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Liu H, Zhu B, Wang T, Dong Y, Ju Y, Li Y, Su W, Zhang R, Dong S, Wang H, Zhou Y, Zhu Y, Wang L, Zhang Z, Zhao P, Zhang S, Guo R, A E, Zhang Y, Liu X, Tamate HB, Liang Q, Ma D, Xing X. Population genomics of sika deer reveals recent speciation and genetic selective signatures during evolution and domestication. BMC Genomics 2025; 26:364. [PMID: 40217144 PMCID: PMC11987376 DOI: 10.1186/s12864-025-11541-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 03/28/2025] [Indexed: 04/15/2025] Open
Abstract
BACKGROUND Population genomic analysis can reconstruct the phylogenetic relationship and demographic history, and identify genomic selective signatures of a species. To date, fundamental aspects of population genomic analyses, such as intraspecies taxonomy, evolutionary history, and adaptive evolution, of sika deer have not been systematically investigated. Furthermore, accumulating lines of evidences have illustrated that incorrect species delimitation will mislead conservation decisions, and even lead to irreversible mistakes in threatened species. RESULTS In this study, we resequenced 81 wild and 71 domesticated sika deer representing 10 main geographic populations and two farms to clarify the species delimitation, demographic and divergence histories, and adaptive evolution of this species. First, our analyses of whole genomes, Y chromosomes and mitochondrial genomes revealed substantial genetic differentiation between the continental and Japanese lineages of sika deer, representing two phylogenetically distinct species. Second, sika deer in Japan were inferred to have experienced a "divergence-mixing-isolation" evolutionary scenario. Third, we identified four candidate genes (XKR4, NPAS3, CTNNA3, and CNTNAP5) possibly involved in body size regulation of sika deer by selective sweep analysis. Furthermore, we also detected two candidate genes (NRP2 and EDIL3) that may be associated with an important economic trait (antler weight) were under selection during the process of domestication. CONCLUSION Population genomic analyses revealed that the continental and Japanese lineages represent distinct phylogenetic species. Moreover, our results provide insights into the genetic selection signatures related to body size differences and a valuable genomic resource for future genetic studies and genomics-informed breeding of sika deer.
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Affiliation(s)
- Huamiao Liu
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Bo Zhu
- Novogene Bioinformatics Institute, Beijing, 100083, China
| | - Tianjiao Wang
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Yimeng Dong
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Yan Ju
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Yang Li
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Weilin Su
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Ranran Zhang
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Shiwu Dong
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Hongliang Wang
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Yongna Zhou
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Yanmin Zhu
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Lei Wang
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Zhengyi Zhang
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Pei Zhao
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China
| | - Shuyan Zhang
- Administration of Zhejiang Qingliangfeng National Nature Reserve, Hangzhou, 310000, China
| | - Rui Guo
- Administration of Zhejiang Qingliangfeng National Nature Reserve, Hangzhou, 310000, China
| | - E A
- Sichuan Tiebu Sika Deer Nature Reserve, Aba, 624000, China
| | - Yuwen Zhang
- Administrative Office of Liugong Island National Forest Park, Weihai, 264200, China
| | - Xin Liu
- Northeast Forestry University, Harbin, 150006, China
| | | | - Qiqi Liang
- Glbizzia Bioinformatics Institute, Beijing, 102208, China.
| | - De Ma
- Novogene Bioinformatics Institute, Beijing, 100083, China.
| | - Xiumei Xing
- State Key Laboratory for Molecular Biology of Special Economic Animals, Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, 130112, China.
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Lovász L, Sommer‐Trembo C, Barth JM, Scasta JD, Grancharova‐Hill R, Lemoine RT, Kerekes V, Merckling L, Bouskila A, Svenning J, Fages A. Rewilded horses in European nature conservation - a genetics, ethics, and welfare perspective. Biol Rev Camb Philos Soc 2025; 100:407-427. [PMID: 39279124 PMCID: PMC11718625 DOI: 10.1111/brv.13146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 09/02/2024] [Accepted: 09/05/2024] [Indexed: 09/18/2024]
Abstract
In recent decades, the integration of horses (Equus ferus) in European rewilding initiatives has gained widespread popularity due to their potential for regulating vegetation and restoring natural ecosystems. However, employing horses in conservation efforts presents important challenges, which we here explore and discuss. These challenges encompass the lack of consensus on key terms inherent to conservation and rewilding, the entrenched culture and strong emotions associated with horses, low genetic diversity and high susceptibility to hereditary diseases in animals under human selection, as well as insufficient consideration for the social behaviour of horses in wild-living populations. In addition, management of wild-living horses involves intricate welfare, ethics and legislative dimensions. Anthropocentric population-control initiatives may be detrimental to horse group structures since they tend to prioritise individual welfare over the health of populations and ecosystems. To overcome these challenges, we provide comprehensive recommendations. These involve a systematic acquisition of genetic information, a focus on genetic diversity rather than breed purity and minimal veterinary intervention in wild-living populations. Further, we advise allowing for natural top-down and bottom-up control - or, if impossible, simulating this by culling or non-lethal removal of horses - instead of using fertility control for population management. We advocate for intensified collaboration between conservation biologists and practitioners and enhanced communication with the general public. Decision-making should be informed by a thorough understanding of the genetic makeup, common health issues and dynamics, and social behaviour in wild-living horse populations. Such a holistic approach is essential to reconcile human emotions associated with horses with the implementation of conservation practices that are not only effective but also sustainable for the long-term viability of functional, biodiverse ecosystems, while rehabilitating the horse as a widespread wild-living species in Europe.
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Affiliation(s)
- Lilla Lovász
- Zoological Institute, Department of Environmental SciencesUniversity of BaselVesalgasse 1Basel4051Switzerland
| | - Carolin Sommer‐Trembo
- Department of PaleontologyUniversity of ZurichKarl‐Schmid‐Strasse 4Zurich8006Switzerland
| | - Julia M.I. Barth
- Zoological Institute, Department of Environmental SciencesUniversity of BaselVesalgasse 1Basel4051Switzerland
| | - John D. Scasta
- Department of Ecosystem Science and ManagementUniversity of Wyoming1000 E University AveLaramieWyoming82071USA
| | | | - Rhys T. Lemoine
- Center for Ecological Dynamics in a Novel Biosphere (ECONOVO), Department of BiologyAarhus UniversityNy Munkegade 116Aarhus C8000Denmark
| | - Viola Kerekes
- Hortobágy National Park DirectorateSumen u. 2Debrecen4024Hungary
| | - Léa Merckling
- Réserve Naturelle Petite Camargue Alsacienne1 Rue de la PiscicultureSaint‐Louis68300France
| | - Amos Bouskila
- Department of Life SciencesBen‐Gurion University of the NegevBen‐Gurion Blvd 1Beer‐Sheva84105Israel
| | - Jens‐Christian Svenning
- Center for Ecological Dynamics in a Novel Biosphere (ECONOVO), Department of BiologyAarhus UniversityNy Munkegade 116Aarhus C8000Denmark
| | - Antoine Fages
- Zoological Institute, Department of Environmental SciencesUniversity of BaselVesalgasse 1Basel4051Switzerland
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3
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An T, Dugarjaviin M, Han H. Expression and Analysis of TBX3 Gene in the Skin from Three Locations on Dun Mongolian Bider Horse. Genes (Basel) 2024; 15:1589. [PMID: 39766856 PMCID: PMC11675668 DOI: 10.3390/genes15121589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 12/09/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND/OBJECTIVES The Mongolian horse, one of the oldest and most genetically diverse breeds, exhibits a wide variety of coat colors and patterns, including both wild-type and unique features. A notable characteristic of dun Mongolian horses is the presence of Bider markings-symmetrical, black-mottled patterns observed on the shoulder blades. These markings are also seen in Przewalski's horses. The dun coat color, a common wild-type phenotype in domestic horses, is characterized by pigment dilution with distinct dark areas and is regulated by mutations in the TBX3 gene. This study aimed to investigate the role of TBX3 in the development of Bider markings in dun Mongolian horses. METHODS Skin tissue samples were collected from three key anatomical regions of dun Mongolian horses with Bider markings: the croup, dorsal midline, and shoulder. Histological staining was conducted to examine the skin and hair follicle structure and pigment distribution. RT-qPCR was used to measure TBX3 mRNA expression, while immunoblotting and immunohistochemistry were employed to analyze TBX3 protein levels and localization. RESULTS Hematoxylin and eosin staining revealed the skin and hair follicle structures, including the epidermis, hair shaft, and hair bulb across different stages of the hair growth cycle. Differences in pigmentation were observed across the sampling sites. The croup and the light-colored area of the shoulder showed asymmetrical pigmentation, while the dorsal midline and dark-colored area of the shoulder displayed symmetrical pigmentation. TBX3 mRNA expression levels were significantly higher in the croup compared to the shoulder and dorsal midline; however, corresponding TBX3 protein expression did not show significant differences. Immunohistochemical analysis localized TBX3 protein predominantly in the hair bulb and epidermis. CONCLUSIONS This study demonstrates region-specific differences in TBX3 expression that correlate with pigmentation patterns in dun Mongolian Bider horses. These findings provide valuable insights into the molecular mechanisms underlying Bider markings, offering a deeper understanding of the genetic regulation of coat color and primitive markings in equines.
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Affiliation(s)
| | | | - Haige Han
- Inner Mongolia Key Laboratory of Equine Science Research and Technology Innovation, Inner Mongolia Agricultural University, Hohhot 010018, China; (T.A.); (M.D.)
