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      Potential of genotyping-by-sequencing for genomic selection in livestock populations

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          Abstract

          Background

          Next-generation sequencing techniques, such as genotyping-by-sequencing (GBS), provide alternatives to single nucleotide polymorphism (SNP) arrays. The aim of this work was to evaluate the potential of GBS compared to SNP array genotyping for genomic selection in livestock populations.

          Methods

          The value of GBS was quantified by simulation analyses in which three parameters were varied: (i) genome-wide sequence read depth ( x) per individual from 0.01 x to 20 x or using SNP array genotyping; (ii) number of genotyped markers from 3000 to 300 000; and (iii) size of training and prediction sets from 500 to 50 000 individuals. The latter was achieved by distributing the total available x of 1000 x, 5000 x, or 10 000 x per genotyped locus among the varying number of individuals. With SNP arrays, genotypes were called from sequence data directly. With GBS, genotypes were called from sequence reads that varied between loci and individuals according to a Poisson distribution with mean equal to x. Simulated data were analyzed with ridge regression and the accuracy and bias of genomic predictions and response to selection were quantified under the different scenarios.

          Results

          Accuracies of genomic predictions using GBS data or SNP array data were comparable when large numbers of markers were used and x per individual was ~1 x or higher. The bias of genomic predictions was very high at a very low x. When the total available x was distributed among the training individuals, the accuracy of prediction was maximized when a large number of individuals was used that had GBS data with low x for a large number of markers. Similarly, response to selection was maximized under the same conditions due to increasing both accuracy and selection intensity.

          Conclusions

          GBS offers great potential for developing genomic selection in livestock populations because it makes it possible to cover large fractions of the genome and to vary the sequence read depth per individual. Thus, the accuracy of predictions is improved by increasing the size of training populations and the intensity of selection is increased by genotyping a larger number of selection candidates.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12711-015-0102-z) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Introduction to Quantitative Genetics

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            Low-coverage sequencing: implications for design of complex trait association studies.

            New sequencing technologies allow genomic variation to be surveyed in much greater detail than previously possible. While detailed analysis of a single individual typically requires deep sequencing, when many individuals are sequenced it is possible to combine shallow sequence data across individuals to generate accurate calls in shared stretches of chromosome. Here, we show that, as progressively larger numbers of individuals are sequenced, increasingly accurate genotype calls can be generated for a given sequence depth. We evaluate the implications of low-coverage sequencing for complex trait association studies. We systematically compare study designs based on genotyping of tagSNPs, sequencing of many individuals at depths ranging between 2× and 30×, and imputation of variants discovered by sequencing a subset of individuals into the remainder of the sample. We show that sequencing many individuals at low depth is an attractive strategy for studies of complex trait genetics. For example, for disease-associated variants with frequency >0.2%, sequencing 3000 individuals at 4× depth provides similar power to deep sequencing of >2000 individuals at 30× depth but requires only ~20% of the sequencing effort. We also show low-coverage sequencing can be used to build a reference panel that can drive imputation into additional samples to increase power further. We provide guidance for investigators wishing to combine results from sequenced, genotyped, and imputed samples.
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              Extremely low-coverage sequencing and imputation increases power for genome-wide association studies.

              Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power.
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                Author and article information

                Contributors
                gregor.gorjanc@roslin.ed.ac.uk
                matthew.cleveland@genusplc.com
                ross.houston@roslin.ed.ac.uk
                john.hickey@roslin.ed.ac.uk
                Journal
                Genet Sel Evol
                Genet. Sel. Evol
                Genetics, Selection, Evolution : GSE
                BioMed Central (London )
                0999-193X
                1297-9686
                1 March 2015
                1 March 2015
                2015
                : 47
                : 1
                : 12
                Affiliations
                [ ]The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland UK
                [ ]Genus Plc, 100 Bluegrass Commons Blvd., Suite 2200, Hendersonville, TN 37075 USA
                Article
                102
                10.1186/s12711-015-0102-z
                4344748
                25887531
                431bfba1-feb5-446d-a4fb-ea72ef6a4f29
                © Gorjanc et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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 May 2014
                : 29 January 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Genetics
                Genetics

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