Two Candidate Genes <i>(FTO</i> and <i>INSIG2)</i> for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes

Abstract

Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The FTO and INSIG2 are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae – the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of INSIG2 and a fragment of the coding sequence of FTO. The FTO gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24–25 (Chinese raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13 in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (–28T>C in the 5′-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (FTO, p < 0.08) and weight of raw skin (INSIG2, p < 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.

Microsatellite polymorphism and its association with body weight and selected morphometrics of farm red fox (Vulpes vulpes L.)

“…The polymorphisms of two candidate genes, the insulin induced gene 2 ( INSIG2 ) and the fat mass and obesity associated gene ( FTO ), in four species belonging to the family Canidae (the dog, red fox, arctic fox and Chinese raccoon dog) were studied by Grzes et al ( 2011 ). Two synonymous SNPs, one in the FTO gene (−28T>C in the 5′-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in the red fox.…”

A Comparative Analysis ofMC4RGene Sequence, Polymorphism, and Chromosomal Localization in Chinese Raccoon Dog and Arctic Fox

“…The low level of the MC4R polymorphism in the Chinese raccoon dog and the high level in the arctic fox are rather surprising, as in a similar study of the MC3R gene, the situation was reversed-in the Chinese raccoon dog, 6 polymorphic sites were identified, whereas the arctic fox was monomorphic . In a recent study of two candidate genes (FTO and INSIG2) for fat tissue accumulation, low levels of polymorphism were observed in both species: two synonymous SNPs in the FTO of the Chinese raccoon dog and one SNP in the arctic fox, whereas the INSIG2 was monomorphic in both species (Grzes et al, 2011). In addition, the MSTN gene, a candidate for muscularity, showed a very low level of polymorphism-one silent SNP in the Chinese raccoon dog and monomorphism in the arctic fox (Grzes et al, 2009).…”

“…Three species studies have already been conducted on several genes involved in muscularity-MSTN (Grzes et al, 2009) MC4R GENE OF THE CHINESE RACCOON DOG AND ARCTIC FOX (Skorczyk et al, 2007;Grzes et al, 2011;Nowacka-Woszuk et al, 2011), and sex determination-SRY, SOX9, AR, and AMH . In these genes, numerous polymorphisms were described, but only a polymorphism of the MC3R was associated with the body weight of red foxes .…”

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

“…FTO Locus FTO, the top association signal on most human GWAS for BMI is of debatable merit as a candidate gene for canine obesity, due to the controversy as to whether FTO itself or neighbouring genes are the true effector pathway causing the association signal (see above). Grzes et al [123] investigated SNPs within the gene FTO in four Canidae species including the dog. In 39 dogs of 14 breeds sequencing identified six polymorphic sites in FTO: one missense variant (c.23C>T, p.Thr8Met; rs852870212 described as "23 C/T; Thr1Met"), two intronic variants, and three 3' flanking variants.…”