Genome-wide association analysis for lethal brachycephalic-like facial dysmorphia in Labrador Retrievers.

A GWAS was performed for inborn X-linked facial dysmorphia with severe growth retardation in Labrador Retrievers. This lethal condition was mapped on the X chromosome at 17-21 Mb and supported by eight SNPs in complete LD. Dams of affected male puppies were heterozygous for the significantly associated SNPs and male affected puppies carried the associated alleles hemizygously. In the near vicinity to the associated region, RPS6KA3 was identified as a candidate gene causing facial dysmorphia in humans and mice known as Coffin-Lowry syndrome. Haplotype analysis showed significant association with the phenotypes of all 18 animals under study. This haplotype was validated through normal male progeny from a dam with the not-associated haplotype on both X chromosomes but male affected full-sibs with the associated haplotype.

Short communication: Lethal mutations in Vorderwald cattle through Montbéliarde incrossings.

Vorderwald cattle are a dual-purpose cattle breed with high migrant contributions from Montbéliarde bulls in the recent past. Through the wide use of Montbéliarde bulls, undesirable alleles were also disseminated into the Vorderwald population. Haplotypes on bovine chromosome 19 (MH1) and 29 (MH2), supposed to harbor lethal mutations, were identified in Montbéliarde cattle. A study in French Montbéliarde cattle identified the PFAS:g.28511199C>T (rs455876205) variant as the most likely MH1 embryonic lethal mutation. The objective of the present study was to determine whether the PFAS:g.28511199C>T variant was introduced into Vorderwald cattle through Montbéliarde bulls and disseminated in this population. The present study expands on previous work on the deleterious SLC37A2 variant (ss2019324563) of the MH2 locus. Herein, we traced the ss2019324563 variant back to the Montbéliarde bull, which was the most likely source for this deleterious mutation in Vorderwald cattle. We genotyped 354 Vorderwald cattle for the PFAS variant, resulting in 41 heterozygous individuals and a T allele frequency of 0.058. An aborted fetus homozygous mutant for SLC37A2 from our previous study on the MH2 locus in Vorderwald cattle was wild type for the PFAS variant. Both lethal mutations were segregating independently of each other, and we found no indications of joint occurrence in a larger number of animals. Neither SLC37A2 nor PFAS double heterozygous mutants were lethal. The earliest animal with a heterozygous PFAS genotype was 1 of 5 migrant Montbéliarde bulls, and this bull was the most likely origin of the deleterious PFAS allele in Vorderwald cattle. All Vorderwald cattle under study born before introgression of this Montbéliarde bull were homozygous wild type. In addition, all 41 heterozygous Vorderwald cattle had genetic contributions from this Montbéliarde bull, whereas in 74 Vorderwald cattle without genes from Montbéliarde bulls, the PFAS T allele was not observed. In a sample of actual German Fleckvieh the PFAS T allele could be found at a very low frequency. Our study demonstrated the introgression of lethal variants through Montbéliarde bulls into a traditional cattle breed highly adapted to harsh local conditions. These findings underline the need to screen bulls for lethal mutations before their wide use in breeding, particularly in breeds with a focus on preservation of their genetic uniqueness.

Analysis of porcine body size variation using re-sequencing data of miniature and large pigs.

BACKGROUND: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs. RESULTS: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds. CONCLUSION: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.

A genome-wide association study for left-sided displacement of the abomasum using a high-density single nucleotide polymorphism array.

