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Roan (Rn) horses show a typical seasonal change of color. Their body is covered with colored and white hair. We performed a descriptive statistical analysis of breeding records of Icelandic horses to challenge the hypothesis of roan being lethal in utero under homozygous condition. The roan to non-roan ratio of foals from roan × roan matings revealed homozygous roan Icelandic horses to be viable. Even though roan is known to be inherited in a dominant mode and epistatic to other coat colors, the causative mutation is still unknown. Nevertheless, an association between roan phenotype and the KIT gene was shown for different horse breeds. In the present study, we identified KIT variants by Sanger sequencing, and show that KIT is also associated with roan in the Icelandic horse breed.

Analysis of the Y chromosome is the best-established way to reconstruct paternal family history in humans. Here, we applied fine-scaled Y-chromosomal haplotyping in horses with biallelic markers and demonstrate the potential of our approach to address the ancestry of sire lines. We de novo assembled a draft reference of the male-specific region of the Y chromosome from Illumina short reads and then screened 5.8 million basepairs for variants in 130 specimens from intensively selected and rural breeds and nine Przewalski's horses. Among domestic horses we confirmed the predominance of a young'crown haplogroup' in Central European and North American breeds. Within the crown, we distinguished 58 haplotypes based on 211 variants, forming three major haplogroups. In addition to two previously characterised haplogroups, one observed in Arabian/Coldblooded and the other in Turkoman/Thoroughbred horses, we uncovered a third haplogroup containing Iberian lines and a North African Barb Horse. In a genealogical showcase, we distinguished the patrilines of the three English Thoroughbred founder stallions and resolved a historic controversy over the parentage of the horse 'Galopin', born in 1872. We observed two nearly instantaneous radiations in the history of Central and Northern European Y-chromosomal lineages that both occurred after domestication 5,500 years ago.

Whole-genome sequencing studies are vital to gain a thorough understanding of genomic variation. Here, we summarize the results of a whole-genome sequencing study comprising 88 horses and ponies from diverse breeds at 19.1× average coverage. The paired-end reads were mapped to the current EquCab3.0 horse reference genome assembly, and we identified approximately 23.5 million single nucleotide variants and 2.3 million short indel variants. Our dataset included at least 7 million variants that were not previously reported. On average, each individual horse genome carried ∼5.7 million single nucleotides and 0.8 million small indel variants with respect to the reference genome assembly. The variants were functionally annotated. We provide two examples for potentially deleterious recessive alleles that were identified in a heterozygous state in individual genome sequences. Appropriate management of such deleterious recessive alleles in horse breeding programs should help to improve fertility and reduce the prevalence of heritable diseases. This comprehensive dataset has been made publicly available, will represent a valuable resource for future horse genetic studies and supports the goal of accelerating the rates of genetic gain in domestic horse., (© 2018 Stichting International Foundation for Animal Genetics.)

Background: To date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array., Results: Using whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of ~5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of ~2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of ~670 thousand SNPs (MNEc670k), was designed for genotype imputation., Conclusions: Here, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.

The Y chromosome directly reflects male genealogies, but the extremely low Y chromosome sequence diversity in horses has prevented the reconstruction of stallion genealogies [1, 2]. Here, we resolve the first Y chromosome genealogy of modern horses by screening 1.46 Mb of the male-specific region of the Y chromosome (MSY) in 52 horses from 21 breeds. Based on highly accurate pedigree data, we estimated the de novo mutation rate of the horse MSY and showed that various modern horse Y chromosome lineages split much later than the domestication of the species. Apart from few private northern European haplotypes, all modern horse breeds clustered together in a roughly 700-year-old haplogroup that was transmitted to Europe by the import of Oriental stallions. The Oriental horse group consisted of two major subclades: the Original Arabian lineage and the Turkoman horse lineage. We show that the English Thoroughbred MSY was derived from the Turkoman lineage and that English Thoroughbred sires are largely responsible for the predominance of this haplotype in modern horses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The casein genes are known to be highly variable in typical dairy species, such as cattle and goat, but the knowledge about equine casein genes is limited. Nevertheless, mare milk production and consumption is gaining importance because of its high nutritive value, use in naturopathy, and hypoallergenic properties with respect to cow milk protein allergies. In the current study, the open reading frames of the 4 casein genes CSN1S1 (αS1-casein), CSN2 (β-casein), CSN1S2 (αS2-casein), and CSN3 (κ-casein) were resequenced in 253 horses of 14 breeds. The analysis revealed 21 nonsynonymous nucleotide exchanges, as well as 11 synonymous nucleotide exchanges, leading to a total of 31 putative protein isoforms predicted at the DNA level, 26 of which considered novel. Although the majority of the alleles need to be confirmed at the transcript and protein level, a preliminary nomenclature was established for the equine casein alleles., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Categorical traits without ordinal representation of classes do not qualify for threshold models. Alternatively, the multinomial problem can be assessed by a sequence of independent binary contrasts using schemes such as one-vs-all or one-vs-one. Class probabilities can be arrived at by normalization or pair-wise coupling strategies. We assessed the predictive ability of whole-genome regression models and support vector machines for the classification of horses into four German Warmblood breeds., Results: Prediction accuracies of leave-one-out cross-validation were high and ranged from 0.75 to 0.97 depending on the binary classifier and breeds incorporated in the training. An analysis of the population structure using eigenvectors of the genomic relationship matrix revealed clustering of individuals beyond the given breed labels. Admixture between two breeds became apparent which had substantial impact on the prediction accuracies between those two breeds and also influenced the contrasts between other breeds., Conclusions: Genomic prediction of unordered categorical traits was successfully applied to subpopulation assignment of German Warmblood horses. The applied methodology is a straightforward extension of existing binary threshold models for genomic prediction.

Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD) as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD.

Background: A cost-effective strategy to increase the density of available markers within a population is to sequence a small proportion of the population and impute whole-genome sequence data for the remaining population. Increased densities of typed markers are advantageous for genome-wide association studies (GWAS) and genomic predictions., Methods: We obtained genotypes for 54 602 SNPs (single nucleotide polymorphisms) in 1077 Franches-Montagnes (FM) horses and Illumina paired-end whole-genome sequencing data for 30 FM horses and 14 Warmblood horses. After variant calling, the sequence-derived SNP genotypes (~13 million SNPs) were used for genotype imputation with the software programs Beagle, Impute2 and FImpute., Results: The mean imputation accuracy of FM horses using Impute2 was 92.0%. Imputation accuracy using Beagle and FImpute was 74.3% and 77.2%, respectively. In addition, for Impute2 we determined the imputation accuracy of all individual horses in the validation population, which ranged from 85.7% to 99.8%. The subsequent inclusion of Warmblood sequence data further increased the correlation between true and imputed genotypes for most horses, especially for horses with a high level of admixture. The final imputation accuracy of the horses ranged from 91.2% to 99.5%., Conclusions: Using Impute2, the imputation accuracy was higher than 91% for all horses in the validation population, which indicates that direct imputation of 50k SNP-chip data to sequence level genotypes is feasible in the FM population. The individual imputation accuracy depended mainly on the applied software and the level of admixture.

A genome-wide association scan for loci affecting withers height was conducted in 782 German Warmblood stallions, which were genotyped using the Illumina EquineSNP50 Bead Chip. A principal components approach was applied to correct for population structure. The analysis revealed a single major QTL on ECA3 explaining ~18 per cent of the phenotypic variance, which is in concordance with recent reports from other horse populations. The LCORL/NCAPG locus represents a strong candidate gene for this QTL. This locus is among a small number that have consistently been identified to influence human height in several large meta-analyses. Furthermore, a mutation within the NCAPG gene was found to affect growth and body frame size in cattle. Together with the results of this study in German Warmbloods, these findings strongly indicate LCORL/NCAPG as a candidate locus for withers height in horses. Further studies are, however, needed to confirm this., (© 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.)