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Pokharel K, Weldenegodguad M, Reilas T, Kantanen J. EquCab_Finn: A new reference genome assembly for the domestic horse, Finnhorse. Anim Genet 2024; 55:766-771. [PMID: 38986537 DOI: 10.1111/age.13463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 06/27/2024] [Accepted: 06/30/2024] [Indexed: 07/12/2024]
Abstract
Finnhorse is Finland's native and national horse breed and it has genetic affinities to northern European and Asian horses. It has historical importance for agriculture, forest work and transport and as a war horse. Finnhorse has four breeding sections in the studbook and is under conservation and characterisation efforts. We sequenced and annotated the genome of a Finnhorse mare from the working horse section using PacBio and Omni-C data. This genome can complement the existing Thoroughbred reference genome (EquCab 3.0) and facilitate genetic studies of horses from northern Eurasia. We assembled 2.4 Gb of the genome with an N50 scaffold length of 83.8 Mb and the genome annotation resulted in a total of 19 748 protein coding genes of which 1200 were Finnhorse specific. The assembly has high quality and synteny with the current horse reference genome. We manually curated five genes of interest and deposited the final assembly in the European Nucleotide Archive under the accession no. PRJEB71364.
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Affiliation(s)
- Kisun Pokharel
- Natural Resources Institute Finland (Luke), Jokioinen, Finland
| | | | - Tiina Reilas
- Natural Resources Institute Finland (Luke), Jokioinen, Finland
| | - Juha Kantanen
- Natural Resources Institute Finland (Luke), Jokioinen, Finland
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5
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Brown C, Stefaniuk-Szmukier M, Decloedt A, Beijerink N, Hamilton NA, Velie BD. Congenital heart defects in Arabian horses and the prospects of genetic testing: A review. Equine Vet J 2024; 56:884-891. [PMID: 38272847 DOI: 10.1111/evj.14062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 01/04/2024] [Indexed: 01/27/2024]
Abstract
Congenital heart defects (CHDs) can have profound and potentially life-threatening consequences on horses' health and performance capability. While CHDs are rare in the general horse population, the Arabian breed is disproportionately overrepresented and thus is widely suspected to be genetically predisposed. This review discusses the most common CHDs in Arabian horses, including ventricular septal defect (VSD), tetralogy of Fallot (TOF), patent duct arteriosus (PDA), tricuspid valve atresia (TVA) and atrial septal defect (ASD). This review also explores how future research into the genetic factors that likely underpin many CHDs can revolutionise the way these disorders are managed in Arabian horses.
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Affiliation(s)
- Caitlin Brown
- Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia
| | - Monika Stefaniuk-Szmukier
- Department of Animal Molecular Biology, National Research Institute of Animal Production, Balice, Poland
| | - Annelies Decloedt
- Equine Cardioteam Ghent, Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Niek Beijerink
- Veterinaire Specialisten Vught, Vught, The Netherlands
- Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia
| | - Natasha A Hamilton
- Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia
| | - Brandon D Velie
- Equine Genetics and Genomics Group, School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia
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Giontella A, Silvestrelli M, Cocciolone A, Pieramati C, Sarti FM. Breeding Value Estimation Based on Morphological Evaluation of the Maremmano Horse Population through Factor Analysis. Animals (Basel) 2024; 14:2232. [PMID: 39123761 PMCID: PMC11310958 DOI: 10.3390/ani14152232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/22/2024] [Accepted: 07/28/2024] [Indexed: 08/12/2024] Open
Abstract
Morphological scoring is a common evaluation method for domestic animals. The National Association of Maremmano Breeders (ANAM) has provided a dataset containing the records of 600 horses, four metric measurements (cm) and 24 traits with a continuous evaluation scale, each one with 15 classes. Moreover, a body condition score (BCS) with five classes is included. In this study, factor analysis was conducted to create a small number of informative factors (3) obtained from these traits, and a new BLUP-AM-MT index was established. The New Estimated Breeding Value (NEBV1) of each horse was computed by adding the genetic indexes of the three factors, with each one multiplied using a coefficient indicated by ANAM. The practical feasibility of the NEBV1 was evaluated through Spearman correlations between the rankings of the NEBV1 and the rankings of the BLUP-AM-MT, estimated through the four biometric measures and the morphological score (MS) assigned to each horse by the ANAM judges. The factorial analysis was used to estimate three factors: the "Trunk Dimension", "Legs" and "Length". As the explained variance was only 32%, the model was rotated, and the heritability of the three factors were 0.51, 0.05 and 0.41, respectively. After rotation, the estimated correlations between the new NEBV1 and the biometric measures were improved. These results should encourage breeders to adopt a breeding value index that takes into consideration the factors derived from all the variables observed in the morphological evaluation of the Maremmano. In this way, breeders can use it to select the best animals for breeding.
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Affiliation(s)
- Andrea Giontella
- Department of Veterinary Medicine—Sportive Horse Research Center, University of Perugia, Via S. Costanzo 4, 06126 Perugia, Italy; (M.S.); (C.P.)
| | - Maurizio Silvestrelli
- Department of Veterinary Medicine—Sportive Horse Research Center, University of Perugia, Via S. Costanzo 4, 06126 Perugia, Italy; (M.S.); (C.P.)
| | - Alessandro Cocciolone
- Department of Agricultural, Food and Environmental Sciences, University of Perugia, Borgo XX Giugno, 74, 06121 Perugia, Italy; (A.C.); (F.M.S.)
| | - Camillo Pieramati
- Department of Veterinary Medicine—Sportive Horse Research Center, University of Perugia, Via S. Costanzo 4, 06126 Perugia, Italy; (M.S.); (C.P.)
| | - Francesca Maria Sarti
- Department of Agricultural, Food and Environmental Sciences, University of Perugia, Borgo XX Giugno, 74, 06121 Perugia, Italy; (A.C.); (F.M.S.)
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7
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Liu X, Peng Y, Zhang X, Wang X, Chen W, Kou X, Liang H, Ren W, Khan MZ, Wang C. Coloration in Equine: Overview of Candidate Genes Associated with Coat Color Phenotypes. Animals (Basel) 2024; 14:1802. [PMID: 38929421 PMCID: PMC11200706 DOI: 10.3390/ani14121802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/12/2024] [Accepted: 06/13/2024] [Indexed: 06/28/2024] Open
Abstract
Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Muhammad Zahoor Khan
- Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 522000, China
| | - Changfa Wang
- Liaocheng Research Institute of Donkey High-Efficiency Breeding and Ecological Feeding, Liaocheng University, Liaocheng 522000, China
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Witkowska-Piłaszewicz O, Malin K, Dąbrowska I, Grzędzicka J, Ostaszewski P, Carter C. Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes? Int J Mol Sci 2024; 25:5210. [PMID: 38791248 PMCID: PMC11121269 DOI: 10.3390/ijms25105210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 04/30/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
Domestic horses routinely participate in vigorous and various athletic activities. This enables the horse to serve as a model for studying athletic physiology and immunology in other species, including humans. For instance, as a model of physical efforts, such as endurance rides (long-distance running/aerobic exercise) and races (anaerobic exercise), the horse can be useful in evaluating post-exercise response. Currently, there has been significant interest in finding biomarkers, which characterize the advancement of training and adaptation to physical exercise in the horse. The parallels in cellular responses to physical exercises, such as changes in receptor expression and blood cell activity, improve our understanding of the mechanisms involved in the body's response to intense physical activity. This study focuses on the changes in levels of the pro- and anti-inflammatory cytokines and cellular response in the context of post-exercise immune response. Both the direction of changes in cytokine levels and cellular responses of the body, such as proliferation and expression of surface markers on lymphocytes, monocytes and neutrophils, show cross-functional similarities. This review reveals that horses are robust research models for studying the immune response to physical exercise in human athletes.
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Affiliation(s)
- Olga Witkowska-Piłaszewicz
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
| | - Katarzyna Malin
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
| | - Izabela Dąbrowska
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
| | - Jowita Grzędzicka
- Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
| | - Piotr Ostaszewski
- Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland
| | - Craig Carter
- Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY 40506, USA;
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De Coster T, Zhao Y, Tšuiko O, Demyda-Peyrás S, Van Soom A, Vermeesch JR, Smits K. Genome-wide equine preimplantation genetic testing enabled by simultaneous haplotyping and copy number detection. Sci Rep 2024; 14:2003. [PMID: 38263320 PMCID: PMC10805710 DOI: 10.1038/s41598-023-48103-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 11/22/2023] [Indexed: 01/25/2024] Open
Abstract
In different species, embryonic aneuploidies and genome-wide errors are a major cause of developmental failure. The increasing number of equine embryos being produced worldwide provides the opportunity to characterize and rank or select embryos based on their genetic profile prior to transfer. Here, we explored the possibility of generic, genome-wide preimplantation genetic testing concurrently for aneuploidies (PGT-A) and monogenic (PGT-M) traits and diseases in the horse, meanwhile assessing the incidence and spectrum of chromosomal and genome-wide errors in in vitro-produced equine embryos. To this end, over 70,000 single nucleotide polymorphism (SNP) positions were genotyped in 14 trophectoderm biopsies and corresponding biopsied blastocysts, and in 26 individual blastomeres from six arrested cleavage-stage embryos. Subsequently, concurrent genome-wide copy number detection and haplotyping by haplarithmisis was performed and the presence of aneuploidies and genome-wide errors and the inherited parental haplotypes for four common disease-associated genes with high carrier frequency in different horse breeds (GBE1, PLOD1, B3GALNT2, MUTYH), and for one color coat-associated gene (STX17) were compared in biopsy-blastocyst combinations. The euploid (n = 12) or fully aneuploid (n = 2) state and the inherited parental haplotypes for 42/45 loci of interest of the biopsied blastocysts were predicted by the biopsy samples in all successfully analyzed biopsy-blastocyst combinations (n = 9). Two biopsies showed a loss of maternal chromosome 28 and 31, respectively, which were confirmed in the corresponding blastocysts. In one of those biopsies, additional complex aneuploidies not present in the blastocyst were found. Five out of six arrested embryos contained chromosomal and/or genome-wide errors in most of their blastomeres, demonstrating their contribution to equine embryonic arrest in vitro. The application of the described PGT strategy would allow to select equine embryos devoid of genetic errors and pathogenetic variants, and with the variants of interest, which will improve foaling rate and horse quality. We believe this approach will be a gamechanger in horse breeding.
