ArticleProceedings of the National Academy of Sciences of the United States of America2012
Impact of copy number variations (CNVs) on long-range gene regulation at the HoxD locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Association ofAnimals : an open access journal from MDPI · 2026Article
- A de Novo 2q23.1-2q23.3 duplication in a neonate with anemia, thrombocytopenia, and hypospadias: clinical and genomic characterization.Molecular cytogenetics · 2025Article
- Genome-wide association testing beyond SNPs.Nature reviews. Genetics · 2025Review
- Three-dimensional genome structure and function.MedComm · 2023Review
- Article
- Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants.Genome medicine · 2019Article
- Evolutionary stability of topologically associating domains is associated with conserved gene regulation.BMC biology · 2018Article
- Large scale genomic reorganization of topological domains at the HoxD locus.Genome biology · 2017Article
- Duplicated Enhancer Region Increases Expression of CTSB and Segregates with Keratolytic Winter Erythema in South African and Norwegian Families.American journal of human genetics · 2017Article
- Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding.Genome research · 2017Article
- When TADs go bad: chromatin structure and nuclear organisation in human disease.F1000Research · 2017Review
- Regulation of disease-associated gene expression in the 3D genome.Nature reviews. Molecular cell biology · 2016Review
- Determining multiallelic complex copy number and sequence variation from high coverage exome sequencing data.BMC genomics · 2015Article
- Article
- A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes.PLoS genetics · 2015Article
- Human gene copy number variation and infectious disease.Human genetics · 2014Review
- Disruption of long-range gene regulation in human genetic disease: a kaleidoscope of general principles, diverse mechanisms and unique phenotypic consequences.Human genetics · 2014Review
- Segmental folding of chromosomes: a basis for structural and regulatory chromosomal neighborhoods?BioEssays : news and reviews in molecular, cellular and developmental biology · 2013Article
- Transgene- and locus-dependent imprinting reveals allele-specific chromosome conformations.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Copy number variations are genomic structural variants that are frequently associated with human diseases. Among these copy number variations, duplications of DNA segments are often assumed to lead to dosage effects by increasing the copy number of either genes or their regulatory elements. We produced a series of large targeted duplications within a conserved gene desert upstream of the murine HoxD locus. This DNA region, syntenic to human 2q31-32, contains a range of regulatory elements required for Hoxd gene transcription, and it is often disrupted and/or reorganized in human genetic conditions collectively known as the 2q31 syndrome. Unexpectedly, one such duplication led to a transcriptional down-regulation in developing digits by impairing physical interactions between the target genes and their upstream regulatory elements, thus phenocopying the effect obtained when these enhancer sequences are deleted. These results illustrate the detrimental consequences of interrupting highly conserved regulatory landscapes and reveal a mechanism where genomic duplications lead to partial loss of function of nearby located genes.
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