The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

Emmeline W Hill - One of the best experts on this subject based on the ideXlab platform.

  • Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred Horse population
    Scientific Reports, 2020
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Lisa M Katz, Haige Han, Leanne R. Corduff, Teruaki Tozaki, Emmeline W Hill
    Abstract:

    The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date ( n  = 10,118), including prominent stallions ( n  = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades ( F _IS R ^2 = 0.942, P  = 2.19 × 10^−13; F _ROH R ^2 = 0.88, P  = 1.81 × 10^−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend.

  • genomic inbreeding trends in the global Thoroughbred Horse population driven by influential sire lines and selection for exercise trait related genes
    bioRxiv, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Haige Han, Leanne R. Corduff, Teruaki Tozaki, L M Katz, Emmeline W Hill
    Abstract:

    Abstract The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades (FISR2 = 0.942, P = 2.19 × 10−13; FROHR2 = 0.88, P = 1.81 × 10−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend. Author Summary In the highly valuable global Thoroughbred Horse industry, there is no systematic industry-mediated genetic population management. Purposeful inbreeding is common practice and there is an increasing use of popular sires. Inbreeding can lead to population health and fertility decline, but there is little objective genomics-based data for the Thoroughbred to catalyse action and support changes in breeding practices. Here, we describe the most comprehensive genetic analysis in the population among 10,000 Thoroughbreds from the major bloodstock regions of the world and reveal a highly significant increase in inbreeding during the last five decades. The main drivers of genetic diversity are the most influential ‘breed-shaping’ sire lines, Sadler’s Wells, Danehill and A.P. Indy. We identified genomic regions subject to positive selection containing genes for athletic traits. Our results highlight the need for population-wide efforts to proactively avert the potential increase of deleterious alleles that may impact on animal health in order to safeguard the future of a breed that is admired for its athleticism and enjoyed for sport worldwide.

  • a genomic prediction model for racecourse starts in the Thoroughbred Horse
    Animal Genetics, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, L M Katz, Belinda Hernandez, S P Mcgovern, Andrew C Parnell, H L Wiencko, Emmeline W Hill
    Abstract:

    Durability traits in Thoroughbred Horses are heritable, economically valuable and may affect Horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a Horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2 = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the Horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the Horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 Horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced Horses (16% unraced) than did low (27% unraced) potential Horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict Horses with a greater chance of a racecourse start.

  • Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred Horse.
    PloS one, 2017
    Co-Authors: Mary F. Rooney, Lisa M Katz, Richard K. Porter, Emmeline W Hill
    Abstract:

    Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the Horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred Horses. Skeletal muscle fibre type proportions were significantly (p T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN Horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred Horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN Horses.

  • Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred Horse skeletal muscle.
    Equine veterinary journal. Supplement, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, Lisa M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a

Beatrice A Mcgivney - One of the best experts on this subject based on the ideXlab platform.

  • Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred Horse population
    Scientific Reports, 2020
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Lisa M Katz, Haige Han, Leanne R. Corduff, Teruaki Tozaki, Emmeline W Hill
    Abstract:

    The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date ( n  = 10,118), including prominent stallions ( n  = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades ( F _IS R ^2 = 0.942, P  = 2.19 × 10^−13; F _ROH R ^2 = 0.88, P  = 1.81 × 10^−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend.

  • genomic inbreeding trends in the global Thoroughbred Horse population driven by influential sire lines and selection for exercise trait related genes
    bioRxiv, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Haige Han, Leanne R. Corduff, Teruaki Tozaki, L M Katz, Emmeline W Hill
    Abstract:

    Abstract The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades (FISR2 = 0.942, P = 2.19 × 10−13; FROHR2 = 0.88, P = 1.81 × 10−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend. Author Summary In the highly valuable global Thoroughbred Horse industry, there is no systematic industry-mediated genetic population management. Purposeful inbreeding is common practice and there is an increasing use of popular sires. Inbreeding can lead to population health and fertility decline, but there is little objective genomics-based data for the Thoroughbred to catalyse action and support changes in breeding practices. Here, we describe the most comprehensive genetic analysis in the population among 10,000 Thoroughbreds from the major bloodstock regions of the world and reveal a highly significant increase in inbreeding during the last five decades. The main drivers of genetic diversity are the most influential ‘breed-shaping’ sire lines, Sadler’s Wells, Danehill and A.P. Indy. We identified genomic regions subject to positive selection containing genes for athletic traits. Our results highlight the need for population-wide efforts to proactively avert the potential increase of deleterious alleles that may impact on animal health in order to safeguard the future of a breed that is admired for its athleticism and enjoyed for sport worldwide.

