A model for the impact of FFPE section thickness on gene copy number measurement by FISH

AbstractStudies assessing the impact of amylase genes copy number (CN) on adiposity report conflicting findings in different global populations, likely reflecting the impact of ancestral and ethnic-specific environment and lifestyle on selection at the amylase loci. Here, we leverage population size and detailed adiposity measures from a large population biobank to resolve confounding effects and determine the relationship between salivary (AMY1) and pancreatic (AMY2A) amylase genes CN and adiposity in 2935 Qatari individuals who underwent whole-genome sequencing (WGS) as part of the Qatar Genome Programme. We observe a negative association between AMY1 CNs and trunk fat percentage in the Qatari population (P = 7.50 × 10−3) and show that Qataris of Arab descent have significantly lower CN at AMY1 (P = 1.32 × 10−10) as well as less favorable adiposity and metabolic profiles (P < 1.34 × 10−8) than Qataris with Persian ancestry. Indeed, lower AMY1 CN was associated with increased total and trunk fat percentages in Arabs (P < 4.60 × 10−3) but not in Persians. Notably, overweight and obese Persians reported a significant trend towards dietary restraint following weight gain compared to Arabs (P = 4.29 × 10−5), with AMY1 CN showing negative association with dietary self-restraint (P = 3.22 × 10−3). This study reports an association between amylase gene CN and adiposity traits in a large Middle Eastern population. Importantly, we leverage rich biobank data to demonstrate that the strength of this association varies with ethnicity, and may be influenced by population-specific behaviors that also contribute to adiposity traits.

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The impact of CUP1 gene copy-number and XVI-VIII/XV-XVI translocations on copper and sulfite tolerance in vineyard Saccharomyces cerevisiae strain populations

FEMS Yeast Research ◽

10.1093/femsyr/foaa028 ◽

2020 ◽

Vol 20 (4) ◽

Author(s):

Giulia Crosato ◽

Chiara Nadai ◽

Milena Carlot ◽

Juliano Garavaglia ◽

Denise Righetto Ziegler ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Copy Number ◽

Gene Copy Number ◽

Copper Tolerance ◽

Gene Copy ◽

Wine Yeasts ◽

Gene Encoding ◽

Wine Production ◽

Cup1 Gene ◽

The Impact

ABSTRACT In wine production, sulfites are widely used as antimicrobials and antioxidants, whereas copper is associated with fungicides and wine fining treatments. Therefore, wine yeasts are constantly exposed to these agents. Copper tolerance is related to the copy number of the CUP1 gene, encoding for a metallothionein involved in copper detoxification. In wine yeasts, sulfite resistance mainly depends on the presence of the translocation t(XVI;VIII) in the promoter region of the SSU1 gene. This gene encodes for a plasma membrane sulfite pump involved in sulfite metabolism and detoxification. Recently, a new translocation, t(XVI;VIII), was identified. In this work, 253 Saccharomyces cerevisiae strains, representing three vineyard populations from two different continents, were analyzed, along with 20 industrial starters. Copper and sulfites tolerance as well as distribution of CUP1 gene copy-number, t(XVI;VIII)and t(XVI;XV) of SSU1 gene were studied to evaluate the impact of these genomic variations on population phenotypes. The CUP1 gene copy-number was found to be highly variable, ranging from zero to 79 per strain. Moreover it differently impacted the copper tolerance in the populations of the two continents. The diffusion of t(XVI;VIII) and, for the first time, t(XVI;XV) was determined in the three vineyard populations. The correlation between the presence of the translocation and strain sulfite tolerance levels was significant only for the t(XVI;VIII).

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The Impact of Pharmacogenomics on Postoperative Nausea and Vomiting

Anesthesiology ◽

10.1097/00000542-200503000-00011 ◽

2005 ◽

Vol 102 (3) ◽

pp. 543-549 ◽

Cited By ~ 126

Author(s):

Keith A. Candiotti ◽

David J. Birnbach ◽

David A. Lubarsky ◽

Fani Nhuch ◽

Aimee Kamat ◽

...

Keyword(s):

