Genome-Wide Homozygosity Patterns and Evidence for Selection in a Set of European and Near Eastern Horse Breeds
Total Page：16
File Type：pdf, Size：1020Kb
G C A T T A C G G C A T genes Article Genome-Wide Homozygosity Patterns and Evidence for Selection in a Set of European and Near Eastern Horse Breeds Gertrud Grilz-Seger 1,*, Markus Neuditschko 2, Anne Ricard 3, Brandon Velie 4,5, Gabriella Lindgren 4,6 , Matjaz Mesariˇc 7, Marko Cotman 8, Michaela Horna 9, Max Dobretsberger 1, Gottfried Brem 1 and Thomas Druml 1 1 Institute of Animal Breeding and Genetics, University of Veterinary Sciences Vienna, Veterinärplatz 1, 1210 Vienna, Austria 2 Agroscope, Swiss National Stud Farm, Les Longs Prés, CH-1580 Avenches, Switzerland 3 UMR 1313 Génétique Animale et Biologie Intégrative, Institut National de la Recherche Agronomique, Domaine de Vilvert, Bat 211, 78352 Jouy-en-Josas, France 4 Department of Animal Breeding & Genetics, Swedish University of Agricultural Sciences, Ulls väg 26, 750 07 Uppsala, Sweden 5 School of Life and Environmental Sciences, University of Sydney, Eastern Ave, Sydney, NSW 2006, Australia 6 Livestock Genetics, Department of Biosystems, KU Leuven, 3001 Leuven, Belgium 7 Clinic for Reproduction and Large Animals, University of Ljubljana, Veterinary, Faculty, Cesta v Mestni log 47, 1000 Ljubljana, Slovenia 8 Institute for Preclinical Sciences, University of Ljubljana, Veterinary Faculty, Gerbiˇceva60, 1000 Ljubljana, Slovenia 9 Department of Animal Husbandry, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia * Correspondence: [email protected] Received: 14 May 2019; Accepted: 26 June 2019; Published: 28 June 2019 Abstract: Intensive artificial and natural selection have shaped substantial variation among European horse breeds. Whereas most equine selection signature studies employ divergent genetic population structures in order to derive specific inter-breed targets of selection, we screened a total of 1476 horses originating from 12 breeds for the loss of genetic diversity by runs of homozygosity (ROH) utilizing a 670,000 single nucleotide polymorphism (SNP) genotyping array. Overlapping homozygous regions (ROH islands) indicating signatures of selection were identified by breed and similarities/dissimilarities between populations were evaluated. In the entire dataset, 180 ROH islands were identified, whilst 100 islands were breed specific, all other overlapped in 36 genomic regions with at least one ROH island of another breed. Furthermore, two ROH hot spots were determined at horse chromosome 3 (ECA3) and ECA11. Besides the confirmation of previously documented target genes involved in selection for coat color (MC1R, STX17, ASIP), body size (LCORL/NCAPG, ZFAT, LASP1, HMGA2), racing ability (PPARGC1A), behavioral traits (GRIN2B, NTM/OPCML) and gait patterns (DMRT3), several putative target genes related to embryonic morphogenesis (HOXB), energy metabolism (IGFBP-1, IGFBP-3), hair follicle morphogenesis (KRT25, KRT27, INTU) and autophagy (RALB) were highlighted. Furthermore, genes were pinpointed which might be involved in environmental adaptation of specific habitats (UVSSA, STXBP4, COX11, HLF, MMD). Keywords: ROH island; selection signature; body size; coat color; autophagy; altitude adaptation; embryonic morphogenesis Genes 2019, 10, 491; doi:10.3390/genes10070491 www.mdpi.com/journal/genes Genes 2019, 10, 491 2 of 22 Keywords: ROH island; selection signature; body size; coat color; autophagy; altitude adaptation; embryonic morphogenesis; Genes 2019, 10, 491 2 of 23 1. Introduction 1. Introduction The scientific interest in the identification of selection signatures in horses successively rose with The scientific interest in the identification of selection signatures in horses successively rose the enhancement of whole-genome sequencing and analysis methods. A milestone in equine genetics with the enhancement of whole-genome sequencing and analysis methods. A milestone in equine is the population study of Gu et al. [1] that concentrated on the identification of selection targets in genetics is the population study of Gu et al. [1] that concentrated on the identification of selection thoroughbreds using microsatellite markers. With the availability of cost extensive high throughput targets in thoroughbreds using microsatellite markers. With the availability of cost extensive high singlethroughput nucleotide single polymorphism nucleotide polymorphism (SNP) data, (SNP) several data, studies several were studies conducted were conducted to scan theto scan genome the of numerousgenome of horse numerous populations horse populations for genetic diversityfor genetic [2 diversity,3], and for [2,3], selection and for signatures selection signatures [4–7]. Furthermore, [4–7]. theFurthermore, capability ofthe archaeogenomics capability of archaeogenomics to