Left-sided displacement of the abomasum (LDA) is a frequent disease in dairy cattle causing significant financial losses for dairy farmers. Heritability (h2) of this complex disease was estimated at up to 0.5 in German Holstein (GH) cattle. Using the Bovine High Density BeadChip (Illumina Inc., San Diego, CA) comprising 588,753 single nucleotide polymorphisms (SNP) after quality control for 126 LDA cases and 280 population-based controls, we used a mixed linear model analysis in a genome-wide association study (GWAS). We identified 6 genomic regions for LDA on bovine chromosomes 2, 8, 13, 20, 24, and X that were significantly associated with LDA. Each of these regions was covered by 4 to 12 LDA-associated SNP. Single SNP within these regions explained up to 7.3% of the phenotypic variance. An independent sample of 1,554 GH cows, including 539 controls and 1,015 cases, were genotyped for 8 SNP highly associated with LDA on Bos taurus autosomes (BTA) 2, 8, 13, and 24, as well as 6 SNP located in previously identified LDA regions on BTA1, 5, 11, and 27 using competitive allele-specific PCR genotyping technology (KASP). The analysis using the KASP genotypes confirmed LDA-associated loci on BTA2, 8, 13, and 27. These genomic regions may contribute to the susceptibility to LDA in Holstein cows and may harbor functional variants for LDA.

Breeding experiments and genome-wide association analysis elucidate two genetically different forms of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in Vorderwald × Montbéliarde cattle. The objective of the present study was to perform a genome-wide association study (GWAS) for 10 CLJ-affected and 50 unaffected Vorderwald × Montbéliarde cattle using the bovine Illumina high density bead chip to identify loci for this condition. Phenotypic classification of CLJ was based on a detailed recording of orofacial structures using computed tomography. A breeding experiment among CLJ-affected Vorderwald × Montbéliarde cattle and CLJ-affected Vorderwald × Montbéliarde cattle with unaffected Holsteins confirmed recessive inheritance and different loci for bilateral or left-sided versus right-sided CLJ. The GWAS for the five cases with right-sided CLJ gave a genome-wide signal on bovine chromosome (BTA) 29 at 16 Mb. For the four left-sided and one bilateral CLJ case, a genome-wide significant association was identified on BTA4 at 32 Mb. Two different loci are very likely to be involved in CLJ in Vorderwald × Montbéliarde cattle because experimental matings among affected cows and bulls with different types of CLJ did not result in CLJ-affected progeny, and in addition, two different loci were also found through GWAS and mapped on two different bovine chromosomes. Validation in 346 Vorderwald × Montbéliarde cattle for the highly associated SNPs on BTA4 and 29 gave ratios of 33/346 (0.095, BTA4) and 6/346 (0.017, BTA29) homozygous mutant genotypes. Further studies should elucidate the responsible mutations underlying the different types of CLJ in Vorderwald × Montbéliarde cattle.

Cranial morphology in the brachygnathic sheep.

BACKGROUND: Craniofacial morphology of sheep with phenotypically observed mandibular distocclusion was analysed using the multivariate techniques principle component analysis and cluster analysis in order to test whether different types of craniofacial malformations can be distinguished. RESULTS: The results showed 8 principal components with a variance of 82.72% in the database. The method creates new variables then used in the Cluster analysis indicating 7 clusters with 3 different facial types: Normal, prognathia inferior and brachygnathia inferior. CONCLUSION: The brachygnathic facial type was mainly characterised as a shortened mandible, the upper jaw is not significantly involved. The correlations to the temporomandibular joint were shown. Molar and premolar malocclusions were revealed in two of three Clusters. Phenotypical distocclusion was not a single criterion for the affected sheep.

Congenital Ichthyosis in 14 Great Dane Puppies With a New Presentation.

The present study describes a generalized congenital skin condition in 14 Great Dane puppies. Macroscopically, all dogs showed generalized gray to yellow scaling and skin wrinkles on the head and all 4 extremities. Skin sections were histologically examined using hematoxylin and eosin, Heidenhain's Azan, and Sudan red III staining methods and by conducting the alcian blue/periodic acid Schiff (AB/PAS) reaction technique on sections. Furthermore, incubation with hyaluronidase was performed. Skin samples were ultrastructurally analyzed using transmission electron microscopy. All affected Great Dane puppies had epidermal and follicular orthokeratotic hyperkeratosis, enlarged keratohyaline granules, vacuolated keratinocytes, and accumulations of an eosinophilic and alcianophilic, lipid-rich material within dilated hair follicular lumina and the cytoplasm of sebocytes. The macroscopic, histopathologic, and ultrastructural skin changes in all 14 Great Dane puppies indicate a new variant of a primary disorder of cornification with congenital, non-epidermolytic, lamellar ichthyosiform appearance.