Background: Defensins represent an important class of antimicrobial peptides. These effector molecules of the innate immune system act as endogenous antibiotics to protect the organism against infections with pathogenic microorganisms. Mammalian defensins are classified into three distinct sub-families (alpha-, beta- and theta-defensins) according to their specific intramolecular disulfide-bond pattern. The peptides exhibit an antimicrobial activity against a broad spectrum of microorganisms including bacteria and fungi. Alpha-Defensins are primarily synthesised in neutrophils and intestinal Paneth cells. They play a role in the pathogenesis of intestinal diseases and may regulate the flora of the intestinal tract. An equine intestinal alpha-defensin (DEFA1), the first characterised in the Laurasiatheria, shows a broad antimicrobial spectrum against human and equine pathogens. Here we report a first investigation of the repertoire of equine intestinal alpha-defensins. The equine genome was screened for putative alpha-defensin genes by using known alpha-defensin sequences as matrices. Based on the obtained sequence information, a set of oligonucleotides specific to the alpha-defensin gene-family was designed. The products generated by reverse-transcriptase PCR with cDNA from the small intestine as template were sub-cloned and numerous clones were sequenced., Results: Thirty-eight equine intestinal alpha-defensin transcripts were determined. After translation it became evident that at least 20 of them may code for functional peptides. Ten transcripts lacked matching genomic sequences and for 14 alpha-defensin genes apparently present in the genome no appropriate transcript could be verified. In other cases the same genomic exons were found in different transcripts., Conclusions: The large repertoire of equine alpha-defensins found in this study points to a particular importance of these peptides regarding animal health and protection from infectious diseases. Moreover, these findings make the horse an excellent species to study biological properties of alpha-defensins. Interestingly, the peptides were not found in other species of the Laurasiatheria to date. Comparison of the obtained transcripts with the genomic sequences in the current assembly of the horse (EquCab2.0) indicates that it is yet not complete and/or to some extent falsely assembled.

Objective: To evaluate systemic effects of i.v. infusion of ATP-MgCl2 subsequent to infusion of a low dose of endotoxin in horses., Animals: 12 adult horses., Procedure: Horses were administered endotoxin (lipopolysaccharide [LPS]) or saline (0.9% NaCl) solution i.v., during a 30-minute period. Immediately thereafter, horses in each group were infused i.v. with ATP-MgCl2 or saline solution. Two weeks later, horses were administered the opposite solution (LPS or saline solution), but it was followed by the same infusion as 2 weeks previously (ie, ATP-MgCl2 or saline solution). Cardiopulmonary and clinicopathologic variables, cytokine activity, and endothelin (ET) concentrations were recorded., Results: IV infusion of ATP-MgCl2 after administration of a low dose of endotoxin failed to attenuate the cardiopulmonary, clinicopathologic, and cytokine alterations that develop secondary to endotoxin exposure. The combination of LPS and ATP-MgCl2 potentiated pulmonary hypertension, leukopenia, and neutropenia when compared with the combination of LPS and saline solution. The combination of LPS and ATP-MgCl2 resulted in thrombocytopenia. Endothelin concentration was increased in jugular venous and pulmonary arterial plasma in horses receiving LPS and ATP-MgCl2. Similar increases were not observed with LPS and saline solution., Conclusions and Clinical Relevance: Administration of ATP-MgCl2 did not protect horses from systemic effects of experimentally induced endotoxemia. Furthermore, the use of ATP-MgCl2 during endotoxemia may worsen the cardiopulmonary and clinicopathologic status of affected horses. Because ATP and other adenine nucleotides are released from cells during shock, their potential role in the development of hemodynamic derangements, leukocyte adherence, and coagulopathies during endotoxemic episodes warrants further investigation.

Reasons for Performing Study: Abdominal insufflation is performed routinely during laparoscopy in horses to improve visualisation and facilitate instrument and visceral manipulations during surgery. It has been shown that high-pressure pneumoperitoneum with carbon dioxide (CO2) has deleterious cardiopulmonary effects in dorsally recumbent, mechanically ventilated, halothane-anaesthetised horses. There is no information on the effects of CO2 pneumoperitoneum on cardiopulmonary function and haematology, plasma chemistry and peritoneal fluid (PF) variables in standing sedated horses during laparoscopic surgery., Objectives: To determine the effects of high pressure CO2 pneumoperitoneum in standing sedated horses on cardiopulmonary function, blood gas, haematology, plasma chemistry and PF variables., Methods: Six healthy, mature horses were sedated with an i.v. bolus of detomidine (0.02 mg/kg bwt) and butorphanol (0.02 mg/kg bwt) and instrumented to determine the changes in cardiopulmonary function, haematology, serum chemistry and PF values during and after pneumoperitoneum with CO2 to 15 mmHg pressure for standing laparoscopy. Each horse was assigned at random to either a standing left flank exploratory laparoscopy (LFL) with CO2 pneumoperitoneum or sham procedure (SLFL) without insufflation, and instrumented for measurement of cardiopulmonary variables. Each horse underwent a second procedure in crossover fashion one month later so that all 6 horses had both an LFL and SLFL performed. Cardiopulmonary variables and blood gas analyses were obtained 5 mins after sedation and every 15 mins during 60 mins baseline (BL), insufflation (15 mmHg) and desufflation. Haematology, serum chemistry analysis and PF analysis were performed at BL, insufflation and desufflation, and 24 h after the conclusion of each procedure., Results: Significant decreases in heart rate, cardiac output and cardiac index and significant increases in mean right atrial pressure, systemic vascular resistance and pulmonary vascular resistance were recorded immediately after and during sedation in both groups of horses. Pneumoperitoneum with CO2 at 15 mmHg had no significant effect on cardiopulmonary function during surgery. There were no significant differences in blood gas, haematology or plasma chemistry values within or between groups at any time interval during the study. There was a significant increase in the PF total nucleated cell count 24 h following LFL compared to baseline values for LFL or SLFL at 24 h. There were no differences in PF protein concentrations within or between groups at any time interval., Conclusions: Pneumoperitoneum with CO2 during standing laparoscopy in healthy horses does not cause adverse alterations in cardiopulmonary, haematology or plasma chemistry variables, but does induce a mild inflammatory response within the peritoneal cavity., Potential Relevance: High pressure (15 mmHg) pneumoperitoneum in standing sedated mature horses for laparoscopic surgery can be performed safely without any short-term or cumulative adverse effects on haemodynamic or cardiopulmonary function.