  • a genomic prediction model for racecourse starts in the Thoroughbred Horse
    Animal Genetics, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, L M Katz, Belinda Hernandez, S P Mcgovern, Andrew C Parnell, H L Wiencko, Emmeline W Hill
    Abstract:

    Durability traits in Thoroughbred Horses are heritable, economically valuable and may affect Horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a Horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2 = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the Horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the Horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 Horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced Horses (16% unraced) than did low (27% unraced) potential Horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict Horses with a greater chance of a racecourse start.

  • Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred Horse skeletal muscle.
    Equine veterinary journal. Supplement, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, Lisa M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a

  • moderate and high intensity sprint exercise induce differential responses in cox4i2 and pdk4 gene expression in Thoroughbred Horse skeletal muscle
    Equine Veterinary Journal, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, L M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a<0.05) was determined using Student's t tests. Results: COX4I2 mRNA expression decreased significantly in Group A and remained unchanged in Group B between T0 vs. T2 (-1.7-fold, P = 0.017; -1.0-fold, P = 0.859). PDK4 mRNA expression increased significantly in Group B but not in Group A between T0 vs. T1 (3.8-fold, P = 0.039; 1.4-fold, P = 0.591). There were no significant changes in the expression in CKM or COX4I1 mRNA abundance in either group. Conclusions: Different exercise protocols elicit variable transcriptional responses in key exercise relevant genes in equine skeletal muscle due to variation in metabolic demand. evj_206

David E Machugh - One of the best experts on this subject based on the ideXlab platform.

  • Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred Horse population
    Scientific Reports, 2020
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Lisa M Katz, Haige Han, Leanne R. Corduff, Teruaki Tozaki, Emmeline W Hill
    Abstract:

    The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date ( n  = 10,118), including prominent stallions ( n  = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades ( F _IS R ^2 = 0.942, P  = 2.19 × 10^−13; F _ROH R ^2 = 0.88, P  = 1.81 × 10^−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend.

  • genomic inbreeding trends in the global Thoroughbred Horse population driven by influential sire lines and selection for exercise trait related genes
    bioRxiv, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Haige Han, Leanne R. Corduff, Teruaki Tozaki, L M Katz, Emmeline W Hill
    Abstract:

    Abstract The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades (FISR2 = 0.942, P = 2.19 × 10−13; FROHR2 = 0.88, P = 1.81 × 10−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend. Author Summary In the highly valuable global Thoroughbred Horse industry, there is no systematic industry-mediated genetic population management. Purposeful inbreeding is common practice and there is an increasing use of popular sires. Inbreeding can lead to population health and fertility decline, but there is little objective genomics-based data for the Thoroughbred to catalyse action and support changes in breeding practices. Here, we describe the most comprehensive genetic analysis in the population among 10,000 Thoroughbreds from the major bloodstock regions of the world and reveal a highly significant increase in inbreeding during the last five decades. The main drivers of genetic diversity are the most influential ‘breed-shaping’ sire lines, Sadler’s Wells, Danehill and A.P. Indy. We identified genomic regions subject to positive selection containing genes for athletic traits. Our results highlight the need for population-wide efforts to proactively avert the potential increase of deleterious alleles that may impact on animal health in order to safeguard the future of a breed that is admired for its athleticism and enjoyed for sport worldwide.

  • a genomic prediction model for racecourse starts in the Thoroughbred Horse
    Animal Genetics, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, L M Katz, Belinda Hernandez, S P Mcgovern, Andrew C Parnell, H L Wiencko, Emmeline W Hill
    Abstract:

    Durability traits in Thoroughbred Horses are heritable, economically valuable and may affect Horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a Horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2 = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the Horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the Horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 Horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced Horses (16% unraced) than did low (27% unraced) potential Horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict Horses with a greater chance of a racecourse start.

  • Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred Horse skeletal muscle.
    Equine veterinary journal. Supplement, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, Lisa M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a

  • moderate and high intensity sprint exercise induce differential responses in cox4i2 and pdk4 gene expression in Thoroughbred Horse skeletal muscle
    Equine Veterinary Journal, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, L M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a<0.05) was determined using Student's t tests. Results: COX4I2 mRNA expression decreased significantly in Group A and remained unchanged in Group B between T0 vs. T2 (-1.7-fold, P = 0.017; -1.0-fold, P = 0.859). PDK4 mRNA expression increased significantly in Group B but not in Group A between T0 vs. T1 (3.8-fold, P = 0.039; 1.4-fold, P = 0.591). There were no significant changes in the expression in CKM or COX4I1 mRNA abundance in either group. Conclusions: Different exercise protocols elicit variable transcriptional responses in key exercise relevant genes in equine skeletal muscle due to variation in metabolic demand. evj_206

Lisa M Katz - One of the best experts on this subject based on the ideXlab platform.

  • Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred Horse population
    Scientific Reports, 2020
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Lisa M Katz, Haige Han, Leanne R. Corduff, Teruaki Tozaki, Emmeline W Hill
    Abstract:

    The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date ( n  = 10,118), including prominent stallions ( n  = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades ( F _IS R ^2 = 0.942, P  = 2.19 × 10^−13; F _ROH R ^2 = 0.88, P  = 1.81 × 10^−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend.

  • Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred Horse.
    PloS one, 2017
    Co-Authors: Mary F. Rooney, Lisa M Katz, Richard K. Porter, Emmeline W Hill
    Abstract:

    Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the Horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred Horses. Skeletal muscle fibre type proportions were significantly (p T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN Horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred Horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN Horses.

  • Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred Horse skeletal muscle.
    Equine veterinary journal. Supplement, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, Lisa M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a

  • alterations in oxidative gene expression in equine skeletal muscle following exercise and training
    Physiological Genomics, 2010
    Co-Authors: Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, Katie Menson, Stephen D E Park, Joseluis L Rivero, Cormac T Taylor, Lisa M Katz, Emmeline W Hill
    Abstract:

    Intense selection for elite racing performance in the Thoroughbred Horse (Equus caballus) has resulted in a number of adaptive physiological phenotypes relevant to exercise; however, the underlying...

L M Katz - One of the best experts on this subject based on the ideXlab platform.

  • genomic inbreeding trends in the global Thoroughbred Horse population driven by influential sire lines and selection for exercise trait related genes
    bioRxiv, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, Haige Han, Leanne R. Corduff, Teruaki Tozaki, L M Katz, Emmeline W Hill
    Abstract:

    Abstract The Thoroughbred Horse is a highly valued domestic animal population under strong selection for athletic phenotypes. Here we present a high resolution genomics-based analysis of inbreeding in the population that may form the basis for evidence-based discussion amid concerns in the breeding industry over the increasing use of small numbers of popular sire lines, which may accelerate a loss of genetic diversity. In the most comprehensive globally representative sample of Thoroughbreds to-date (n = 10,118), including prominent stallions (n = 305) from the major bloodstock regions of the world, we show using pan-genomic SNP genotypes that there has been a highly significant decline in global genetic diversity during the last five decades (FISR2 = 0.942, P = 2.19 × 10−13; FROHR2 = 0.88, P = 1.81 × 10−10) that has likely been influenced by the use of popular sire lines. Estimates of effective population size in the global and regional populations indicate that there is some level of regional variation that may be exploited to improve global genetic diversity. Inbreeding is often a consequence of selection, which in managed animal populations tends to be driven by preferences for cultural, aesthetic or economically advantageous phenotypes. Using a composite selection signals approach, we show that centuries of selection for favourable athletic traits among Thoroughbreds acts on genes with functions in behaviour, musculoskeletal conformation and metabolism. As well as classical selective sweeps at core loci, polygenic adaptation for functional modalities in cardiovascular signalling, organismal growth and development, cellular stress and injury, metabolic pathways and neurotransmitters and other nervous system signalling has shaped the Thoroughbred athletic phenotype. Our results demonstrate that genomics-based approaches to identify genetic outcrosses will add valuable objectivity to augment traditional methods of stallion selection and that genomics-based methods will be beneficial to actively monitor the population to address the marked inbreeding trend. Author Summary In the highly valuable global Thoroughbred Horse industry, there is no systematic industry-mediated genetic population management. Purposeful inbreeding is common practice and there is an increasing use of popular sires. Inbreeding can lead to population health and fertility decline, but there is little objective genomics-based data for the Thoroughbred to catalyse action and support changes in breeding practices. Here, we describe the most comprehensive genetic analysis in the population among 10,000 Thoroughbreds from the major bloodstock regions of the world and reveal a highly significant increase in inbreeding during the last five decades. The main drivers of genetic diversity are the most influential ‘breed-shaping’ sire lines, Sadler’s Wells, Danehill and A.P. Indy. We identified genomic regions subject to positive selection containing genes for athletic traits. Our results highlight the need for population-wide efforts to proactively avert the potential increase of deleterious alleles that may impact on animal health in order to safeguard the future of a breed that is admired for its athleticism and enjoyed for sport worldwide.

