Genomic inbreeding trends in the global Thoroughbred horse population driven by influential sire lines and selection for exercise trait-related genes

Abstract

13The Thoroughbred horse is a highly valued domestic animal population under strong 14 selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of 15 inbreeding in the population that may form the basis for evidence-based discussion amid concerns 16 in the breeding industry over the increasing use of small numbers of popular sire lines, which 17 may accelerate a loss of genetic diversity. In the most comprehensive globally representative 18 sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the 19 major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has 20 been a highly significant decline in global genetic diversity during the last five decades (FIS R 2 = 21 0.942, P = 2.19 × 10 -13 ; FROH R 2 = 0.88, P = 1.81 × 10 -10 ) that has likely been influenced by the use 22 of popular sire lines. Estimates of effective population size in the global and regional populations 23 indicate that there is some level of regional variation that may be exploited to improve global 24 genetic diversity. Inbreeding is often a consequence of selection, which in managed animal 25 populations tends to be driven by preferences for cultural, aesthetic or economically 26 advantageous phenotypes. Using a composite selection signals approach, we show that centuries 27 of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in 28 behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at 29 core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal 30 growth and development, cellular stress and injury, metabolic pathways and neurotransmitters 31 and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our 32 results demonstrate that genomics-based approaches to identify genetic outcrosses will add 33 valuable objectivity to augment traditional methods of stallion selection and that genomics-based 34 methods will be beneficial to actively monitor the population to address the marked inbreeding 35 trend. 36 Author Summary 37In the highly valuable global Thoroughbred horse industry, there is no systematic industry-38 mediated genetic population management. Purposeful inbreeding is common practice and there is an 39 increasing use of popular sires. Inbreeding can lead to population health and fertility decline, but there 40 is little objective genomics-based data for the Thoroughbred to catalyse action and support changes in 41 breeding practices. Here, we describe the most comprehensive genetic analysis in the population among 42 10,000 Thoroughbreds from the major bloodstock regions of the world and reveal a highly significant 43 increase in inbreeding during the last five decades. The main drivers of genetic diversity are the most 44 influential 'breed-shaping' sire lines, Sadler's Wells, Danehill and A.P. Indy. We identified genomic 45 regions subject to positive selection containing genes f...