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

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Forsberg , S K G , Kierczak , M , Ljungvall , I , Merveille , A-C , Gouni , V , Wiberg , M , Willesen , J L , Hanas , S , Lequarre , A-S , Sorensen , L M , Tiret , L , McEntee , K , Seppälä , E , Koch , J , Battaille , G , Lohi , H , Fredholm , M , Chetboul , V , Haggstrom , J , Carlborg , O , Lindblad-Toh , K & Hoglund , K 2015 , ' The Shepherds' Tale : A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds ' , PLoS One , vol. 10 , no. 5 , 0123173 . https://doi.org/10.1371/journal.pone.0123173

Title: The Shepherds' Tale : A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds
Author: Forsberg, Simon K. G.; Kierczak, Marcin; Ljungvall, Ingrid; Merveille, Anne-Christine; Gouni, Vassiliki; Wiberg, Maria; Willesen, Jakob Lundgren; Hanas, Sofia; Lequarre, Anne-Sophie; Sorensen, Louise Mejer; Tiret, Laurent; McEntee, Kathleen; Seppälä, Eija; Koch, Jorgen; Battaille, Geraldine; Lohi, Hannes; Fredholm, Merete; Chetboul, Valerie; Haggstrom, Jens; Carlborg, Orjan; Lindblad-Toh, Kerstin; Hoglund, Katja
Contributor organization: Departments of Faculty of Veterinary Medicine
Maria Wiberg / Principal Investigator
Equine and Small Animal Medicine
Hannes Tapani Lohi / Principal Investigator
Department of Medical and Clinical Genetics
Research Programs Unit
Veterinary Biosciences
Research Programme for Molecular Neurology
Medicum
Date: 2015-05-13
Language: eng
Number of pages: 17
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0123173
URI: http://hdl.handle.net/10138/156986
Abstract: 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 (rho(corrected) approximate to 1:68 x 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 (rho = 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.
Subject: CANINE DIABETES-MELLITUS
MITOCHONDRIAL CA2+/H+ ANTIPORTER
RECEPTOR MUTATIONS
ASSOCIATION
OBESITY
LETM1
SUSCEPTIBILITY
POPULATION
METABOLISM
PATTERNS
413 Veterinary science
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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