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Affiliation(s)
- T De Coster
- Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Belgium.
- Department of Human Genetics, KU Leuven, Leuven, Belgium.
| | - Y Zhao
- Department of Human Genetics, KU Leuven, Leuven, Belgium
| | - O Tšuiko
- Department of Human Genetics, KU Leuven, Leuven, Belgium
| | - S Demyda-Peyrás
- Department of Genetics, University of Córdoba, Córdoba, Spain
- Department of Animal Production, Veterinary School, National University of La Plata, La Plata, Argentina
| | - A Van Soom
- Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Belgium
| | - J R Vermeesch
- Department of Human Genetics, KU Leuven, Leuven, Belgium
| | - K Smits
- Department of Internal Medicine, Reproduction and Population Medicine, Ghent University, Merelbeke, Belgium.
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Hlongwane NL, Dzomba EF, Hadebe K, van der Nest MA, Pierneef R, Muchadeyi FC. Identification of Signatures of Positive Selection That Have Shaped the Genomic Landscape of South African Pig Populations. Animals (Basel) 2024; 14:236. [PMID: 38254405 PMCID: PMC10812692 DOI: 10.3390/ani14020236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/17/2023] [Accepted: 01/10/2024] [Indexed: 01/24/2024] Open
Abstract
South Africa boasts a diverse range of pig populations, encompassing intensively raised commercial breeds, as well as indigenous and village pigs reared under low-input production systems. The aim of this study was to investigate how natural and artificial selection have shaped the genomic landscape of South African pig populations sampled from different genetic backgrounds and production systems. For this purpose, the integrated haplotype score (iHS), as well as cross population extended haplotype homozygosity (XP-EHH) and Lewontin and Krakauer's extension of the Fst statistic based on haplotype information (HapFLK) were utilised. Our results revealed several population-specific signatures of selection associated with the different production systems. The importance of natural selection in village populations was highlighted, as the majority of genomic regions under selection were identified in these populations. Regions under natural and artificial selection causing the distinct genetic footprints of these populations also allow for the identification of genes and pathways that may influence production and adaptation. In the context of intensively raised commercial pig breeds (Large White, Kolbroek, and Windsnyer), the identified regions included quantitative loci (QTLs) associated with economically important traits. For example, meat and carcass QTLs were prevalent in all the populations, showing the potential of village and indigenous populations' ability to be managed and improved for such traits. Results of this study therefore increase our understanding of the intricate interplay between selection pressures, genomic adaptations, and desirable traits within South African pig populations.
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Affiliation(s)
- Nompilo L. Hlongwane
- Agricultural Research Council, Biotechnology Platform, Private Bag X5, Onderstepoort 0110, South Africa; (K.H.); (R.P.); (F.C.M.)
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Private Bag X01, Scottsville 3209, South Africa;
| | - Edgar F. Dzomba
- Discipline of Genetics, School of Life Sciences, University of KwaZulu-Natal, Private Bag X01, Scottsville 3209, South Africa;
| | - Khanyisile Hadebe
- Agricultural Research Council, Biotechnology Platform, Private Bag X5, Onderstepoort 0110, South Africa; (K.H.); (R.P.); (F.C.M.)
| | - Magriet A. van der Nest
- Agricultural Research Council, Biotechnology Platform, Private Bag X5, Onderstepoort 0110, South Africa; (K.H.); (R.P.); (F.C.M.)
- Hans Merensky Chair in Avocado Research, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, Pretoria 0002, South Africa;
| | - Rian Pierneef
- Agricultural Research Council, Biotechnology Platform, Private Bag X5, Onderstepoort 0110, South Africa; (K.H.); (R.P.); (F.C.M.)
- Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria 0002, South Africa
| | - Farai C. Muchadeyi
- Agricultural Research Council, Biotechnology Platform, Private Bag X5, Onderstepoort 0110, South Africa; (K.H.); (R.P.); (F.C.M.)
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11
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Bredemeyer KR, Hillier L, Harris AJ, Hughes GM, Foley NM, Lawless C, Carroll RA, Storer JM, Batzer MA, Rice ES, Davis BW, Raudsepp T, O'Brien SJ, Lyons LA, Warren WC, Murphy WJ. Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution. Nat Genet 2023; 55:1953-1963. [PMID: 37919451 PMCID: PMC10845050 DOI: 10.1038/s41588-023-01548-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/20/2023] [Indexed: 11/04/2023]
Abstract
The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite DXZ4 evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.
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Affiliation(s)
- Kevin R Bredemeyer
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA
- Interdisciplinary Program in Genetics & Genomics, Texas A&M University, College Station, TX, USA
| | - LaDeana Hillier
- Department of Genome Sciences, University of Washington, Seattle, WA, USA
| | - Andrew J Harris
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA
- Interdisciplinary Program in Genetics & Genomics, Texas A&M University, College Station, TX, USA
| | - Graham M Hughes
- School of Biology & Environmental Sciences, University College Dublin, Dublin, Ireland
| | - Nicole M Foley
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA
| | - Colleen Lawless
- School of Biology & Environmental Sciences, University College Dublin, Dublin, Ireland
| | - Rachel A Carroll
- Department of Animal Sciences, University of Missouri, Columbia, MO, USA
| | | | - Mark A Batzer
- Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA
| | - Edward S Rice
- Department of Animal Sciences, University of Missouri, Columbia, MO, USA
| | - Brian W Davis
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA
- Interdisciplinary Program in Genetics & Genomics, Texas A&M University, College Station, TX, USA
| | - Terje Raudsepp
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA
- Interdisciplinary Program in Genetics & Genomics, Texas A&M University, College Station, TX, USA
| | - Stephen J O'Brien
- Guy Harvey Oceanographic Center, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Leslie A Lyons
- Department of Veterinary Medicine & Surgery, University of Missouri, Columbia, MO, USA
| | - Wesley C Warren
- Department of Animal Sciences, University of Missouri, Columbia, MO, USA.
| | - William J Murphy
- Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
- Interdisciplinary Program in Genetics & Genomics, Texas A&M University, College Station, TX, USA.
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12
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Cappelletti E, Piras FM, Sola L, Santagostino M, Petersen JL, Bellone RR, Finno CJ, Peng S, Kalbfleisch TS, Bailey E, Nergadze SG, Giulotto E. The localization of centromere protein A is conserved among tissues. Commun Biol 2023; 6:963. [PMID: 37735603 PMCID: PMC10514049 DOI: 10.1038/s42003-023-05335-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 09/08/2023] [Indexed: 09/23/2023] Open
Abstract
Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.
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Affiliation(s)
| | - Francesca M Piras
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
| | - Lorenzo Sola
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
| | - Marco Santagostino
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
| | - Jessica L Petersen
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Rebecca R Bellone
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
| | - Carrie J Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
| | - Sichong Peng
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA
| | - Ted S Kalbfleisch
- Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA
| | - Ernest Bailey
- Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA
| | - Solomon G Nergadze
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
| | - Elena Giulotto
- Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
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13
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Sheikh A. Mitochondrial DNA sequencing of Kehilan and Hamdani horses from Saudi Arabia. Saudi J Biol Sci 2023; 30:103741. [PMID: 37575470 PMCID: PMC10413190 DOI: 10.1016/j.sjbs.2023.103741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 07/04/2023] [Accepted: 07/14/2023] [Indexed: 08/15/2023] Open
Abstract
The Arabian horse breed is well known for its purity and played a key role in the genetic improvement of other horses worldwide. The mitochondrial genome plays a vital role in maternal inheritance and it's helpful to evaluate its genetic diversity and conservation. It has higher mutation rates than nuclear DNA in vertebrates and therefore reveals phylogenetic relationships and haplotypes. In this study, the mitochondrial genome mutations in two Saudi horse strains, Kehilan and Hamdani demonstrated various changes in the gene and amino acid levels and included two other Saudi horses (Hadban and Seglawi) from the previous study for phylogenetic comparison. The whole mitochondrial genome sequencing resulted in intra and inter mtDNA variations between the studied horses. Interestingly, the Hamdani horse has nucleotide substitutions similar to those of the Hadban horse, which is reflected in the phylogenetic tree as a significantly close relationship. This type of study provides a better understanding of mitogenome structure and conservation of livestock species genetic data.
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Affiliation(s)
- Abdullah Sheikh
- Camel Research Center, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
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14
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Pozharskiy A, Abdrakhmanova A, Beishova I, Shamshidin A, Nametov A, Ulyanova T, Bekova G, Kikebayev N, Kovalchuk A, Ulyanov V, Turabayev A, Khusnitdinova M, Zhambakin K, Sapakhova Z, Shamekova M, Gritsenko D. Genetic structure and genome-wide association study of the traditional Kazakh horses. Animal 2023; 17:100926. [PMID: 37611435 DOI: 10.1016/j.animal.2023.100926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 07/17/2023] [Accepted: 07/20/2023] [Indexed: 08/25/2023] Open
Abstract
Horses are traditionally used in Kazakhstan as a source of food and as working and saddle animals as well. Here, for the first time, microarray-based medium-density single nucleotide polymorphism (SNP) genotyping of six traditionally defined types and breeds of indigenous Kazakh horses was conducted to reveal their genetic structure and find markers associated with animal size and weight. The results showed that the predefined separation between breeds and sampled populations was not supported by the molecular data. The lack of genetic variation between breeds and populations was revealed by the principal component analysis, ADMIXTURE, and distance-based analyses, as well as the general population parameters expected and observed heterozygosity (He and Ho) and between-group fixation index (Fst). The analysis revealed that the studied types and breeds should be considered as a single breed, namely the 'Kazakh horse'. The comparison with previously published data on global horse breed diversity revealed the relatively high level of individual diversity of Kazakh horses in comparison with the well-known foreign breeds. The Mongolian and Tuva breeds were identified as the closest horse landraces, demonstrating similar patterns of internal variability. The genome-wide association analysis was performed for animal size and weight as the traits directly related with the meat productivity of horses. The analysis identified a set of 60 SNPs linked with horse genes involved in the regulation of processes of development of connective tissues and the bone system, neural system, immune system regulation, and other processes. The present study is novel and introduces Kazakh horses as a promising genetic source for horse breeding and selection both on the domestic and international levels.