Implication of FKBP6 for male fertility in horses.

In stallions, impaired acrosome reaction (IAR) may often cause subfertility. Single nucleotide polymorphisms (SNPs) within FK506-binding protein (FKBP6) seem to be associated with IAR in stallions. However, their effect on stallion fertility has not yet been quantified. Using whole-genome sequence data of seven stallions, we searched FKBP6 for mutations to perform an association study in Hanoverian stallions with estimated breeding values for the paternal component of the pregnancy rate per oestrus cycle (EBV-PAT) as target trait. Genotyping five exonic mutations within FKBP6 revealed a significant association of the SNP g.11040379C>A (p.167H>N) with EBV-PAT in 216 Hanoverian stallions. The difference among the two homozygous genotypes was 7.62% in EBV-PAT, corresponding to one standard deviation of EBV-PAT. In conclusion, in Hanoverian stallions, the FKBP6-associated SNP g.11040379C>A confers higher conception rates in A/A homozygous and lower conception rates in C/C homozygous Hanoverian stallions. Thus, an FKBP6-associated missense mutation is significantly associated with stallion fertility.

Genetic parameters and breeding values for semen characteristics in Hanoverian stallions.

The objectives of this study were to show whether semen traits of 30 Hanoverian stallions regularly used in AI may be useful for breeding purposes. Semen characteristics were studied using 15 149 ejaculates from 30 Hanoverian stallions of the State Stud Celle of Lower Saxony. Semen samples were collected between 2005 and 2009. Traits analysed were gel-free volume, sperm concentration, total and motile sperm number and progressive motility. A linear multivariate animal model was employed to estimate heritabilities and permanent environmental variances for stallions. The same model was used to predict breeding values for all traits simultaneously. Heritabilities were high for gel-free volume (h(2) = 0.43) and moderate for total number of sperm (h(2) = 0.29) and progressive motility (h(2) = 0.20). Gel-free volume, sperm concentration and total number of sperm were genetically negatively correlated with progressive motility. The effect of the permanent environment for stallions accounted for 9-55% of the trait variance. The total variance among stallions explained 37-69% of the trait variance. The average reliabilities of the breeding values were 0.43-0.76 for the 30 Hanoverian stallions. In conclusion, the study could demonstrate large effects of stallions, routinely employed in a breeding programme, on semen characteristics analysed here. We could demonstrate that estimated breeding values (EBV) with sufficient high reliabilities can be predicted using data from these stallions and these EBV are useful in horse breeding programmes to achieve genetic improvement in semen quality.

Heritabilities and genetic correlations between fetlock, hock and stifle osteochondrosis and fetlock osteochondral fragments in Hanoverian Warmblood horses.

The main objective of this study is to estimate genetic parameters for osteochondrosis (OC) and osteochondrosis dissecans (OCD) in fetlock, hock and stifle joints as well as for palmar or plantar osteochondral fragments (POFs) and dorsodistal osteochondral fragments (DOFs) in fetlock joints. For this purpose, the results of a standardized radiographic examination of 7396 Hanoverian Warmblood horses were used. Heritabilities and genetic correlations were estimated using residual maximum likelihood (REML) under a linear animal model. Heritability estimates for OC at the different joints were at 0.17-0.34, for OCD at 0.16-0.46, for POFs at 0.19 and for DOFs at 0.22 after transformation onto the liability scale. For osteochondral fragments (OFs), lower heritabilities were estimated, especially in fetlock joints. POFs were genetically negatively correlated with OC in each joint. The size of the heritability estimates indicates that the prevalence of these radiographic findings can be reduced by breeding measures. However, differentiation among the different clinical entities is crucial to avoid underestimation of heritabilities. The analysis of genetic parameters performed in this study indicates that OC and OCD in fetlock, OC and OCD in hock, OC and OCD in stifle joints, POFs of the hindlimbs and DOFs may be treated as different traits.

