An evolving view of copy number variants

Lauer, Stephanie; Gresham, David

doi:10.1007/s00294-019-00980-0

Cited by 100 publications

(86 citation statements)

References 104 publications

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“…Transposable elements are not the only destabilizers in genomes. Deletions and duplications, collectively termed copy number variations (CNVs), may total 5%-9% of the human genome [92,93] . Genomes of vertebrate animals are similar to those in humans; a recent report identified 3538 CNV regions in the porcine genome [94] .…”

Section: Concerns Of Plasmid and Prokaryotic Dna Sequence Contaminationmentioning

confidence: 99%

Regulatory issues for genetically modified animals

Hackett

2020

Front. Agr. Sci. Eng.

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Precision genetics and breeding have the potential to meet the agricultural needs and goals of the world in the 21st century. These needs include increasing the efficiency of production of animals and improving their products with minimal impact on the environment. The USA is the major innovator in genomic science and the acknowledged leader in formulating policies to regulate genetic applications in medicine and agriculture. However, governments worldwide have been exceedingly reluctant to support the introduction of genetically modified (GM) animals into agriculture. Regulatory policies have stagnated due to legal guidelines that could not anticipate the needs and solutions that are evident today. This must change if we are to maintain planetary integrity. I propose a new, market-based regulatory model for GM livestock that has both a strong scientific foundation and has worked for 10000 years. The model is similar to that for information technology in which specific algorithms drive computer and cell phone applications. Genome engineers write genetic algorithms that drive the traits in biological organisms. Accordingly, GM products should be viewed in terms of their use and public benefit rather than by limitations to the genetic programing coming from a few highly vocal groups. Genetic algorithms (Genapps) of the 21st century will include not only introduction of synthetic genes, but also complete natural and synthetic biochemical pathways to produce agricultural products that are maximally efficient, healthy to humans and animals, and sustainable in an era of changing climates while avoiding environmental degradation.

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Section: Concerns Of Plasmid and Prokaryotic Dna Sequence Contaminationmentioning

confidence: 99%

Regulatory issues for genetically modified animals

Hackett

2020

Front. Agr. Sci. Eng.

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“…By identifying and studying causal genetic variants, important insights into beneficial mutations have been gained, such as their occurrence frequency, the complexity of their molecular basis, the role of contingency and genetic background into their effect, and their fitness effects in specific environments. A number of studies have demonstrated that genomic rearrangements can spread in these populations due to the actions of positive selection [28,29,[39][40][41][42][43][44]. In some of these experiments, gene duplicates are thought to facilitate the metabolism or transport of a limiting nutrient due to increased protein product responsible for a rate-limiting step of metabolism.…”

Section: Introductionmentioning

confidence: 99%

A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans

et al. 2020

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Over long evolutionary timescales, major changes to the copy number, function, and genomic organization of genes occur, however, our understanding of the individual mutational events responsible for these changes is lacking. In this report, we study the genetic basis of adaptation of two strains of C. elegans to laboratory food sources using competition experiments on a panel of 89 recombinant inbred lines (RIL). Unexpectedly, we identified a single RIL with higher relative fitness than either of the parental strains. This strain also displayed a novel behavioral phenotype, resulting in higher propensity to explore bacterial lawns. Using bulk-segregant analysis and short-read resequencing of this RIL, we mapped the change in exploration behavior to a spontaneous, complex rearrangement of the rcan-1 gene that occurred during construction of the RIL panel. We resolved this rearrangement into five unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1 calcipressin gene, which has been implicated as a causal gene for Down syndrome. The genomic rearrangement in rcan-1 creates two complete and two truncated versions of the rcan-1 coding region, with a variety of modified 5' and 3' non-coding regions. While most copy-number variations (CNVs) are thought to act by increasing expression of duplicated genes, these changes to rcan-1 ultimately result in the reduction of its whole-body expression due to changes in the upstream regions. By backcrossing this rearrangement into a common genetic background to create a near isogenic line (NIL), we demonstrate that both the competitive advantage and exploration behavioral changes are linked to this complex genetic variant. This NIL strain does not phenocopy a strain containing an rcan-1 loss-of-function allele, which suggests that the residual expression of rcan-1 is necessary for its fitness effects. Our results demonstrate how colonization of new environments, such as those encountered in the laboratory, can create a1111111111 a1111111111 a1111111111 a1111111111 a1111111111

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“…It is a type of structural variation that is larger than 50bp, and involves unbalanced rearrangements that result in gains or losses of DNA content [4]. CNV drives genome evolution and alters the expressions of genes [5], which in uence the progress of diseases such as cancers [6]. For example, in acute lymphoblastic leukemia (ALL) IKZF CNV was identi ed as a poor prognosis marker [7].…”

Section: Introductionmentioning

confidence: 99%

Identification of Prognostic Signature Based on the Copy Number Variation (CNV) and Expression in Acute Myeloid Leukemia

Niu¹,

Wu²,

Li³

et al. 2020

Preprint

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Purpose Acute myeloid leukemia (AML) is caused by multiple genetic alterations in the hematopoietic progenitors, and molecular genetic analysis has provided useful information for AML diagnosis and prognosis. However, an integrative understanding about the prognosis value of specific copy number variation (CNV) and CNV-modulated gene expression has been limited. Methods We conducted an integrative analysis of CNV profiling and gene expression using data from the TARGET and TCGA AML cohorts. The CNV data from TCGA were analyzed using the GISTIC. CNV survival analysis and mRNA survival analysis were conducted with the Multivariate Cox proportional hazards regression model using R software with “survminer” and “survival” packages. KEGG cancer panel genes were extracted from the cancer related pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG). The R package “circlize” was used for mapping the CNV genes to chromosomes. Results From this investigation, we observed distinct CNV patterns in the AML risk groups as well as the expression of 251 genes significantly modulated by CNV in both cohorts. There were 102 CNV genes (located at 7q31-34, 16q24) associated with clinical outcomes in AML, which were identified in the TARGET cohort and validated in the TCGA cohort, three of which being miRNA genes (MIR29A, MIR183, MIR335) that overlapped with a KEGG cancer panel. Five genes were identified whose expressions were modulated by CNV and significantly associated with clinical outcomes, and among them, the deletion of SEMA4D and CBFB were found to potentially have protective effects against AML. Moreover, the distribution of CNV in these five CNV-modulated genes was independent of the risk groups, which suggests that they are independent prognosis factors. Conclusion Overall, this study identified 102 CNV genes and five CNV-modulated gene expressions that are crucial for developing new modes of prognosis evaluation and target therapy for AML.

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An evolving view of copy number variants

Cited by 100 publications

References 104 publications

Regulatory issues for genetically modified animals

Regulatory issues for genetically modified animals

A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans

Identification of Prognostic Signature Based on the Copy Number Variation (CNV) and Expression in Acute Myeloid Leukemia

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