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Affiliation(s)
- Alexandr Pozharskiy
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan; Al-Farabi Kazakh National University, Al-Farabi Ave. 71, 050040 Almaty, Kazakhstan
| | - Aisha Abdrakhmanova
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
| | - Indira Beishova
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan.
| | - Alzhan Shamshidin
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Askar Nametov
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Tatyana Ulyanova
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Gulmira Bekova
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Nabidulla Kikebayev
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Alexandr Kovalchuk
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Vadim Ulyanov
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Amangeldy Turabayev
- Zhengir Khan West-Kazakhstan Agrarian Technical University, Zhengir Khan Str. 51, 090009 Oral, Kazakhstan
| | - Marina Khusnitdinova
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
| | - Kabyl Zhambakin
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
| | - Zagipa Sapakhova
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
| | - Malika Shamekova
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
| | - Dilyara Gritsenko
- Institute of Plant Biology and Biotechnology, Timiryazev Str. 45, 050040 Almaty, Kazakhstan
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15
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Mutti G, Oteo-Garcia G, Caldon M, da Silva MJF, Minhós T, Cowlishaw G, Gottelli D, Huchard E, Carter A, Martinez FI, Raveane A, Capelli C. Assessing the recovery of Y chromosome microsatellites with population genomic data using Papio and Theropithecus genomes. Sci Rep 2023; 13:13839. [PMID: 37620368 PMCID: PMC10449864 DOI: 10.1038/s41598-023-40931-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/18/2023] [Indexed: 08/26/2023] Open
Abstract
Y chromosome markers can shed light on male-specific population dynamics but for many species no such markers have been discovered and are available yet, despite the potential for recovering Y-linked loci from available genome sequences. Here, we investigated how effective available bioinformatic tools are in recovering informative Y chromosome microsatellites from whole genome sequence data. In order to do so, we initially explored a large dataset of whole genome sequences comprising individuals at various coverages belonging to different species of baboons (genus: Papio) using Y chromosome references belonging to the same genus and more distantly related species (Macaca mulatta). We then further tested this approach by recovering Y-STRs from available Theropithecus gelada genomes using Papio and Macaca Y chromosome as reference sequences. Identified loci were validated in silico by a) comparing within-species relationships of Y chromosome lineages and b) genotyping male individuals in available pedigrees. Each STR was selected not to extend in its variable region beyond 100 base pairs, so that loci can be developed for PCR-based genotyping of non-invasive DNA samples. In addition to assembling a first set of Papio and Theropithecus Y-specific microsatellite markers, we released TYpeSTeR, an easy-to-use script to identify and genotype Y chromosome STRs using population genomic data which can be modulated according to available male reference genomes and genomic data, making it widely applicable across taxa.
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Affiliation(s)
- Giacomo Mutti
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area Delle Scienze, 11/a, 43124, Parma, Italy
- Barcelona Supercomputing Centre (BSC-CNS), Plaça Eusebi Güell, 1-3, 08034, Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028, Barcelona, Spain
| | - Gonzalo Oteo-Garcia
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area Delle Scienze, 11/a, 43124, Parma, Italy
| | - Matteo Caldon
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area Delle Scienze, 11/a, 43124, Parma, Italy
| | - Maria Joana Ferreira da Silva
- BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, Campus de Vairão, Vairão, Portugal
- Centro de Investigação Em Biodiversidade E Recursos Genéticos, CIBIOInBIO Laboratório AssociadoUniversidade Do Porto, Campus de Vairão, Vairão, Portugal
- ONE ‑ Organisms and Environment Group, School of Biosciences, Cardiff University, Sir Martin Evans Building, Cardiff, UK
| | - Tânia Minhós
- Centre for Research in Anthropology (CRIA-NOVA FCSH), Av. Forças Armadas, Edifício ISCTE, Sala 2w2, 1649-026, Lisboa, Portugal
- Anthropology Department, School of Social Sciences and Humanities, Universidade Nova de Lisboa (NOVA FCSH), Av. de Berna, 26-C, 1069-061, Lisboa, Portugal
| | - Guy Cowlishaw
- Institute of Zoology, Zoological Society of London, Regent's Park, London, NW1 4RY, UK
| | - Dada Gottelli
- Institute of Zoology, Zoological Society of London, Regent's Park, London, NW1 4RY, UK
| | - Elise Huchard
- Institut Des Sciences de L'Evolution, CNRS, Universite de Montpellier, CC 065, 34095, Montpellier 05, France
| | - Alecia Carter
- Department of Anthropology, University College London, 14 Taviton Street, London, WC1H 0BW, UK
| | - Felipe I Martinez
- Escuela de Antropología, Facultad de Ciencias Sociales, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | - Cristian Capelli
- Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area Delle Scienze, 11/a, 43124, Parma, Italy.
- Department of Biology, University of Oxford, 11a Mansfield Road, Oxford, OX1 3SZ, UK.
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16
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Giontella A, Cardinali I, Sarti FM, Silvestrelli M, Lancioni H. Y-Chromosome Haplotype Report among Eight Italian Horse Breeds. Genes (Basel) 2023; 14:1602. [PMID: 37628653 PMCID: PMC10454838 DOI: 10.3390/genes14081602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/26/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Horse domestication and breed selection processes have profoundly influenced the development and transformation of human society and civilization over time. Therefore, their origin and history have always attracted much attention. In Italy, several local breeds have won prestigious awards thanks to their unique traits and socio-cultural peculiarities. Here, for the first time, we report the genetic variation of three loci of the male-specific region of the Y chromosome (MSY) of four local breeds and another one (Lipizzan, UNESCO) well-represented in the Italian Peninsula. The analysis also includes data from three Sardinian breeds and another forty-eight Eurasian and Mediterranean horse breeds retrieved from GenBank for comparison. Three haplotypes (HT1, HT2, and HT3) were found in Italian stallions, with different spatial distributions between breeds. HT1 (the ancestral haplotype) was frequent, especially in Bardigiano and Monterufolino, HT2 (Neapolitan/Oriental wave) was found in almost all local breeds, and HT3 (Thoroughbred wave) was detected in Maremmano and two Sardinian breeds (Sardinian Anglo-Arab and Sarcidano). This differential distribution is due to three paternal introgressions of imported stallions from foreign countries to improve local herds; however, further genetic analyses are essential to reconstruct the genetic history of native horse breeds, evaluate the impact of selection events, and enable conservation strategies.
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Affiliation(s)
- Andrea Giontella
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.G.); (M.S.)
| | - Irene Cardinali
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
| | - Francesca Maria Sarti
- Department of Agricultural, Food and Environmental Sciences, University of Perugia, 06121 Perugia, Italy;
| | - Maurizio Silvestrelli
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy; (A.G.); (M.S.)
| | - Hovirag Lancioni
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
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17
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Peng S, Dahlgren AR, Donnelly CG, Hales EN, Petersen JL, Bellone RR, Kalbfleisch T, Finno CJ. Functional annotation of the animal genomes: An integrated annotation resource for the horse. PLoS Genet 2023; 19:e1010468. [PMID: 36862752 PMCID: PMC10013926 DOI: 10.1371/journal.pgen.1010468] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 03/14/2023] [Accepted: 01/28/2023] [Indexed: 03/03/2023] Open
Abstract
The genomic sequence of the horse has been available since 2009, providing critical resources for discovering important genomic variants regarding both animal health and population structures. However, to fully understand the functional implications of these variants, detailed annotation of the horse genome is required. Due to the limited availability of functional data for the equine genome, as well as the technical limitations of short-read RNA-seq, existing annotation of the equine genome contains limited information about important aspects of gene regulation, such as alternate isoforms and regulatory elements, which are either not transcribed or transcribed at a very low level. To solve above problems, the Functional Annotation of the Animal Genomes (FAANG) project proposed a systemic approach to tissue collection, phenotyping, and data generation, adopting the blueprint laid out by the Encyclopedia of DNA Elements (ENCODE) project. Here we detail the first comprehensive overview of gene expression and regulation in the horse, presenting 39,625 novel transcripts, 84,613 candidate cis-regulatory elements (CRE) and their target genes, 332,115 open chromatin regions genome wide across a diverse set of tissues. We showed substantial concordance between chromatin accessibility, chromatin states in different genic features and gene expression. This comprehensive and expanded set of genomics resources will provide the equine research community ample opportunities for studies of complex traits in the horse.
