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

Forsberg, Simon and Kierczak, Marcin and Bersås Ljungvall, Ingrid and Anne-Christine, Merveille and Vassiliki, Gouni and Wiberg, Maria and Lundgren Willesen, Jakob and Hanås, Sofia and Lequarre, Anne-Sophie and Sorensen, Louise Mejer and Tiret, Laurent and McEntee, Kathleen and Seppala, Eija and Koch, Jorgen and Battaille, Geraldine and Lohi, Hannes and Fredholm, Merete and Chetboul, Valerie and Häggström, Jens and Carlborg, Örjan and Lindblad-Toh, Kerstin and Höglund, Katja (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. 10:5, 1-17
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Official URL: http://dx.doi.org/10.1371/journal.pone.0123173

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.

Authors/Creators:Forsberg, Simon and Kierczak, Marcin and Bersås Ljungvall, Ingrid and Anne-Christine, Merveille and Vassiliki, Gouni and Wiberg, Maria and Lundgren Willesen, Jakob and Hanås, Sofia and Lequarre, Anne-Sophie and Sorensen, Louise Mejer and Tiret, Laurent and McEntee, Kathleen and Seppala, Eija and Koch, Jorgen and Battaille, Geraldine and Lohi, Hannes and Fredholm, Merete and Chetboul, Valerie and Häggström, Jens and Carlborg, Örjan and Lindblad-Toh, Kerstin and Höglund, Katja
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
Series/Journal:PloS one (1932-6203)
Year of publishing :2015
Depositing date:24 October 2015
Volume:10
Number:5
Page range:1-17
Number of Pages:17
Publisher:Public Library of Science
ISSN:1932-6203
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Other Veterinary Science
Agrovoc terms:diabetes, glycaemia, genetics
Keywords:canine diabetes-mellitus, receptor mutations, mitochondrial Ca 2+/H+ antiporter
URN:NBN:urn:nbn:se:slu:epsilon-e-3082
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3082
Additional ID:
Type of IDID
Web of Science (WoS)000354544200009
DOI10.1371/journal.pone.0123173
ID Code:12816
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
(VH) > Dept. of Anatomy, Physiology and Biochemistry
Deposited By: SLUpub Connector
Deposited On:24 Nov 2015 09:38
Metadata Last Modified:11 Feb 2016 15:34

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