03274nas a2200469   4500008004100000022001400041245010000055210006900155260001600224520184400240653001202084653000802096653001802104653002402122653001902146653000802165100002102173700001902194700001702213700002402230700002302254700002902277700002302306700002302329700002102352700001902373700002202392700003302414700002302447700001602470700002602486700002802512700002002540700002002560700002702580700002002607700002702627700001902654700002702673700002502700856007902725       2016                        eng d  a1537-171900a267 Spanish exomes reveal population-specific differences in disease-related genetic variation.0 a267 Spanish exomes reveal populationspecific differences in dise  c2016 Jan 133 aRecent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalogue of local variability motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including about 10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies in order to distinguish real disease associations from population-specific polymorphisms.10adisease10aNGS10apolymorphisms10aPopulation genomics10aprioritization10aSNP1 aDopazo, Joaquín1 aAmadoz, Alicia1 aBleda, Marta1 aGarcía-Alonso, Luz1 aAlemán, Alejandro1 aGarcia-Garcia, Francisco1 aRodriguez, Juan, A1 aDaub, Josephine, T1 aMuntané, Gerard1 aRueda, Antonio1 aVela-Boza, Alicia1 aLópez-Domingo, Francisco, J1 aFlorido, Javier, P1 aArce, Pablo1 aRuiz-Ferrer, Macarena1 aMéndez-Vidal, Cristina1 aArnold, Todd, E1 aSpleiss, Olivia1 aAlvarez-Tejado, Miguel1 aNavarro, Arcadi1 aBhattacharya, Shomi, S1 aBorrego, Salud1 aSantoyo-López, Javier1 aAntiňolo, Guillermo  uhttps://mbe.oxfordjournals.org/content/early/2016/02/17/molbev.msw005.full01715nas a2200265   4500008004100000245014300041210006900184300001300253490000700266520085600273653001501129653001301144653001101157653002701168653000801195100002001203700002001223700002101243700002601264700002101290700002301311700002401334700002001358856007101378       2009                        eng d00aGene set-based analysis of polymorphisms: finding pathways or biological processes associated to traits in genome-wide association studies0 aGene setbased analysis of polymorphisms finding pathways or biol  aW340-3440 v373 a<p>Genome-wide association studies have become a popular strategy to find associations of genes to traits of interest. Despite the high-resolution available today to carry out genotyping studies, the success of its application in real studies has been limited by the testing strategy used. As an alternative to brute force solutions involving the use of very large cohorts, we propose the use of the Gene Set Analysis (GSA), a different analysis strategy based on testing the association of modules of functionally related genes. We show here how the Gene Set-based Analysis of Polymorphisms (GeSBAP), which is a simple implementation of the GSA strategy for the analysis of genome-wide association studies, provides a significant increase in the power testing for this type of studies. GeSBAP is freely available at http://bioinfo.cipf.es/gesbap/</p>10ababelomics10agene set10aGESBAP10apathway-based analysis10aSNP1 aMedina, Ignacio1 aMontaner, David1 aBonifaci, Núria1 aPujana, Miguel, Angel1 aCarbonell, José1 aTárraga, Joaquín1 aAl-Shahrour, Fatima1 aDopazo, Joaquin  uhttp://nar.oxfordjournals.org/cgi/content/abstract/37/suppl_2/W34002872nas a2200241   4500008004100000245013000041210006900171300000700240490000600247520211000253653001302363653000902376653000802385100001702393700001802410700001302428700001402441700002002455700001502475700001502490700001902505856010602524       2008                        eng d00aBiological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes0 aBiological processes properties and molecular wiring diagrams of  a620 v13 a<p>ABSTRACT: BACKGROUND: Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. METHODS: We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. RESULTS: First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the &quot;omic&quot; properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes after BRCA1 perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk. CONCLUSION: This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional effects of candidate genes and proteins.</p>10agene set10aGWAS10aSNP1 aBonifaci, N.1 aBerenguer, A.1 aDiez, J.1 aReina, O.1 aMedina, Ignacio1 aDopazo, J.1 aMoreno, V.1 aPujana, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19094230