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      Genome-wide association study reveals novel loci for litter size and its variability in a Large White pig population

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          Abstract

          Background

          In many traits, not only individual trait levels are under genetic control, but also the variation around that level. In other words, genotypes do not only differ in mean, but also in (residual) variation around the genotypic mean. New statistical methods facilitate gaining knowledge on the genetic architecture of complex traits such as phenotypic variability. Here we study litter size (total number born) and its variation in a Large White pig population using a Double Hierarchical Generalized Linear model, and perform a genome-wide association study using a Bayesian method.

          Results

          In total, 10 significant single nucleotide polymorphisms (SNPs) were detected for total number born (TNB) and 9 SNPs for variability of TNB (varTNB). Those SNPs explained 0.83 % of genetic variance in TNB and 1.44 % in varTNB. The most significant SNP for TNB was detected on Sus scrofa chromosome (SSC) 11. A possible candidate gene for TNB is ENOX1, which is involved in cell growth and survival. On SSC7, two possible candidate genes for varTNB are located. The first gene is coding a swine heat shock protein 90 ( HSPCB = Hsp90), which is a well-studied gene stabilizing morphological traits in Drosophila and Arabidopsis. The second gene is VEGFA, which is activated in angiogenesis and vasculogenesis in the fetus. Furthermore, the genetic correlation between additive genetic effects on TNB and on its variation was 0.49. This indicates that the current selection to increase TNB will also increase the varTNB.

          Conclusions

          To the best of our knowledge, this is the first study reporting SNPs associated with variation of a trait in pigs. Detected genomic regions associated with varTNB can be used in genomic selection to decrease varTNB, which is highly desirable to avoid very small or very large litters in pigs. However, the percentage of variance explained by those regions was small. The SNPs detected in this study can be used as indication for regions in the Sus scrofa genome involved in maintaining low variability of litter size, but further studies are needed to identify the causative loci.

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          Inference from Iterative Simulation Using Multiple Sequences

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            Hsp90 as a capacitor of phenotypic variation.

            Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation in morphogenetic pathways. Levels and patterns of genetic variation differ greatly between obligatorily outbreeding species such as fruitflies and self-fertilizing species such as the plant Arabidopsis thaliana. Also, plant development is more plastic, being coupled to environmental cues. Here we report that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90 function produces an array of morphological phenotypes, which are dependent on underlying genetic variation. The strength and breadth of Hsp90's effects on the buffering and release of genetic variation suggests it may have an impact on evolutionary processes. We also show that Hsp90 influences morphogenetic responses to environmental cues and buffers normal development from destabilizing effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a tool for harnessing cryptic genetic variation and for elucidating the interplay between genotypes, environments and stochastic events in the determination of phenotype.
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              Macrophage activation by endogenous danger signals.

              Macrophages are cells that function as a first line of defence against invading microorganisms. One of the hallmarks of macrophages is their ability to become activated in response to exogenous 'danger signals'. Most microbes have molecular patterns (PAMPS) that are recognized by macrophages and trigger this activation response. There are many aspects of the activation response to PAMPS that are recapitulated when macrophages encounter endogenous danger signals. In response to damaged or stressed self, macrophages undergo physiological changes that include the initiation of signal transduction cascades from germline-encoded receptors, resulting in the elaboration of chemokines, cytokines and toxic mediators. This response to endogenous mediators can enhance inflammation, and thereby contribute to autoimmune pathologies. Often the overall inflammatory response is the result of cooperative activation signals from both exogenous and endogenous signals. Macrophage activation plays a critical role, not only in the initiation of the inflammatory response but also in the resolution of this response. The clearance of granulocytes and the elaboration of anti-inflammatory mediators by macrophages contribute to the dissolution of the inflammatory response. Thus, macrophages are a key player in the initiation, propagation and resolution of inflammation. This review summarizes our understanding of the role of macrophages in inflammation. We pay particular attention to the endogenous danger signals that macrophages may encounter and the responses that these signals induce. The molecular mechanisms responsible for these responses and the diseases that result from inappropriately controlled macrophage activation are also examined. 2007 Pathological Society of Great Britain and Ireland
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                Author and article information

                Contributors
                ewa.sell.kubiak@gmail.com
                naomi.duijvesteijn@topigsnorsvin.com
                marcos.lopes@topigsnorsvin.com
                luc.janss@mbg.au.dk
                egbert.knol@topigsnorsvin.com
                piter.bijma@wur.nl
                han.mulder@wur.nl
                Journal
                BMC Genomics
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                9 December 2015
                9 December 2015
                2015
                : 16
                : 1049
                Affiliations
                [ ]Animal Breeding and Genomics Center, Wageningen University, P.O. Box 338, 6700 Wageningen, AH The Netherlands
                [ ]Topigs Norsvin Research Center B.V, P.O. Box 43, 6640 Beuningen, AA The Netherlands
                [ ]Department of Molecular Biology and Genetics, Aarhus University, P.O. Box 50, 8830 Tjele, Denmark
                Article
                2273
                10.1186/s12864-015-2273-y
                4674943
                26652161
                976e9a4c-7c01-4812-b964-a79c206b63a9
                © Sell-Kubiak et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 August 2015
                : 3 December 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003958, Technologiestichting STW (NL);
                Award ID: 10477
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Genetics
                double hierarchical glm,gwas,pigs,residual variance,total number born
                Genetics
                double hierarchical glm, gwas, pigs, residual variance, total number born

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