Objective: To report an neodymium:yttrium-aluminum garnet (Nd:YAG) laser-assisted modified Forssell's surgical technique and outcome for treatment of cribbing (crib-biting) in horses., Study Design: Retrospective clinical study., Animals: Ten adult horses with stereotypic cribbing behavior., Methods: Data were obtained from medical records and telephone conversations with owners, trainers, and veterinarians. Surgical technique involved an approximately 34-cm ventral median skin incision starting rostral to the larynx and extending caudally. A 10-cm section of the ventral branch of the spinal accessory nerve was removed, using an Nd:YAG laser at 25 W and continuous pulse with a contact, sculpted-fiber tip. After neurectomy, approximately 34-cm sections of the paired omohyoideus and sternothyrohyoideus muscles were removed starting 2 cm rostral to the ventral aspect of the larynx, at the basihyoid bone, using the Nd:YAG laser., Results: Median horse age was 7 years (range, 1 to 11 years). Median surgical time was 90 minutes (range, 75 to 130 minutes). Long-term outcome (range, 7 to 72 months) was available for all horses. None of the horses had cribbing behavior after surgery, and all returned to their previous use. Four horses had complications (two of which were unrelated to the surgical site), but all recovered fully., Conclusion: The successful outcome we obtained is better than reported previously using a modified Forssell's technique., Clinical Relevance: Surgical treatment for cribbing by Nd: YAG laser-assisted myectomy and neurectomy resulted in an excellent prognosis for resolution of the stereotypical behavior with minimal complications., (Copyright 2002 by The American College of Veterinary Surgeons)

Objective: To evaluate the in vitro effects of adenosine tryphosphate (ATP) on vasomotor tone of equine colonic vasculature., Sample Population: Arteries and veins from the left ventral colon of 14 mixed-breed horses euthanatized for reasons unrelated to cardiovascular or gastrointestinal tract disease., Procedures: Endothelium-intact and -denuded arterial and venous rings were precontracted with 10(-7) and 1.8 x 10(-8) M endothelin-1, respectively. In 1 trial, endothelium-intact rings were also incubated with 10(-4) M N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide (NO) production. Adenosine triphosphate (10(-8) to 10(-3) M) was added in a noncumulative manner, and relaxation percentage versus time curves were generated. Areas under the curves (ie, percentage of relaxation time) were calculated., Results: Relaxation response of arterial and venous rings to ATP was dose-dependent. Percentage of relaxation time in response to 10(-4) and 10(-3) MATP was significantly greater, compared with that for rings not treated with ATP Removal of endothelium attenuated but did not eliminate the relaxation response. Addition of L-NAME did not attenuate the relaxation response in arteries. At higher concentrations, the vascular response to ATP was biphasic., Conclusions and Clinical Relevance: ATP applied to equine colonic arterial and venous rings with and without intact endothelium induced a biphasic response characterized by transient contraction followed by slow, substantial, and sustained relaxation. This ATP-induced response is possibly mediated by a mechanism other than NO. Adenosine triphosphate may be a useful treatment to modulate colonic vasomotor tone in horses with strangulating volvulus of the ascending colon.

