Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies - PubMed (original) (raw)

. 2019 Oct 19;10(10):826.

doi: 10.3390/genes10100826.

Tosso Leeb 2, James Rushton 3, Thomas R Famula 4, Maura Mack 5, Vidhya Jagannathan 6, Christine Flury 7, Iris Bachmann 8, John Eberth 9, Sue M McDonnell 10, Maria Cecilia T Penedo 11, Rebecca R Bellone 12 13

Affiliations

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

Jocelyn Tanaka et al. Genes (Basel). 2019.

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 (_P_corrected = 2.08 × 10-10). 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 MFSD12 gene encoding the major facilitator superfamily domain containing 12 protein. This variant was perfectly concordant with phenotype in 96 Shetland Ponies (P = 1.15 × 10-22), was identified in the closely related Miniature Horse for which the mushroom phenotype is suspected to occur (fmu = 0.02), and was absent in 252 individuals from seven additional breeds not reported to have the mushroom phenotype. MFSD12 is highly expressed in melanocytes and variants in this gene in humans, mice, and dogs impact pigmentation. Given the role of MFSD12 in melanogenesis, we propose that p.Asp201fs is causal for the dilution observed in mushroom ponies.

Keywords: Equus caballus; MFSD12; coat color; dilution; pigmentation.

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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.

Figures

Figure 1

Figure 1

Mushroom and chestnut coat color phenotypes. The mushroom dilution on a chestnut background results in a dilute sepia shade ranging from light (A) to dark (B) and is often accompanied by a flaxen (lighter) mane and tail. Chestnut Shetland pony without the mushroom dilution displaying a typical red chestnut base coat color (C). Chestnut Shetland Pony also showing the tobiano white spotting pattern (D). Photo credits (A,B) Maria and Joana Tammi (C,D) Christine Mirjam Sorli.

Figure 2

Figure 2

A genome wide association study (GWAS) identifies the locus for mushroom phenotype in Shetland Ponies. (A) Manhattan Plot for the χ2 basic allelic association test. (B) Single locus mixed linear model (SLMM) utilizing an F-test to calculate p-values. (A,B) Plotted on the y-axis are the -log 10P values calculated for each test against the chromosomes plotted on the x-axis. The horizontal black line across each plot represents Bonferroni significance (P < 1.4 × 10−7). (C) A 326 kb region on ECA7 reaching genome wide significance. Plotted in blue are the data points from the SLMM GWAS analysis (N = 24). Plotted in green are the eight SNPs from this region genotyped in our replication sample set, displaying the combined p-values under a recessive model for the GWAS and replication sample sets (N = 40 mushroom ponies, N = 29 chestnut).

Figure 3

Figure 3

Bay mushroom Shetland Ponies. (A–C) Three bay ponies homozygous for the mushroom variant showing a coat lacking the red hue as typically seen in bay horses without the mushroom dilution. These bay mushroom ponies have normally pigmented mane and tail with countershading on the shoulders neck and head of these ponies. (D) Buckskin homozygous for the mushroom variant. The countershading is consistent with other “bay mushroom” ponies though the combination of mushroom and cream is likely contributing to the lighter shade in the coat of this pony as compared to the other bay mushrooms. Photo credits (A) Maria and Joana Tammi (B) Mira Ruotsalainen (C) and (D) Katrin Lach and Claudia Rahlmeier

Figure 4

Figure 4

Palomino Mushroom Shetland Ponies. (A–C) Three palomino mushroom ponies (chestnut background and heterozygous at the cream locus), displaying a phenotype consistent with other mushroom individuals without the cream dilution ranging in shade of mushroom phenotype. (D) Dunalino (palomino with the dun dilution) homozygous for the mushroom dilution, displaying an extremely dilute phenotype likely caused by a combination of dun and cream. On all four ponies the head appears to be a darker shade, similar to what is seen on the bay mushroom ponies. Photo credits (A) David Hodge. (D) Marc and Cecile Letouzé.

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