PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes

Conde, Lucía; Vaquerizas, Juan M.; Dopazo, Hernán; Arbiza, Leonardo; Reumers, Joke; Rousseau, Frédéric; Schymkowitz, Joost; Dopazo, Joaquín

doi:10.1093/nar/gkl071

Cited by 195 publications

(149 citation statements)

References 32 publications

(55 reference statements)

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“…The programme PMut (Ferrer-Costa et al, 2005) predicted that the rare allele (coding for leucine), with a score of 3/10 had a 'pathological significance' and was classed as 'damaging' using the SIFT programme (Cheng et al, 2006). The bioinformatics tool, PupaSNP (http://pupasuite.bioinfo.cipf.es/) (Conde et al, 2006;Reumers et al, 2008), also suggested that this allele may disrupt the binding of exonic splicing enhancers. In addition, PupaSNP indicated that rs11683487 and rs11730 may have transcription and translation regulatory functions, and that rs11730 may affect exon splicing.…”

Section: Discussionmentioning

confidence: 99%

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer

et al. 2009

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Low -moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in B1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P dominant ¼ 0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case -control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80 -0.99) and remained statistically significant (P dominant ¼ 0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P global ¼ 0.034) and a haplotype in BRAF that had a protective effect (P global ¼ 0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC.

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Section: Discussionmentioning

confidence: 99%

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer

et al. 2009

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“…However, Yu et al (2004) suppose the rs2298383 Intron 1a polymorphism to be located in one of the potential promoter regions upstream of several newly identified ADORA2A exon 1 variants (at position 21521648 of chromosome 22, UCSC, Nov. 2002 freeze). In silico analysis using the online tool PupaSuite (Conde et al, 2006) has revealed the location of the rs2298383 Intron 1a polymorphism within a triplex-forming oligonucleotide target. This position is potentially functionally relevant since these sequences are described to regulate gene expression (Goni et al, 2004).…”

Section: Gene Polymorphisms and Caffeine Anxiety E Childs Et Almentioning

confidence: 99%

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

Childs

Hohoff

Deckert

et al. 2008

Neuropsychopharmacol

210

170

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Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A 1 and A 2A receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A 2A (ADORA2A) and DRD 2 (DRD2) receptors. Healthy male and female individuals (n ¼ 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety (Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3 0 -flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.

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“…15 The top GWAS and immunochip SNPs (overall and specific for the CEGEC cohort) were genotyped in biopsy donors using commercially available TaqMan allelic discrimination assays (rs802734, rs72975916, rs10484718 and rs9491896, a proxy for rs9402010) or a custom assay designed using Primer Express Software for rs55743914 (forward primer: 5 0 -ACCCACAGATATCTCT CGTTAGAAGTAA-3 0 , reverse primer: 5 0 -GGCTCGTAAAGTCAGAACATAG CTT-3 0 , probes: 5 0 -FAM-TCTGCATACAGTTTCACCTA-MGB-3 0 and 5 0 -VIC-CATACAGCTTCACCTAGA-MGB-3 0 ) in an 7900HT Real-Time PCR sequence detection system (all from Applied Biosystems). The putative effects of the genotyped SNPs on predicted splicing sites and microRNA or transcription factor-binding sites were analyzed with the online tool PupaSuite (http:// pupasuite.bioinfo.cipf.es) 16 and in the Haploreg web site (http://www. broadinstitute.org/mammals/haploreg/haploreg.php).…”

Section: Association Analysis Snp Selection and Genotyping Assaysmentioning

confidence: 99%

THEMIS and PTPRK in celiac intestinal mucosa: coexpression in disease and after in vitro gliadin challenge

et al. 2013

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Celiac disease (CD) is an immune mediated, polygenic disorder, where HLA-DQ2/DQ8 alleles contribute around 35% to genetic risk, but several other genes are also involved. Genome-wide association studies (GWASs) and the more recent immunochip genotyping projects have fine-mapped 39 regions of genetic susceptibility to the disease, most of which harbor candidate genes that could participate in this disease process. We focused our attention to the GWAS peak on chr6: 127.99-128.38 Mb, a region including two genes, thymocyte-expressed molecule involved in selection (THEMIS) and protein tyrosine phosphatase, receptor type, kappa (PTPRK), both of which have immune-related functions. The aim of this work was to evaluate the expression levels of these two genes in duodenal mucosa of active and treated CD patients and in controls, and to determine whether SNPs (rs802734, rs55743914, rs72975916, rs10484718 and rs9491896) associated with CD have any influence on gene expression. THEMIS showed higher expression in active CD compared with treated patients and controls, whereas PTPRK showed lower expression. Our study confirmed the association of this region with CD in our population, but only the genotype of rs802734 showed some influence in the expression of THEMIS. On the other hand, we found a significant positive correlation between THEMIS and PTPRK mRNA levels in CD patients but not in controls. Our results suggest a possible role for both candidate genes in CD pathogenesis and the existence of complex, regulatory relationships that reside in the vast non-coding, functional intergenic regions of the genome. Further investigation is needed to clarify the impact of the disease-associated SNPs on gene function.

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PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes

Cited by 195 publications

References 32 publications

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer

Association between ADORA2A and DRD2 Polymorphisms and Caffeine-Induced Anxiety

THEMIS and PTPRK in celiac intestinal mucosa: coexpression in disease and after in vitro gliadin challenge

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