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David E. Machugh - One of the best experts on this subject based on the ideXlab platform.
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targets of selection in the Thoroughbred genome contain exercise relevant gene snps associated with elite racecourse performance
Animal Genetics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, David E. MachughAbstract:Summary Athletic performance is influenced by a complex interplay among the environment and a suite of genes, which contributes to system-wide structure and function. In a panel of elite and non-elite Thoroughbred horses (n = 148), we genotyped 68 SNPs in 17 putative exercise-relevant genes chosen from a genome scan for selection. We performed a series of case–control and quantitative association tests for relationships with racecourse performance. Thirteen SNPs in nine genes were significantly (P < 0.05) associated with a performance phenotype. We selected five SNPs in four genes (ACSS1, ACN9, COX4I1, PDK4) for validation in an independent sample set of elite and non-elite Thoroughbreds (n = 130). Two SNPs in the PDK4 gene were validated (P < 0.01) for associations with elite racing performance. When all samples were considered together (n = 278), the PDK4_ 38973231 SNP was strongly associated (P < 0.0005) with elite racing performance. Individuals with the A:A and A:G genotypes had a 16.2–16.6 lb advantage over G:G individuals in terms of handicap rating. Re-sequencing of the PDK4 gene and further genotyping will be required to identify the causative variant that is likely influencing exercise-induced variation in expression of the gene. Notwithstanding, this information may be employed as a marker for the selection of racehorses with the genetic potential for superior racing ability.
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a genome wide snp association study confirms a sequence variant g 66493737c t in the equine myostatin mstn gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86). Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Background Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. Results A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin ( MSTN ) [ P _unadj. = 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 ( P _unadj. = 1.61 × 10^-9; P _Bonf. = 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 ( r ^2 = 0.86). Conclusions Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10^-10; BIEC2-417495, P _unadj. = 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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a sequence polymorphism in mstn predicts sprinting ability and racing stamina in Thoroughbred horses
PLOS ONE, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Lisa M. Katz, Suzanne S Eivers, Rita G Fonseca, Beatrice A Mcgivney, Preethi Govindarajan, David E. MachughAbstract:Variants of the MSTN gene encoding myostatin are associated with muscle hypertrophy phenotypes in a range of mammalian species, most notably cattle, dogs, mice, and humans. Using a sample of registered Thoroughbred horses (n = 148), we have identified a novel MSTN sequence polymorphism that is strongly associated (g.66493737C>T, P = 4.85×10−8) with best race distance among elite racehorses (n = 79). This observation was independently validated (P = 1.91×10−6) in a resampled group of Thoroughbreds (n = 62) and in a cohort of Thoroughbreds (n = 37, P = 0.0047) produced by the same trainer. We observed that C/C horses are suited to fast, short-distance races; C/T horses compete favorably in middle-distance races; and T/T horses have greater stamina. Evaluation of retrospective racecourse performance (n = 142) and stallion progeny performance predict that C/C and C/T horses are more likely to be successful two-year-old racehorses than T/T animals. Here we describe for the first time the identification of a gene variant in Thoroughbred racehorses that is predictive of genetic potential for an athletic phenotype.
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A genome scan for positive selection in Thoroughbred horses.
PLOS ONE, 2009Co-Authors: Jingjing Gu, Stephen D. E. Park, Lisa M. Katz, G. E. Sulimova, David E. Machugh, Emmeline W HillAbstract:: Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1) deviations from expected heterozygosity (Ewens-Watterson test) in Thoroughbred (n = 112) and (2) global differentiation among four geographically diverse horse populations (F(ST)). We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P
Emmeline W Hill - One of the best experts on this subject based on the ideXlab platform.
