OMIA:002750-9615 : Reduced hair shedding, MC5R-related in Canis lupus familiaris (dog)
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 600042 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2016
Inheritance: The exact mode of inheritance for hair shedding has not been published. Hayward et al. (2016) documented epistatic interactions of MC5R with FGF5 and RSPO2, which also affect hair morphology in dogs.
Mapping: Hayward et al. (2016) used 1873 dogs from 158 breeds in GWAS for various morphological traits. Phenotypes for fur length and extent of hair shedding were based on breed averages. Two independent GWAS identified the same locus on chromosome 1 harboring the MC5R gene associated with fur length and extent of hair shedding.
Molecular basis: Hayward et al. (2016) included a missense variant in the MC5R gene (p.A237T) in their GWAS for hair length and extent of hair shedding that had previously been identified in village dogs. In both GWAS, this variant was the strongest associated marker. Based on in silico structure modeling Hayward et al. (2016) found "evidence that the A237T mutation causes a conformational change in the tertiary structure of the protein, with a change in binding sites ... that is ‘probably damaging’ (Polyphen-2 HumDiv = 0.992)." MC5R is expressed in sebaceous glands and involved in the production of sebum. Hayward et al. (2016) cautioned "While functional studies are needed to determine whether this variant is indeed the causal mutation at this QTL" and concluded "the identification of a third coat length locus improves our understanding of fur-type genetics in the dog and hypothesizes a relationship between sebum production and fur type in some breeds."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: The derived allele at MC5R (237-Thr) is associated with reduced hair shedding and shorter hair length. However, epistatic interactions with the genotypes at MC5R, RSPO2 and FGF5 exist (Hayward et al. 2016).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MC5R||melanocortin 5 receptor||Canis lupus familiaris||1||NC_051805.1 (24331495..24326030)||MC5R||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1603||reduced hair shedding||MC5R||missense||Naturally occurring variant||UU_Cfam_GSD_1.0||1||g.24541931C>T||c.709G>A||p.(A237T)||XM_038525579.1; XP_038381507.1; the variant is reported to be associated with reduced hair shedding and shorter hair length and may not be causal||2016||26795439|
Cite this entry
|2016||Hayward, J.J., Castelhano, M.G., Oliveira, K.C., Corey, E., Balkman, C., Baxter, T.L., Casal, M.L., Center, S.A., Fang, M., Garrison, S.J., Kalla, S.E., Korniliev, P., Kotlikoff, M.I., Moise, N.S., Shannon, L.M., Simpson, K.W., Sutter, N.B., Todhunter, R.J., Boyko, A.R. :|
|Complex disease and phenotype mapping in the domestic dog. Nat Commun 7:10460, 2016. Pubmed reference: 26795439. DOI: 10.1038/ncomms10460.|
- Created by Tosso Leeb on 16 Aug 2023
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