A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R) gene is associated with the Japanese brindling coat colour in rabbits (Oryctolagus cuniculus)

Abstract

BackgroundIn the domestic rabbit (Oryctolagus cuniculus), classical genetic studies have identified five alleles at the Extension locus: ED (dominant black), ES (steel, weaker version of ED), E (wild type, normal extension of black), eJ(Japanese brindling, mosaic distribution of black and yellow) and e (non-extension of black, yellow/red with white belly). Sequencing almost the complete coding sequence (CDS) of the rabbit MC1R gene, we recently identified two in-frame deletions associated with dominant black (c.280_285del6; alleles ED or ES) and recessive red (c.304_333del30; allele e) coat colours. It remained to characterize the eJallele whose phenotypic effect is similar to the Orange and Sex-linked yellow loci of cat and Syrian hamster.ResultsWe sequenced the whole CDS in 25 rabbits of different coat colours including 10 Japanese and 10 Rhinelander (tricolour) rabbits and identified another 6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6]) that was present in all animals with Japanese brindling coat colour and pattern. These mutations eliminate two amino acids in the first transmembrane domain and, in addition, cause an amino acid substitution at position 44 of the wild type sequence. Genotyping 371 rabbits of 31 breeds with different coat colour this allele (eJ) was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit). Rabbits with eJ/eJ genotype were non fixed at the non-agouti mutation we previously identified in the ASIP gene. Segregation in F1 and F2 families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing eJ/eJ and eJ/e animals. MC1R mRNA was expressed in black hair skin regions only.ConclusionsThe c.[124A;125_130del6] allele may be responsible for a MC1R variant determining eumelanin production in the black areas. However, the mechanism determining the presence of both red and black hairs in the same animal seems more complex. Expression analyses of the c.[124A;125_130del6] allele suggest that MC1R transcription may be regulated epigenetically in rabbits with the Japanese brindling phenotype. Further studies are needed to clarify this issue.

Agouti Revisited: Transcript Quantification of the ASIP Gene in Bovine Tissues Related to Protein Expression and Localization

“…In farm animals, ASIP mRNA was recently detected in different tissues of cattle, rabbit and chicken and a potential role for fat-related traits was proposed [6], [12], [14], [31]. For this reason, we conducted a comparative, quantitative analysis of ASIP mRNA abundance in bovine adipose and further tissues and analyzed protein abundance and localization.…”

No association between the melanocortin-1 receptor (MC1R) and black belly stripe size variation in the Great TitParus major

“…Future studies should focus on additional melanogenesis genes, including MITF, ASIP, TYR and TYRP1, as earlier found in other species (Chang et al 2006, Minvielle et al 2010, Lehtonen et al 2011. Furthermore, other mechanisms of gene expression alterations such as mRNA expression and/or epigenetic alteration in the MC1R gene promoter should be considered (Fontanesi et al 2010, Emaresi et al 2013, Scriba et al 2013. Finally, we suggest that the architecture of phenotypic variation for this kind of small-scale variation such as black belly colouration may have a regulatory background rather than genetic polymorphism in the coding regions.…”

Exploring copy number variation in the rabbit (Oryctolagus cuniculus) genome by array comparative genome hybridization

“…A preliminary low coverage version (2X) of the rabbit genome has been recently improved and reassembled at~7X (OryCun2.0 version; http://www.ensembl.org/Oryctolagus_cuniculus/ Info/Index). In rabbits only a few reports have characterized the genetic basis of phenotypic traits, like coat colour [6][7][8][9] and hair morphology [4,10], or have investigated quantitative trait loci for biomedical and production traits [11][12][13].…”