Postoperative Nausea ◽

Copy Number ◽

Polymerase Chain Reaction Amplification ◽

Gene Copy Number ◽

Postoperative Nausea And Vomiting ◽

Nausea And Vomiting ◽

Gene Copy ◽

Cyp2d6 Gene ◽

Ultrarapid Metabolizers ◽

The Impact

Background Some patients treated with ondansetron for postoperative nausea and vomiting do not respond to therapy. One possible mechanism for this failure is ultrarapid drug metabolism via the cytochrome P-450 system, specifically the enzyme 2D6 (CYP2D6). Ultrarapid metabolism is seen in patients with multiple functional copies (>/= 3) of the CYP2D6 allele. This study was designed to determine whether patients who were given prophylactic ondansetron and had multiple CYP2D6 alleles had an increased rate of postoperative nausea and vomiting. Methods Two hundred fifty female patients undergoing standardized general anesthesia were given 4 mg ondansetron 30 min before extubation. Patients were observed for symptoms of nausea and vomiting. DNA was extracted from blood in all patients and was analyzed by using a gene-specific probe to determine the CYP2D6 gene copy number and genotyped by polymerase chain reaction amplification with a custom oligonucleotide microarray to determine the specific CYP2D6 genotypes. Results Eighty-eight patients experienced nausea, and 37 of those patients also had vomiting. In patients with one, two, or three CYP2D6 copies, the incidences of vomiting were 3 in 33 (27%), 27 in 198 (14%), and 7 in 23 (30%), respectively. The incidence of vomiting in subjects with three CYP2D6 copies was significantly different from those with two copies, but not from those with one copy. When analyzed by genotype, the incidences of vomiting in poor, intermediate, extensive, and ultrarapid metabolizers were 1 in 12 (8%), 5 in 30 (17%), 26 in 176 (15%), and 5 in 11 (45%), respectively (P < 0.01 vs. all other groups). There were no differences between groups in the incidence of nausea based on CYP2D6 copy number or genotype. Conclusions Patients with three copies of the CYP2D6 gene, a genotype consistent with ultrarapid metabolism, or both have an increased incidence of ondansetron failure for the prevention of postoperative vomiting but not nausea.

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Assessment of HER-2/neu, с-MYC and CCNE1 gene copy number variations and protein expression in endometrial carcinomas

Experimental Oncology ◽

10.32471/exp-oncology.2312-8852.vol-41-no-2.12973 ◽

2019 ◽

Vol 41 (2) ◽

Author(s):

L.G. Buchynska ◽

◽

O.V. Brieieva* ◽

N.P. Iurchenko ◽

◽

...

Keyword(s):

Protein Expression ◽

Copy Number ◽

Gene Copy Number ◽

Copy Number Variations ◽

Gene Copy ◽

Her 2 ◽

Endometrial Carcinomas

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Faculty Opinions recommendation of Diet and the evolution of human amylase gene copy number variation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1092307.546722 ◽

2007 ◽

Author(s):

Magnus Ingelman-Sundberg

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Amylase Gene ◽

Gene Copy Number Variation ◽

Number Variation

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Faculty Opinions recommendation of RNA polymerase I activators count and adjust ribosomal RNA gene copy number.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734776122.793556076 ◽

2019 ◽

Author(s):

Angela Taddei

Keyword(s):

Rna Polymerase ◽

Ribosomal Rna ◽

Copy Number ◽

Gene Copy Number ◽

Rna Polymerase I ◽

Gene Copy ◽

Ribosomal Rna Gene ◽

Polymerase I

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Estimating Copy-Number Proportions: The Comeback of Sanger Sequencing

Genes ◽

10.3390/genes12020283 ◽

2021 ◽

Vol 12 (2) ◽

pp. 283

Author(s):

Eyal Seroussi

Keyword(s):

Copy Number ◽

Sanger Sequencing ◽

Cytosine Methylation ◽

Direct Sequencing ◽

Information Source ◽

Gene Copy Number ◽

Cost Effective ◽

Gene Copy ◽

Base Editing ◽

Recent Developments

Determination of the relative copy numbers of mixed molecular species in nucleic acid samples is often the objective of biological experiments, including Single-Nucleotide Polymorphism (SNP), indel and gene copy-number characterization, and quantification of CRISPR-Cas9 base editing, cytosine methylation, and RNA editing. Standard dye-terminator chromatograms are a widely accessible, cost-effective information source from which copy-number proportions can be inferred. However, the rate of incorporation of dye terminators is dependent on the dye type, the adjacent sequence string, and the secondary structure of the sequenced strand. These variable rates complicate inferences and have driven scientists to resort to complex and costly quantification methods. Because these complex methods introduce their own biases, researchers are rethinking whether rectifying distortions in sequencing trace files and using direct sequencing for quantification will enable comparable accurate assessment. Indeed, recent developments in software tools (e.g., TIDE, ICE, EditR, BEEP and BEAT) indicate that quantification based on direct Sanger sequencing is gaining in scientific acceptance. This commentary reviews the common obstacles in quantification and the latest insights and developments relevant to estimating copy-number proportions based on direct Sanger sequencing, concluding that bidirectional sequencing and sophisticated base calling are the keys to identifying and avoiding sequence distortions.

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Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

Scientific Reports ◽

10.1038/s41598-021-86120-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raimonda Kubiliute ◽

Indre Januskeviciene ◽

Ruta Urbanaviciute ◽

Kristina Daniunaite ◽

Monika Drobniene ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Protein Level ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Common Mechanism ◽

Dna Hypomethylation ◽

Mesenchymal Transition ◽

Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

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