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Food, fibre and pharmaceuticals from animals
RESEARCH ARTICLE

Bayesian genome-wide analysis of cattle traits using variants with functional and evolutionary significance

Ruidong Xiang https://orcid.org/0000-0002-1584-7605 A B C , Ed J. Breen B , Claire P. Prowse-Wilkins A B , Amanda J. Chamberlain B and Michael E. Goddard A B
+ Author Affiliations
- Author Affiliations

A Faculty of Veterinary and Agricultural Science, The University of Melbourne, 142 Royal Parade, Parkville, Vic. 3052, Australia.

B Agriculture Victoria, AgriBio, Centre for AgriBiosciences, 5 Ring Road, Bundoora, Vic. 3083, Australia.

C Corresponding author. Email: ruidong.xiang@unimelb.edu.au

Animal Production Science - https://doi.org/10.1071/AN21061
Submitted: 8 February 2021  Accepted: 12 May 2021   Published online: 21 July 2021

Abstract

Context: Functional genomics studies have highlighted genomic regions with regulatory and evolutionary significance. Such information independent of association analysis may benefit fine-mapping and genomic selection of economically important traits. However, systematic evaluation of the use of functional information in mapping, and genomic selection of cattle traits, is lacking. Also, single-nucleotide polymorphisms (SNPs) from the high-density (HD) panel are known to tag informative variants, but the performance of genomic prediction using HD SNPs together with variants supported by different functional genomics is unknown.

Aims: We selected six sets of functionally important variants and modelled each set together with HD SNPs in Bayesian models to map and predict protein, fat and milk yield as well as mastitis, somatic cell count and temperament of dairy cattle.

Methods: Two models were used, namely (1) BayesR, which includes priors of four distribution of variant effects, and (2) BayesRC, which includes additional priors of different functional classes of variants. Bayesian models were trained in three breeds of 28 000 cows of Holstein, Jersey and Australian Red and predicted into 2600 independent bulls.

Key results: Adding functionally important variants significantly increased the enrichment of genetic variance explained for mapped variants, suggesting improved genome-wide mapping precision. Such improvement was significantly higher when the same set of variants was modelled by BayesRC than by BayesR. Combining functional variant sets with HD SNPs improves genomic prediction accuracy in the majority of the cases and such improvement was more common and stronger for non-Holstein breeds and traits such as mastitis, somatic cell count and temperament. In contrast, adding a large number of random sequence variants to HD SNPs reduces mapping precision and has a worse or similar prediction accuracy, compared with using HD SNPs alone to map or predict. While BayesRC tended to have better genomic prediction accuracy than did BayesR, the overall difference in prediction accuracy between the two models was insignificant.

Conclusions: Our findings demonstrated the usefulness of functional data in genomic mapping and prediction.

Implications: We have highlighted the need for effective tools exploiting complex functional datasets to improve genomic prediction.

Additional keywords: functional genomics, animal breeding, genetic mapping, quantitative genetics.


References

Amariuta T, Ishigaki K, Sugishita H, Ohta T, Koido M, Dey KK, Matsuda K, Murakami Y, Price AL, Kawakami E (2020) Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements. Nature Genetics 52, 1346–1354.
Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements.Crossref | GoogleScholarGoogle Scholar | 33257898PubMed |

Benedet A, Ho P, Xiang R, Bolormaa S, De Marchi M, Goddard M, Pryce J (2019) The use of mid-infrared spectra to map genes affecting milk composition. Journal of Dairy Science 102, 7189–7203.
The use of mid-infrared spectra to map genes affecting milk composition.Crossref | GoogleScholarGoogle Scholar | 31178181PubMed |

Carey MF, Peterson CL, Smale ST (2009) Chromatin immunoprecipitation (ChIP). Cold Spring Harbor Protocols 4, pdb.prot5279

Chamberlain A, Hayes B, Xiang R, Vander Jagt C, Reich C, Macleod I, Prowse-Wilkins C, Mason B, Daetwyler H, Goddard M (2018) Identification of regulatory variation in dairy cattle with RNA sequence data. In ‘11th World Congress on Genetics Applied to Livestock Production (WCGALP)’, Auckland, New Zealand. p. 254.

Clark EL, Archibald AL, Daetwyler HD, Groenen MA, Harrison PW, Houston RD, Kühn C, Lien S, Macqueen DJ, Reecy JM (2020) From FAANG to fork: application of highly annotated genomes to improve farmed animal production. Genome Biology 21, 285
From FAANG to fork: application of highly annotated genomes to improve farmed animal production.Crossref | GoogleScholarGoogle Scholar | 33234160PubMed |

Daetwyler HD, Capitan A, Pausch H, Stothard P, Van Binsbergen R, Brøndum RF, Liao X, Djari A, Rodriguez SC, Grohs C (2014) Whole-genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle. Nature Genetics 46, 858
Whole-genome sequencing of 234 bulls facilitates mapping of monogenic and complex traits in cattle.Crossref | GoogleScholarGoogle Scholar | 25017103PubMed |