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Thoroughbred racehorse mitochondrial dna demonstrates closer than expected links between maternal genetic history and pedigree records
Journal of Animal Breeding and Genetics, 2013Co-Authors: Mim A Bower, Mark Whitten, R E R Nisbet, Matthew Spencer, K M Dominy, A Murphy, R Cassidy, Elizabeth S Barrett, Emmeline W Hill, M M BinnsAbstract:Summary The potential future earnings and therefore value of Thoroughbred foals untested in the racing arena are calculated based on the performance of their forebears. Thus, lineage is of key importance. However, previous research indicates that maternally inherited mitochondrial DNA (mtDNA) does not correspond to maternal lineage according to recorded pedigree, casting doubt on the voracity of historic pedigrees. We analysed mtDNA of 296 Thoroughbred horses from 33 maternal lineages and identified an interesting trend. Subsequent to the founding of the Thoroughbred breed in the 16th century, well-populated maternal lineages were divided into sub-lineages. Only six in 10 of the Thoroughbreds sampled shared mitochondrial haplotype with other members of their maternal lineage, despite having a common maternal ancestor according to pedigree records. However, nine in 10 Thoroughbreds from the 103 sub-lineages sampled shared mtDNA with horses of their maternal pedigree sub-lineage. Thus, Thoroughbred maternal sub-lineage pedigree represents a more accurate breeding record than previously thought. Errors in pedigrees must have occurred largely, though, not exclusively, at sub-lineage foundation events, probably due to incomplete understanding of modes of inheritance in the past, where maternal sub-lineages were founded from individuals, related, but not by female descent.
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the cosmopolitan maternal heritage of the Thoroughbred racehorse breed shows a significant contribution from british and irish native mares
Biology Letters, 2011Co-Authors: Mim A Bower, R E R Nisbet, R Cassidy, Elizabeth S Barrett, Emmeline W Hill, Michael G. Campana, M Whitten, Ceiridwen J Edwards, Huw Jones, Christopher J HoweAbstract:The paternal origins of Thoroughbred racehorses trace back to a handful of Middle Eastern stallions, imported to the British Isles during the seventeenth century. Yet, few details of the foundation mares were recorded, in many cases not even their names (several different maternal lineages trace back to ‘A Royal Mare’). This has fuelled intense speculation over their origins. We examined mitochondrial DNA from 1929 horses to determine the origin of Thoroughbred foundation mares. There is no evidence to support exclusive Arab maternal origins as some historical records have suggested, or a significant importation of Oriental mares (the term used in historic records to refer to Middle East and western Asian breeds including Arab, Akhal-Teke, Barb and Caspian). Instead, we show that Thoroughbred foundation mares had a cosmopolitan European heritage with a far greater contribution from British and Irish Native mares than previously recognized.
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targets of selection in the Thoroughbred genome contain exercise relevant gene snps associated with elite racecourse performance
Animal Genetics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, David E. MachughAbstract:Summary Athletic performance is influenced by a complex interplay among the environment and a suite of genes, which contributes to system-wide structure and function. In a panel of elite and non-elite Thoroughbred horses (n = 148), we genotyped 68 SNPs in 17 putative exercise-relevant genes chosen from a genome scan for selection. We performed a series of case–control and quantitative association tests for relationships with racecourse performance. Thirteen SNPs in nine genes were significantly (P < 0.05) associated with a performance phenotype. We selected five SNPs in four genes (ACSS1, ACN9, COX4I1, PDK4) for validation in an independent sample set of elite and non-elite Thoroughbreds (n = 130). Two SNPs in the PDK4 gene were validated (P < 0.01) for associations with elite racing performance. When all samples were considered together (n = 278), the PDK4_ 38973231 SNP was strongly associated (P < 0.0005) with elite racing performance. Individuals with the A:A and A:G genotypes had a 16.2–16.6 lb advantage over G:G individuals in terms of handicap rating. Re-sequencing of the PDK4 gene and further genotyping will be required to identify the causative variant that is likely influencing exercise-induced variation in expression of the gene. Notwithstanding, this information may be employed as a marker for the selection of racehorses with the genetic potential for superior racing ability.
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a genome wide snp association study confirms a sequence variant g 66493737c t in the equine myostatin mstn gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86). Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Background Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. Results A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin ( MSTN ) [ P _unadj. = 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 ( P _unadj. = 1.61 × 10^-9; P _Bonf. = 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 ( r ^2 = 0.86). Conclusions Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10^-10; BIEC2-417495, P _unadj. = 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
Jingjing Gu - One of the best experts on this subject based on the ideXlab platform.
