Associations between candidate gene markers at a quantitative trait locus on equine chromosome 4 responsible for osteochondrosis dissecans in fetlock joints of South German Coldblood horses

A previously accomplished whole-genome scan for osteochondrosis (OC) and OC dissecans (OCD) in South German Coldblood horses using 250 microsatellite markers identified putative quantitative trait loci (QTL). A chromosome-wide significant QTL for fetlock OCD was found on Equus caballus chromosome (ECA) 4q at a relative position of 70.0-73.3 cM. The aim of this study was to analyze associations of single nucleotide polymorphisms (SNPs) in candidate genes for OC in this region. The association analysis included 32 affected and 64 unaffected horses. Three SNPs located in intron 8, intron 9, and 3'-untranslated region (UTR) of the acyloxyacyl hydrolase (AOAH) gene on ECA4q were significantly associated with OCD in fetlock joints. In order to control for systematic environmental and quantitative genetic effects, we employed a linear animal model. The association of the SNP (AJ543065:g.703A>G) in the 3'-UTR of exon 21 was confirmed in the animal model analysis and a significant additive genetic effect for fetlock OCD of 0.42 (P = 0.002) and a dominance effect of -0.32 (P = 0.03) was estimated. This is the first report on a marker in population-wide linkage disequilibrium with equine OCD in fetlock joints.     

Genome-wide search for markers associated with osteochondrosis in Hanoverian warmblood horses

A genome-wide scan was performed to detect quantitative trait loci (QTLs) for osteochondrosis (OC) and osteochondrosis dissecans (OCD) in horses. The marker set comprised 260 microsatellites. We collected data from 211 Hanoverian warmblood horses consisting of 14 paternal half-sib families. Traits used were OC (fetlock and/or hock joints affected), OCD (fetlock and/or hock joints affected), fetlock OC, fetlock OCD, hock OC, and hock OCD. The first genome scan included 172 microsatellite markers. In a second step 88 additional markers were chosen to refine putative QTLs found in the first scan. Genome-wide significant QTLs were located on equine chromosomes 2, 4, 5, and 16. QTLs for fetlock OC and hock OC partly overlapped on the same chromosomes, indicating that these traits may be genetically related. QTLs reached the chromosome-wide significance level on eight different equine chromosomes: 2, 3, 4, 5, 15, 16, 19, and 21. This whole-genome scan was a first step toward the identification of candidate genome regions harboring genes responsible for equine OC. Further investigations are necessary to refine the map positions of the QTLs already identified for OC. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Refinement of a quantitative gene locus on equine chromosome 16 responsible for osteochondrosis in Hanoverian warmblood horses

Osteochondrosis (OC) is an inherited developmental disease in young horses most frequently observed in thoroughbreds, trotters, warmblood and coldblood horses. Quantitative trait loci (QTL) for equine OC have been identified in Hanoverian warmblood horses employing a whole genome scan with microsatellites. A QTL on ECA16 reached the genome-wide significance level for hock osteochondrosis dissecans (OCD). The aim of this study was to refine this QTL on ECA16 using an extended marker set of 34 newly developed microsatellites and 15 single nucleotide polymorphisms (SNPs). We used the same 14 paternal half-sib groups as in the above-mentioned whole genome scan. The QTL for OCD in hock joints on ECA16 could be delimited at an interval between 17.60 and 45.18 Mb using multipoint non-parametric linkage analyses. In addition, six microsatellites and one SNP were significantly associated with hock OCD in the QTL region between 24.26 and 42.41 Mb. Furthermore, our analysis revealed a second QTL for fetlock OC between 6.55 and 24.26 Mb on ECA16. This report is a further step towards unravelling the genes underlying QTL for equine OC and towards the development of a marker test for OC in Hanoverian warmblood horses.     

Equine developmental orthopaedic diseases – a genome‐wide association study of first phalanx plantar osteochondral fragments in Standardbred trotters

Palmar/plantar osteochondral fragments (POF) in fetlock joints commonly affect and influence the athletic performance of horses. In this study, we used the Equine SNP50 BeadChip^® to perform a genome‐wide association study of metatarsophalangeal POF in 176 Norwegian Standardbred trotter yearlings. Putative quantitative trait loci (QTL) for medial and/or lateral POF, and medial POF only were identified on ECA1, 2, 7, 9 and 31, whereas for lateral POF, only on ECA7, 11, 27 and X. The moderate number of QTL evidences a complex inheritance and suggests various genes controlling POF development in medial and lateral locations.     

