scholarly journals Chemical Exposure Generates DNA Copy Number Variants and Impacts Gene Expression

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Samuel M. Peterson ◽  
Jennifer L. Freeman
Keyword(s):  
Gene Expression ◽  
Copy Number Variation ◽  
Copy Number ◽  
Copy Number Variants ◽  
Complex Diseases ◽  
Chemical Exposure ◽  
Environmental Chemicals ◽  
Comparative Genomic ◽  
Dna Copy Number ◽  
Number Variation

DNA copy number variation is long associated with highly penetrant genomic disorders, but it was not until recently that the widespread occurrence of copy number variation among phenotypically normal individuals was realized as a considerable source of genetic variation. It is also now appreciated that copy number variants (CNVs) play a role in the onset of complex diseases. Many of the complex diseases in which CNVs are associated are reported to be influenced by yet to be identified environmental factors. It is hypothesized that exposure to environmental chemicals generates CNVs and influences disease onset and pathogenesis. In this study a proof of principle experiment was completed with ethyl methanesulfonate (EMS) and cytosine arabinoside (Ara-C) to investigate the generation of CNVs using array comparative genomic hybridization (CGH) and the zebrafish vertebrate model system. Exposure to both chemicals resulted in CNVs. CNVs were detected in similar genomic regions among multiple exposure concentrations with EMS and five CNVs were common among both chemicals. Furthermore, CNVs were correlated to altered gene expression. This study suggests that chemical exposure generates CNVs with impacts on gene expression warranting further investigation of this phenomenon with environmental chemicals.

DNA Copy Number Variation and Gene Expression Analyses Reveal the Implication of Specific Oncogenes and Genes in GBM

2009 ◽  
Vol 27 (5) ◽  
pp. 541-548 ◽  
Author(s):  
Javier Margareto ◽  
Olatz Leis ◽  
Eider Larrarte ◽  
Iñigo C. Pomposo ◽  
Jesús María Garibi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number Variation ◽  
Copy Number ◽  
Dna Copy Number ◽  
Dna Copy Number Variation ◽  
Gene Expression Analyses ◽  
Number Variation

DNA copy number variation screening in familial hypercholesterolemia-related genes

2018 ◽  
Vol 275 ◽  
pp. e79
Author(s):  
M. Iacocca ◽  
J. Wang ◽  
J. Dron ◽  
H. Cao ◽  
J. Robinson ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Familial Hypercholesterolemia ◽  
Copy Number ◽  
Dna Copy Number ◽  
Dna Copy Number Variation ◽  
Number Variation

scholarly journals Insights into dispersed duplications and complex structural mutations from whole genome sequencing 706 families

2020 ◽  
Author(s):  
Christopher W. Whelan ◽  
Robert E. Handsaker ◽  
Giulio Genovese ◽  
Seva Kashin ◽  
Monkol Lek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number Variation ◽  
Copy Number ◽  
De Novo ◽  
Whole Genome ◽  
Sequencing Data ◽  
Number Variation ◽  
Structural Mutations ◽  
Or Gene ◽  
Genomic Locations

