large-insert sequencing in 259 individuals diagnosed with autism spectrum disorder (ASD) from the Simons Simplex Collection. These analyses revealed a diverse landscape of complex duplications in the human genome. One remarkably common class of complex rearrangement, which we term dupINVdup, involves two closely located duplications ("paired duplications") that flank the breakpoints of an inversion. This complex variant class is cryptic to CMA, but we observed it in 8.1% of all subjects. We also detected other paired-duplication signatures and duplication-mediated complex rearrangements in 15.8% of all ASD subjects. Breakpoint analysis showed that the predominant mechanism of formation of these complex duplication-associated variants was microhomology-mediated repair. On the basis of the striking prevalence of dupINVdups in this cohort, we explored the landscape of all inversion variation among the 235 highest-quality libraries and found abundant complexity among these variants: only 39.3% of inversions were canonical, or simple, inversions without additional rearrangement. Collectively, these findings indicate that dupINVdups, as well as other complex duplication-associated rearrangements, represent relatively common sources of genomic variation that is cryptic to population-based microarray and low-depth whole-genome sequencing. They also suggest that paired-duplication signatures detected by CMA warrant further scrutiny in genetic diagnostic testing given that they might mark complex rearrangements of potential clinical relevance.
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