Allelic heterogeneity of FGF5 mutations causes the long-hair phenotype in dogs.

Hitherto, the only known mutant gene leading to the long-hair phenotype in mammals is the fibroblast growth factor 5 (FGF5). In many dog breeds, the previously discovered FGF5:p.Cys95Phe mutation appeared completely concordant with the long-hair phenotype, but for some breeds, the long-hair phenotype could not be resolved. First, we studied the role of the FGF5:p.Cys95Phe and FGF5:g.145_150dupACCAGC mutations in 268 dogs descending from 27 breeds and seven wolves. As these mutations did not explain all the long-hair phenotypes, all exons and their neighbouring regions of FGF5 were re-sequenced. We detected three novel mutations in the coding sequence and one novel non-coding splice-site mutation in FGF5 associated with the long-hair phenotype. The FGF5:p.Ala193Val polymorphism was perfectly consistent with long hair in Akitas and probably in Siberian huskies, too. Dogs of the long-hair breed Samoyed were either homozygous or compound heterozygous for the FGF5:p.Ala193Val or the FGF5:p.Cys95Phe polymorphisms respectively. The two newly detected polymorphisms FGF5:c.559_560dupGG and FGF5:g.8193T>A and the known mutation FGF5:p.Cys95Phe explained the long-hair phenotype of all Afghan hounds analysed. An FGF5:c.556_571del16 mutation was found in one longhaired Eurasier. All long-hair-associated mutations follow a recessive mode of inheritance, and allelic heterogeneity was a common finding in breeds other than Akita.

Genome-wide association analysis identifies loci for left-sided displacement of the abomasum in German Holstein cattle.

Left-sided displacement of the abomasum (LDA) is one of the most common disorders of the digestive system in many dairy breeds and particularly in Holstein dairy cows. We performed a genome-wide association study for 854 German Holstein cows, including 225 cases and 629 controls. All cows were genotyped using the Illumina Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA). After quality control of genotypes, a total of 36,226 informative single nucleotide polymorphisms (SNP) were left for analysis. We used a mixed linear model approach for a genome-wide association study of LDA. In total, 36 SNP located on 17 bovine (Bos taurus) chromosomes (BTA) showed associations with LDA at nominal -log10P-values >3.0. Two of these SNP, located on BTA11 at 46.70 Mb and BTA20 at 16.67 Mb, showed genome-wide significant associations with LDA at -log10P-values >4.6. Pathway analyses indicated genes involved in calcium metabolism and insulin-dependent diabetes mellitus to be factors in the pathogenesis of LDA in German Holstein cows.

Evaluation of bone strength, keel bone status, plumage condition and egg quality of two layer lines kept in small group housing systems.

1. The aim of the present study was to determine the influence of large (54 or 60) and small (36 or 40) group sizes and tiers of the small group housing system "Eurovent German" on tibia and humerus bone breaking strength, keel bone status, plumage condition and egg quality for two commercial layer lines, Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB), at the same stocking density (890 or 830 cm(2)/bird). 2. In 4 consecutive trials, 4752 hens were recorded for keel bone status. Evaluation of plumage condition was made for 1440 hens and bone breaking strength was recorded for 1200 hens. A total of 4962 eggs were analysed for internal and external egg quality traits. Analyses involved 30 small group compartments per trial. 3. The layer line had a much more pronounced influence on humerus breaking strength than on tibia breaking strength. 4. Plumage condition, particularly on the neck, was positively correlated with humerus breaking strength in both layer lines. 5. An average of 34% of LB and 23% of LSL hens showed keel bone deformities, with higher proportions of slight deformities. 6. Slight keel bone deformities, rather than moderate to severe, increased significantly during the laying period. 7. Stocking density had no influence on bone breaking strength, keel bone status and egg quality traits. 8. LB layers had a 1.4-fold higher humerus, but only a 1.06-fold higher tibia breaking strength compared to LSL layers. 9. Tibia breaking strength was significantly affected by the interaction of group size and layer line. LSL layers in small groups had lower tibia breaking strengths than those of the large groups.

