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      Fixed-length haplotypes can improve genomic prediction accuracy in an admixed dairy cattle population

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          Abstract

          Background

          Fitting covariates representing the number of haplotype alleles rather than single nucleotide polymorphism (SNP) alleles may increase genomic prediction accuracy if linkage disequilibrium between quantitative trait loci and SNPs is inadequate. The objectives of this study were to evaluate the accuracy, bias and computation time of Bayesian genomic prediction methods that fit fixed-length haplotypes or SNPs. Genotypes at 37,740 SNPs that were common to Illumina BovineSNP50 and high-density panels were phased for ~58,000 New Zealand dairy cattle. Females born before 1 June 2008 were used for training, and genomic predictions for milk fat yield (n = 24,823), liveweight (n = 13,283) and somatic cell score (n = 24,864) were validated within breed (predominantly Holstein–Friesian, predominantly Jersey, or admixed KiwiCross) in later-born females. Covariates for haplotype alleles of five lengths (125, 250, 500 kb, 1 or 2 Mb) were generated and rare haplotypes were removed at four thresholds (1, 2, 5 or 10%), resulting in 20 scenarios tested. Genomic predictions fitting covariates for either SNPs or haplotypes were calculated by using BayesA, BayesB or BayesN. This is the first study to quantify the accuracy of genomic prediction using haplotypes across the whole genome in an admixed population.

          Results

          A correlation of 0.349 ± 0.016 between yield deviation and genomic breeding values was obtained for milk fat yield in Holstein–Friesians using BayesA fitting covariates. Genomic predictions were more accurate with short haplotypes than with SNPs but less accurate with longer haplotypes than with SNPs. Fitting only the most frequent haplotype alleles reduced computation time with little decrease in prediction accuracy for short haplotypes. Trends were similar for all traits and breeds and there was little difference between Bayesian methods.

          Conclusions

          Fitting covariates for haplotype alleles rather than SNPs can increase prediction accuracy, although it decreased drastically for long (>500 kb) haplotypes. In this population, fitting 250 kb haplotypes with a 1% frequency threshold resulted in the highest genomic prediction accuracy and fitting 125 kb haplotypes with a 10% frequency threshold improved genomic prediction accuracy with comparable computation time to fitting SNPs. This increased accuracy is likely to increase genetic gain by changing the ranking of selection candidates.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12711-017-0329-y) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          Introduction to Quantitative Genetics

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            Development and Characterization of a High Density SNP Genotyping Assay for Cattle

            The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of <350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative copy number variants in cattle. Utility for GWA was demonstrated by localizing known variation for coat color and the presence/absence of horns to their correct genomic locations. The combination of SNP selection and the novel spacing algorithm allows an efficient approach for the development of high-density genotyping platforms in species having full or even moderate quality draft sequence. Aspects of the approach can be exploited in species which lack an available genome sequence. The BovineSNP50 assay described here is commercially available from Illumina and provides a robust platform for mapping disease genes and QTL in cattle.
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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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                Author and article information

                Contributors
                melanie.k.hess@gmail.com
                tom.druet@ulg.ac.be
                andrew.hess@agresearch.co.nz
                d.garrick@massey.ac.nz
                Journal
                Genet Sel Evol
                Genet. Sel. Evol
                Genetics, Selection, Evolution : GSE
                BioMed Central (London )
                0999-193X
                1297-9686
                3 July 2017
                3 July 2017
                2017
                : 49
                : 54
                Affiliations
                [1 ]ISNI 0000 0004 1936 7312, GRID grid.34421.30, , Iowa State University, ; Ames, IA USA
                [2 ]ISNI 0000 0001 0251 0731, GRID grid.466921.e, , LIC, ; Hamilton, New Zealand
                [3 ]ISNI 0000 0001 0805 7253, GRID grid.4861.b, , University of Liege, ; Liège, Belgium
                [4 ]GRID grid.148374.d, , Massey University, ; Palmerston North, New Zealand
                Article
                329
                10.1186/s12711-017-0329-y
                5494768
                28673233
                41f904d7-7c7f-4a36-9fca-152e7f1b261e
                © The Author(s) 2017

                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
                : 18 October 2016
                : 26 June 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Genetics
                Genetics

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