OMIA 001438-9796 : Coat colour, silver in Equus caballus
In other species: domestic cat
Category: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 155550 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2006
Species-specific name: Silver dapple
Species-specific symbol: Z or SILV
Species-specific description: The Silver coat color, also called Silver dapple, is characterized by dilution of the black pigment (eumelanin) in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs (Brunberg et al. 2006). A likely causal variant responsible for silver dilution was identified in the PMEL gene in 2006 (Brunbereg et al., 2006; Reissmann et al., 2007).
See also: OMIA000733-9796 Multiple Congenital Ocular Anomalies (MCOA)
[IT thanks Mary Katherine Easterwood, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]
Mapping: Linkage mapping of a half sib family consisting of 1 stallion, 29 dams and 34 offspring using microsatellite DNA markers implicated a region on Chromosome 6 as being the site of the gene for SILV (Brunberg et al., 2006). PMEL17 was a candidate gene for this trait and previously mapped to this region using fluorescence in situ hybridization [S. Rieder, PhD thesis, 1999].
Molecular basis: Brunberg et al. (2006) reported that "a missense mutation in exon 11 [of PMEL17] changing the second amino acid in the cytoplasmic region from arginine to cysteine (Arg618Cys) . . . showed complete association with the Silver phenotype across multiple horse breeds [Icelandic horse; American miniature; Rocky mountain horse; Morgan horse; Swedish warmblood, Ardenne], and was not found among non-Silver horses with one clear exception; a chestnut colored individual that had several Silver offspring when mated to different non-Silver stallions also carried the exon 11 mutation." The authors conclude that a "chestnut or sorrel horse that only express pheomelanin, will not show any obvious phenotypic effects of the Silver mutation". On protein level, this change is located in a transmembrane portion of the protein, previously shown to regulate hypopigmented phenotypes in mouse, chicken, dog, and zebrafish (reviewed in Brunberg et al., 2006).
Reissman et al. (2007) reported that the same variant (named Q665301:g.1457C>T in their study) was part of a hapotype associated with Silver in Icelandic horses and Shetland ponies. Reissman et al. (2016) reported that the silver mutation Z in the Pmel17 gene was also present in Comtois and Kabardian horses.
Andersson et al. (2013) concluded that this same mutation (reported as g.73665304C>T, p.(Arg625Cys) in their study) is causal for Multiple Congenital Ocular Anomalies (MCOA) with an autosomal co-dominant mode of inheritance (i.e horses with the MCOA-phenotype are homozygous for the likely causal variant, Cyst-phenotype horses are heterozygous and unaffected horses are homozygous wildtype; see OMIA 000733-9796, i.e. this mutation in PMEL17 is pleiotropic.
PMEL17, also known as SILV, is now known as PMEL.
Breeds: American Miniatur Horse (Horse) (VBO_0000896), American Paint (Horse) (VBO_0000897), American Saddle Horse (Horse) (VBO_0000898), Arab (Horse) (VBO_0000905), Ardennes (Horse) (VBO_0000907), Comtois (Horse) (VBO_0000936), Iceland Pony (Horse) (VBO_0000990), Missouri Fox Trotter, Germany (Horse) (VBO_0011358), Morgan (Horse) (VBO_0001022), Quarter Horse (Horse) (VBO_0001057), Rocky Mountain, United States of America (Bighorn sheep) (VBO_0016854), Shetland Pony (Horse) (VBO_0001066), Welsh Pony (Horse) (VBO_0001091).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|PMEL||premelanosome protein||Equus caballus||6||NC_009149.3 (74578149..74569524)||PMEL||Homologene, Ensembl, NCBI gene|
By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.