Whole-genome scan identifies quantitative trait loci for chronic pastern dermatitis in German draft horses

Chronic pastern dermatitis (CPD), also known as chronic progressive lymphedema (CPL), is a skin disease that affects draft horses. This disease causes painful lower-leg swelling, nodule formation, and skin ulceration, interfering with movement. The aim of this whole-genome scan was to identify quantitative trait loci (QTL) for CPD in German draft horses. We recorded clinical data for CPD in 917 German draft horses and collected blood samples from these horses. Of these 917 horses, 31 paternal half-sib families comprising 378 horses from the breeds Rhenish German, Schleswig, Saxon-Thuringian, and South German were chosen for genotyping. Each half-sib family was constituted by only one draft horse breed. Genotyping was done for 318 polymorphic microsatellites evenly distributed on all equine autosomes and the X chromosome with a mean distance of 7.5 Mb. An across-breed multipoint linkage analysis revealed chromosome-wide significant QTL on horse chromosomes (ECA) 1, 9, 16, and 17. Analyses by breed confirmed the QTL on ECA1 in South German and the QTL on ECA9, 16, and 17 in Saxon-Thuringian draft horses. For the Rhenish German and Schleswig draft horses, additional QTL on ECA4 and 10 and for the South German draft horses an additional QTL on ECA7 were found. This is the first whole-genome scan for CPD in draft horses and it is an important step toward the identification of candidate genes.     

Differences between horse selection based on two forms of osteochondrosis in fetlock

Horses lose potential opportunities because of health problems. Available breeding strategies are not effective enough, probably also because of the different definition used and its genetic usefulness. The aim of the study was to compare the genetic background estimated by the genome-wide association study (GWAS) for osteochondrosis using two different scaling osteochondrosis (OC)/healthy and osteochondrosis dissecans (OCD)/healthy systems for evaluating the disease status of investigated fetlock joints. Two hundred one Warmblood horses trained for performance tests (87 stallions and 114 mares) were phenotyped and genotyped. Four fetlock x-ray images per horse were collected using the RTG Girth HF 80 and Vet Scan ray 3600. The DNA of each horse was genotyped using the BeadChip 70K. To identify SNPs that significantly affect the probability of osteochondrosis, two different methods were applied: the Cochran-Armitage test based on an additive mode of inheritance and logistic regression. The genetic background for osteochondrosis, expressed in the number of SNPs found with significant associations with osteochondrosis, was higher by evaluation in the scale of OCD/healthy horses (16 SNPs on several chromosomes mainly on the ECA1 and ECA10) than OC/healthy (2 SNPs on the ECA15 and one SNP on the ECA10). Detailed definition of osteochondrosis is needed in breeding and in veterinary practice. The genetic background for osteochondrosis and osteochondrosis dissecans seems not the same. Suggestive SNPs could be the candidate markers for osteochondrosis but should be checked on a larger population before usage.     

Individual-based assessment of population structure and admixture in Austrian, Croatian and German draught horses

All over Europe, the number of draught horses has decreased drastically during the last 50 years. As a prerequisite for efficient management decisions, we analysed the conservation status in Austrian (Noriker Carinthia - NC, Noriker Salzburg - NS), Croatian (Croatian Coldblood - C, Posavina horse - P) and German (Altmaerkisch Coldblood - A, Black Forest horse - BF, Mecklenburg Coldblood - M, Rhenish German Draught horse - R, Saxon Thuringa Coldblood - ST, Schleswig Draught horse - Sch, South German Coldblood - SG) draught horses (434) using multilocus genotypic information from 30 (effectively 27) microsatellite loci. Populations located in areas with less intensive agricultural production (C, NC, NS, P and SG) had greater diversity within the population and estimated effective population size than A, BF, Sch, M, R and ST populations. The PCA plots revealed that populations form five separate groups. The 'Noriker' group (NC, NS and SG) and the 'Rhenish' group (A, M, R and ST) were the most distinctive (pairwise F(ST) values ranged from 0.078 to 0.094). The 'Croatian' group (C and P) was in the centre, while the BF and Sch populations formed two out-groups. A posterior Bayesian analysis detected further differentiation, mainly caused by political and geographical factors. Thus, it was possible to separate the South German Coldblood from the Austrian Noriker population where no subpopulation structure was detected. The admixture analysis revealed imprecise classification between C and P populations. A small but notable separation of R from A, M and ST populations was detected, while Sch and BF populations remained as out-groups. The information obtained should aid in making efficient conservation decisions.     

