ArticleAmerican journal of human genetics2023
Patterns of mosaicism for sequence and copy-number variants discovered through clinical deep sequencing of disease-related genes in one million individuals.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Genomic mosaicism in colorectal cancer and polyposis syndromes: a systematic review and meta-analysis.International journal of colorectal disease · 2024Pooled it
- Review
- Characterization of subclonal variants in HG002 Genome in a Bottle reference material as a resource for benchmarking variant callers.Cell genomics · 2026Article
- Mosaic variants in the LIM homeobox 1 (LHX1) gene contribute to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome.Human genetics · 2026Article
- Article
- MosaicSim: A Novel Mosaic Variant Simulator Reveals Diminishing Returns of Ultra-High Coverage for Mosaic Variant Detection.bioRxiv : the preprint server for biology · 2025Article
- Multiple Genomic Technologies Validate Rare Novel Variant and Direct Medical Care in Vascular Anomalies.American journal of medical genetics. Part A · 2025Article
- KRAS Copy Number Gain in Cell-Free DNA Analysis-Based Liquid Biopsy of Plasma and Bile in Patients with Various Pancreatic Neoplasms.International journal of molecular sciences · 2025Article
- Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder.Journal of autism and developmental disorders · 2025Article
- Low Allele Frequency Variants Identified on Germline Multi-Gene Panel Testing for Cancer Predisposition Can Suggest the Presence of Constitutional Mosaicism.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Mosaic X-linked adrenoleukodystrophy in males identified by newborn screening and next-generation sequencing.NPJ genomic medicine · 2025Article
- A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.bioRxiv : the preprint server for biology · 2024Article
- Postzygotic mosaicism of SMARCB1 variants in patients with rhabdoid tumors: A not-so-rare condition exposing to successive tumors.Neuro-oncology · 2024Article
- Genome sequencing as a generic diagnostic strategy for rare disease.Genome medicine · 2024Article
- Case report: Deep sequencing and long-read genome sequencing refine prior genetic analyses in families with apparent gonadal mosaicism inFrontiers in immunology · 2024Article
- Ordering genetic testing by neurologists: points to consider.Journal of neurology · 2023Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
DNA variants that arise after conception can show mosaicism, varying in presence and extent among tissues. Mosaic variants have been reported in Mendelian diseases, but further investigation is necessary to broadly understand their incidence, transmission, and clinical impact. A mosaic pathogenic variant in a disease-related gene may cause an atypical phenotype in terms of severity, clinical features, or timing of disease onset. Using high-depth sequencing, we studied results from one million unrelated individuals referred for genetic testing for almost 1,900 disease-related genes. We observed 5,939 mosaic sequence or intragenic copy number variants distributed across 509 genes in nearly 5,700 individuals, constituting approximately 2% of molecular diagnoses in the cohort. Cancer-related genes had the most mosaic variants and showed age-specific enrichment, in part reflecting clonal hematopoiesis in older individuals. We also observed many mosaic variants in genes related to early-onset conditions. Additional mosaic variants were observed in genes analyzed for reproductive carrier screening or associated with dominant disorders with low penetrance, posing challenges for interpreting their clinical significance. When we controlled for the potential involvement of clonal hematopoiesis, most mosaic variants were enriched in younger individuals and were present at higher levels than in older individuals. Furthermore, individuals with mosaicism showed later disease onset or milder phenotypes than individuals with non-mosaic variants in the same genes. Collectively, the large compendium of variants, disease correlations, and age-specific results identified in this study expand our understanding of the implications of mosaic DNA variation for diagnosis and genetic counseling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.