Daetwyler H, Xiang R, Yuan Z, Bolormaa S, Vander Jagt C, Hayes B, van der Werf J, Pryce J, Chamberlain A, Macleod I (2019) Integration of functional genomics and phenomics into genomic prediction raises its accuracy in sheep and dairy cattle. In ‘Proceedings of the Association for the Advancement of Animal Breeding and Genetics’, Armidale, NSW, Australia. pp. 11–14.

de las Heras-Saldana S, Lopez BI, Moghaddar N, Park W, Park J-e, Chung KY, Lim D, Lee SH, Shin D, van der Werf JH (2020) Use of gene expression and whole-genome sequence information to improve the accuracy of genomic prediction for carcass traits in Hanwoo cattle. Genetics, Selection, Evolution 52, 54
Use of gene expression and whole-genome sequence information to improve the accuracy of genomic prediction for carcass traits in Hanwoo cattle.Crossref | GoogleScholarGoogle Scholar | 32993481PubMed |

Erbe M, Hayes B, Matukumalli L, Goswami S, Bowman P, Reich C, Mason B, Goddard M (2012) Improving accuracy of genomic predictions within and between dairy cattle breeds with imputed high-density single nucleotide polymorphism panels. Journal of Dairy Science 95, 4114–4129.
Improving accuracy of genomic predictions within and between dairy cattle breeds with imputed high-density single nucleotide polymorphism panels.Crossref | GoogleScholarGoogle Scholar | 22720968PubMed |

Fang L, Sahana G, Ma P, Su G, Yu Y, Zhang S, Lund MS, Sørensen P (2017a) Exploring the genetic architecture and improving genomic prediction accuracy for mastitis and milk production traits in dairy cattle by mapping variants to hepatic transcriptomic regions responsive to intra-mammary infection. Genetics, Selection, Evolution 49, 44
Exploring the genetic architecture and improving genomic prediction accuracy for mastitis and milk production traits in dairy cattle by mapping variants to hepatic transcriptomic regions responsive to intra-mammary infection.Crossref | GoogleScholarGoogle Scholar | 28499345PubMed |

Fang L, Sahana G, Ma P, Su G, Yu Y, Zhang S, Lund MS, Sørensen P (2017b) Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds. BMC Genomics 18, 604
Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds.Crossref | GoogleScholarGoogle Scholar | 28797230PubMed |

Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD (2020) Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle. Genome Research 30, 790–801.
Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.Crossref | GoogleScholarGoogle Scholar | 32424068PubMed |

Fink T, Lopdell TJ, Tiplady K, Handley R, Johnson TJ, Spelman RJ, Davis SR, Snell RG, Littlejohn MD (2020) A new mechanism for a familiar mutation–bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement. BMC Genomics 21, 591
A new mechanism for a familiar mutation–bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement.Crossref | GoogleScholarGoogle Scholar | 32847516PubMed |

Fuchsberger C, Abecasis GR, Hinds DA (2015) minimac2: faster genotype imputation. Bioinformatics 31, 782–784.
minimac2: faster genotype imputation.Crossref | GoogleScholarGoogle Scholar | 25338720PubMed |

Hayes BJ, Daetwyler HD (2018) 1000 Bull Genomes Project to map simple and complex genetic traits in cattle: applications and outcomes. Annual Review of Animal Biosciences 7, 89–102.

Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nature Genetics 44, 955
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing.Crossref | GoogleScholarGoogle Scholar | 22820512PubMed |

Kern C, Wang Y, Xu X, Pan Z, Halstead M, Chanthavixay G, Saelao P, Waters S, Xiang R, Chamberlain A (2021) Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research. Nature Communications 12, 1821
Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research.Crossref | GoogleScholarGoogle Scholar | 33758196PubMed |

Koufariotis LT, Chen Y-PP, Stothard P, Hayes BJ (2018) Variance explained by whole genome sequence variants in coding and regulatory genome annotations for six dairy traits. BMC Genomics 19, 237
Variance explained by whole genome sequence variants in coding and regulatory genome annotations for six dairy traits.Crossref | GoogleScholarGoogle Scholar | 29618315PubMed |

Lee SH, Van der Werf JH (2016) MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information. Bioinformatics 32, 1420–1422.
MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information.Crossref | GoogleScholarGoogle Scholar | 26755623PubMed |

Li YI, van de Geijn B, Raj A, Knowles DA, Petti AA, Golan D, Gilad Y, Pritchard JK (2016) RNA splicing is a primary link between genetic variation and disease. Science 352, 600–604.
RNA splicing is a primary link between genetic variation and disease.Crossref | GoogleScholarGoogle Scholar | 27126046PubMed |

Liu S, Fang L, Zhou Y, Santos DJA, Xiang R, Daetwyler HD, Chamberlain AJ, Cole JB, Li CJ, Yu Y, Ma L, Zhang S, Liu GE (2019) Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle. BMC Genomics 20, 888
Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle.Crossref | GoogleScholarGoogle Scholar | 31752687PubMed |