Genetic diversity in German draught horse breeds compared with a group of primitive, riding and wild horses by means of microsatellite DNA markers

We compared the genetic diversity and distance among six German draught horse breeds to wild (Przewalski's Horse), primitive (Icelandic Horse, Sorraia Horse, Exmoor Pony) or riding horse breeds (Hanoverian Warmblood, Arabian) by means of genotypic information from 30 microsatellite loci. The draught horse breeds included the South German Coldblood, Rhenish German Draught Horse, Mecklenburg Coldblood, Saxon Thuringa Coldblood, Black Forest Horse and Schleswig Draught Horse. Despite large differences in population sizes, the average observed heterozygosity (H(o)) differed little among the heavy horse breeds (0.64-0.71), but was considerably lower than in the Hanoverian Warmblood or Icelandic Horse population. The mean number of alleles (N(A)) decreased more markedly with declining population sizes of German draught horse breeds (5.2-6.3) but did not reach the values of Hanoverian Warmblood (N(A) = 6.7). The coefficient of differentiation among the heavy horse breeds showed 11.6% of the diversity between the heavy horse breeds, as opposed to 21.2% between the other horse populations. The differentiation test revealed highly significant genetic differences among all draught horse breeds except the Mecklenburg and Saxon Thuringa Coldbloods. The Schleswig Draught Horse was the most distinct draught horse breed. In conclusion, the study demonstrated a clear distinction among the German draught horse breeds and even among breeds with a very short history of divergence like Rhenish German Draught Horse and its East German subpopulations Mecklenburg and Saxon Thuringa Coldblood.     

Mapping quantitative trait loci for canine hip dysplasia in German Shepherd dogs

Canine hip dysplasia (CHD) is a common hereditary developmental disease of the coxofemoral joints. CHD is characterized by subluxation of the femoral head and deformation of the acetabulum leading to a painful osteoarthrosis. Analyses of mode of inheritance have shown the involvement of a major gene in expression of CHD in German Shepherd dogs. Thus, a whole genome scan for quantitative trait loci (QTL) was performed in German Shepherd dogs. For this purpose 11 paternal half-sib families, including a total of 459 purebred German Shepherd dogs with sires, dams, and offspring, were genotyped for 261 microsatellites. These markers were equidistantly distributed over all 38 autosomes and the X chromosome with an average marker distance of 11.7 cM. The mean observed heterozygosity of the marker set was 50%. The CHD status for the dogs was scored according to the official rules of the Fédération Cynologique Internationale. At the genome-wide level of significance at p < 0.05, QTL for CHD were located on nine different canine chromosomes: 1, 3, 4, 8, 9, 16, 19, 26, and 33. The minimal QTL regions containing the CHD genes spanned on average 5 Mb with a range between 1 and 8.2 Mb. Chromosome-wide level of significance at p < 0.05 was found for QTL on 19 chromosomes. Further analyses can now be performed to refine these map positions of QTL already identified in German Shepherd dogs. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

QTL affecting fleece traits in Angora goats

With the aim to detect chromosome segment (quantitative traits loci, QTL) affecting fleece traits in Angora goats, a genome scan using 76 microsatellite markers spanning 1261 cM on 21 chromosomes was conducted. Eight paternal half-sib families were used, which included a total of 288 kids from a dispersed nucleus herd.Mid-side mohair samples were taken from kids at 4 months of age and eight phenotypic fleece traits were measured.We found putatives QTL for coefficient of variation of average fiber diameter (CVAFD) in chromosome 1 and 13, for kemp fiber (KEMP) in chromosome 5 and for discontinuous medullated fibers (DISC) and staple length (SL) in chromosome 2.These results demonstrate the segregation of quantitative traits involved in mohair production. Further studies will concentrate on these regions to characterize the variation of these QTL.     

Detection of quantitative trait loci for resistance to gastrointestinal nematode infections in Creole goats

This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome‐wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half‐sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti‐Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti‐L3, and IgE anti‐ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.     

Genetic correlations between conformation traits and radiographic findings in the limbs of German Warmblood riding horses

Studbook inspection (SBI) data of 20 768 German Warmblood mares and radiography results (RR) data of 5102 Hanoverian Warmblood horses were used for genetic correlation analyses. The scores on a scale from 0 to 10 were given for conformation and basic quality of gaits, resulting in 14 SBI traits which were used for the correlation analyses. The radiographic findings considered included osseous fragments in fetlock (OFF) and hock joints (OFH), deforming arthropathy in hock joints (DAH) and distinct radiographic findings in the navicular bones (DNB) which were analyzed as binary traits, and radiographic appearance of the navicular bones (RNB) which was analyzed as a quasi-linear trait. Genetic parameters were estimated multivariately in linear animal models with REML using information on 24 448 horses with SBI and/or RR records. The ranges of heritability estimates were h² = 0.14–0.34 for the RR traits and h² = 0.09–0.50 for the SBI traits. Negative additive genetic correlations of r_g = -0.19 to -0.56 were estimated between OFF and conformation of front and hind limbs and walk at hand, and between DNB and hind limb conformation. There were indications of negative additive genetic correlations between DAH and all SBI traits, but because of low prevalence and low heritability of DAH, these results require further scrutiny. Positive additive genetic correlations of r_g = 0.37–0.52 were estimated between OFF and withers height and between OFH and withers height, indicating that selection for taller horses will increase disposition to develop OFF and OFH. Selection of broodmares with regards to functional conformation will assist, but cannot replace possible selection against radiographic findings in the limbs of young Warmblood riding horses, particularly with regards to OFF.     

