ArticlePLoS biology2010
Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed.
- Article
- RETRACTED: Retinoic Acid Induced 1 and Smith-Magenis Syndrome: From Genetics to Biology and Possible Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Premature ovarian insufficiency is associated with global alterations in the regulatory landscape and gene expression in balanced X-autosome translocations.Epigenetics & chromatin · 2023Article
- Altered motor learning and coordination in mouse models of autism spectrum disorder.Frontiers in cellular neuroscience · 2023Review
- TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions.American journal of human genetics · 2022Article
- The multiple de novo copy number variant (MdnCNV) phenomenon presents with peri-zygotic DNA mutational signatures and multilocus pathogenic variation.Genome medicine · 2022Article
- A phenome-wide association study identifies effects of copy-number variation of VNTRs and multicopy genes on multiple human traits.American journal of human genetics · 2022Article
- Biology in balance: human diploid genome integrity, gene dosage, and genomic medicine.Trends in genetics : TIG · 2022Review
- Computational identification of variables in neonatal vocalizations predictive for postpubertal social behaviors in a mouse model of 16p11.2 deletion.Molecular psychiatry · 2021Article
- Emerging Role of mFrontiers in cell and developmental biology · 2021Review
- Epitranscriptomic regulation by mJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- Short stature and growth hormone deficiency in a subset of patients with Potocki-Lupski syndrome: Expanding the phenotype of PTLS.American journal of medical genetics. Part A · 2020Article
- Disease-modifying effects of anNeurology. Genetics · 2020Article
- IncreasedJournal of medical genetics · 2020Article
- Modeling and Predicting Developmental Trajectories of Neuropsychiatric Dimensions Associated With Copy Number Variations.The international journal of neuropsychopharmacology · 2019Review
- A large interactive visual database of copy number variants discovered in taurine cattle.GigaScience · 2019Article
- 2018 Victor A. McKusick Leadership Award: Molecular Mechanisms for Genomic and Chromosomal Rearrangements.American journal of human genetics · 2019Article
- De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome.Genome medicine · 2019Article
1 more citing papers are in PubMed but not listed here.
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11 authors.
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Abstract
A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.
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