03226nas a2200433   4500008004100000245012400041210006900165300001100234490000700245520156900252653002601821653003101847653001201878653013601890653023502026653003902261100002202300700002202322700001802344700001702362700001602379700001402395700001502409700001902424700001402443700001602457700002402473700002302497700002302520700001802543700001602561700002302577700001602600700002002616700001502636700001902651700001602670856010602686       2007                        eng d00aAssociation study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma0 aAssociation study of 69 genes in the ret pathway identifies lowp  a9561-70 v673 aTo date, few association studies have been done to better understand the genetic basis for the development of sporadic medullary thyroid carcinoma (sMTC). To identify additional low-penetrance genes, we have done a two-stage case-control study in two European populations using high-throughput genotyping. We selected 417 single nucleotide polymorphisms (SNP) belonging to 69 genes either related to RET signaling pathway/functions or involved in key processes for cancer development. TagSNPs and functional variants were included where possible. These SNPs were initially studied in the largest known series of sMTC cases (n = 266) and controls (n = 422), all of Spanish origin. In stage II, an independent British series of 155 sMTC patients and 531 controls was included to validate the previous results. Associations were assessed by an exhaustive analysis of individual SNPs but also considering gene- and linkage disequilibrium-based haplotypes. This strategy allowed us to identify seven low-penetrance genes, six of them (STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. The potential role of CDKN2B was confirmed by a functional assay showing a role of a SNP (rs7044859) in the promoter region in altering the binding of the transcription factor HNF1. These results highlight the utility of association studies using homogeneous series of cases for better understanding complex diseases.10a80 and over Carcinoma10aAdolescent Adult Aged Aged10aGenetic10aGenetic Proto-Oncogene Proteins c-ret/*genetics/metabolism Signal Transduction Thyroid Neoplasms/*genetics/metabolism Transcription10aMedullary/*genetics/metabolism Case-Control Studies Cyclin-Dependent Kinase Inhibitor p15/biosynthesis/genetics Female Genetic Predisposition to Disease Germ-Line Mutation Haplotypes Humans Male Middle Aged Penetrance Polymorphism10aSingle Nucleotide Promoter Regions1 aRuiz-Llorente, S.1 aMontero-Conde, C.1 aMilne, R., L.1 aMoya, C., M.1 aCebrian, A.1 aLeton, R.1 aCascon, A.1 aMercadillo, F.1 aLanda, I.1 aBorrego, S.1 ade Nanclares, Perez1 aAlvarez-Escola, C.1 aDiaz-Perez, J., A.1 aCarracedo, A.1 aUrioste, M.1 aGonzalez-Neira, A.1 aBenitez, J.1 aSantisteban, P.1 aDopazo, J.1 aPonder, B., A.1 aRobledo, M.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1790906702164nas a2200229   4500008004100000245009400041210006900135300001100204490000700215520128900222653008201511653001201593653009301605100001401698700002301712700001601735700002401751700002201775700001601797700001501813856010601828       2004                        eng d00aPupaSNP Finder: a web tool for finding SNPs with putative effect at transcriptional level0 aPupaSNP Finder a web tool for finding SNPs with putative effect   aW242-80 v323 aWe have developed a web tool, PupaSNP Finder (PupaSNP for short), for high-throughput searching for single nucleotide polymorphisms (SNPs) with potential phenotypic effect. PupaSNP takes as its input lists of genes (or generates them from chromosomal coordinates) and retrieves SNPs that could affect the conserved regions that the cellular machinery uses for the correct processing of genes (intron/exon boundaries or exonic splicing enhancers), predicted transcription factor binding sites (TFBS) and changes in amino acids in the proteins. The program uses the mapping of SNPs in the genome provided by Ensembl. Additionally, user-defined SNPs (not yet mapped in the genome) can be easily provided to the program. Also, additional functional information from Gene Ontology, OMIM and homologies in other model organisms is provided. In contrast to other programs already available, which focus only on SNPs with possible effect in the protein, PupaSNP includes SNPs with possible transcriptional effect. PupaSNP will be of significant help in studies of multifactorial disorders, where the use of functional SNPs will increase the sensitivity of identification of the genes responsible for the disease. The PupaSNP web interface is accessible through http://pupasnp.bioinfo.cnio.es.10aAmino Acid Substitution Binding Sites Humans Internet Phenotype *Polymorphism10aGenetic10aSingle Nucleotide RNA Splicing *Software Transcription Factors/metabolism *Transcription1 aConde, L.1 aVaquerizas, J., M.1 aSantoyo, J.1 aAl-Shahrour, Fatima1 aRuiz-Llorente, S.1 aRobledo, M.1 aDopazo, J.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15215388