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Affiliation(s)
- Sichong Peng
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
| | - Anna R. Dahlgren
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
| | - Callum G. Donnelly
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
| | - Erin N. Hales
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
| | - Jessica L. Petersen
- Department of Animal Science, University of Nebraska—Lincoln, Lincoln, Nebraska, United States of America
| | - Rebecca R. Bellone
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
| | - Ted Kalbfleisch
- Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, United States of America
| | - Carrie J. Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, United States of America
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18
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Cardinali I, Giontella A, Tommasi A, Silvestrelli M, Lancioni H. Unlocking Horse Y Chromosome Diversity. Genes (Basel) 2022; 13:genes13122272. [PMID: 36553539 PMCID: PMC9777570 DOI: 10.3390/genes13122272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/30/2022] [Accepted: 11/30/2022] [Indexed: 12/11/2022] Open
Abstract
The present equine genetic variation mirrors the deep influence of intensive breeding programs during the last 200 years. Here, we provide a comprehensive current state of knowledge on the trends and prospects on the variation in the equine male-specific region of the Y chromosome (MSY), which was assembled for the first time in 2018. In comparison with the other 12 mammalian species, horses are now the most represented, with 56 documented MSY genes. However, in contrast to the high variability in mitochondrial DNA observed in many horse breeds from different geographic areas, modern horse populations demonstrate extremely low genetic Y-chromosome diversity. The selective pressures employed by breeders using pedigree data (which are not always error-free) as a predictive tool represent the main cause of this lack of variation in the Y-chromosome. Nevertheless, the detailed phylogenies obtained by recent fine-scaled Y-chromosomal genotyping in many horse breeds worldwide have contributed to addressing the genealogical, forensic, and population questions leading to the reappraisal of the Y-chromosome as a powerful genetic marker to avoid the loss of biodiversity as a result of selective breeding practices, and to better understand the historical development of horse breeds.
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Affiliation(s)
- Irene Cardinali
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
- Correspondence: (I.C.); (A.G.)
| | - Andrea Giontella
- Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy
- Correspondence: (I.C.); (A.G.)
| | - Anna Tommasi
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
| | | | - Hovirag Lancioni
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy
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19
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Shilton CA, Kahler A, Roach JM, Raudsepp T, de Mestre AM. Lethal variants of equine pregnancy: is it the placenta or foetus leading the conceptus in the wrong direction? Reprod Fertil Dev 2022; 35:51-69. [PMID: 36592981 DOI: 10.1071/rd22239] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5-10% of established day 15 pregnancies and a further 5-10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses in pregnancy and pregnancy loss, as well as infectious agents such as pathogens, and until recently very little was known about the both small and large genetic variants associated with reduced foetal viability in the horse. In this review, we first introduce key aspects of equine placental and foetal development. We then discuss incidence, risk factors and causes of pregnancy loss, with the latter focusing on genetic variants described to date that can impact equine foetal viability.
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Affiliation(s)
- Charlotte A Shilton
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, Herts, AL9 7TA, UK
| | - Anne Kahler
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, Herts, AL9 7TA, UK
| | - Jessica M Roach
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, Herts, AL9 7TA, UK
| | - Terje Raudsepp
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843-4458, USA
| | - Amanda M de Mestre
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, Herts, AL9 7TA, UK
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20
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Y Chromosome Haplotypes Enlighten Origin, Influence, and Breeding History of North African Barb Horses. Animals (Basel) 2022; 12:ani12192579. [PMID: 36230320 PMCID: PMC9559282 DOI: 10.3390/ani12192579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/16/2022] [Accepted: 09/23/2022] [Indexed: 11/17/2022] Open
Abstract
In horses, demographic patterns are complex due to historical migrations and eventful breeding histories. Particularly puzzling is the ancestry of the North African horse, a founding horse breed, shaped by numerous influences throughout history. A genetic marker particularly suitable to investigate the paternal demographic history of populations is the non-recombining male-specific region of the Y chromosome (MSY). Using a recently established horse MSY haplotype (HT) topology and KASP™ genotyping, we illustrate MSY HT spectra of 119 Barb and Arab-Barb males, collected from the Maghreb region and European subpopulations. All detected HTs belonged to the Crown haplogroup, and the broad MSY spectrum reflects the wide variety of influential stallions throughout the breed’s history. Distinct HTs and regional disparities were characterized and a remarkable number of early introduced lineages were observed. The data indicate recent refinement with Thoroughbred and Arabian patrilines, while 57% of the dataset supports historical migrations between North Africa and the Iberian Peninsula. In the Barb horse, we detected the HT linked to Godolphin Arabian, one of the Thoroughbred founders. Hence, we shed new light on the question of the ancestry of one Thoroughbred patriline. We show the strength of the horse Y chromosome as a genealogical tool, enlighten recent paternal history of North African horses, and set the foundation for future studies on the breed and the formation of conservation breeding programs.
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Panigrahi M, Kumar H, Saravanan KA, Rajawat D, Sonejita Nayak S, Ghildiyal K, Kaisa K, Parida S, Bhushan B, Dutt T. Trajectory of livestock genomics in South Asia: A comprehensive review. Gene 2022; 843:146808. [PMID: 35973570 DOI: 10.1016/j.gene.2022.146808] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/08/2022] [Accepted: 08/10/2022] [Indexed: 02/07/2023]
Abstract
Livestock plays a central role in sustaining human livelihood in South Asia. There are numerous and distinct livestock species in South Asian countries. Several of them have experienced genetic development in recent years due to the application of genomic technologies and effective breeding programs. This review discusses genomic studies on cattle, buffalo, sheep, goat, pig, horse, camel, yak, mithun, and poultry. The frontiers covered in this review are genetic diversity, admixture studies, selection signature research, QTL discovery, genome-wide association studies (GWAS), and genomic selection. The review concludes with recommendations for South Asian livestock systems to increasingly leverage genomic technologies, based on the lessons learned from the numerous case studies. This paper aims to present a comprehensive analysis of the dichotomy in the South Asian livestock sector and argues that a realistic approach to genomics in livestock can ensure long-term genetic advancements.
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Affiliation(s)
- Manjit Panigrahi
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India.
| | - Harshit Kumar
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - K A Saravanan
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Divya Rajawat
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Sonali Sonejita Nayak
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Kanika Ghildiyal
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Kaiho Kaisa
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Subhashree Parida
- Division of Pharmacology & Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Bharat Bhushan
- Division of Animal Genetics, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
| | - Triveni Dutt
- Livestock Production and Management Section, Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, UP, India
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22
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Finno CJ. Science-in-brief: Genomic and transcriptomic approaches to the investigation of equine diseases. Equine Vet J 2022; 54:444-448. [PMID: 35133024 PMCID: PMC9095347 DOI: 10.1111/evj.13549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 12/17/2021] [Indexed: 12/01/2022]
Affiliation(s)
- Carrie J Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA
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Y-Chromosomal Insights into Breeding History and Sire Line Genealogies of Arabian Horses. Genes (Basel) 2022; 13:genes13020229. [PMID: 35205275 PMCID: PMC8871751 DOI: 10.3390/genes13020229] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/13/2022] [Accepted: 01/21/2022] [Indexed: 12/24/2022] Open
Abstract
The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data of 157 males from several breeds. Y-chromosomal haplotypes specific for Arabian horses were inferred by genotyping a collection of 145 males representing most Arabian sire lines that are active around the globe. These lines formed three discrete haplogroups, and the same haplogroups were detected in Arabian populations native to the Middle East. The Arabian haplotypes were clearly distinct from the ones detected in Akhal Tekes, Turkoman horses, and the progeny of two Thoroughbred foundation sires. However, a haplotype introduced into the English Thoroughbred by the stallion Byerley Turk (1680), was shared among Arabians, Turkomans, and Akhal Tekes, which opens a discussion about the historic connections between Oriental horse types. Furthermore, we genetically traced Arabian sire line breeding in the Western World over the past 200 years. This confirmed a strong selection for relatively few male lineages and uncovered incongruences to written pedigree records. Overall, we demonstrate how fine-scaled Y-analysis contributes to a better understanding of the historical development of horse breeds.
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Durward-Akhurst SA, Schaefer RJ, Grantham B, Carey WK, Mickelson JR, McCue ME. Genetic Variation and the Distribution of Variant Types in the Horse. Front Genet 2021; 12:758366. [PMID: 34925451 PMCID: PMC8676274 DOI: 10.3389/fgene.2021.758366] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/10/2021] [Indexed: 11/13/2022] Open
Abstract
Genetic variation is a key contributor to health and disease. Understanding the link between an individual's genotype and the corresponding phenotype is a major goal of medical genetics. Whole genome sequencing (WGS) within and across populations enables highly efficient variant discovery and elucidation of the molecular nature of virtually all genetic variation. Here, we report the largest catalog of genetic variation for the horse, a species of importance as a model for human athletic and performance related traits, using WGS of 534 horses. We show the extent of agreement between two commonly used variant callers. In data from ten target breeds that represent major breed clusters in the domestic horse, we demonstrate the distribution of variants, their allele frequencies across breeds, and identify variants that are unique to a single breed. We investigate variants with no homozygotes that may be potential embryonic lethal variants, as well as variants present in all individuals that likely represent regions of the genome with errors, poor annotation or where the reference genome carries a variant. Finally, we show regions of the genome that have higher or lower levels of genetic variation compared to the genome average. This catalog can be used for variant prioritization for important equine diseases and traits, and to provide key information about regions of the genome where the assembly and/or annotation need to be improved.
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Affiliation(s)
- S. A. Durward-Akhurst
- Department of Veterinary Population Medicine, University of Minnesota, Minneapolis, MN, United States
| | - R. J. Schaefer
- Department of Veterinary Population Medicine, University of Minnesota, Minneapolis, MN, United States
| | - B. Grantham
- Interval Bio LLC, Mountain View, CA, United States
| | - W. K. Carey
- Interval Bio LLC, Mountain View, CA, United States
| | - J. R. Mickelson
- Department of Veterinary and Biomedical Sciences, University of Minnesota, Minneapolis, MN, United States
| | - M. E. McCue
- Department of Veterinary Population Medicine, University of Minnesota, Minneapolis, MN, United States
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25
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Peng S, Petersen JL, Bellone RR, Kalbfleisch T, Kingsley NB, Barber AM, Cappelletti E, Giulotto E, Finno CJ. Decoding the Equine Genome: Lessons from ENCODE. Genes (Basel) 2021; 12:genes12111707. [PMID: 34828313 PMCID: PMC8625040 DOI: 10.3390/genes12111707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 12/23/2022] Open
Abstract
The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data from more than 400 experiments using over 50 tissues, targeting a variety of regulatory features of the equine genome. In this review, we examine how valuable lessons learned from the ENCODE project informed our decisions in the equine FAANG project. We report the current state of the equine FAANG project and discuss how FAANG can serve as a template for future expansion of functional annotation in the equine genome and be used as a reference for studies of complex traits in horse. A well-annotated reference functional atlas will also help advance equine genetics in the pan-genome and precision medicine era.