A genome-wide association study for quantitative trait loci of show-jumping in Hanoverian warmblood horses.

Show-jumping is an economically important breeding goal in Hanoverian warmblood horses. The aim of this study was a genome-wide association study (GWAS) for quantitative trait loci (QTL) for show-jumping in Hanoverian warmblood horses, employing the Illumina equine SNP50 Beadchip. For our analyses, we genotyped 115 stallions of the National State stud of Lower Saxony. The show-jumping talent of a horse includes style and ability in free-jumping. To control spurious associations based on population stratification, two different mixed linear animal model (MLM) approaches were employed, besides linear models with fixed effects only and adaptive permutations for correcting multiple testing. Population stratification was explained best in the MLM considering Hanoverian, Thoroughbred, Trakehner and Holsteiner genes and the marker identity-by-state relationship matrix. We identified six QTL for show-jumping on horse chromosomes (ECA) 1, 8, 9 and 26 (-log(10) P-value >5) and further putative QTL with -log(10) P-values of 3-5 on ECA1, 3, 11, 17 and 21. Within six QTL regions, we identified human performance-related genes including PAPSS2 on ECA1, MYL2 on ECA8, TRHR on ECA9 and GABPA on ECA26 and within the putative QTL regions NRAP on ECA1, and TBX4 on ECA11. The results of our GWAS suggest that genes involved in muscle structure, development and metabolism are crucial for elite show-jumping performance. Further studies are required to validate these QTL in larger data sets and further horse populations.

Rapid genetic diversification within dog breeds as evidenced by a case study on Schnauzers.

As a result of strong artificial selection, the domesticated dog has arguably become one of the most morphologically diverse vertebrate species, which is mirrored in the classification of around 400 different breeds. To test the influence of breeding history on the genetic structure and variability of today's dog breeds, we investigated 12 dog breeds using a set of 19 microsatellite markers from a total of 597 individuals with about 50 individuals analysed per breed. High genetic diversity was noted over all breeds, with the ancient Asian breeds (Akita, Chow Chow, Shar Pei) exhibiting the highest variability, as was indicated chiefly by an extraordinarily high number of rare and private alleles. Using a Bayesian clustering method, we detected significant genetic stratification within the closely related Schnauzer breeds. The individuals of these three recently differentiated breeds (Miniature, Standard and Giant Schnauzer) could not be assigned to a single cluster each. This hidden genetic structure was probably caused by assortative mating owing to breeders' preferences regarding coat colour types and the underlying practice of breeding in separate lineages. Such processes of strong artificial disruptive selection for different morphological traits in isolated and relatively small lineages can result in the rapid creation of new dog types and potentially new breeds and represent a unique opportunity to study the evolution of genetic and morphological differences in recently diverged populations.

Fatal rectal perforation following boar-to-boar mounting.

Although abnormal sexual behavior, including boar-to-boar mounting with anal penetration, is recognized in pubescent pigs, reports of the pathologic consequences are scarce. A 7-month-old male minipig, housed with age-matched males, died within 1 day of the onset of lethargy and reluctance to rise. At necropsy, 2 rectal tears were identified as the cause for fibrinous peritonitis, and spermatozoa were identified in the pelvic and peritoneal cavity by light and transmission electron microscopy. According to DNA typing results, using 11 porcine microsatellites, the intraperitoneal semen was from at least 2 pen mates. The prohibition of castration of fattening pigs, implemented or planned in multiple European countries, could increase the risk of rectal perforation in co-housed pigs.

Genetic analyses of new movement traits using detailed evaluations of warmblood foals and mares.

