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      A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep

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          Abstract

          Background

          Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly Lucilia cuprina are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.

          Results

          The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.

          Conclusions

          We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.

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          Most cited references34

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            PermutMatrix: a graphical environment to arrange gene expression profiles in optimal linear order.

            PermutMatrix is a work space designed to graphically explore gene expression data. It relies on the graphical approach introduced by Eisen and also offers several methods for the optimal reorganization of rows and columns of a numerical dataset. For example, several methods are proposed for optimal reorganization of the leaves of a hierarchical clustering tree, along with several seriation or unidimensional scaling methods that do not require any preliminary hierarchical clustering. This program, developed for MS Windows, with MS-Visual C++, has a clear and efficient graphical interface. Large datasets can be thoroughly and quickly analyzed.
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              Fibulins: physiological and disease perspectives.

              The fibulins are a family of proteins that are associated with basement membranes and elastic extracellular matrix fibres. This review summarizes findings from studies of animal models of fibulin deficiency, human fibulin gene mutations, human tumours and injury models that have advanced our understanding of the normal and pathological roles of members of this formerly obscure family.
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                Author and article information

                Journal
                BMC Vet Res
                BMC Veterinary Research
                BioMed Central
                1746-6148
                2010
                26 May 2010
                : 6
                : 27
                Affiliations
                [1 ]CSIRO Livestock Industries, 306 Carmody Rd, St Lucia, QLD 4067, Australia
                [2 ]Industry and Investment NSW, Agricultural Research Centre, Trangie, NSW 2823, Australia
                [3 ]SheepGENOMICS, Wool Sub-Program, 306 Carmody Rd, St Lucia, QLD 4067, Australia
                [4 ]Australian Animal Health Laboratory, CSIRO Livestock Industries, Private Bag 24, Geelong, Vic. 3220, Australia
                Article
                1746-6148-6-27
                10.1186/1746-6148-6-27
                2886023
                20500888
                016de20f-a445-4bdb-9eae-a1b614664502
                Copyright ©2010 Smith et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2009
                : 26 May 2010
                Categories
                Research article

                Veterinary medicine
                Veterinary medicine

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