Suchergebnisse

PUBLISHED ; Export Date: 13 January 2017 ; Background Bovine tuberculosis (bTB) infection in cattle is a significant economic concern in many countries, with annual costs to the UK and Irish governments of approximately ?190 million and ?63 million, respectively, for bTB control. The existence of host additive and non-additive genetic components to bTB susceptibility has been established. Methods Two approaches i.e. single-SNP (single nucleotide polymorphism) regression and a Bayesian method were applied to genome-wide association studies (GWAS) using high-density SNP genotypes (n = 597,144 SNPs) from 841 dairy artificial insemination (AI) sires. Deregressed estimated breeding values for bTB susceptibility were used as the quantitative dependent variable. Network analysis was performed using the quantitative trait loci (QTL) that were identified as significant in the single-SNP regression and Bayesian analyses separately. In addition, an identity-by-descent analysis was performed on a subset of the most prolific sires in the dataset that showed contrasting prevalences of bTB infection in daughters. Results A significant QTL region was identified on BTA23 (P value >1 ? 10?5, Bayes factor >10) across all analyses. Sires with the minor allele (minor allele frequency = 0.136) for this QTL on BTA23 had estimated breeding values that conferred a greater susceptibility to bTB infection than those that were homozygous for the major allele. Imputation of the regions that flank this QTL on BTA23 to full sequence indicated that the most significant associations were located within introns of the FKBP5 gene. Conclusions A genomic region on BTA23 that is strongly associated with host susceptibility to bTB infection was identified. This region contained FKBP5, a gene involved in the TNF?/NF?-B signalling pathway, which is a major biological pathway associated with immune response. Although there is no study that validates this region in the literature, our approach represents one of the most powerful studies for the analysis of bTB susceptibility to date. ; This work was supported by Science Foundation Ireland Principal Investigator award grant number 09/IN.1/B2642, and the Irish Research Stimulus Fund 11/S/112. The authors would also like to acknowledge Dr. Karin Meyer for altering the Wombat software for our analysis. We gratefully acknowledge the 1000 Bull Genomes Consortium for providing accessibility to whole-genome sequence data which was used in this study.

PUBLISHED ; Under selection pressure from pathogens, variable NK cell receptors that recognize polymorphic MHC class I evolved convergently in different species of placental mammal. Unexpectedly, diversified killer cell Ig?like receptors (KIRs) are shared by simian primates, including humans, and cattle, but not by other species. Whereas much is known of human KIR genetics and genomics, knowledge of cattle KIR is limited to nine cDNA sequences. To facilitate comparison of the cattle and human KIR gene families, we determined the genomic location, structure, and sequence of two cattle KIR haplotypes and defined KIR sequences of aurochs, the extinct wild ancestor of domestic cattle. Larger than its human counterpart, the cattle KIR locus evolved through successive duplications of a block containing ancestral KIR3DL and KIR3DX genes that existed before placental mammals. Comparison of two cattle KIR haplotypes and aurochs KIR show the KIR are polymorphic and the gene organization and content appear conserved. Of 18 genes, 8 are functional and 10 were inactivated by point mutation. Selective inactivation of KIR3DL and activating receptor genes leaves a functional cohort of one inhibitory KIR3DL, one activating KIR3DX, and six inhibitory KIR3DX. Functional KIR diversity evolved from KIR3DX in cattle and from KIR3DL in simian primates. Although independently evolved, cattle and human KIR gene families share important function-related properties, indicating that cattle KIR are NK cell receptors for cattle MHC class I. Combinations of KIR and MHC class I are the major genetic factors associated with human disease and merit investigation in cattle. ; This work was supported by the Biotechnology and Biological Sciences Research Council through a Doctoral Training Award, Institute Strategic Program on Livestock Viral Diseases awarded to The Pirbright Institute, Grants BB/J006211/1 and BBS/E/I/00001410 (to J.A.H.) and National Institutes of Health Grant AI17892 (to P.J.N., L.A.G., and P.P.). The aurochs genome sequencing work was supported by Science Foundation Ireland Investigator Grant SFI/08/IN.1/B2038 and European Union Framework 7 Project Grant KBBE-211602-MACROSYS.

PUBLISHED ; Cited By :8 Export Date: 13 January 2017 ; One of the most enduring and widely debated questions in prehistoric archaeology concerns the origins of Europe?s earliest farmers: Were they the descendants of local hunter-gatherers, or did they migrate from southwestern Asia, where farming began? We recover genome-wide DNA sequences from early farmers on both the European and Asian sides of the Aegean to reveal an unbroken chain of ancestry leading from central and southwestern Europe back to Greece and northwestern Anatolia. Our study provides the coup de gr?ce to the notion that farming spread into and across Europe via the dissemination of ideas but without, or with only a limited, migration of people. ; We thank Song?l Alpaslan for help with sampling in Barc?n and Eleni Stravopodi for help with sampling in Theopetra. Z.H. and R.M. are supported by a Marie Curie Initial Training Network (BEAN/Bridging the European and Anatolian Neolithic, GA 289966) awarded to M.C., S.J.S., D.G.B., M.G.T., and J. Burger. C.P., J. Burger and S.K. received funding from DFG (BU 1403/6-1). C.P. and J. Burger received funding from the Alexander von Humboldt Foundation. C.S. and M.S. were supported by the European Union (EU) SYNTHESYS/Synthesis of Systematic Resources GA 226506-CP-CSA-INFRA, DFG: (BO 4119/1) and Volkswagenstiftung (FKZ: 87161). L.M.C. is funded by the Irish Research Council (GOIPG/2013/1219). A.S. was supported by the EU CodeX Project 295729. K. Kotsakis, S.T., D.U.-K., P.H., and C.P. were cofinanced by the EU Social Fund and Greek national funds research funding program THALES. C.P., M.U., K. Kotsakis, S.T., and D.U.-K. were cofinanced by the EU Social Fund and the Greek national funds research funding program ARISTEIA II. M.C. was supported by Swiss NSF Grant 31003A_156853. A.K. and D.W. were supported by Swiss NSF Grant 31003A_149920. S.L. is supported by the BBSRC (Grant BB/L009382/1). L.v.D. is supported by CoMPLEX via EPSRC (Grant EP/F500351/1). G.H. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant 098386/Z/12/Z) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.G.T. and Y.D. are supported by a Wellcome Trust Senior Research Fellowship Grant 100719/Z/12/Z (to M.G.T.). J. Burger is grateful for support by the University of Mainz and the HPC cluster MOGON (funded by DFG; INST 247/602-1 FUGG). F.G. was supported by Grant 380-62-005 of the Netherlands Organization for Scientific Research.

AbstractWe examine executive stock option exercises around a sample of merger and acquisition announcements between 1996 and 2006, focusing on a subset we identify as potentially informed. For stock‐financed acquisitions, we find a surge in informed exercises by acquirer insiders in the year leading up to the acquisition announcement, but target insiders display no similar increase. We find the market reaction upon the announcement for acquirers is negatively related to extreme early exercises and find some evidence of long‐run underperformance. Overall, our evidence indicates that insiders knowingly bid for firms when they personally believe their own firm is overvalued.