A QTL for the degree of spotting in cattle shows synteny with the KIT locus on chromosome 6

The proportion of unpigmented coat on the trunk was determined from photographs of 38 German Simmental and 627 German Holstein bulls distributed over three generations. All 665 animals were members of 18 Holstein and 3 Simmental half-sib families. A Bayesian estimation of heritability yielded a posterior mean of 0.88 and a standard error of 0.08. A quantitative trait loci (QTL) scan over all chromosomes covered by 229 microsatellite marker loci (2926 cM) was performed by fitting a multiple marker regression model to 625 observations from the youngest generation in 18 families. On chromosome 6 a QTL for the proportion of white coat with large effects (experiment-wise error probability < .0001) was found and a less important one on chromosome 3 (chromosome-wise error probability < .009). Chromosome 6 is known to harbor the KIT locus (receptor tyrosinase kinase), which is associated with various depigmentation phenotypes in mice, humans, and pigs. Similarity of phenotypic KIT effects in other species and synteny with the reported QTL suggest that KIT is a serious candidate gene for the degree of spotting in cattle. The results are also discussed with respect to resistance to solar radiation, heat stress, and photosensitization.     

Multiple-trait selection for radiographic health of the limbs, conformation and performance in Warmblood riding horses

Information on 26 434 German Warmblood horses born between 1992 and 2001 was used for multivariate genetic analyses of radiographic health, conformation and performance traits to compare different modes of single- and multiple-trait selection of sires. Results of standardized radiological examinations of 5155 Hanoverian Warmblood horses, conformation evaluations from studbook inspections of 20 603 mares, and performance evaluations from mare performance tests and auction horse inspections of 16 098 horses were used for multivariate genetic analyses. Genetic parameters were estimated with restricted maximum likelihood (REML), and relative breeding values (RBV) were predicted with best linear unbiased prediction (BLUP) in multivariate linear animal models for four radiographic health traits, three conformation traits and five performance traits. Heritability estimates for osseous fragments in fetlock joints (OFF), osseous fragments in hock joints (OFH), deforming arthropathy in hock joints (DAH) and distinct radiographic findings in the navicular bones (DNB) ranged between 0.15 and 0.35 after transformation to the liability scale. Front limb conformation, hind limb conformation, withers height, walk, trot, canter, rideability and free jumping showed heritabilities between 0.09 and 0.49 and additive genetic correlations with OFF, OFH, DAH and DNB ranging between -0.53 and +0.52. Selection of sires was based on RBV or combinations of RBV, with selection for individual traits or traits from one of the three considered trait groups being considered as single-trait selection, and selection for traits from more than one trait group being considered as multiple-trait selection. The selection modes were compared by means of the expected selection response after one generation, calculated as the relative change in the prevalences of the radiographic findings or the mean conformation or performance scores in the offspring of the selected sires when compared with the offspring of all sires. The prevalences of OFF, OFH, DAH and DNB decreased by 30% to 57% after single-trait selection and 14% to 29% after multiple-trait selection, while mean conformation and performance scores increased by up to 4%. The results indicated that it is possible to simultaneously improve the radiographic health of the limbs, limb conformation, quality of gaits and rideability. However, genetic progress in free jumping ability and style could only be achieved by single- or multiple-trait selection with focus on jumping performance.     

Interval mapping of carcass and meat quality traits in a divergent swine cross.

An autosomal scan of the swine genome with 119 polymorphic microsatellite (ms) markers and data from 116 F2 barrows of the University of Illinois Meishan x Yorkshire Swine Resource Families identified genomic regions with effects on variance in carcass composition and meat quality at nominal significance (p-value <0.05). Marker intervals on chromosomes 1, 6, 7, 8 and 12 (SSC1, SSC6, SSC7, SSC8, SSC12) with phenotypic effects on carcass length, 10th rib backfat thickness, average backfat thickness, leaf fat, loin eye area and intramuscular fat content confirm QTL effects identified previously based on genome wide significance (p-value <0.05). Several marker intervals included nominally significant (p-value <0.05) dominance effects on leaf fat, 10th rib backfat thickness, loin eye area, muscle pH and intramuscular fat content.     

