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      Genome-wide association analysis of milk yield traits in Nordic Red Cattle using imputed whole genome sequence variants

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          Abstract

          Background

          The Nordic Red Cattle consisting of three different populations from Finland, Sweden and Denmark are under a joint breeding value estimation system. The long history of recording of production and health traits offers a great opportunity to study production traits and identify causal variants behind them. In this study, we used whole genome sequence level data from 4280 progeny tested Nordic Red Cattle bulls to scan the genome for loci affecting milk, fat and protein yields.

          Results

          Using a genome-wise significance threshold, regions on Bos taurus chromosomes 5, 14, 23, 25 and 26 were associated with fat yield. Regions on chromosomes 5, 14, 16, 19, 20 and 25 were associated with milk yield and chromosomes 5, 14 and 25 had regions associated with protein yield. Significantly associated variations were found in 227 genes for fat yield, 72 genes for milk yield and 30 genes for protein yield. Ingenuity Pathway Analysis was used to identify networks connecting these genes displaying significant hits. When compared to previously mapped genomic regions associated with fertility, significantly associated variations were found in 5 genes common for fat yield and fertility, thus linking these two traits via biological networks.

          Conclusion

          This is the first time when whole genome sequence data is utilized to study genomic regions affecting milk production in the Nordic Red Cattle population. Sequence level data offers the possibility to study quantitative traits in detail but still cannot unambiguously reveal which of the associated variations is causative. Linkage disequilibrium creates difficulties to pinpoint the causative genes and variations. One solution to overcome these difficulties is the identification of the functional gene networks and pathways to reveal important interacting genes as candidates for the observed effects. This information on target genomic regions may be exploited to improve genomic prediction.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12863-016-0363-8) contains supplementary material, which is available to authorized users.

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          Most cited references35

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          Ensembl BioMarts: a hub for data retrieval across taxonomic space

          For a number of years the BioMart data warehousing system has proven to be a valuable resource for scientists seeking a fast and versatile means of accessing the growing volume of genomic data provided by the Ensembl project. The launch of the Ensembl Genomes project in 2009 complemented the Ensembl project by utilizing the same visualization, interactive and programming tools to provide users with a means for accessing genome data from a further five domains: protists, bacteria, metazoa, plants and fungi. The Ensembl and Ensembl Genomes BioMarts provide a point of access to the high-quality gene annotation, variation data, functional and regulatory annotation and evolutionary relationships from genomes spanning the taxonomic space. This article aims to give a comprehensive overview of the Ensembl and Ensembl Genomes BioMarts as well as some useful examples and a description of current data content and future objectives. Database URLs: http://www.ensembl.org/biomart/martview/; http://metazoa.ensembl.org/biomart/martview/; http://plants.ensembl.org/biomart/martview/; http://protists.ensembl.org/biomart/martview/; http://fungi.ensembl.org/biomart/martview/; http://bacteria.ensembl.org/biomart/martview/
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            Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition.

            We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition--particularly fat content--to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (1) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics.
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              Developmental progress and current status of the Animal QTLdb

              The Animal QTL Database (QTLdb; http://www.animalgenome.org/QTLdb) has undergone dramatic growth in recent years in terms of new data curated, data downloads and new functions and tools. We have focused our development efforts to cope with challenges arising from rapid growth of newly published data and end users’ data demands, and to optimize data retrieval and analysis to facilitate users’ research. Evidenced by the 27 releases in the past 11 years, the growth of the QTLdb has been phenomenal. Here we report our recent progress which is highlighted by addition of one new species, four new data types, four new user tools, a new API tool set, numerous new functions and capabilities added to the curator tool set, expansion of our data alliance partners and more than 20 other improvements. In this paper we present a summary of our progress to date and an outlook regarding future directions.
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                Author and article information

                Contributors
                terhi.iso-touru@luke.fi
                goutam.sahana@mbg.au.dk
                bernt.guldbrandtsen@mbg.au.dk
                mogens.lund@mbg.au.dk
                johanna.vilkki@luke.fi
                Journal
                BMC Genet
                BMC Genet
                BMC Genetics
                BioMed Central (London )
                1471-2156
                22 March 2016
                22 March 2016
                2016
                : 17
                : 55
                Affiliations
                [ ]Animal Genomics, Green Technology, Natural Resources Institute Finland (Luke), Jokioinen, Finland
                [ ]Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus University, Tjele, Denmark
                Article
                363
                10.1186/s12863-016-0363-8
                4804490
                27006194
                03c8c367-8bfb-4aeb-a34e-9a9d7a8b0b22
                © Iso-Touru et al. 2016

                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
                : 21 December 2015
                : 17 March 2016
                Funding
                Funded by: Betty Väänänen Foundation
                Funded by: University of Turku, Doctoral Programme in Biology, Geography and Geology
                Funded by: Ministry of Agriculture and forestry, Finland
                Award ID: 1729/03.01.02
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Genetics
                milk traits,nordic red cattle,whole genome sequence,association study
                Genetics
                milk traits, nordic red cattle, whole genome sequence, association study

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