Common protein-coding variants influence the racing phenotype in galloping racehorse breeds

Creators: Han, Haige; McGivney, Beatrice A.; Allen, Lucy; Bai, Dongyi; Corduff, Leanne R.; Davaakhuu, Gantulga; Davaasambuu, Jargalsaikhan; Dorjgotov, Dulguun; Hall, Thomas J.; Hemmings, Andrew J.; Holtby, Amy R.; Jambal, Tuyatsetseg; Jargalsaikhan, Badarch; Jargalsaikhan, Uyasakh; Kadri, Naveen K.; MacHugh, David E.; Pausch, Hubert; Readhead, Carol; Warburton, David; Dugarjaviin, Manglai; Hill, Emmeline W.

Abstract

Selection for system-wide morphological, physiological, and metabolic adaptations has led to extreme athletic phenotypes among geographically diverse horse breeds. Here, we identify genes contributing to exercise adaptation in racehorses by applying genomics approaches for racing performance, an end-point athletic phenotype. Using an integrative genomics strategy to first combine population genomics results with skeletal muscle exercise and training transcriptomic data, followed by whole-genome resequencing of Asian horses, we identify protein-coding variants in genes of interest in galloping racehorse breeds (Arabian, Mongolian and Thoroughbred). A core set of genes, G6PC2, HDAC9, KTN1, MYLK2, NTM, SLC16A1 and SYNDIG1, with central roles in muscle, metabolism, and neurobiology, are key drivers of the racing phenotype. Although racing potential is a multifactorial trait, the genomic architecture shaping the common athletic phenotype in horse populations bred for racing provides evidence for the influence of protein-coding variants in fundamental exercise-relevant genes. Variation in these genes may therefore be exploited for genetic improvement of horse populations towards specific types of racing.

Additional Information

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. We thank the Khentii herdsmen and Henry Seebach for assistance with collection of the Mongolian Racing horse samples; horse owners for agreement for the use of samples in research; Jonathan O'Grady (O'Grady Advisors) for assistance compiling the Thoroughbred race record phenotypes; and Gillian McHugo for assistance with data visualisation. This work was supported by National Key R&D Program of China (Grant Code 2017YFE0108700); National Natural Science Foundation of China (Grant Code 3191101008,31960657); Science Foundation Ireland (Grant Code 19FFP6879); National Institutes of Health (Grant Code NIEHS-1D43ES02286201); Royal Agricultural University Cirencester Fund; Plusvital Ltd. Contributions. H.H. compiled the SNP data, performed the population genomics analyses, coordinated the sample acquisition of Asian horses, coordinated the WGS study, interpreted the results, and assisted with writing the original manuscript. B.A.M. designed and performed the SNP association analyses, assisted with the population genomics analyses, assisted with the WGS study, interpreted the results, and assisted with writing the original manuscript. L.A. and A.J.H. were involved in planning and performing the sample acquisition and DNA extraction of Mongolian Racing horses. D.B., D.D. and T.J. were involved in the sample acquisition of Asian horses. B.J., J.D. and U.J. facilitated and were involved in the sample acquisition of Mongolian Racing horses. A.R.H. and L.R.C. prepared the phenotypes and samples for the SNP association analyses. N.K.K. and H.P. performed the downstream WGS analyses. T.J.H. and D.E.M. designed and performed the integrative genomics analyses and assisted with writing the original manuscript. C.R. and D.W. conceived the study and facilitated and performed the sample acquisition of Mongolian Racing horses. M.D. facilitated the sample acquisition of Asian horses and supervised the WGS study. E.W.H. conceived, designed and coordinated the study, performed the sample acquisition of Mongolian Racing horses, supervised the analyses, interpreted the results and wrote the original manuscript. Data availability. SNP array derived genotypes generated in this study have been deposited in the European Variation Archive with the accession IDs PRJEB55561 (Project), ERZ12817059 (Mongolian horse analysis), and ERZ12817060 (Arabian horse analysis). The whole genome sequence data have been deposited in the Sequence Read Archive with the BioProject ID: PRJNA867509. The source data for Fig. 2 is available at Source data is available at https://doi.org/10.5061/dryad.g79cnp5sm. The SNP genotype data generated for the validation study are subject to the following licenses/restrictions: The phenotype and genotype data are the property of Plusvital Ltd. and subject to a confidentiality agreement with the animal owners.

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