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The genetic origin and history of speed in the Thoroughbred racehorse
Nature Communications, 2012Co-Authors: Mim A Bower, Jingjing Gu, Beatrice A Mcgivney, Michael G. Campana, Lisa S. Andersson, Elizabeth Barrett, Catherine R. Davis, Sofia Mikko, Frauke Stock, Valery VoronkovaAbstract:A genetic variation in the horse myostatin gene is found at a very high frequency in the best Thoroughbred sprinters. This study shows, using molecular and pedigree data from modern and historic horses, that a single introduction of the variant occurred at the foundation stages of the Thoroughbred from a British native mare. Selective breeding for speed in the racehorse has resulted in an unusually high frequency of the C-variant (g.66493737C/T) at the myostatin gene ( MSTN ) in cohorts of the Thoroughbred horse population that are best suited to sprint racing. Here we show using a combination of molecular- and pedigree-based approaches in 593 horses from 22 Eurasian and North-American horse populations, museum specimens from 12 historically important Thoroughbred stallions (b.1764–1930), 330 elite-performing modern Thoroughbreds and 42 samples from three other equid species that the T-allele was ancestral and there was a single introduction of the C-allele at the foundation stages of the Thoroughbred from a British-native mare. Furthermore, we show that although the C-allele was rare among the celebrated racehorses of the 18th and 19th centuries, it has proliferated recently in the population via the stallion Nearctic (b.1954), the sire of the most influential stallion of modern time, Northern Dancer (b.1961).
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targets of selection in the Thoroughbred genome contain exercise relevant gene snps associated with elite racecourse performance
Animal Genetics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, David E. MachughAbstract:Summary Athletic performance is influenced by a complex interplay among the environment and a suite of genes, which contributes to system-wide structure and function. In a panel of elite and non-elite Thoroughbred horses (n = 148), we genotyped 68 SNPs in 17 putative exercise-relevant genes chosen from a genome scan for selection. We performed a series of case–control and quantitative association tests for relationships with racecourse performance. Thirteen SNPs in nine genes were significantly (P < 0.05) associated with a performance phenotype. We selected five SNPs in four genes (ACSS1, ACN9, COX4I1, PDK4) for validation in an independent sample set of elite and non-elite Thoroughbreds (n = 130). Two SNPs in the PDK4 gene were validated (P < 0.01) for associations with elite racing performance. When all samples were considered together (n = 278), the PDK4_ 38973231 SNP was strongly associated (P < 0.0005) with elite racing performance. Individuals with the A:A and A:G genotypes had a 16.2–16.6 lb advantage over G:G individuals in terms of handicap rating. Re-sequencing of the PDK4 gene and further genotyping will be required to identify the causative variant that is likely influencing exercise-induced variation in expression of the gene. Notwithstanding, this information may be employed as a marker for the selection of racehorses with the genetic potential for superior racing ability.
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a genome wide snp association study confirms a sequence variant g 66493737c t in the equine myostatin mstn gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86). Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Background Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. Results A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin ( MSTN ) [ P _unadj. = 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 ( P _unadj. = 1.61 × 10^-9; P _Bonf. = 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 ( r ^2 = 0.86). Conclusions Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10^-10; BIEC2-417495, P _unadj. = 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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a sequence polymorphism in mstn predicts sprinting ability and racing stamina in Thoroughbred horses
PLOS ONE, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Lisa M. Katz, Suzanne S Eivers, Rita G Fonseca, Beatrice A Mcgivney, Preethi Govindarajan, David E. MachughAbstract:Variants of the MSTN gene encoding myostatin are associated with muscle hypertrophy phenotypes in a range of mammalian species, most notably cattle, dogs, mice, and humans. Using a sample of registered Thoroughbred horses (n = 148), we have identified a novel MSTN sequence polymorphism that is strongly associated (g.66493737C>T, P = 4.85×10−8) with best race distance among elite racehorses (n = 79). This observation was independently validated (P = 1.91×10−6) in a resampled group of Thoroughbreds (n = 62) and in a cohort of Thoroughbreds (n = 37, P = 0.0047) produced by the same trainer. We observed that C/C horses are suited to fast, short-distance races; C/T horses compete favorably in middle-distance races; and T/T horses have greater stamina. Evaluation of retrospective racecourse performance (n = 142) and stallion progeny performance predict that C/C and C/T horses are more likely to be successful two-year-old racehorses than T/T animals. Here we describe for the first time the identification of a gene variant in Thoroughbred racehorses that is predictive of genetic potential for an athletic phenotype.
Beatrice A Mcgivney - One of the best experts on this subject based on the ideXlab platform.
