doi:10.1111/j.1365-2052.2010.02096.x Refinement of quantitative trait loci on equine chromosome 10 for radiological signs of navicular disease in Hanoverian warmblood horses M. S. Lopes* ,† , U. Diesterbeck*, A. da Ca ˆ mara Machado † and O. Distl* *Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bu ¨ nteweg 17p, 30559 Hannover, Germany. † Biotechnology Centre of Azores, Department of Agriculture, University of Azores, Terra-Cha ˜ , 9701-851 Angra do Heroı ´smo, Portugal Summary Navicular disease is characterized by a progressive degenerative alteration of the equine podotrochlea. In this study, we refined a previously identified quantitative trait locus (QTL) on horse chromosome 10 for the abnormal development of canales sesamoidales (DCS) of the navicular bone in Hanoverian warmblood horses. Genotyping was done in 192 Han- overian warmblood horses from 17 paternal half-sib groups. The whole marker set com- prised 45 markers including seven newly developed microsatellites and 13 single nucleotide polymorphisms (SNPs) within positional candidate genes. Chromosome-wide significant QTL were confirmed and refined for DCS on horse chromosome (ECA) 10 at 0.16–2.70 Mb and at 14.45–36.37 Mb. Nine microsatellites and three SNP markers reached the highest multipoint Zmeans and LOD scores at 19.34–20.38 Mb and at 23.17–30.73 Mb with genome-wide error probabilities of P < 0.05. In addition, a significant association of a SNP within VSTM1 and a significant haplotype-trait association within IRF3 could be shown. These results support a possible role of the candidate genes VSTM1 and IRF3 within the QTL on ECA10 for DCS. This study is a further step towards the identification of the genes responsible for navicular disease in Hanoverian warmblood horses. Keywords horse, horse chromosome 10, navicular disease, quantitative trait locus. Introduction HorseÕs health is a fundamental prerequisite for its perfor- mance and durability in all sectors of the horse industry. Diseases of the locomotor system particularly interfere with the horseÕs usability. Podotrochlosis, navicular disease or navicular syndrome is one of the main causes of chronic and often therapy-resistant forelimb lameness because of progressive degenerative alterations of the equine podo- trochlea. The podotrochlea comprises the navicular bone, the bursa podotrochlearis and the insertion part of the deep digital flexor tendon. Horses affected by navicular disease show pathological changes that primarily affect the navic- ular bone, the navicular bursa and/or the distal end of the deep flexor tendon. Radiography of the navicular bone is the primary method to evaluate number, location, size and form of the nutrient foramina (canales sesamoidales) along the distal border of the navicular bone as well as the contour and structure of the navicular bone (Brunken 1986; Mac- Gregor 1986; Dik & van den Broek 1995). Pathological signs include an increased number of canales sesamoidales, the appearance of branched canales sesamoidales, very deep or lollypop-shaped (bulbed ends) canales sesamoidales, a reduced radiographic density of the navicular bone (cyst- like lesion) and spurs at the margins of navicular bone (insertion desmopathy). The inheritance of pathological changes of the navicular bone has been shown by signifi- cant differences in prevalences between paternal progeny groups (Bos et al. 1986; Dik & van den Broek 1995; Stock & Distl 2006). Heritability estimates varied from 0.10 to 0.31 in threshold models (Diesterbeck et al. 2007). Furthermore, a recent study demonstrated quantitative trait loci (QTL) associated with radiological alterations in the navicular bone of Hanoverian warmblood horses (Diesterbeck et al. 2007). The phenotypic traits for navicular disease were based on the evaluation scheme of Brunken (1986). Diag- nostic criteria were size, shape and distribution of canales Address for correspondence Dr. O. Distl, Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Bu ¨ nteweg 17 p, 30559 Hannover, Germany. E-mail: ottmar.distl@tiho-hannover.de Accepted for publication 20 September 2010 Ó 2010 The Authors, Journal compilation Ó 2010 Stichting International Foundation for Animal Genetics, 41 (Suppl. 2), 36–40 36