A calcareous nannofossil and organic geochemical study of marine palaeoenvironmental changes across the Sinemurian/Pliensbachian (early Jurassic, ~191Ma) in Portugal

The Sinemurian/Pliensbachian boundary (~ 191 Ma) is acknowledged as one of the most important steps in the radiation of planktonic organisms, especially primary producers such as dinoflagellates and coccolithophores. To date, there is no detailed study documenting changes in planktonic assemblages related to palaeoceanographic changes across this boundary. The aim of this study is to characterize the palaeoenvironmental changes occurring across the Sinemurian/Pliensbachian boundary at the São Pedro de Moel section (Lusitanian Basin, Portugal) using micropalaeontology and organic geochemistry approaches. Combined calcareous nannofossil assemblage and lipid biomarker data document for a decrease in primary productivity in relation to a major sea-level rise occurring above the boundary. The Lusitanian Basin was particularly restricted during the late Sinemurian with a relatively low sea level, a configuration that led to the recurrent development of black shales. After a sharp sea-level fall, the basin became progressively deeper and more open during the earliest Pliensbachian, subsequently to a major transgression. This sea-level increase seems to have been a global feature and could have been related to the opening of the Hispanic Corridor that connected the Tethys and palaeo-Pacific oceans. The palaeoceanographic and palaeoclimatic changes induced by this opening may have played a role in the diversification of coccolithophores with the first occurrence or colonization of Tethyan waters by placolith-type coccoliths

Genome-Wide Analysis Reveals Selection Signatures Involved in Meat Traits and Local Adaptation in Semi-Feral Maremmana Cattle

The Maremmana cattle is an ancient Podolian-derived Italian breed raised in semi-wild conditions with distinctive morphological and adaptive traits. The aim of this study was to detect potential selection signatures in Maremmana using medium-density single nucleotide polymorphism array. Putative selection signatures were investigated combining three statistical approaches designed to quantify the excess of haplotype homozygosity either within (integrated haplotype score, iHS) or among pairs of populations (Rsb and XP-EHH), and contrasting the Maremmana with a single reference population composed of a pool of seven Podolian-derived Italian breeds. Overall, the three haplotype-based analyses revealed selection signatures distributed over 19 genomic regions. Of these, six relevant candidate regions were identified by at least two approaches. We found genomic signatures of selective sweeps spanning genes related to mitochondrial function, muscle development, growth, and meat traits (SCIN, THSD7A, ETV1, UCHL1, and MYOD1), which reflects the different breeding schemes between Maremmana (semi-wild conditions) and the other Podolian-derived Italian breeds (semi-extensive). We also identified several genes linked to Maremmana adaptation to the environment of the western-central part of Italy, known to be hyperendemic for malaria and other tick-borne diseases. These include several chemokine (C-C motif) ligand genes crucially involved in both innate and adaptive immune responses to intracellular parasite infections and other genes playing key roles in pulmonary disease (HEATR9, MMP28, and ASIC2) or strongly associated with malaria resistance/susceptibility (AP2B1). Our results provide a glimpse into diverse selection signatures in Maremmana cattle and can be used to enhance our understanding of the genomic basis of environmental adaptation in cattle

Identification and characterization of copy number variations in cattle

Copy number variations (CNVs) are an important source of genetic changes. They are defined as a gain or loss of genomic region ranging from 50 bp to several megabases. CNVs have been shown to be associated with many diseases and some phenotypic traits in several species, including cattle. We used Pindel, Delly, BreakDancer, and CNVnator to identify CNVs using whole-genome sequencing data of 200 animals from eight French dairy and beef cattle breeds. We selected only deletions and duplications predicted by at least two tools and present in at least two animals. We identified a total of 29,132 autosomal deletions and duplications which cover between 31 to 34% (784 to 865 Mb) of the autosomal genome, with an average of 6,000 events per animal. Among these deletions and duplications, 27,690 were present in at least two animals. Out of theses, 26,417 events were deletions, 674 were duplications and 599 regions were both (deletion and duplication within the same region). We defined a CNV as deletion and duplication in the same region, and we termed this region as CNV-Region (CNVR). The size of CNVRs ranged from 100 bp to 9.3 Mb with a median of 1.3 kb and a mean of 45 kb. From the identified deletions and duplications, 8,283 overlapped with 9,733 annotated genes including 290 CNVRs overlapping with 974 annotated genes, including some genes known to be implicated in some traits of economic importance. Our study provides an extensive view of the CNVRs in French dairy and beef breeds. CNVRs with an effect on some commercially interesting phenotypes could be used to improve genetic selection of these eight French breeds

prediction of overall survival with 2nd line l2os chemotherapy ct in patients with advanced biliary tract cancer abtc ageo ct2bil cohort update and international multicenter external validations

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Analysis of BAC-end sequences in rainbow trout: Content characterization and assessment of synteny between trout and other fish genomes

