Family of melanocortin receptor (MCR) genes in mammals—mutations, polymorphisms and phenotypic effects

Abstract

The melanocortin receptor gene family consists of five single-exon members, which are located on autosomes. Three genes (MC2R, MC4R and MC5R) are syntenic in the human, mouse, cattle and dog genomes, while in the pig, the syntenic group comprises MC1R, MC2R and MC5R. Two genes (MC1R and MC4R) have been extensively studied due to their function in melanogenesis (MC1R) and energy control (MC4R). Conservative organisation of these genes in five mammalian species (human, mouse, cattle, pig and dog), in terms of the encoded amino acid sequence, is higher in the case of MC4R compared to MC1R. Polymorphisms of these two genes are responsible or associated with variation of pigmentation (MC1R) and adipose tissue deposition (MC4R). Polymorphic variants in MC1R, causing coat colour variation, were described in humans and domestic mammals (cattle, horse, pig, sheep, dog), as well as farm red and arctic foxes. The MC4R gene is very polymorphic in humans and it is well known that some variants cause monogenic obesity or significantly contribute to the development of polygenic obesity. Such relationships are not so evident in domestic mammals; however, at least one missense substitution (298Asp > Asn) in the porcine MC4R significantly contributes, at least in some breeds, to fat tissue accumulation, feed conversion ratio and daily weight gain. Knowledge on the phenotypic effects of polymorphisms of MC2R, MC3R and MC5R in domestic mammals is scarce, probably due to the small number of reports addressing these genes. Thus, further studies focused on these genes should be undertaken.

The Application of Genomic Technologies to Investigate the Inheritance of Economically Important Traits in Goats

“…In cattle, dominant black (L99P) and recessive red (premature stop codon) coat colors are produced by alleles at the MC1R gene ( [91,92], reviewed by [93]), and in sheep a M73K mutation is associated with dominant black [94]. In goats, Fontanesi et al [95] characterized the diversity of the MC1R gene and found one nonsense mutation (p.Q225X), three missense mutations (p.A81V, p.F250V, and p.C267W), and one silent mutation.…”

A local duplication of theMelanocortin receptor 1locus inAstyanax

“…In humans, a splice form has been reported, however its functional significance is unknown (Tan et al 1999). Although Mc1r is among a family of five structurally similar melanocortin receptors (Switonski et al 2013), copy number variants of this gene have not been reported in the literature.…”

RNA sequencing as a powerful tool in searching for genes influencing health and performance traits of horses

“…To date, in horses, many genes have been investigated and significantly associated with important phenotypic traits, such as coat color variations (KIT, MITF, MC1R) Świtoński et al 2013), reproduction traits (STK31, TSPY, AEG1, CRISP1) (Giese et al 2002;Sabeur et al 2008), and inherited diseases (SCN4A: HYPP syndrome; PPIB: HERDA syndrome; MYO5: LFS syndrome) (Rudolph et al 1992;Tryon et al 2007;Brooks et al 2010).…”