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Affiliation(s)
- Sichong Peng
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA; (S.P.); (R.R.B.); (N.B.K.)
| | - Jessica L. Petersen
- Department of Animal Science, University of Nebraska, Lincoln, NE 68583-0908, USA; (J.L.P.); (A.M.B.)
| | - Rebecca R. Bellone
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA; (S.P.); (R.R.B.); (N.B.K.)
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
| | - Ted Kalbfleisch
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY 40503, USA;
| | - N. B. Kingsley
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA; (S.P.); (R.R.B.); (N.B.K.)
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
| | - Alexa M. Barber
- Department of Animal Science, University of Nebraska, Lincoln, NE 68583-0908, USA; (J.L.P.); (A.M.B.)
| | - Eleonora Cappelletti
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy; (E.C.); (E.G.)
| | - Elena Giulotto
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy; (E.C.); (E.G.)
| | - Carrie J. Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA; (S.P.); (R.R.B.); (N.B.K.)
- Correspondence:
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Castaneda C, Juras R, Kjöllerström J, Hernandez Aviles C, Teague SR, Love CC, Cothran EG, Varner DD, Raudsepp T. Thoroughbred stallion fertility is significantly associated with FKBP6 genotype but not with inbreeding or the contribution of a leading sire. Anim Genet 2021; 52:813-823. [PMID: 34610162 DOI: 10.1111/age.13142] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2021] [Indexed: 12/12/2022]
Abstract
This is a follow-up study to validate the previously detected association of the FKBP6 gene with stallion subfertility. Using a select cohort of 150 Thoroughbred stallions with detailed breeding records, we confirm significant association (P < 0.0001) between low per-cycle pregnancy rates (≤50%) and a combined A/A-A/A genotype of SNPs chr13:11 353 372G>A and chr13:11 353 436A>C in FKBP6 exon 5. We also show that stallion subfertility and the combined genotype A/A-A/A are not associated with the level of genetic diversity based on 12 autosomal microsatellite markers, or with pedigree-based inbreeding rate, or the extent of contribution of a leading Thoroughbred sire, Northern Dancer, in a stallion's pedigree. We develop a TaqMan allelic discrimination assay for the two SNPs to facilitate accurate and high-throughput genotyping. We determine allele, genotype and combined genotype frequencies of FKBP6 exon 5 SNPs in a global cohort of 518 Thoroughbreds (76% stallions or geldings and 24% mares) and show that the frequency of the A/A-A/A genotype is 4%. Because there is no similar association between the FKBP6 exon 5 genotype and stallion subfertility in Hanoverians, we suggest that the two SNPs are not causative but rather tagging a breed-specific haplotype with genetic variants unique to Thoroughbreds. Further WGS-based research is needed to identify the molecular causes underlying the observed genotype-phenotype association in Thoroughbred stallions.
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Affiliation(s)
- C Castaneda
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
| | - R Juras
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
| | - J Kjöllerström
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
| | - C Hernandez Aviles
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - S R Teague
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - C C Love
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - E G Cothran
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
| | - D D Varner
- Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA
| | - T Raudsepp
- Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA
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Cieslak J, Brooks SA, Wodas L, Mantaj W, Borowska A, Sliwowska JH, Ziarniak K, Mackowski M. Genetic Background of the Polish Primitive Horse (Konik) Coat Color Variation-New Insight into Dun Dilution Phenotypic Effect. J Hered 2021; 112:436-442. [PMID: 34432873 DOI: 10.1093/jhered/esab034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 05/26/2021] [Accepted: 06/02/2021] [Indexed: 11/13/2022] Open
Abstract
Only the blue dun coat color, produced by the action of the dun allele on the background of a black base coat, is officially permitted in the Polish primitive horse (PPH, Konik) breed, yet the population is not visually homogenous and various coat color shades occur. Herein, the molecular background of PPH coat color was studied based on genotyping of known causative variants in equine coat color-related genes (ASIP, MC1R, TBX3, SLC36A1, SLC45A2, PMEL17, and RALY). Additionally, screening for the new polymorphisms was conducted for the ASIP gene coding sequence and the TBX3 1.6-kb insert (associated with the dun dilution). We did not observe the champagne, silver, or cream color dilution variants in the PPH breed. A significant association (P < 0.01) was recorded for the genotype in TBX3 gene 1.6 kb in/del and the degree of dun coat dilution, demonstrating that the dominant action of the dun mutation is not fully penetrant. In addition to the effect of the 1.6 kb in/del zygosity, variants within the TBX3 insert were significantly associated with PPH coat color variability (P < 0.01), suggesting the presence of an additional allele at this locus. Finally, we identified a high frequency (35%) of genetically bay dun-colored PPH individuals that are officially recorded as blue (black base coat) duns. We propose that the difficulty in distinguishing these 2 phenotypes visually is due to an independent locus upstream of the ASIP gene, which was recently described as darkening the typical bay pigmentation shade.
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Affiliation(s)
- Jakub Cieslak
- Horse Breeding Unit, Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637 Poznan,Poland
| | - Samantha Ann Brooks
- Department of Animal Sciences, UF Genetics Institute, University of Florida, Gainesville, FL 32611-0910, USA
| | - Lukasz Wodas
- Horse Breeding Unit, Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637 Poznan,Poland
| | - Weronika Mantaj
- Laboratory of Neurobiology, Department of Zoology, Poznan University of Life Sciences, 60-625 Poznan, Poland (Sliwowska and Ziarniak)
| | - Alicja Borowska
- Horse Breeding Unit, Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637 Poznan,Poland
| | - Joanna Helena Sliwowska
- Laboratory of Neurobiology, Department of Zoology, Poznan University of Life Sciences, 60-625 Poznan, Poland (Sliwowska and Ziarniak)
| | - Kamil Ziarniak
- Laboratory of Neurobiology, Department of Zoology, Poznan University of Life Sciences, 60-625 Poznan, Poland (Sliwowska and Ziarniak)
| | - Mariusz Mackowski
- Horse Breeding Unit, Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637 Poznan,Poland.,Horse Genetic Markers Laboratory, Poznan University of Life Sciences, 60-637 Poznan, Poland (Mackowski)
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Rare and common variant discovery by whole-genome sequencing of 101 Thoroughbred racehorses. Sci Rep 2021; 11:16057. [PMID: 34362995 PMCID: PMC8346562 DOI: 10.1038/s41598-021-95669-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 07/29/2021] [Indexed: 11/08/2022] Open
Abstract
The Thoroughbred breed was formed by crossing Oriental horse breeds and British native horses and is currently used in horseracing worldwide. In this study, we constructed a single-nucleotide variant (SNV) database using data from 101 Thoroughbred racehorses. Whole genome sequencing (WGS) revealed 11,570,312 and 602,756 SNVs in autosomal (1–31) and X chromosomes, respectively, yielding a total of 12,173,068 SNVs. About 6.9% of identified SNVs were rare variants observed only in one allele in 101 horses. The number of SNVs detected in individual horses ranged from 4.8 to 5.3 million. Individual horses had a maximum of 25,554 rare variants; several of these were functional variants, such as non-synonymous substitutions, start-gained, start-lost, stop-gained, and stop-lost variants. Therefore, these rare variants may affect differences in traits and phenotypes among individuals. When observing the distribution of rare variants among horses, one breeding stallion had a smaller number of rare variants compared to other horses, suggesting that the frequency of rare variants in the Japanese Thoroughbred population increases through breeding. In addition, our variant database may provide useful basic information for industrial applications, such as the detection of genetically modified racehorses in gene-doping control and pedigree-registration of racehorses using SNVs as markers.
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29
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Peng S, Bellone R, Petersen JL, Kalbfleisch TS, Finno CJ. Successful ATAC-Seq From Snap-Frozen Equine Tissues. Front Genet 2021; 12:641788. [PMID: 34220931 PMCID: PMC8242358 DOI: 10.3389/fgene.2021.641788] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/21/2021] [Indexed: 11/20/2022] Open
Abstract
An assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) has become an increasingly popular method to assess genome-wide chromatin accessibility in isolated nuclei from fresh tissues. However, many biobanks contain only snap-frozen tissue samples. While ATAC-seq has been applied to frozen brain tissues in human, its applicability in a wide variety of tissues in horse remains unclear. The Functional Annotation of Animal Genome (FAANG) project is an international collaboration aimed to provide high quality functional annotation of animal genomes. The equine FAANG initiative has generated a biobank of over 80 tissues from two reference female animals and experiments to begin to characterize tissue specificity of genome function for prioritized tissues have been performed. Due to the logistics of tissue collection and storage, extracting nuclei from a large number of tissues for ATAC-seq at the time of collection is not always practical. To assess the feasibility of using stored frozen tissues for ATAC-seq and to provide a guideline for the equine FAANG project, we compared ATAC-seq results from nuclei isolated from frozen tissue to cryopreserved nuclei (CN) isolated at the time of tissue harvest in liver, a highly cellular homogenous tissue, and lamina, a relatively acellular tissue unique to the horse. We identified 20,000-33,000 accessible chromatin regions in lamina and 22-61,000 in liver, with consistently more peaks identified using CN isolated at time of tissue collection. Our results suggest that frozen tissues are an acceptable substitute when CN are not available. For more challenging tissues such as lamina, nuclei extraction at the time of tissue collection is still preferred for optimal results. Therefore, tissue type and accessibility to intact nuclei should be considered when designing ATAC-seq experiments.
