scholarly journals Mouse Models of Aneuploidy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Olivia Sheppard ◽  
Frances K. Wiseman ◽  
Aarti Ruparelia ◽  
Victor L. J. Tybulewicz ◽  
Elizabeth M. C. Fisher
Keyword(s):  
Mouse Models ◽  
Copy Number ◽  
Gene Dosage ◽  
Altered States ◽  
Cognitive Effects ◽  
Complex Phenotype ◽  
Animal System ◽  
Segmental Aneuploidy ◽  
Number Of Genes ◽  
Number Variation

Abnormalities of chromosome copy number are called aneuploidies and make up a large health load on the human population. Many aneuploidies are lethal because the resulting abnormal gene dosage is highly deleterious. Nevertheless, some whole chromosome aneuploidies can lead to live births. Alterations in the copy number of sections of chromosomes, which are also known as segmental aneuploidies, are also associated with deleterious effects. Here we examine how aneuploidy of whole chromosomes and segmental aneuploidy of chromosomal regions are modeled in the mouse. These models provide a whole animal system in which we aim to investigate the complex phenotype-genotype interactions that arise from alteration in the copy number of genes. Although our understanding of this subject is still in its infancy, already research in mouse models is highlighting possible therapies that might help alleviate the cognitive effects associated with changes in gene number. Thus, creating and studying mouse models of aneuploidy and copy number variation is important for understanding what it is to be human, in both the normal and genomically altered states.

scholarly journals Genome plasticity in Paramecium bursaria revealed by population genomics

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yu-Hsuan Cheng ◽  
Chien-Fu Jeff Liu ◽  
Yen-Hsin Yu ◽  
Yu-Ting Jhou ◽  
Masahiro Fujishima ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Population Genomics ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Paramecium Bursaria ◽  
Gene Copy ◽  
Genome Plasticity ◽  
Ciliate Species ◽  
Number Variation

Abstract Background Ciliates are an ancient and diverse eukaryotic group found in various environments. A unique feature of ciliates is their nuclear dimorphism, by which two types of nuclei, the diploid germline micronucleus (MIC) and polyploidy somatic macronucleus (MAC), are present in the same cytoplasm and serve different functions. During each sexual cycle, ciliates develop a new macronucleus in which newly fused genomes are extensively rearranged to generate functional minichromosomes. Interestingly, each ciliate species seems to have its way of processing genomes, providing a diversity of resources for studying genome plasticity and its regulation. Here, we sequenced and analyzed the macronuclear genome of different strains of Paramecium bursaria, a highly divergent species of the genus Paramecium which can stably establish endosymbioses with green algae. Results We assembled a high-quality macronuclear genome of P. bursaria and further refined genome annotation by comparing population genomic data. We identified several species-specific expansions in protein families and gene lineages that are potentially associated with endosymbiosis. Moreover, we observed an intensive chromosome breakage pattern that occurred during or shortly after sexual reproduction and contributed to highly variable gene dosage throughout the genome. However, patterns of copy number variation were highly correlated among genetically divergent strains, suggesting that copy number is adjusted by some regulatory mechanisms or natural selection. Further analysis showed that genes with low copy number variation among populations tended to function in basic cellular pathways, whereas highly variable genes were enriched in environmental response pathways. Conclusions We report programmed DNA rearrangements in the P. bursaria macronuclear genome that allow cells to adjust gene copy number globally according to individual gene functions. Our results suggest that large-scale gene copy number variation may represent an ancient mechanism for cells to adapt to different environments.

scholarly journals Phenotypic Consequences of Copy Number Variation: Insights from Smith-Magenis and Potocki-Lupski Syndrome Mouse Models

PLoS Biology ◽  
2010 ◽  
Vol 8 (11) ◽  
pp. e1000543 ◽  
Author(s):  
Guénola Ricard ◽  
Jessica Molina ◽  
Jacqueline Chrast ◽  
Wenli Gu ◽  
Nele Gheldof ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Mouse Models ◽  
Copy Number ◽  
Number Variation

scholarly journals Copy-Number Variation: The Balance between Gene Dosage and Expression in Drosophila melanogaster

2011 ◽  
Vol 3 ◽  
pp. 1014-1024 ◽  
Author(s):  
Jun Zhou ◽  
Bernardo Lemos ◽  
Erik B. Dopman ◽  
Daniel L. Hartl
Keyword(s):  
Drosophila Melanogaster ◽  
Copy Number Variation ◽  
Copy Number ◽  
Gene Dosage ◽  
Number Variation

scholarly journals Duplications at 19q13.33 in patients with neurodevelopmental disorders