Detailed movement evaluations of warmblood foals and mares were performed in connection with regular breeding events of the Oldenburg horse breeding societies in 2009 and 2010. Unfavourable movement characteristics considered indicative for impaired balance were noted by a special judge (SJ) and the regular judges of the breeding events (RJ) and served as the basis for definition of new movement traits. Detailed movement information on 3374 foals and 2844 mares showed that more severe findings like irregular motion pattern in hind legs or irregularity in general motion pattern occurred only sporadically (prevalences of 1-2%). Irregular tail tone or posture was documented for 4% of the foals and 5% of the mares, resulting in prevalences of the comprehensive trait indications of imbalance (IMB) of 6.2% (foals) and 5.5% (mares). Binary coding was used for all traits, and genetic parameters were estimated bivariately in linear animal models with residual maximum likelihood. Comparative analyses between judges revealed that differences between trait definitions of SJ and RJ were larger in the mares than in the foals, but justified combined use of SJ and RJ information in both age groups. Heritability estimates for the movement traits ranged on the original scale from 0.02 to 0.26 in the foals and from 0.03 to 0.12 in the mares, with heritabilities for IMB on the underlying liability scale of 0.46 (foals) and 0.22 (mares). Comparative analyses between age groups indicated that common genetic factors may be responsible for findings of impaired balance in foals and mares. The results implied that horse breeding may benefit from using the early available information on the movement of foals obtained by detailed movement evaluations, although favourable combination of foal and mare data in future genetic evaluations may require refined recording of unfavourable movement characteristics in the adult horses.

Genetic diversity of ten Egyptian chicken strains using 29 microsatellite markers.

In this study, we assessed the genetic diversity of three Egyptian local chicken strains (Fayoumi, Dandarawi and Sinai) and six synthetic breeds derived from Fayoumi and Sinai by intercrossing with Barren Plymouth Rock, Rhode Island Red or White Cornish. Diversity measures were based on interrogation of 29 microsatellites. We identified three main clusters of chicken populations encompassing selected Fayoumi lines and Doki-4 (cluster-1), native Dandarawi (cluster-2) and Sinai, and all six synthetic breeds (cluster-3). Dandarawi and Fayoumi lines exhibited lower intra-population genetic diversity and allelic privacy than Sinai and synthetic breeds. The global inbreeding (F(IT) ) was 0.11, among-population differentiation (F(ST) ) was 0.07, and within-population differentiation (F(IS) ) was 0.04. The between-population marker-estimated kinship was lower than within-population estimates. The cluster analysis classified the Fayoumi lines, Dandarawi and Gimmizah as clearly separated populations. The other strains were configured in mosaic admixed groups.

Genetic analyses of elbow and hip dysplasia in the German shepherd dog.

Results from radiographic screening for canine hip dysplasia (CHD) and elbow dysplasia (CED) of 48 367 German shepherd dogs born in 2001-07 were used for the population genetic analyses. Available information included CHD scores for 47 730 dogs, CED scores for 28 011 dogs and detailed veterinary diagnoses of primary ED lesions for a subsample of 18 899 dogs. Quasi-continuous traits were CHD, CED and cases of CED without radiographically visible primary lesion (CED-ARTH). Binary coding was used for fragmented medial coronoid process of the ulna (FCP), borderline findings and mild to severe signs of dysplasia in hip and elbow joints. Genetic parameters were estimated in univariate threshold and multivariate linear and mixed linear-threshold models using Gibbs sampling. Correlations between univariately predicted breeding values (BV) indicated genetic differences between borderline and affected disease status for both CHD (r(BV) = 0.5) and CED (r(BV) = 0.3). Multivariate genetic analyses with separate consideration of borderline findings revealed moderate heritabilities of 0.2-0.3 for the quasi-continuous traits with positive additive genetic correlation of 0.3 between CHD and both CED and CED-ARTH. For FCP, heritability of 0.6 and additive genetic correlations of +0.1 to CHD and -0.1 to CED-ARTH were estimated. Results supported the relevant genetic determination of CHD and CED, argued for both diseases against interpretation of borderline findings as healthy and implied genetic heterogeneity of CED. Accordingly, future breeding strategies to reduce the prevalences of CHD and CED in the German shepherd dog should be most efficient when based on BV from multivariate genetic evaluation for CHD, CED-ARTH and FCP with use of the whole scale of categories for classification of CHD and CED.

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.