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Home / Equine Research Bank / Genes (Basel) / Frameshift Variant in MFSD12 Explains the Mushroom Coat Colo...
Genes2019; 10(10); 826; doi: 10.3390/genes10100826

Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies.

Abstract: Mushroom is a unique coat color phenotype in Shetland Ponies characterized by the dilution of the chestnut coat color to a sepia tone and is hypothesized to be a recessive trait. A genome wide association study (GWAS), utilizing the Affymetrix 670K array (MNEc670k) and a single locus mixed linear model analysis (EMMAX), identified a locus on ECA7 for further investigation ( = 2.08 × 10). This locus contained a 3 Mb run of homozygosity in the 12 mushroom ponies tested. Analysis of high throughput Illumina sequencing data from one mushroom Shetland pony compared to 87 genomes from horses of various breeds, uncovered a frameshift variant, p.Asp201fs, in the gene encoding the major facilitator superfamily domain containing 12 protein. This variant was perfectly concordant with phenotype in 96 Shetland Ponies ( = 1.15 × 10), was identified in the closely related Miniature Horse for which the mushroom phenotype is suspected to occur (f = 0.02), and was absent in 252 individuals from seven additional breeds not reported to have the mushroom phenotype. is highly expressed in melanocytes and variants in this gene in humans, mice, and dogs impact pigmentation. Given the role of in melanogenesis, we propose that p.Asp201fs is causal for the dilution observed in mushroom ponies.
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Publication Date: 2019-10-19 PubMed ID: 31635058PubMed Central: PMC6827053DOI: 10.3390/genes10100826Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study discovered the genetic variant responsible for the light, sepia-toned coat color, known as “mushroom”, seen in Shetland Ponies. The genetic mutation, a frameshift variant, was found in the MFSD12 gene and is believed to have a direct impact on pigmentation, diluting the usual chestnut color to create the unique mushroom shade.

Research Purpose and Methodology

  • The research aimed to identify the genetic origin of the distinctive “mushroom” coat color in Shetland Ponies, believed to be a recessive trait. This unique coloration results in a dilution of the standard chestnut coat color to a sepia shade.
  • To investigate this, they performed a genome-wide association study (GWAS), utilizing an Affymetrix 670K array (MNEc670k) to scan the genome and identify potential genes involved. A single locus mixed linear model analysis (EMMAX) found one area of interest on chromosome 7 (ECA7).
  • Homozygosity in a 3 Mb region of this locus was found in the 12 mushroom-colored ponies in the study, indicating a likely location for the responsible gene.

Findings

  • Upon sequencing the DNA in this region, a frameshift variant (a mutation causing a change in the reading frame of the genetic code), designated p.Asp201fs, was found in the MFSD12 gene. This was done by comparing the high throughput Illumina sequencing data from one mushroom Shetland pony to the genomes of 87 horses of various breeds.
  • The mutation was found to be perfectly associated with the mushroom phenotype in all 96 Shetland Ponies tested. Notably, it was also found in the closely related Miniature Horse breed, where the mushroom color has been suspected but not confirmed.
  • In contrast, this mutation was absent in 252 individuals across seven other breeds that are not known to display the mushroom coat color.

Interpretation and Conclusion

  • The MFSD12 gene holds interest due to its high expression in melanocytes — the cells responsible for pigment production. Alterations have been found in this gene in humans, mice, and dogs, with effects on pigmentation noticed in each case.
  • Based on its role in pigmentation, the researchers propose that the identified variant (p.Asp201fs) in the MFSD12 gene is the cause of the mushroom coat color dilution in Shetland Ponies.

Cite This Article

APA
Tanaka J, Leeb T, Rushton J, Famula TR, Mack M, Jagannathan V, Flury C, Bachmann I, Eberth J, McDonnell SM, Penedo MCT, Bellone RR. (2019). Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies. Genes (Basel), 10(10), 826. https://doi.org/10.3390/genes10100826

Publication

Genes
ISSN: 2073-4425
NlmUniqueID: 101551097
Country: Switzerland
Language: English
Volume: 10
Issue: 10
PII: 826

Researcher Affiliations

Tanaka, Jocelyn
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. jltanaka@ucdavis.edu.
Leeb, Tosso
  • Institute of Genetics, University of Bern, 3001 Bern, Switzerland. tosso.leeb@vetsuisse.unibe.ch.
Rushton, James
  • Rowe Equine Ltd, Wotton Under Edge, GLOS GL12 7PP, UK. jamesrushton@rowevetgroup.com.
Famula, Thomas R
  • Department of Animal Science, University of California, One Shields Ave, Davis, CA 95616, USA. trfamula@ucdavis.edu.
Mack, Maura
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. Maura.Mack@colostate.edu.
Jagannathan, Vidhya
  • Institute of Genetics, University of Bern, 3001 Bern, Switzerland. vidhya.jagannathan@vetsuisse.unibe.ch.
Flury, Christine
  • School of Agricultural Forest and Food Sciences, Bern University of Applied Sciences, 3052 Zollikofen, Switzerland. christine.flury@bfh.ch.
Bachmann, Iris
  • Agroscope, Swiss National Stud Farm, 1580 Avenches, Switzerland. iris.bachmann@agroscope.admin.ch.
Eberth, John
  • College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY 40546, USA. john.eberth@uky.edu.
McDonnell, Sue M
  • Havemeyer Equine Behavior Program, University of Pennsylvania School of Veterinary Medicine, New Bolton Center Department of Clinical Studies, Kennett Square, PA 19348, USA. suemcd@vet.upenn.edu.
Penedo, Maria Cecilia T
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. mctorrespenedo@ucdavis.edu.
Bellone, Rebecca R
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. rbellone@ucdavis.edu.
  • Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. rbellone@ucdavis.edu.

MeSH Terms

  • Animal Fur / metabolism
  • Animals
  • Frameshift Mutation
  • Horses / genetics
  • Membrane Transport Proteins / genetics
  • Pigmentation / genetics

Conflict of Interest Statement

R.R.B., J.T., and M.C.T.P., are affiliated with the Veterinary Genetics Laboratory, a genetic testing laboratory offering genetic diagnostic testing in horses.

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Citations

This article has been cited 5 times.
  1. Avila F, Hughes SS, Magdesian KG, Penedo MCT, Bellone RR. Breed Distribution and Allele Frequencies of Base Coat Color, Dilution, and White Patterning Variants across 28 Horse Breeds.. Genes (Basel) 2022 Sep 13;13(9).
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  4. Esdaile E, Kallenberg A, Avila F, Bellone RR. Identification of W13 in the American Miniature Horse and Shetland Pony Populations.. Genes (Basel) 2021 Dec 14;12(12).
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