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The genetic origin and history of speed in the Thoroughbred racehorse
Nature Communications, 2012Co-Authors: Mim A Bower, Jingjing Gu, Beatrice A Mcgivney, Michael G. Campana, Lisa S. Andersson, Elizabeth Barrett, Catherine R. Davis, Sofia Mikko, Frauke Stock, Valery VoronkovaAbstract:A genetic variation in the horse myostatin gene is found at a very high frequency in the best Thoroughbred sprinters. This study shows, using molecular and pedigree data from modern and historic horses, that a single introduction of the variant occurred at the foundation stages of the Thoroughbred from a British native mare. Selective breeding for speed in the racehorse has resulted in an unusually high frequency of the C-variant (g.66493737C/T) at the myostatin gene ( MSTN ) in cohorts of the Thoroughbred horse population that are best suited to sprint racing. Here we show using a combination of molecular- and pedigree-based approaches in 593 horses from 22 Eurasian and North-American horse populations, museum specimens from 12 historically important Thoroughbred stallions (b.1764–1930), 330 elite-performing modern Thoroughbreds and 42 samples from three other equid species that the T-allele was ancestral and there was a single introduction of the C-allele at the foundation stages of the Thoroughbred from a British-native mare. Furthermore, we show that although the C-allele was rare among the celebrated racehorses of the 18th and 19th centuries, it has proliferated recently in the population via the stallion Nearctic (b.1954), the sire of the most influential stallion of modern time, Northern Dancer (b.1961).
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targets of selection in the Thoroughbred genome contain exercise relevant gene snps associated with elite racecourse performance
Animal Genetics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, David E. MachughAbstract:Summary Athletic performance is influenced by a complex interplay among the environment and a suite of genes, which contributes to system-wide structure and function. In a panel of elite and non-elite Thoroughbred horses (n = 148), we genotyped 68 SNPs in 17 putative exercise-relevant genes chosen from a genome scan for selection. We performed a series of case–control and quantitative association tests for relationships with racecourse performance. Thirteen SNPs in nine genes were significantly (P < 0.05) associated with a performance phenotype. We selected five SNPs in four genes (ACSS1, ACN9, COX4I1, PDK4) for validation in an independent sample set of elite and non-elite Thoroughbreds (n = 130). Two SNPs in the PDK4 gene were validated (P < 0.01) for associations with elite racing performance. When all samples were considered together (n = 278), the PDK4_ 38973231 SNP was strongly associated (P < 0.0005) with elite racing performance. Individuals with the A:A and A:G genotypes had a 16.2–16.6 lb advantage over G:G individuals in terms of handicap rating. Re-sequencing of the PDK4 gene and further genotyping will be required to identify the causative variant that is likely influencing exercise-induced variation in expression of the gene. Notwithstanding, this information may be employed as a marker for the selection of racehorses with the genetic potential for superior racing ability.
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a genome wide snp association study confirms a sequence variant g 66493737c t in the equine myostatin mstn gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (MSTN) [Punadj. = 6.96 × 10-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (Punadj. = 1.61 × 10-9; PBonf. = 6.58 × 10-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (r2 = 0.86). Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10-10; BIEC2-417495, Punadj. = 1.61 × 10-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses
BMC Genomics, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Beatrice A Mcgivney, Ronan Whiston, David E. MachughAbstract:Background Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important. Results A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of n = 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin ( MSTN ) [ P _unadj. = 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 ( P _unadj. = 1.61 × 10^-9; P _Bonf. = 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in MSTN associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the MSTN gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 ( r ^2 = 0.86). Conclusions Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, P = 1.02 × 10^-10; BIEC2-417495, P _unadj. = 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.
