FTO and IRX3 Genes are Not Promising Markers for Obesity in Labrador Retriever Dogs

Abstract

Obesity is a serious problem in numerous dog breeds, but knowledge of its hereditary background is scarce. On the contrary, numerous DNA polymorphisms associated with human obesity have been identified, with the strongest effect being demonstrated for FTO gene. We used targeted next-generation sequencing (tNGS) to search for polymorphisms in the region harboring FTO and IRX3 in 32 Labrador dogs. Moreover, we investigated the selected regions of FTO and IRX3, orthologous to the human regions associated with obesity, in 165 Labradors. For all dogs, the following information was available: age, sex, gonadal status, body weight, and body conformation score (BCS). The use of tNGS revealed 12,217 polymorphisms, but none of these obtained significance when lean and obese dogs were compared. Study of two SNPs in the 5’-flanking region of FTO in 165 dogs – creating two upstream reading frames (uORFs) – also showed no association with body weight and BCS but suggested the need for improvement in FTO annotation. No polymorphism was found in the 5’UTR of IRX3. Additionally, no differences of CpG islands methylation status between lean and obese dogs were found. Our study suggests that FTO and IRX3 are not useful markers of obesity in Labrador dogs.

Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis

“…A genome-wide association study (GWAS) was performed using a logistic regression model implemented in PLINK v.1.9, to test the association between disease trait and allele in each SNP. Significant factors such as age (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), sex (85 females 68 males), and breed (18) were fitted in the GWAS statistical model for all the traits. We generated a total of 20 principal components (PCs); the eigenvalues of all the PCs were fit as co-variance to account for population stratification.…”

“…In addition, compared to obesity in humans, there are only limited reports on genetic markers associated with canine obesity. In humans, more than 220 obesity-related genetic markers have been documented throughout the last decade [16]. Among these, FTO, BDNF, MC4R, PCSK1, MC3R, and PPARG genes were considered as promising candidate genes for canine obesity [16][17][18]43].…”

“…Post-genome-wide association study (GWAS) analyses have been performed in several studies to discover obesity-related markers [16][17][18]. Previous association studies have revealed that polymorphism of POMC and TNF gene can affect the body weight and appetite in obesity [16,19]. A few other genes such as FTO, PPARG, BDNF, MC4R, and MC3R have been reported to be associated with obesity in canines [16][17][18].…”

“…Previous association studies have revealed that polymorphism of POMC and TNF gene can affect the body weight and appetite in obesity [16,19]. A few other genes such as FTO, PPARG, BDNF, MC4R, and MC3R have been reported to be associated with obesity in canines [16][17][18]. Till now, only a few studies on the effect of polymorphism of canine genes on obesity have been published.…”

The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals

“…Grzemski et al, [124] used targeted next generation sequencing (NGS) in 32 Labrador retrievers in a region incorporating FTO and IRX3, also implicated as an effector gene in humans. Several polymorphisms were identified and tested for association with body condition on a 5-point scale in a larger Labrador retriever cohort (n=165), suitably adjusted for sex, age and multiple testing.…”