The Shepherds' Tale: A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds.

Autor:	Forsberg SK; Computational Genetics Section, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden., Kierczak M; Computational Genetics Section, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden; Science for Life Laboratory & Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Ljungvall I; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden., Merveille AC; Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège Belgium., Gouni V; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort, Maisons-Alfort, France., Wiberg M; Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland., Lundgren Willesen J; Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hanås S; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden; Evidensia, Animal Clinic Västerås, Västerås, Sweden., Lequarré AS; Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège Belgium., Mejer Sørensen L; Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Tiret L; INRA, UMR955 de Génétique Fonctionnelle et Médicale, Maisons-Alfort, France; Université Paris-Est Créteil, CNM project, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France., McEntee K; Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège Belgium; Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Bruxelles, Belgium., Seppälä E; Department of Veterinary Biosciences, Research Program in Molecular Neurology Research Programs Unit, University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland., Koch J; Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Battaille G; Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège Belgium., Lohi H; Department of Veterinary Biosciences, Research Program in Molecular Neurology Research Programs Unit, University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland., Fredholm M; Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Chetboul V; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, Unité de Cardiologie d'Alfort (UCA), Centre Hospitalier Universitaire Vétérinaire d'Alfort, Maisons-Alfort, France; INSERM, U955, Equipe 03, Créteil, France., Häggström J; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden., Carlborg Ö; Computational Genetics Section, Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden., Lindblad-Toh K; Science for Life Laboratory & Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Höglund K; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2015 May 13; Vol. 10 (5), pp. e0123173. Date of Electronic Publication: 2015 May 13 (Print Publication: 2015).
DOI:	10.1371/journal.pone.0123173
Abstrakt:	Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (pcorrected ≈ 1:68 × 10-6) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (p = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.
Databáze:	MEDLINE
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