isolate and to analyze isolate ancientand analyze DNA ancient enabled DNA the enabled comparison the of thecomparison ancient equine of the genome ancient withequine modern genome breeds, with whichmodern highlighted breeds, which the genomichighlighted changes the genomic during the domesticationchanges during process the domestication [8,9]. Most of theseprocess studies [8,9]. employ Most of methods these studies which ascertainemploy methods the loss of which diversity inascertain order to the capture loss of breed diversity divergent in order patterns to captur of moleculare breed divergent variation, patterns among of them molecular FST statistics variation, being theamong most popularthem FST [ 10statistics,11]. In otherbeing livestockthe most species, popular authors [10,11]. investigated In other livestock selection signaturesspecies, authors based on commoninvestigated shared selection runs ofsignatures homozygosity based on (ROH common islands) shared [12 runs–15]. of To homozygosity date, several (ROH studies islands) applying [12– this approach15]. To date, on horses several were studies published applying [16– 21this]. Toapproach our knowledge, on horses one were of the published first equine [16–21]. studies To scanning our theknowledge, genome for one runs of the of homozygosityfirst equine studies (ROH) scanning in order the to genome detect selectionfor runs of signatures homozygosity was performed (ROH) in by Metzgerorder to etdetect al. [16 selection] using thesignatures next generation was performed sequencing by Metzger data et of al. 10 [16] horses using (three the next horses generation originating fromsequencing primitive data breeds of 10 and horses seven (three horses horses originating originating from modernfrom primitive breeds). breedsGrilz-Seger and seven et al. [ 17horses,18] and Velieoriginating et al. [19 from] investigated modern breeds). ROH island Grilz-Seger patterns et within al. [17,18] single and breeds Velie using et al. genotype [19] investigated information ROH of the 670kisland SNP patterns genotyping within array. single A breeds comparison using ofgenotype overlapping information homozygous of the 670k regions SNP between genotyping three array. different A comparison of overlapping homozygous regions between three different breeds with a small breeds with a small population size using 670k SNP data was performed by Grilz-Seger et al. [20], population size using 670k SNP data was performed by Grilz-Seger et al. [20], whilst Nolte et al. [21] whilst Nolte et al. [21] investigated four German sport horse breeds based upon 50k SNP data. In this investigated four German sport horse breeds based upon 50k SNP data. In this study, we study, we investigated a highly diverse breed panel of 12 European and Near-Eastern horse breeds, investigated a highly diverse breed panel of 12 European and Near-Eastern horse breeds, comprising in total 1476 horses, for potential signatures of selection utilizing the 670kSNP genotyping comprising in total 1476 horses, for potential signatures of selection utilizing the 670kSNP arraygenotyping (Table1 array). The (Table horses 1). were The horses selected were to representselected to a represent North–South a North–South gradient ranginggradient fromranging Great Britainfrom Great over CentralBritain over and Central South-Eastern and South-Ea Europestern to theEurope Near to East the Near (Figure East1). (Figure 1). Figure 1. Geographic origin of twelve investigated European and Near Eastern horse breeds (Graphics Thomas Druml). Genes 2019, 10, 491 3 of 23 Table 1. Characterization of breeds, population history, sample location and number of sampled horses (N). Region of Breed/Classification Gene Pool Population Notes and Census Origin/Sample Origin Exmoor Pony Closed stud book since 1921, ca. small sized, multipurpose Native English breed British Isles/UK 2.000 animals [2] working horse Selle Francais French Trotter, Stud book founded 1958; ca. 12.700 France/FRA Riding horse Thoroughbred, Arabian breeding animals [22] Stud book closed since 1937, allows French Trotter Anglo Norman, France/FRA Standardbred; 15.500 breeding harness racing (trot) Standardbred animals [23] Austro—Hungarian/Lipizzan Founded 1580, closed studbook since Lipizzan Old-Spanish and Stud farms AT, SLK, 1880; ca. 2.000 breeding animals in riding, driving Oriental breeds HUN, HR European state stud farms [24] Noriker Very old breed, closed stud book since Native Austrian breed Austria/AT heavy working draught horse 1880; ca. 4.000 breeding animals [25] Derived from local and Haflinger Founded 1898, closed studbook since Galizian mares, and light draught horse, Austria/AT 1928; ca. 6.000 breeding animals in influenced by Arabian, multipurpose Austria [26] Gidran, Noriker Posavina Native Croatian breed, Closed studbook since 1994; ca.