Loh P-R, Danecek P, Palamara PF, Fuchsberger C, Reshef YA, Finucane HK, Schoenherr S, Forer L, McCarthy S, Abecasis GR (2016) Reference-based phasing using the Haplotype Reference Consortium panel. Nature Genetics 48, 1443
Reference-based phasing using the Haplotype Reference Consortium panel.Crossref | GoogleScholarGoogle Scholar | 27694958PubMed |

Lopdell TJ, Tiplady K, Struchalin M, Johnson TJ, Keehan M, Sherlock R, Couldrey C, Davis SR, Snell RG, Spelman RJ (2017) DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content. BMC Genomics 18, 968
DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content.Crossref | GoogleScholarGoogle Scholar | 29246110PubMed |

MacLeod I, Bowman P, Vander Jagt C, Haile-Mariam M, Kemper K, Chamberlain A, Schrooten C, Hayes B, Goddard M (2016) Exploiting biological priors and sequence variants enhances QTL discovery and genomic prediction of complex traits. BMC Genomics 17, 144
Exploiting biological priors and sequence variants enhances QTL discovery and genomic prediction of complex traits.Crossref | GoogleScholarGoogle Scholar | 26920147PubMed |

McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, Flicek P, Cunningham F (2016) The Ensembl Variant Effect Predictor. Genome Biology 17, 122
The Ensembl Variant Effect Predictor.Crossref | GoogleScholarGoogle Scholar | 27268795PubMed |

Prowse-Wilkins CP, Wang J, Xiang R, Garner JB, Goddard ME, Chamberlain AJ (2021) Putative causal variants are enriched in annotated functional regions from six bovine tissues. Frontiers in Genetics 12,

Rosen BD, Bickhart DM, Schnabel RD, Koren S, Elsik CG, Tseng E, Rowan TN, Low WY, Zimin A, Couldrey C (2020) De novo assembly of the cattle reference genome with single-molecule sequencing. GigaScience 9, giaa021
De novo assembly of the cattle reference genome with single-molecule sequencing.Crossref | GoogleScholarGoogle Scholar | 32543654PubMed |

Sargolzaei M, Chesnais JP, Schenkel FS (2014) A new approach for efficient genotype imputation using information from relatives. BMC Genomics 15, 478
A new approach for efficient genotype imputation using information from relatives.Crossref | GoogleScholarGoogle Scholar | 24935670PubMed |

Silva DB, Fonseca LF, Pinheiro DG, Magalhães AF, Muniz MM, Ferro JA, Baldi F, Chardulo LA, Schnabel RD, Taylor JF (2020) Spliced genes in muscle from Nelore Cattle and their association with carcass and meat quality. Scientific Reports 10, 14701
Spliced genes in muscle from Nelore Cattle and their association with carcass and meat quality.Crossref | GoogleScholarGoogle Scholar | 32895448PubMed |

Weissbrod O, Hormozdiari F, Benner C, Cui R, Ulirsch J, Gazal S, Schoech AP, Van De Geijn B, Reshef Y, Márquez-Luna C (2020) Functionally informed fine-mapping and polygenic localization of complex trait heritability. Nature Genetics 52, 1355–1363.
Functionally informed fine-mapping and polygenic localization of complex trait heritability.Crossref | GoogleScholarGoogle Scholar | 33199916PubMed |

Xiang R, Hayes BJ, Vander Jagt CJ, MacLeod IM, Khansefid M, Bowman PJ, Yuan Z, Prowse-Wilkins CP, Reich CM, Mason BA, Garner JB, Marett LC, Chen Y, Bolormaa S, Daetwyler HD, Chamberlain AJ, Goddard ME (2018) Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues. BMC Genomics 19, 521
Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues.Crossref | GoogleScholarGoogle Scholar | 29973141PubMed |

Xiang R, Berg Id, MacLeod IM, Hayes BJ, Prowse-Wilkins CP, Wang M, Bolormaa S, Liu Z, Rochfort SJ, Reich CM, Mason BA, Vander Jagt CJ, Daetwyler HD, Lund MS, Chamberlain AJ, Goddard ME (2019) Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits. Proceedings of the National Academy of Sciences of the United States of America 116, 19398–19408.
Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits.Crossref | GoogleScholarGoogle Scholar | 31501319PubMed |

Xiang R, van den Berg I, MacLeod IM, Daetwyler HD, Goddard ME (2020) Effect direction meta-analysis of GWAS identifies extreme, prevalent and shared pleiotropy in a large mammal. Communications Biology 3, 88
Effect direction meta-analysis of GWAS identifies extreme, prevalent and shared pleiotropy in a large mammal.Crossref | GoogleScholarGoogle Scholar | 32111961PubMed |

Xiang R, MacLeod IM, Daetwyler HD, de Jong G, O’Connor E, Schrooten C, Chamberlain AJ, Goddard ME (2021) Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations. Nature Communications 12, 860
Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations.Crossref | GoogleScholarGoogle Scholar | 33558518PubMed |

Xu L, Gao N, Wang Z, Xu L, Liu Y, Chen Y, Xu L, Gao X, Zhang L, Gao H (2020) Incorporating genome annotation into genomic prediction for carcass traits in Chinese simmental beef cattle. Frontiers in Genetics 11, 481.