AbstractTwo intriguing forms of genome structural variation (SV) – dispersed duplications, and de novo rearrangements of complex, multi-allelic loci – have long escaped genomic analysis. We describe a new way to find and characterize such variation by utilizing identity-by-descent (IBD) relationships between siblings together with high-precision measurements of segmental copy number. Analyzing whole-genome sequence data from 706 families, we find hundreds of “IBD-discordant” (IBDD) CNVs: loci at which siblings’ CNV measurements and IBD states are mathematically inconsistent. We found that commonly-IBDD CNVs identify dispersed duplications; we mapped 95 of these common dispersed duplications to their true genomic locations through family-based linkage and population linkage disequilibrium (LD), and found several to be in strong LD with genome-wide association (GWAS) signals for common diseases or gene expression variation at their revealed genomic locations. Other CNVs that were IBDD in a single family appear to involve de novo mutations in complex and multi-allelic loci; we identified 26 de novo structural mutations that had not been previously detected in earlier analyses of the same families by diverse SV analysis methods. These included a de novo mutation of the amylase gene locus and multiple de novo mutations at chromosome 15q14. Combining these complex mutations with more-conventional CNVs, we estimate that segmental mutations larger than 1kb arise in about one per 22 human meioses. These methods are complementary to previous techniques in that they interrogate genomic regions that are home to segmental duplication, high CNV allele frequencies, and multi-allelic CNVs.Author SummaryCopy number variation is an important form of genetic variation in which individuals differ in the number of copies of segments of their genomes. Certain aspects of copy number variation have traditionally been difficult to study using short-read sequencing data. For example, standard analyses often cannot tell whether the duplicated copies of a segment are located near the original copy or are dispersed to other regions of the genome. Another aspect of copy number variation that has been difficult to study is the detection of mutations in the copy number of DNA segments passed down from parents to their children, particularly when the mutations affect genome segments which already display common copy number variation in the population. We develop an analytical approach to solving these problems when sequencing data is available for all members of families with at least two children. This method is based on determining the number of parental haplotypes the two siblings share at each location in their genome, and using that information to determine the possible inheritance patterns that might explain the copy numbers we observe in each family member. We show that dispersed duplications and mutations can be identified by looking for copy number variants that do not follow these expected inheritance patterns. We use this approach to determine the location of 95 common duplications which are dispersed to distant regions of the genome, and demonstrate that these duplications are linked to genetic variants that affect disease risk or gene expression levels. We also identify a set of copy number mutations not detected by previous analyses of sequencing data from a large cohort of families, and show that repetitive and complex regions of the genome undergo frequent mutations in copy number.

scholarly journals Copy Number Variation of Multiple Genes in SAPHO Syndrome

2019 ◽  
Vol 47 (9) ◽  
pp. 1323-1329
Author(s):  
Changlong Guo ◽  
Xin Tian ◽  
Feifei Han ◽  
Lihong Liu ◽  
Jianen Gao ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Candidate Genes ◽  
Copy Number ◽  
Nuclear Family ◽  
Sapho Syndrome ◽  
Unknown Etiology ◽  
Comparative Genomic ◽  
Number Variation ◽  
And Control ◽  
Control Samples

Objective.SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a type of rare chronic aseptic inflammation of unknown etiology. To date, no research to our knowledge has reported copy number variation (CNV) of genes that could affect predisposition to SAPHO syndrome. We investigated the association between CNV profile and SAPHO syndrome.Methods.We used array comparative genomic hybridization (CGH) to screen for CNV in a nuclear family including 2 patients and a healthy control. We then validated the copy numbers of candidate genes found in the array CGH assay and other candidate genes by TaqMan real-time PCR in 360 case and control samples.Results.Ten regions from 8 chromosomes were found to have abnormal gene copies in the nuclear family, so the CNV of candidate genes (ADAM5, CSF2RA, IL3RA, and 9 other genes) were tested by TaqMan PCR. Significant copy number loss of CSF2RA (p = 0.000) and NOD2 (p = 0.005), and significant copy number gain of MEGF6 (p = 0.002) and ADAM5 (p = 0.000) were seen in patients with SAPHO compared with controls at the a = 0.05 level. There were no differences in the other 8 candidate genes between patient and control samples (p > 0.05).Conclusion.Our study established the first association between CNV in CSF2RA, NOD2, MEGF6, and ADAM5 and SAPHO syndrome. These findings may offer insight into the pathogenesis of SAPHO and provide the basis for improved diagnosis and treatment.

Copy number variation, gene expression and histological localization of human beta-defensin 2 in patients with adeno-tonsillar hypertrophy

2020 ◽  
Vol 95 (8) ◽  
pp. 634-640
Author(s):  
Fulvio Celsi ◽  
Luisa Zupin ◽  
Emmanouil Athanasakis ◽  
Eva Orzan ◽  
Domenico Leonardo Grasso ◽  
...  
Keyword(s):  
Gene Expression ◽  
Copy Number Variation ◽  
Copy Number ◽  
Tonsillar Hypertrophy ◽  
Number Variation
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