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Affiliation(s)
- Sichong Peng
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
| | - Rebecca Bellone
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
| | - Jessica L. Petersen
- Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE, United States
| | - Theodore S. Kalbfleisch
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, United States
| | - Carrie J. Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
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Horse Clinical Cytogenetics: Recurrent Themes and Novel Findings. Animals (Basel) 2021; 11:ani11030831. [PMID: 33809432 PMCID: PMC8001954 DOI: 10.3390/ani11030831] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/12/2021] [Accepted: 03/13/2021] [Indexed: 12/17/2022] Open
Abstract
Clinical cytogenetic studies in horses have been ongoing for over half a century and clearly demonstrate that chromosomal disorders are among the most common non-infectious causes of decreased fertility, infertility, and congenital defects. Large-scale cytogenetic surveys show that almost 30% of horses with reproductive or developmental problems have chromosome aberrations, whereas abnormal karyotypes are found in only 2-5% of the general population. Among the many chromosome abnormalities reported in the horse, most are unique or rare. However, all surveys agree that there are two recurrent conditions: X-monosomy and SRY-negative XY male-to-female sex reversal, making up approximately 35% and 11% of all chromosome abnormalities, respectively. The two are signature conditions for the horse and rare or absent in other domestic species. The progress in equine genomics and the development of molecular tools, have qualitatively improved clinical cytogenetics today, allowing for refined characterization of aberrations and understanding the underlying molecular mechanisms. While cutting-edge genomics tools promise further improvements in chromosome analysis, they will not entirely replace traditional cytogenetics, which still is the most straightforward, cost-effective, and fastest approach for the initial evaluation of potential breeding animals and horses with reproductive or developmental disorders.
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Laseca N, Anaya G, Peña Z, Pirosanto Y, Molina A, Demyda Peyrás S. Impaired Reproductive Function in Equines: From Genetics to Genomics. Animals (Basel) 2021; 11:393. [PMID: 33546520 PMCID: PMC7913728 DOI: 10.3390/ani11020393] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 01/29/2021] [Accepted: 01/31/2021] [Indexed: 12/15/2022] Open
Abstract
Fertility is one of the key factors in the economic and productive success of the equine industry. Despite this, studies on the genetic causes affecting reproductive performance are scarce, especially in mares, where the genetic architecture of the reproductive traits is extremely complex. Today, with the increasing availability of new genomic methodologies for this species, we are presented with an interesting opportunity to understand the genetic basis of equine reproductive disorders. These include, among others, novel techniques for detecting chromosomal abnormalities, whose association with infertility in horses was established over 50 years ago; new sequencing technologies permitting an accurate detection of point mutations influencing fertility, as well as the study of inbreeding and molecular homozygosity, which has been widely suggested as one of the main causes of low reproductive performance in horses. Finally, over the last few years, reproductive performance has also been associated with copy number variants and candidate genes detected by genome-wide association studies on fertility traits. However, such studies are still scarce, probably because they depend on the existence of large and accurate phenotypic datasets of reproductive and/or fertility traits, which are still difficult to obtain in equines.
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Affiliation(s)
- Nora Laseca
- Departamento de genética, Universidad de Córdoba, Campus de Rabanales Ctra, Madrid-Cádiz, km 396, 14071 Córdoba, Spain; (N.L.); (G.A.); (Z.P.); (A.M.)
| | - Gabriel Anaya
- Departamento de genética, Universidad de Córdoba, Campus de Rabanales Ctra, Madrid-Cádiz, km 396, 14071 Córdoba, Spain; (N.L.); (G.A.); (Z.P.); (A.M.)
| | - Zahira Peña
- Departamento de genética, Universidad de Córdoba, Campus de Rabanales Ctra, Madrid-Cádiz, km 396, 14071 Córdoba, Spain; (N.L.); (G.A.); (Z.P.); (A.M.)
| | - Yamila Pirosanto
- Departamento de Producción Animal, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata 1900, Argentina;
- Consejo Superior de Investigaciones Científicas y Tecnológicas (CONICET), CCT-La Plata, La Plata 1900, Argentina
| | - Antonio Molina
- Departamento de genética, Universidad de Córdoba, Campus de Rabanales Ctra, Madrid-Cádiz, km 396, 14071 Córdoba, Spain; (N.L.); (G.A.); (Z.P.); (A.M.)
| | - Sebastián Demyda Peyrás
- Departamento de Producción Animal, Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata 1900, Argentina;
- Consejo Superior de Investigaciones Científicas y Tecnológicas (CONICET), CCT-La Plata, La Plata 1900, Argentina
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Dall'Olio S, Bovo S, Tinarelli S, Schiavo G, Padalino B, Fontanesi L. Association between candidate gene markers and harness racing traits in Italian trotter horses. Livest Sci 2021. [DOI: 10.1016/j.livsci.2020.104351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kvist L, Honka J, Niskanen M, Liedes O, Aspi J. Selection in the Finnhorse, a native all-around horse breed. J Anim Breed Genet 2020; 138:188-203. [PMID: 33226152 PMCID: PMC7894145 DOI: 10.1111/jbg.12524] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 10/20/2020] [Accepted: 11/01/2020] [Indexed: 12/19/2022]
Abstract
Selection by breeders modifies the morphology, behaviour and performance of domesticated species. Here, we examined signs of selection in Finnhorse, the only native horse breed in Finland. We first searched divergent genomic regions between Finnhorses and other breeds, as well as between different breeding sections of the Finnhorse with data from Illumina Equine SNP70 BeadChip, and then studied several of the detected regions in more detail. We found altogether 35 common outlier SNPs between Finnhorses and other breeds using two different selection tests. Many of the SNPs were located close to genes affecting coat colour, performance, size, sugar metabolism, immune response and olfaction. We selected genes affecting coat colour (KIT, MITF, PMEL), performance (MSTN) and locomotion (DMRT3) for a more detailed examination. In addition, we looked for, and found, associations with height at withers and SNPs located close to gene LCORL. Among the four breeding sections of Finnhorses (harness trotters, riding horses, draught horses and pony‐sized horses), a single SNP located close to the DMRT3 gene was significantly differentiated and only between harness trotters and pony‐sized horses.
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Affiliation(s)
- Laura Kvist
- Department of Ecology and Genetics, University of Oulu, Oulu, Finland
| | - Johanna Honka
- Department of Ecology and Genetics, University of Oulu, Oulu, Finland
| | - Markku Niskanen
- Research Unit of History, Culture and Communications, University of Oulu, Oulu, Finland
| | - Oona Liedes
- Department of Ecology and Genetics, University of Oulu, Oulu, Finland
| | - Jouni Aspi
- Department of Ecology and Genetics, University of Oulu, Oulu, Finland
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Abstract
The equid family contains only one single extant genus, Equus, including seven living species grouped into horses on the one hand and zebras and asses on the other. In contrast, the equine fossil record shows that an extraordinarily richer diversity existed in the past and provides multiple examples of a highly dynamic evolution punctuated by several waves of explosive radiations and extinctions, cross-continental migrations, and local adaptations. In recent years, genomic technologies have provided new analytical solutions that have enhanced our understanding of equine evolution, including the species radiation within Equus; the extinction dynamics of several lineages; and the domestication history of two individual species, the horse and the donkey. Here, we provide an overview of these recent developments and suggest areas for further research.
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Affiliation(s)
- Pablo Librado
- Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, Université Paul Sabatier, Toulouse 31000, France;
| | - Ludovic Orlando
- Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, Université Paul Sabatier, Toulouse 31000, France;
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Klumplerova M, Splichalova P, Oppelt J, Futas J, Kohutova A, Musilova P, Kubickova S, Vodicka R, Orlando L, Horin P. Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae. BMC Genomics 2020; 21:677. [PMID: 32998693 PMCID: PMC7525986 DOI: 10.1186/s12864-020-07089-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 09/21/2020] [Indexed: 02/08/2023] Open
Abstract
Background The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. The MHC class II sub-region contains genes expressed in antigen presenting cells. The antigen binding site is encoded by the second exon of genes encoding antigen presenting molecules. The exon 2 sequences of these MHC genes have evolved under the selective pressure of pathogens. Interspecific differences can be observed in the class II sub-region. The family Equidae includes a variety of domesticated, and free-ranging species inhabiting a range of habitats exposed to different pathogens and represents a model for studying this important part of the immunogenome. While equine MHC class II DRA and DQA loci have received attention, the genetic diversity and effects of selection on DRB and DQB loci have been largely overlooked. This study aimed to provide the first in-depth analysis of the MHC class II DRB and DQB loci in the Equidae family. Results Three DRB and two DQB genes were identified in the genomes of all equids. The genes DRB2, DRB3 and DQB3 showed high sequence conservation, while polymorphisms were more frequent at DRB1 and DQB1 across all species analyzed. DQB2 was not found in the genome of the Asiatic asses Equus hemionus kulan and E. h. onager. The bioinformatic analysis of non-zero-coverage-bases of DRB and DQB genes in 14 equine individual genomes revealed differences among individual genes. Evidence for recombination was found for DRB1, DRB2, DQB1 and DQB2 genes. Trans-species allele sharing was identified in all genes except DRB1. Site-specific selection analysis predicted genes evolving under positive selection both at DRB and DQB loci. No selected amino acid sites were identified in DQB3. Conclusions The organization of the MHC class II sub-region of equids is similar across all species of the family. Genomic sequences, along with phylogenetic trees suggesting effects of selection as well as trans-species polymorphism support the contention that pathogen-driven positive selection has shaped the MHC class II DRB/DQB sub-regions in the Equidae.