<p>Abstract</p> <p>Background</p> <p>Rainbow trout (<it>Oncorhynchus mykiss</it>) are cultivated worldwide for aquaculture production and are widely used as a model species to gain knowledge of many aspects of fish biology. The common ancestor of the salmonids experienced a whole genome duplication event, making extant salmonids such as the rainbow trout an excellent model for studying the evolution of tetraploidization and re-diploidization in vertebrates. However, the lack of a reference genome sequence hampers research progress for both academic and applied purposes. In order to enrich the genomic tools already available in this species and provide further insight on the complexity of its genome, we sequenced a large number of rainbow trout BAC-end sequences (BES) and characterized their contents.</p> <p>Results</p> <p>A total of 176,485 high quality BES, were generated, representing approximately 4% of the trout genome. BES analyses identified 6,848 simple sequence repeats (SSRs), of which 3,854 had high quality flanking sequences for PCR primers design. The first rainbow trout repeat elements database (INRA RT rep1.0) containing 735 putative repeat elements was developed, and identified almost 59.5% of the BES database in base-pairs as repetitive sequence. Approximately 55% of the BES reads (97,846) had more than 100 base pairs of contiguous non-repetitive sequences. The fractions of the 97,846 non-repetitive trout BES reads that had significant BLASTN hits against the zebrafish, medaka and stickleback genome databases were 15%, 16.2% and 17.9%, respectively, while the fractions of the non-repetitive BES reads that had significant BLASTX hits against the zebrafish, medaka, and stickleback protein databases were 10.7%, 9.5% and 9.5%, respectively. Comparative genomics using paired BAC-ends revealed several regions of conserved synteny across all the fish species analyzed in this study.</p> <p>Conclusions</p> <p>The characterization of BES provided insights on the rainbow trout genome. The discovery of specific repeat elements will facilitate analyses of sequence content (e.g. for SNPs discovery and for transcriptome characterization) and future genome sequence assemblies. The numerous microsatellites will facilitate integration of the linkage and physical maps and serve as valuable resource for fine mapping QTL and positional cloning of genes affecting aquaculture production traits. Furthermore, comparative genomics through BES can be used for identifying positional candidate genes from QTL mapping studies, aid in future assembly of a reference genome sequence and elucidating sequence content and complexity in the rainbow trout genome.</p

Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

International audienceBACKGROUND: The nitric oxide (NO) pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms (SNPs) of NO synthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma) and blood eosinophil counts. METHODOLOGY: SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO (Fe(NO)), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2-NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. PRINCIPAL FINDINGS: In non-asthmatics, after correction for multiple comparisons, we found significant associations of Fe(NO) levels with three SNPs in NOS3 and NOS2 (P ≤ 0.002), and of EBC NO2-NO3 level with NOS2 (P = 0.002). In asthmatics, a single significant association was detected between Fe(NO) levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on Fe(NO) between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No significant association was found between any SNP and NO2-NO3 plasma levels or blood eosinophil counts. CONCLUSIONS: Variants in NO synthase genes influence Fe(NO) and EBC NO2-NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid

Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p &lt; 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals

peer-reviewedH.D.D., A.J.C., P.J.B. and B.J.H. would like to acknowledge the Dairy Futures Cooperative Research Centre for funding. H.P. and R.F. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the AgroClustEr ‘Synbreed—Synergistic Plant and Animal Breeding’ (grant 0315527B). H.P., R.F., R.E. and K.-U.G. acknowledge the Arbeitsgemeinschaft Süddeutscher Rinderzüchter, the Arbeitsgemeinschaft Österreichischer Fleckviehzüchter and ZuchtData EDV Dienstleistungen for providing genotype data. A. Bagnato acknowledges the European Union (EU) Collaborative Project LowInputBreeds (grant agreement 222623) for providing Brown Swiss genotypes. Braunvieh Schweiz is acknowledged for providing Brown Swiss phenotypes. H.P. and R.F. acknowledge the German Holstein Association (DHV) and the Confederación de Asociaciones de Frisona Española (CONCAFE) for sharing genotype data. H.P. was financially supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG) (grant PA 2789/1-1). D.B. and D.C.P. acknowledge funding from the Research Stimulus Fund (11/S/112) and Science Foundation Ireland (14/IA/2576). M.S. and F.S.S. acknowledge the Canadian Dairy Network (CDN) for providing the Holstein genotypes. P.S. acknowledges funding from the Genome Canada project entitled ‘Whole Genome Selection through Genome Wide Imputation in Beef Cattle’ and acknowledges WestGrid and Compute/Calcul Canada for providing computing resources. J.F.T. was supported by the National Institute of Food and Agriculture, US Department of Agriculture, under awards 2013-68004-20364 and 2015-67015-23183. A. Bagnato, F.P., M.D. and J.W. acknowledge EU Collaborative Project Quantomics (grant 516 agreement 222664) for providing Brown Swiss and Finnish Ayrshire sequences and genotypes. A.C.B. and R.F.V. acknowledge funding from the public–private partnership ‘Breed4Food’ (code BO-22.04-011- 001-ASG-LR) and EU FP7 IRSES SEQSEL (grant 317697). A.C.B. and R.F.V. acknowledge CRV (Arnhem, the Netherlands) for providing data on Dutch and New Zealand Holstein and Jersey bulls.Stature is affected by many polymorphisms of small effect in humans1. In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10−8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP–seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals