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Boxer dataset for genome-wide association study of modifiers of risk of canine degenerative myelopathy in dogs homozygous for SOD1 mutation

ABSTRACT: Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE80315 | GEO | 2016/06/01

SECONDARY ACCESSION(S): PRJNA318537

REPOSITORIES: GEO

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Project description:Diabetes mellitus (DM) is a disorder that disrupts the body from shifting glucose into the cells resulting in hyperglycaemia (1). Insulin dependence or DM that resembles type I diabetes in humans is commonly observed in dogs (2). Canine DM diagnosis is based on fasting hyperglycaemia and glucosuria with clinical presentation of polyuria, polydipsia, polyphagia and weight loss (2). Its treatment goal is blood glucose control, which can be accomplished through insulin therapy, dietary modification and control of concurrent disorders (3). The major complications of DM include diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy and atherosclerosis induced by chronic hyperglycaemia via several pathways (4). The proposed unifying mechanism that mediates the tissue-damaging effects of hyperglycaemia is superoxide overproduction (5). Effective monitoring is required for DM treatment to reduce the risk of progression and complication. Hence, the identification of novel biomarkers is being researched (6, 7). Proteomics has been recognised as an important tool for establishing a diagnosis of disease aetiology and monitoring therapy outcomes (8, 9). Proteomic patterns were applied to detect diabetes and complications, as well as to evaluate treatment effectiveness in humans (10-12). There is limited information on proteomic data in DM dogs (13-15). In a proteomic analysis of serum samples from DM dogs, most upregulated proteins are involved in oxidative state, defence and inflammation (13). Medicinal plants are utilised in DM dogs as an adjunct medicine in combination with standard treatment to prevent the development of long-term diabetes complications and improve overall well-being. Curcumin, the most phytochemically active curcuminoid extracted from Curcuma longa, has gained attention in human and laboratory animals. Curcumin is known to have antioxidant, anti-inflammatory and anticancer properties (16-18). In humans and experimental animals with DM, curcumin has an antioxidant potential of enhanced reduced glutathione (GSH) and reduced malondialdehyde (MDA) levels (19, 20). The anti-inflammatory effects of curcumin in DM were reported via decreased interleukin-1β (IL‐1β), interleukin-6 (IL‐6), interleukin-8 (IL‐8) and tumour necrosis factor-α levels and also diminished monocyte chemoattractant protein-1 and C-reactive protein levels (19-21). There has been no published evidence of the impact, safety and proteomic profiles of curcuminoids, particularly curcumin, in client-own DM dogs. Accordingly, the aims of the present study were (1) to evaluate the effects of curcuminoid supplementation on canine DM-associated oxidative stress and inflammation, (2) to determine the safety of curcuminoid supplementation in canine diabetes and (3) to determine whether curcuminoid has an impact on proteins implicated in DM-associated complications by a proteomic analysis.

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Boxer dataset for genome-wide association study of modifiers of risk of canine degenerative myelopathy in dogs homozygous for SOD1 mutation

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