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Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle

BACKGROUND: Whole-genome sequence data is expected to capture genetic variation more completely than common genotyping panels. Our objective was to compare the proportion of variance explained and the accuracy of genomic prediction by using imputed sequence data or preselected SNPs from a genome-wid...

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Autores principales: Veerkamp, Roel F., Bouwman, Aniek C., Schrooten, Chris, Calus, Mario P. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134274/
https://www.ncbi.nlm.nih.gov/pubmed/27905878
http://dx.doi.org/10.1186/s12711-016-0274-1
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author Veerkamp, Roel F.
Bouwman, Aniek C.
Schrooten, Chris
Calus, Mario P. L.
author_facet Veerkamp, Roel F.
Bouwman, Aniek C.
Schrooten, Chris
Calus, Mario P. L.
author_sort Veerkamp, Roel F.
collection PubMed
description BACKGROUND: Whole-genome sequence data is expected to capture genetic variation more completely than common genotyping panels. Our objective was to compare the proportion of variance explained and the accuracy of genomic prediction by using imputed sequence data or preselected SNPs from a genome-wide association study (GWAS) with imputed whole-genome sequence data. METHODS: Phenotypes were available for 5503 Holstein–Friesian bulls. Genotypes were imputed up to whole-genome sequence (13,789,029 segregating DNA variants) by using run 4 of the 1000 bull genomes project. The program GCTA was used to perform GWAS for protein yield (PY), somatic cell score (SCS) and interval from first to last insemination (IFL). From the GWAS, subsets of variants were selected and genomic relationship matrices (GRM) were used to estimate the variance explained in 2087 validation animals and to evaluate the genomic prediction ability. Finally, two GRM were fitted together in several models to evaluate the effect of selected variants that were in competition with all the other variants. RESULTS: The GRM based on full sequence data explained only marginally more genetic variation than that based on common SNP panels: for PY, SCS and IFL, genomic heritability improved from 0.81 to 0.83, 0.83 to 0.87 and 0.69 to 0.72, respectively. Sequence data also helped to identify more variants linked to quantitative trait loci and resulted in clearer GWAS peaks across the genome. The proportion of total variance explained by the selected variants combined in a GRM was considerably smaller than that explained by all variants (less than 0.31 for all traits). When selected variants were used, accuracy of genomic predictions decreased and bias increased. CONCLUSIONS: Although 35 to 42 variants were detected that together explained 13 to 19% of the total variance (18 to 23% of the genetic variance) when fitted alone, there was no advantage in using dense sequence information for genomic prediction in the Holstein data used in our study. Detection and selection of variants within a single breed are difficult due to long-range linkage disequilibrium. Stringent selection of variants resulted in more biased genomic predictions, although this might be due to the training population being the same dataset from which the selected variants were identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0274-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-51342742016-12-15 Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle Veerkamp, Roel F. Bouwman, Aniek C. Schrooten, Chris Calus, Mario P. L. Genet Sel Evol Research Article BACKGROUND: Whole-genome sequence data is expected to capture genetic variation more completely than common genotyping panels. Our objective was to compare the proportion of variance explained and the accuracy of genomic prediction by using imputed sequence data or preselected SNPs from a genome-wide association study (GWAS) with imputed whole-genome sequence data. METHODS: Phenotypes were available for 5503 Holstein–Friesian bulls. Genotypes were imputed up to whole-genome sequence (13,789,029 segregating DNA variants) by using run 4 of the 1000 bull genomes project. The program GCTA was used to perform GWAS for protein yield (PY), somatic cell score (SCS) and interval from first to last insemination (IFL). From the GWAS, subsets of variants were selected and genomic relationship matrices (GRM) were used to estimate the variance explained in 2087 validation animals and to evaluate the genomic prediction ability. Finally, two GRM were fitted together in several models to evaluate the effect of selected variants that were in competition with all the other variants. RESULTS: The GRM based on full sequence data explained only marginally more genetic variation than that based on common SNP panels: for PY, SCS and IFL, genomic heritability improved from 0.81 to 0.83, 0.83 to 0.87 and 0.69 to 0.72, respectively. Sequence data also helped to identify more variants linked to quantitative trait loci and resulted in clearer GWAS peaks across the genome. The proportion of total variance explained by the selected variants combined in a GRM was considerably smaller than that explained by all variants (less than 0.31 for all traits). When selected variants were used, accuracy of genomic predictions decreased and bias increased. CONCLUSIONS: Although 35 to 42 variants were detected that together explained 13 to 19% of the total variance (18 to 23% of the genetic variance) when fitted alone, there was no advantage in using dense sequence information for genomic prediction in the Holstein data used in our study. Detection and selection of variants within a single breed are difficult due to long-range linkage disequilibrium. Stringent selection of variants resulted in more biased genomic predictions, although this might be due to the training population being the same dataset from which the selected variants were identified. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0274-1) contains supplementary material, which is available to authorized users. BioMed Central 2016-12-01 /pmc/articles/PMC5134274/ /pubmed/27905878 http://dx.doi.org/10.1186/s12711-016-0274-1 Text en © The Author(s) 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.
spellingShingle Research Article
Veerkamp, Roel F.
Bouwman, Aniek C.
Schrooten, Chris
Calus, Mario P. L.
Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title_full Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title_fullStr Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title_full_unstemmed Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title_short Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein–Friesian cattle
title_sort genomic prediction using preselected dna variants from a gwas with whole-genome sequence data in holstein–friesian cattle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134274/
https://www.ncbi.nlm.nih.gov/pubmed/27905878
http://dx.doi.org/10.1186/s12711-016-0274-1
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