Objective: To characterize alterations in systemic and local colonic hemodynamic variables associated with IV infusion of ATP-MgCl2 in healthy anesthetized horses., Animals: 12 adult horses., Procedure: Six horses were given ATP-MgCl2, IV, beginning at a rate of 0.1 mg of ATP/kg of body weight/min with incremental increases until a rate of 1.0 mg/kg/min was achieved. The remaining 6 horses were given an equivalent volume of saline (0.9% NaCl) solution over the same time period. Colonic and systemic hemodynamic variables and colonic plasma nitric oxide (NO) concentrations were determined before, during, and after infusion., Results: Infusion of ATP-MgCl2 caused a rate-dependent decrease in systemic and colonic vascular resistance, principally via its vasodilatory effects. A rate of 0.3 mg of ATP/kg/min caused a significant decrease in systemic and colonic arterial pressure and colonic vascular resistance without a significant corresponding decrease in colonic arterial blood flow. Consistent alterations in NO concentrations of plasma obtained from colonic vasculature were not detected, despite profound vasodilatation of the colonic arterial vasculature., Conclusions and Clinical Relevance: Results revealed that IV infusion of ATP-MgCl2 may be beneficial in maintaining colonic perfusion in horses with ischemia of the gastrointestinal tract, provided a sufficient pressure gradient exists to maintain blood flow.

Objective: To determine hemodynamic and metabolic effects of IV infusion of ATP-MgCl2 combination and maximal safe IV infusion rate in conscious horses., Animals: 6 adult female horses., Procedure: All horses received an IV infusion of ATP-MgCl2 combination, beginning at a rate of 0.05 mg of ATP/kg of body weight/min, which was increased by 0.05 mg/kg/min increments at 10-minute intervals until a rate of 1.0 mg/kg/min was achieved. Data were collected prior to the start of the infusion, at the end of each infusion rate, and at 15-minute intervals for the next hour after discontinuation of the infusion. Measured or calculated hemodynamic variables included cardiac output, cardiac index, heart rate, stroke volume, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistances. Arterial blood gas tensions, CBC, plasma biochemical profiles, urine volume and specific gravity, and selected clinical signs of disease also were evaluated., Results: Intravenous infusion of ATP-MgCl2 significantly increased cardiac output, decreased systemic vascular resistance, and caused mild pulmonary hypertension. Magnitude of the hemodynamic alterations was dependent on rate of infusion. Maximal safe infusion rate for these horses was 0.3 mg/kg/min. All horses became lethargic, and their appetites diminished during the infusion; 5 horses had mild signs of abdominal discomfort. Flank sweating was observed in all horses as infusion rate increased. Urine volume and specific gravity and hematologic, biochemical, and arterial blood gas alterations were detected during and after infusion., Conclusions and Clinical Relevance: Intravenous administration of ATP-MgCl2 in healthy, conscious, adult horses caused various metabolic and hemodynamic alterations that were without appreciable detrimental effects.

Objective: To assess the effect of incomplete, midsagittal fractures of the proximal phalanx (P1) on racing performance in Standardbreds., Design: Retrospective cohort study., Animals: 49 Standardbred horses admitted to the George D. Widener Hospital for Large Animals between July 1986 and December 1992 with a definitive radiographic diagnosis of an incomplete, midsagittal fracture of P1 and a known method of treatment., Procedure: Performance index and racing time were compared before and after diagnosis and treatment of fracture, using ANOVA that controlled for the effects of horse, gender, age, track length, and track condition., Results: Expected racing time increased by 0.7 seconds and performance index decreased by 0.7 points, although controlling for factors known to affect racing performance had a substantial impact on these results., Clinical Implications: Standardbreds with incomplete, midsagittal fractures of P1 have a favorable prognosis for return to racing; recovered horses will likely have slower racing times and decreased performance indices.

A genome-wide association scan for loci affecting withers height was conducted in 782 German Warmblood stallions, which were genotyped using the Illumina Equine SNP50 Bead Chip. A principal components approach was applied to correct for population structure. The analysis revealed a single major QTL on ECA3 explaining ~18 per cent of the phenotypic variance, which is in concordance with recent reports from other horse populations. The LCORL/ NCAPG locus represents a strong candidate gene for this QTL. This locus is among a small number that have consistently been identified to influence human height in several large meta-analyses. Furthermore, a mutation within the NCAPG gene was found to affect growth and body frame size in cattle. Together with the results of this study in German Warmbloods, these findings strongly indicate LCORL/ NCAPG as a candidate locus for withers height in horses. Further studies are, however, needed to confirm this. [ABSTRACT FROM AUTHOR]