2017 ◽  
Author(s):  
Eduardo Pérez-Palma ◽  
Elmo Saarentaus ◽  
Joris Andrieux ◽  
Marie Ravoet ◽  
Giancarlo V. De Ferrari ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Gene Dosage ◽  
Clinical Databases ◽  
Consensus Region ◽  
Number Variation ◽  
Reference Databases ◽  
Copy Number Changes ◽  
Future Evaluation

AbstractOBJECTIVEAfter recent publication of the first patients with disease associated missense variants in GRIN2D, we evaluate the effect of copy number variation (CNV) overlapping this gene towards the presentation of neurodevelopmental disorders.METHODSWe explored ClinVar (N°CNV = 41,398) and DECIPHER (N°CNV = 30,222) clinical databases of genomic variations for patients with copy number changes overlapping the GRIN2D gene at the 19q13.33 locus and evaluated their respective phenotype alongside their frequency, gene content and expression with publicly available reference databases.RESULTSWe identified 13 patients with microduplications at the 19q13.33 locus. The majority of CNVs arose de novo and comparable CNVs are not present in control databases. All patients were reported to have neurodevelopmental disorders and dysmorphic features as the most common clinical phenotype (N= 10/13), followed by seizures (N= 6/13) and intellectual disability (N= 5/13). All duplications shared a consensus region of 405 kb overlapping 13 genes. After screening for duplication tolerance in control populations, positive gene brain expression and gene dosage sensitivity analysis, we highlight four genes for future evaluation: CARD8, C19orf68, KDELR1 and GRIN2D, which are promising candidates for disease causality. Further, investigation of the literature especially supports GRIN2D as the best candidate gene.CONCLUSIONSOur study presents dup19q13.33 as novel duplication syndrome locus associated with neurodevelopmental disorders. CARD8, C19orf68, KDELR1 and GRIN2D are promising candidates for functional follow up.

scholarly journals Dosage compensation can buffer copy-number variation in wild yeast

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
James Hose ◽  
Chris Mun Yong ◽  
Maria Sardi ◽  
Zhishi Wang ◽  
Michael A Newton ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Gene Amplification ◽  
Dosage Compensation ◽  
Copy Number ◽  
Gene Dosage ◽  
Phenotypic Evolution ◽  
Wild Populations ◽  
Causal Gene ◽  
Wild Yeast ◽  
Number Variation

Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10–30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.

Identification of Novel Germline and Tumor-Specific Nucleotide Variants and Copy Number Variation in Clival Chordomas by Exome Sequencing

2015 ◽  
Vol 76 (S 01) ◽  
Author(s):  
Georgios Zenonos ◽  
Peter Howard ◽  
Maureen Lyons-Weiler ◽  
Wang Eric ◽  
William LaFambroise ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Exome Sequencing ◽  
Copy Number ◽  
Number Variation ◽  
Specific Nucleotide

The impact of paralog genes: detection of copy number variation in spinal muscle atrophy patients

BIOCELL ◽  
2018 ◽  
Vol 42 (3) ◽  
pp. 87-91 ◽  
Author(s):  
Sergio LAURITO ◽  
Juan A. CUETO ◽  
Jimena PEREZ ◽  
Mar韆 ROQU�
Keyword(s):  
Copy Number Variation ◽  
Muscle Atrophy ◽  
Copy Number ◽  
Number Variation ◽  
The Impact

Transcriptional profiling of iPSC-derived neurons with reciprocal monogenic CNV in 3p26.3 region

2020 ◽  
pp. 10-11
Author(s):  
М.Е. Лопаткина ◽  
В.С. Фишман ◽  
М.М. Гридина ◽  
Н.А. Скрябин ◽  
Т.В. Никитина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
System Development ◽  
Transcriptional Profiling ◽  
Global Gene Expression ◽  
Nervous System Development ◽  
Number Variation ◽  
The Central Nervous System ◽  
Cntn6 Gene ◽  
Copy Number Changes

Проведен анализ генной экспрессии в нейронах, дифференцированных из индуцированных плюрипотентных стволовых клеток пациентов с идиопатическими интеллектуальными нарушениями и реципрокными хромосомными мутациями в регионе 3p26.3, затрагивающими единственный ген CNTN6. Для нейронов с различным типом хромосомных аберраций была показана глобальная дисрегуляция генной экспрессии. В нейронах с вариациями числа копий гена CNTN6 была снижена экспрессия генов, продукты которых вовлечены в процессы развития центральной нервной системы. The gene expression analysis of iPSC-derived neurons, obtained from patients with idiopathic intellectual disability and reciprocal microdeletion and microduplication in 3p26.3 region affecting the single CNTN6 gene was performed. The global gene expression dysregulation was demonstrated for cells with CNTN6 copy number variation. Gene expression in neurons with CNTN6 copy number changes was downregulated for genes, whose products are involved in the central nervous system development.

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