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Affiliation(s)
- Marie Klumplerova
- Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic.,Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic
| | - Petra Splichalova
- Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic.,Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic
| | - Jan Oppelt
- Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic.,Ceitec MU, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic.,National Centre for Biomolecular research, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic
| | - Jan Futas
- Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic.,Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic
| | - Aneta Kohutova
- Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic.,Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic
| | - Petra Musilova
- Department of Genetics and Reproductive Biotechnologies, Veterinary Research Institute, Brno, Czech Republic.,Ceitec VRI, RG Animal Cytogenomics, Brno, Czech Republic
| | - Svatava Kubickova
- Department of Genetics and Reproductive Biotechnologies, Veterinary Research Institute, Brno, Czech Republic.,Ceitec VRI, RG Animal Cytogenomics, Brno, Czech Republic
| | - Roman Vodicka
- Zoo Prague, U Trojského zámku 120/3, 171 00, Praha 7, Czech Republic
| | - Ludovic Orlando
- Laboratoire d'Anthropobiologie Moléculaire et d'Imagerie de Synthèse, CNRS UMR 5288, Université de Toulouse, Université Paul Sabatier, 31000, Toulouse, France.,Centre for GeoGenetics, Natural History Museum of Denmark, Øster Voldgade 5-7, 1350K, Copenhagen, Denmark
| | - Petr Horin
- Department of Animal Genetics, Veterinary and Pharmaceutical University, Brno, Czech Republic. .,Ceitec VFU, RG Animal Immunogenomics, Brno, Czech Republic.
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Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity. Equine Vet J 2020; 53:231-249. [PMID: 32881079 DOI: 10.1111/evj.13341] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 07/07/2020] [Accepted: 08/13/2020] [Indexed: 12/11/2022]
Abstract
The mononuclear phagocyte system (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macrophages have revealed many functional differences. In this review, we provide an overview of the equine MPS, describing the variation in the function and phenotype of macrophages depending on their location and the similarities and differences between the rodent, human and equine immune response. We discuss the use of the horse as a large animal model in which to study macrophage biology and pathological processes shared with humans. Finally, following the recent update to the horse genome, facilitating further comparative analysis of regulated gene expression between the species, we highlight the importance of future transcriptomic macrophage studies in the horse, the findings of which may also be applicable to human as well as veterinary research.
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Affiliation(s)
- Anna E Karagianni
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK
| | - Zofia M Lisowski
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK
| | - David A Hume
- Mater Research Institute-UQ, Translational Research Institute, Woolloongabba, QLD, Australia
| | - R Scott Pirie
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK
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Schaefer RJ, Cullen J, Manfredi J, McCue M. Functional contexts of adipose and gluteal muscle tissue gene co-expression networks in the domestic horse. Integr Comp Biol 2020; 63:icaa134. [PMID: 32970803 DOI: 10.1093/icb/icaa134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 08/14/2020] [Accepted: 08/27/2020] [Indexed: 11/13/2022] Open
Abstract
A gene's response to an environment is tightly bound to the underlying genetic variation present in an individual's genome and varies greatly depending on the tissue it is being expressed in. Gene co-expression networks provide a mechanism to understand and interpret the collective transcriptional responses of genes. Here, we use the Camoco co-expression network framework to characterize the transcriptional landscape of adipose and gluteal muscle tissue in 83 domestic horses (Equus caballus) representing 5 different breeds. In each tissue, gene expression profiles, capturing transcriptional response due to variation across individuals, were used to build two separate, tissue-focused, genotypically-diverse gene co-expression networks. The aim of our study was to identify significantly co-expressed clusters of genes in each tissue, then compare the clusters across networks to quantify the extent that clusters were found in both networks as well as to identify clusters found in a single network. The known and unknown functions for each network were quantified using complementary, supervised and unsupervised approaches. First, supervised ontological enrichment was utilized to quantify biological functions represented by each network. Curated ontologies (GO and KEGG) were used to measure the known biological functions present in each tissue. Overall, a large percentage of terms (40.3% of GO and 41% of KEGG) were co-expressed in at least one tissue. Many terms were co-expressed in both tissues, however a small proportion of terms exhibited single tissue co-expression suggesting functional differentiation based on curated, functional annotation. To complement this, an unsupervised approach not relying on ontologies was employed. Strongly co-expressed sets of genes defined by Markov clustering identified sets of unannotated genes showing similar patterns of co-expression within a tissue. We compared gene sets across tissues and identified clusters of genes the either segregate in co-expression by tissue or exhibit high levels of co-expression in both tissues. Clusters were also integrated with GO and KEGG ontologies to identify gene sets containing previously curated annotations versus unannotated gene sets indicating potentially novel biological function. Coupling together these transcriptional datasets, we mapped the transcriptional landscape of muscle and adipose setting up a generalizable framework for interpreting gene function for additional tissues in the horse and other species.
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Affiliation(s)
- Robert J Schaefer
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
| | - Jonah Cullen
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
| | - Jane Manfredi
- Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI
| | - Molly McCue
- Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN
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Futas J, Oppelt J, Janova E, Musilova P, Horin P. Complex variation in the KLRA (LY49) immunity-related genomic region in horses. HLA 2020; 96:257-267. [PMID: 32421927 DOI: 10.1111/tan.13939] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 04/22/2020] [Accepted: 05/14/2020] [Indexed: 12/30/2022]
Abstract
Natural killer (NK) cells play important roles in innate and adaptive immunity, as well as in the reproduction of placental mammals. Ly49 (KLRA) molecules represent a lectin-like type of NK cell receptor encoded within a complex genomic region, the NK cell complex. In rodents and horses, an expansion of the genes encoding Ly49 receptors leading to the formation of a gene family was observed. High sequence similarities and frequent high polymorphism of multiple family members represent an obstacle both for their individual identification and for annotation in the reference genomes of their respective species. Here, we focused on resolving complex variation of the KLRA gene family observed in domestic and Przewalski's horses. The KLRA (LY49) genomic region contains six genes (KLRA2-KLRA7) and one putative pseudogene, KLRA1. Two types of polymorphism were observed in the horses analyzed. Copy number variation between haplotypes was documented for the gene KLRA7 by polymerase chain reaction. As expected, the major source of variation of all KLRA genes, including KLRA7, is because of single nucleotide polymorphisms, many of them being nonsynonymous substitutions. Extensive allelic variability of the expanded KLRA (LY49) genes was observed. For four out of the six functional KLRA, high numbers of novel allelic amino acid sequence variants were identified in the genes studied, suggesting that this variation might be of functional importance, especially in the context of high polymorphism of their presumed ligands encoded by major histocompatibility complex class I genes. In fact, polymorphic amino acid sites were mostly found in the ligand-binding C-type lectin-like domain of the putative receptor molecule.
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Affiliation(s)
- Jan Futas
- RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.,Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic
| | - Jan Oppelt
- RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic
| | - Eva Janova
- RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.,Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic
| | - Petra Musilova
- RG Cytogenomics, Central European Institute of Technology (CEITEC)-Veterinary Research Institute, Brno, Czech Republic
| | - Petr Horin
- RG Animal Immunogenomics, Central European Institute of Technology (CEITEC)-VFU Brno, Brno, Czech Republic.,Department of Animal Genetics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences (VFU) Brno, Brno, Czech Republic
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Abstract
Reproductive disorders are genetically heterogeneous and complex; available genetic tests are limited to chromosome analysis and 1 susceptibility gene. Cytogenetic analysis should be the first test to confirm or rule out chromosomal aberrations. No causative genes/mutations are known. The only available genetic test for stallion subfertility is based on a susceptibility gene FKBP6. The ongoing progress in equine genomics will improve the status of genetic testing. However, because subfertile phenotypes do not facilitate collection of large numbers of samples or pedigrees, and clinical causes of many cases remain unknown, further progress requires constructive cross-talk between geneticists, clinicians, breeders, and owners.
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Affiliation(s)
- Terje Raudsepp
- Department of Veterinary Integrative Biosciences, Molecular Cytogenetics Laboratory, Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Veterinary Research Building Room 306, 588 Raymond Stotzer Parkway, College Station, TX 77843-4458, USA.
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40
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Characterization of A Homozygous Deletion of Steroid Hormone Biosynthesis Genes in Horse Chromosome 29 as A Risk Factor for Disorders of Sex Development and Reproduction. Genes (Basel) 2020; 11:genes11030251. [PMID: 32120906 PMCID: PMC7140900 DOI: 10.3390/genes11030251] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 02/21/2020] [Accepted: 02/25/2020] [Indexed: 12/24/2022] Open
Abstract
Disorders of sex development (DSD) and reproduction are not uncommon among horses, though knowledge about their molecular causes is sparse. Here we characterized a ~200 kb homozygous deletion in chromosome 29 at 29.7-29.9 Mb. The region contains AKR1C genes which function as ketosteroid reductases in steroid hormone biosynthesis, including androgens and estrogens. Mutations in AKR1C genes are associated with human DSDs. Deletion boundaries, sequence properties and gene content were studied by PCR and whole genome sequencing of select deletion homozygotes and control animals. Deletion analysis by PCR in 940 horses, including 622 with DSDs and reproductive problems and 318 phenotypically normal controls, detected 67 deletion homozygotes of which 79% were developmentally or reproductively abnormal. Altogether, 8-9% of all abnormal horses were homozygous for the deletion, with the highest incidence (9.4%) among cryptorchids. The deletion was found in ~4% of our phenotypically normal cohort, ~1% of global warmblood horses and ponies, and ~7% of draught breeds of general horse population as retrieved from published data. Based on the abnormal phenotype of the carriers, the functionally relevant gene content, and the low incidence in general population, we consider the deletion in chromosome 29 as a risk factor for equine DSDs and reproductive disorders.
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41
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Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq. Genes (Basel) 2019; 11:genes11010003. [PMID: 31861495 PMCID: PMC7017286 DOI: 10.3390/genes11010003] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 12/10/2019] [Accepted: 12/16/2019] [Indexed: 01/02/2023] Open
Abstract
One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein–protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.
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