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|
|903||American Miniatur Horse (Horse) Ardennes (Horse) Comtois (Horse) Iceland Pony (Horse) Missouri Fox Trotter, Germany (Horse) Morgan (Horse) Rocky Mountain, United States of America (Bighorn sheep)||Coat colour, silver AND Multiple congenital ocular anomalies||PMEL||missense||Naturally occurring variant||EquCab3.0||6||g.74569773G>A||c.1849C>T||p.(R617C)||NM_001163889.1; NP_001157361.1; previously listed in OMIA as g.73665304 and published a C (wild type) to T (Silver) transition, p.Arg618Cys, as well as p.(R625C); coordinates in this table have been updated to a recent reference genome and / or transcript||2006||17029645||The genomic position in EquCab3.0 was provided by Mary Katherine Easterwood, working under the guidance of Professor Ernie Bailey in April 2022|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2021||Herb, V.M., Zehetner, V., Blohm, K.O. :|
|Multiple congenital ocular anomalies in a silver coat Missouri Fox Trotter stallion. Tierarztl Prax Ausg G Grosstiere Nutztiere 49:350-354, 2021. Pubmed reference: 34666370. DOI: 10.1055/a-1581-4810.|
|2016||Reissmann, M., Musa, L., Zakizadeh, S., Ludwig, A. :|
|Distribution of coat-color-associated alleles in the domestic horse population and Przewalski's horse. J Appl Genet 57:519-525, 2016. Pubmed reference: 27194311. DOI: 10.1007/s13353-016-0352-7.|
|2013||Andersson, L.S., Wilbe, M., Viluma, A., Cothran, G., Ekesten, B., Ewart, S., Lindgren, G. :|
|Equine multiple congenital ocular anomalies and silver coat colour result from the pleiotropic effects of mutant PMEL. PLoS One 8:e75639, 2013. Pubmed reference: 24086599. DOI: 10.1371/journal.pone.0075639.|
|2012||Svensson, E.M., Telldahl, Y., Sjöling, E., Sundkvist, A., Hulth, H., Sjøvold, T., Götherström, A. :|
|Coat colour and sex identification in horses from Iron Age Sweden. Ann Anat 194:82-7, 2012. Pubmed reference: 22154005. DOI: 10.1016/j.aanat.2011.11.001.|
|2011||Watt, B., Tenza, D., Lemmon, M.A., Kerje, S., Raposo, G., Andersson, L., Marks, M.S. :|
|Mutations in or near the transmembrane domain alter PMEL amyloid formation from functional to pathogenic. PLoS Genet 7:e1002286, 2011. Pubmed reference: 21949659. DOI: 10.1371/journal.pgen.1002286.|
|2010||Bellone, RR. :|
|Pleiotropic effects of pigmentation genes in horses. Anim Genet 41 Suppl 2:100-10, 2010. Pubmed reference: 21070283. DOI: 10.1111/j.1365-2052.2010.02116.x.|
|Li, B., He, XL., Zhao, YP., Wang, XJ., Manglai, D., Zhang, YR. :|
|[Molecular basis and applicability in equine color genetics]. Yi Chuan 32:1133-40, 2010. Pubmed reference: 21513164.|
|2009||Lewin, H.A. :|
|Genetics. It's a bull's market. Science 324:478-9, 2009. Pubmed reference: 19390037. DOI: 10.1126/science.1173880.|
|Rieder, S. :|
|Molecular tests for coat colours in horses. J Anim Breed Genet 126:415-24, 2009. Pubmed reference: 19912415. DOI: 10.1111/j.1439-0388.2009.00832.x.|
|2007||Reissmann, M., Bierwolf, J., Brockmann, GA. :|
|Two SNPs in the SILV gene are associated with silver coat colour in ponies. Anim Genet 38:1-6, 2007. Pubmed reference: 17257181. DOI: 10.1111/j.1365-2052.2006.01553.x.|
|2006||Brunberg, E., Andersson, L., Cothran, G., Sandberg, K., Mikko, S., Lindgren, G. :|
|A missense mutation in PMEL17 is associated with the Silver coat color in the horse. BMC Genetics 7:46, 2006. Pubmed reference: 17029645. DOI: 10.1186/1471-2156-7-46.|
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