Fine mapping of a quantitative trait locus for osteochondrosis on horse chromosome 2

In this study, we refine a quantitative trait locus for equine osteochondrosis (OC) on horse chromosome (ECA) 2 to a genome-wide significant interval at 20.08-30.94 Mb. The marker set contained 27 newly developed microsatellites equidistantly distributed over ECA2 and 44 nucleotide polymorphisms, located in 16 positional candidate genes for OC. Genotyping was performed in 211 Hanoverian horses from 14 paternal half-sib groups. A NCDN-associated SNP and haplotype were significantly associated with OC in fetlock and/or hock joints. This study is a further step towards the identification of genes responsible for OC in horses.     

Genome-wide search for microsatellite markers associated with radiologic alterations in the navicular bone of Hanoverian warmblood horses

The aim of this study was to identify quantitative trait loci (QTLs) for pathologic changes in the navicular bone in Hanoverian warmblood horses. Seventeen paternal half-sib groups comprising 192 individuals were analyzed in a whole-genome scan. These families included 144 progeny and grandchildren, which were randomly chosen from the Hanoverian warmblood. Three different traits were considered: deformed canales sesamoidales and radiographic changes in the contour and in the structure of the navicular bone. The genome scan included in total 214 highly polymorphic microsatellite markers. The putatively linked genomic regions on equine chromosomes (ECA) 2, 3, 10, and 15 were refined using 53 additional microsatellites. Chromosome-wide significant QTLs were located on five different equine chromosomes (ECA2, 3, 4, 10, and 26). Genome-wide significant QTLs were on ECA2 at 48 cM and on ECA10 from 45.5 to 49.8 cM. This study was a first step to get more insight into the molecular genetic determination of radiologic changes in the equine navicular bone. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Interval mapping of growth in divergent swine cross

A genomic scan of 18 swine autosomal chromosomes was constructed with 119 polymorphic microsatellite (ms) markers to identify quantitative trait loci (QTL) for 11 growth traits in the University of Illinois Meishan × Yorkshire Swine Resource Family. A significant QTL effect was found for post-weaning average daily gain (ADG) between 5.5 and 56 kg of body weight that mapped between markers SW373 and SW1301 near the telomere of Chromosome (Chr) 1 q (SSC1). This QTL effect had a nominal (pointwise) p-value of 0.000007, a genome wide p-value of 0.012, and accounted for 26% of the F₂ phenotypic variance. The same chromosome region also had significant effects on ADG between birth and 56 kg body weight (p-value = .000227), and on ADG between 35 and 56 kg (p-value = .00077). These observations suggest that a significant QTL for post-weaning growth resides on SSC1. Received: 18 May 1998 / Accepted: 6 October 1998     

Quantitative trait loci mapping for fatty acid contents in the backfat on porcine chromosomes 1, 13, and 18

A partial genome scan using microsatellite markers was conducted in order to detect quantitative trait loci (QTLs) for 10 fatty acid contents of the backfat in a pig reference population. Two QTLs were found by studying SSC1, SSC13, and SSC18, where QTLs had already been identified for backfat thickness. A QTL was located between marker loci S0113 and SW974 on chromosome 1; this QTL was only significantly detected (P < 0.05) for linoleic acid. The other QTL was discovered between markers S0062 and S0120 on chromosome 18, and its significance only showed (P < 0.05) for myristic acid. The two QTLs mapped to the same location as the backfat thickness QTL. A third of the phenotypic variation was explained for linoleic acid by the QTL on chromosome 1, and a quarter for myristic acid by the QTL on chromosome 18. Further studies on fine mapping and positional comparative candidate gene analyses will be the next step toward a better understanding of the genetic architecture of fatty acid contents.     

Refinement of a quantitative trait locus on equine chromosome 5 responsible for fetlock osteochondrosis in Hanoverian warmblood horses

In this report, we provide 29 new informative microsatellites distributed over a region of 21 Mb on horse chromosome (ECA) 5 and refine a quantitative trait locus (QTL) for fetlock osteochondrosis dissecans (OCD) to a genome-wide significant interval between 78.03 and 90.23 Mb on ECA5. Genotyping was performed in 211 Hanoverian warmblood horses from 14 paternal half-sib groups. Within this OCD-QTL, collagen type XXIV alpha 1 was identified as a potential functional candidate gene for equine osteochondrosis. This report is a further step towards unravelling the genes that cause equine osteochondrosis.