  • a genomic prediction model for racecourse starts in the Thoroughbred Horse
    Animal Genetics, 2019
    Co-Authors: Beatrice A Mcgivney, David E Machugh, L M Katz, Belinda Hernandez, S P Mcgovern, Andrew C Parnell, H L Wiencko, Emmeline W Hill
    Abstract:

    Durability traits in Thoroughbred Horses are heritable, economically valuable and may affect Horse welfare. The aims of this study were to test the hypotheses that (i) durability traits are heritable and (ii) genetic data may be used to predict a Horse's potential to have a racecourse start. Heritability for the phenotype 'number of 2- and 3-year-old starts' was estimated to be h m 2 = 0.11 ± 0.02 (n = 4499). A genome-wide association study identified SNP contributions to the trait. The neurotrimin (NTM), opioid-binding protein/cell adhesion molecule like (OPCML) and prolylcarboxypeptidase (PRCP) genes were identified as candidate genes associated with the trait. NTM functions in brain development and has been shown to have been selected during the domestication of the Horse. PRCP is an established expression quantitative trait locus involved in the interaction between voluntary exercise and body composition in mice. We hypothesise that variation at these loci contributes to the motivation of the Horse to exercise, which may influence its response to the demands of the training and racing environment. A random forest with mixed effects (RFME) model identified a set of SNPs that contributed to 24.7% of the heritable variation in the trait. In an independent validation set (n = 528 Horses), the cohort with high genetic potential for a racecourse start had significantly fewer unraced Horses (16% unraced) than did low (27% unraced) potential Horses and had more favourable race outcomes among those that raced. Therefore, the information from SNPs included in the model may be used to predict Horses with a greater chance of a racecourse start.

  • moderate and high intensity sprint exercise induce differential responses in cox4i2 and pdk4 gene expression in Thoroughbred Horse skeletal muscle
    Equine Veterinary Journal, 2010
    Co-Authors: Emmeline W Hill, Suzanne S Eivers, Beatrice A Mcgivney, Rita G Fonseca, David E Machugh, N. A. Smith, John A. Browne, L M Katz
    Abstract:

    Summary Reasons for performing study: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred Horse has not been reported previously. Objective: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred Horses. Materials and methods: Two groups of trained 3-year-old Thoroughbred Horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HRmax on a Sato high speed treadmill (distance = 5418.67m 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all- weather gallop (distance = 812.83 m 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T0), immediately post exercise (T1) and 4 h post exercise (T2). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (a<0.05) was determined using Student's t tests. Results: COX4I2 mRNA expression decreased significantly in Group A and remained unchanged in Group B between T0 vs. T2 (-1.7-fold, P = 0.017; -1.0-fold, P = 0.859). PDK4 mRNA expression increased significantly in Group B but not in Group A between T0 vs. T1 (3.8-fold, P = 0.039; 1.4-fold, P = 0.591). There were no significant changes in the expression in CKM or COX4I1 mRNA abundance in either group. Conclusions: Different exercise protocols elicit variable transcriptional responses in key exercise relevant genes in equine skeletal muscle due to variation in metabolic demand. evj_206