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a sequence polymorphism in mstn predicts sprinting ability and racing stamina in Thoroughbred horses
PLOS ONE, 2010Co-Authors: Emmeline W Hill, Jingjing Gu, Lisa M. Katz, Suzanne S Eivers, Rita G Fonseca, Beatrice A Mcgivney, Preethi Govindarajan, David E. MachughAbstract:Variants of the MSTN gene encoding myostatin are associated with muscle hypertrophy phenotypes in a range of mammalian species, most notably cattle, dogs, mice, and humans. Using a sample of registered Thoroughbred horses (n = 148), we have identified a novel MSTN sequence polymorphism that is strongly associated (g.66493737C>T, P = 4.85×10−8) with best race distance among elite racehorses (n = 79). This observation was independently validated (P = 1.91×10−6) in a resampled group of Thoroughbreds (n = 62) and in a cohort of Thoroughbreds (n = 37, P = 0.0047) produced by the same trainer. We observed that C/C horses are suited to fast, short-distance races; C/T horses compete favorably in middle-distance races; and T/T horses have greater stamina. Evaluation of retrospective racecourse performance (n = 142) and stallion progeny performance predict that C/C and C/T horses are more likely to be successful two-year-old racehorses than T/T animals. Here we describe for the first time the identification of a gene variant in Thoroughbred racehorses that is predictive of genetic potential for an athletic phenotype.
K L P Verheyen - One of the best experts on this subject based on the ideXlab platform.
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descriptive epidemiology of joint injuries in Thoroughbred racehorses in training
Equine Veterinary Journal, 2012Co-Authors: Suzanne R Reed, B F Jackson, C Mc W Ilwraith, I M Wright, R Pilsworth, S Knapp, J L N Wood, Joanna S Price, K L P VerheyenAbstract:Summary Reasons for performing study: No large scale epidemiological studies have previously quantified the occurrence of carpal, metacarpo- and metatarsophalangeal (MCP/MTP) joint injuries in Thoroughbred racehorses. Objectives: To develop an objective classification system for carpal and MCP/MTP joint injuries and estimate the incidence of these injuries in young Thoroughbreds in flat race training. Methods: In a prospective cohort study, data on daily exercise and veterinary-diagnosed carpal and MCP/MTP joint injuries were collected from Thoroughbreds monitored since starting training as yearlings, for up to 2 years. Cases were classified in one of 4 categories: 1) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; no diagnostic imaging performed; 2) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; radiographs taken but no abnormalities detected; 3) evidence of abnormality of subchondral bone and/or articular margin(s) on diagnostic imaging and 4) evidence of discontinuity of the articular surface on diagnostic imaging. Incidence rates and rate ratios were estimated using Poisson regression, adjusting for trainer-level clustering. Results: A total of 647 horses from 13 trainers throughout England contributed 7785 months at risk of joint injury. One-hundred-and-eighty-four cases of carpal (n = 82) or MCP/MTP (n = 102) joint injury were reported in 165 horses and classified in Category 1 (n = 21), Category 2 (n = 21), Category 3 (n = 72) or Category 4 (n = 70). The overall joint injury rate was 1.8 per 100 horse months (95% CI = 1.2, 2.8); rates did not differ significantly between 2- and 3-year-olds but females sustained Category 1 injuries at triple the rate of males (P = 0.03). Joint injury rates differed significantly between trainers (P<0.001) and there was trainer variation in anatomical site and severity of injury. Conclusions and potential relevance: Carpal and MCP/MTP joint injuries are an important cause of morbidity in Thoroughbred racehorses. Identification of modifiable risk factors for these injuries may reduce their incidence.
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descriptive epidemiology of fractures occurring in british Thoroughbred racehorses in training
Equine Veterinary Journal, 2010Co-Authors: K L P Verheyen, J L N WoodAbstract:Summary Reasons for performing study: Musculoskeletal injury is the major cause of days lost from training and wastage in Thoroughbred racehorses. Little scientific information is available on the majority of injuries occurring in training. Objectives: To estimate the incidence of fractures in British racehorses in training and describe the occurrence of different fracture types and bones involved. Methods: Thirteen UK racehorse trainers participated in a prospective study, providing data on horses in their care for 2 years. Details on horses, their daily exercise and fracture occurrence were recorded. Results: A total of 1178 horses provided 12,893 months at risk. Nontraumatic fracture incidence was 1.15/100 horse months (95% CI = 0.98, 1.35) and 78% of fractures occurred during training. A wide variety of fracture types and bones were involved, although at least 57% were stress fractures. Pelvic and tibial stress injuries accounted for 28% of fractures diagnosed. Conclusions: It is important to study injuries in training as well as in racing. The number of stress fractures suggests that training regimes for young Thoroughbreds could often be improved to create a more robust skeleton, able to withstand injury. Potential relevance: Studying injuries in racehorses in training can provide a scientific basis for the design of safer training regimes.;