Ensembl 2012

Flicek, Paul; Amode, M Ridwan; Barrell, Daniel; Beal, Kathryn; Brent, Simon; Carvalho-Silva, Denise; Clapham, Peter; Coates, Guy; Fairley, Susan; Fitzgerald, Stephen; Gil, Laurent; Gordon, Leo I.; Hendrix, Maurice; Hourlier, Thibaut; Johnson, Nathan; Kähäri, Andreas; Keefe, Damian; Keenan, Stephen; Kinsella, Rhoda; Komorowska, Monika; Koscielny, Gautier; Kulesha, Eugene; Larsson, Pontus; Longden, Ian; McLaren, William; Muffato, Matthieu; Overduin, Bert; Pignatelli, Miguel; Pritchard, Bethan; Riat, Harpreet Singh; Ritchie, Graham R. S.; Ruffier, Magali; Schuster, Michael; Sobral, Daniel; Tang, Y. Amy; Taylor, Kieron; Trevanion, Stephen J.; Vandrovcová, Jana; White, Simon; Wilson, Mark; Wilder, Steven P.; Aken, Bronwen; Birney, Ewan; Cunningham, Fiona; Dunham, Ian; Durbin, Richard; Fernández‐Suárez, Xosé M.; Harrow, Jennifer; Herrero, Javier; Hubbard, Tim; Parker, Anne; Proctor, G; Spudich, Giulietta; Vogel, Jan; Yates, Andy; Zadissa, Amonida; Searle, Stephen M. J.

doi:10.1093/nar/gkr991

Cited by 856 publications

(810 citation statements)

References 45 publications

(53 reference statements)

Supporting

Mentioning

804

Contrasting

Unclassified

Order By: Relevance

“…The PDE5A:E90K polymorphism also changes the amino acid within a highly conserved region of the PDE5A gene across species (Table 2). Mutation Taster evaluation predicted this alteration to be damaging with an excellent probability score (0.9635/1.0) 20, 21. Additionally, Mutation Taster predictions find this amino acid substitution to result in splice site changes and possibly to alter the protein features 20, 21.…”

Section: Resultsmentioning

confidence: 98%

“…If amino acid changes were observed, their relevance was evaluated with the PolyPhen‐2 program (http://genetics.bwh.harvard.edu/pph2/) to predict possible functional significance and determine the conservation of this protein region across species 19. Additionally, functional relevance was predicted by use of the Mutation Ttaster program (www.mutationtaster.org), which reports likelihood of a mutation to cause disease, predicts functional consequences and scores the prediction for accuracy using a Bayes classifier 20, 21…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Stern

Reina-Doreste

Chdid

et al. 2013

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundCyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs.Hypothesis/ObjectiveFunctional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance.AnimalsSeventy healthy dogs.MethodsThe exonic, splice‐site, 3′ and 5′ untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t‐test and one‐way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP.ResultsA common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3′ untranslated region were identified that did not alter cGMP concentrations.Conclusions and Clinical ImportanceA polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Stern

Reina-Doreste

Chdid

et al. 2013

Veterinary Internal Medicne

View full text Add to dashboard Cite

show abstract

“…Circadian transcripts from Hughes et al 16 were identified after fitting of the array data to a cosine-model with a Bonferroni-corrected P value <0.05, a minimal magnitude of six and a minimal amplitude of 0.5. E-box motifs from Rey et al 17 were used to calculate the TRAP scores 66 genome wide for all promoter regions from −1,000 to 1,000 bp relative to the potential transcription start site 67 . The maximum number of background sets was randomly sampled without replacement in the same sizes as the foreground sets (genes in clusters), and the scores were tested for higher values in the foreground sets with single-sided Wilcoxon rank-sum tests.…”

Section: Microarray Experimentsmentioning

confidence: 99%

Reciprocal regulation of carbon monoxide metabolism and the circadian clock

Klemz

Reischl

Wallach

et al. 2016

Nat Struct Mol Biol

View full text Add to dashboard Cite

“…To assay lncRNA expression, the mRNA expression profile was repurposed by probe level re‐annotation (Du et al ., 2013). The probe sequences provided by Affymetrix (http://www.affymetrix.com/) were aligned to the lncRNA transcript sequences derived from the Ensembl database (Homo sapiens GRCh37, release 67) (Flicek et al ., 2012) and Cabili et al . (2011) and to protein‐coding and pseudogene transcript sequences derived from the Ensembl (Flicek et al ., 2012) and UCSC (Kuhn et al ., 2013) databases.…”

Section: Methodsmentioning

confidence: 94%

Inferences of individual drug responses across diverse cancer types using a novel competing endogenous RNA network

Zhang

Zhou

et al. 2018

Molecular Oncology

View full text Add to dashboard Cite

Differences in individual drug responses are an obstacle to progression in cancer treatment, and predicting responses would help to plan treatment. The accumulation of cancer molecular profiling and drug response data provides opportunities and challenges to identify novel molecular signatures and mechanisms of tumor responsiveness to drugs. This study evaluated drug responses with a competing endogenous RNA (ceRNA) system that depended on competition between diverse RNA species. We identified drug response‐related ceRNA (DRCEs) by combining the sequence and expression data of long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA), and the survival data of cancer patients treated with drugs. We constructed a patient–drug two‐layer integrated network and used a linear weighting method to predict individual drug responses. DRCEs were found to be significantly enriched in known cancer and drug‐associated data resources, involved in biological processes known to mediate drug responses, and correlated to drug activity in cancer cell lines. The dysregulation of DRCE expression influenced drug response‐associated functions and pathways, suggesting DRCEs as potential therapeutic targets affecting drug responses. A further case study in breast invasive carcinoma (BRCA) found that DRCE expression was consistent with the drug response pattern and the aberrant expression of the two NEAT1‐related DRCEs may lead to poor response to tamoxifen therapy for patients with TP53 mutations. In summary, this study provides a framework for ceRNA‐based evaluation of clinical drug responses across multiple cancer types. Understanding the underlying molecular mechanisms of drug responses will allow improved response to chemotherapy and outcomes of cancer treatment.

show abstract

Ensembl 2012

Cited by 856 publications

References 45 publications

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs

Reciprocal regulation of carbon monoxide metabolism and the circadian clock

Inferences of individual drug responses across diverse cancer types using a novel competing endogenous RNA network

Contact Info

Product

Resources

About