OMIA 002197-9615 : Coat colour, phaeomelanin dilution, MFSD12-related in Canis lupus familiaris

In other species: horse

Possibly relevant human trait(s) and/or gene(s) (MIM number): 617745

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: This entry describes the Intensity (I) locus; sometimes called the Intense (Int) locus

Species-specific symbol: I; previously called Int

Species-specific description: Hédan et al. (2019): "Thanks to a multiple step GWAS approach, we confirmed that solid white coat color in dogs may result from the absence of eumelanin (e/e at the MC1R locus) and an extreme dilution of phaeomelanin, confirming the hypothesis of Sponenberg and Rothschild [2001] on the existence of an I locus and later, the work of Schmutz and Berryere [2007; J. Heredity]."

History: As summarised by Carver (1984), Iljin (1932) proposed a locus with "a series of phaeomelanin intensifying alleles" with order of dominance "Int/- (cream) > int^f/- (fawn) > int/int (tan)". Iljin (1941) named the locus "intensification of the zonarity", with the symbol "Int", where "zonarity" refers to the differentially-pigmented band on a hair fibre that is characteristic of the agouti coat colour (OMIA 000201-9615). Following Iljin (1941), Carver (1984) called this the Int locus. Citing Iljin (1932) and Carver (1984), Sponenberg and Rothschild (2001) hypothesised "an autosomal locus [that] affects the intensity of phaeomelanic areas but leaves eumelanic areas relatively unchanged". They called this the Intense locus (Int). Schmutz and Berryere (2007; Animal Genetics) changed the locus symbol to "I", to render it consistent with the convention for single-letter canine pigmentation locus symbols. Hédan et al. (2019) refer to the locus as "Intensity" with symbol "I", which can now be regarded as the preferred name and symbol. (Thanks to Sheila Schmutz for invaluable contributions to this summary)

Mapping: Hédan et al. (2019) mapped the I locus to chromosome CFA20 at around 55Mb.

Molecular basis: Hédan et al. (2019) "identified a unique missense variant that was located in the first exon of MFSD12 [CFA20: g.55,850,145C>T]. . . , based on alignments with the human genome and the annotation of the human orthologous transcript ENST00000355415: MFSD12: p.(Arg51Cys). This dog variant is exactly orthologous to the human variant rs751585493 (ENST00000355415 Chr19:3557253 G > A; p.(Arg51Cys)."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MFSD12 major facilitator superfamily domain containing 12 Canis lupus familiaris 20 NC_006602.3 (55855102..55863606) MFSD12 Homologene, Ensembl, NCBI gene

Variants

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
White or cream MFSD12 missense CanFam3.1 20 g.55,850,145C>T c.151C>T p.(Arg51Cys) 2019 31117290 The cDNA coordinate kindly provided by Tosso Leeb 190523

References


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.
2019 Hédan et al., Hédan, B., Cadieu, E., Botherel, N., Dufaure de Citres, C., Letko, A., Rimbault, M., Drögemüller, C., Jagannathan, V., Derrien, T., Schmutz, S., Leeb, T., André, C. :
Identification of a Missense Variant in <i>MFSD12</i> Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs. Genes (Basel) 10:386, 2019. Pubmed reference: 31117290. DOI: 10.3390/genes10050386.
2007 Schmutz, SM., Berryere, TG. :
The genetics of cream coat color in dogs. J Hered 98:544-8, 2007. Pubmed reference: 17485734. DOI: 10.1093/jhered/esm018.
Schmutz, SM., Berryere, TG. :
Genes affecting coat colour and pattern in domestic dogs: a review. Anim Genet 38:539-49, 2007. Pubmed reference: 18052939. DOI: 10.1111/j.1365-2052.2007.01664.x.
2001 Sponenberg, D.P., Rothschild, M.F. :
Genetics of coat colour and hair texture (chapter 4) The Genetics of the Dog (eds A. Runinsky and J. Sampson) CAB International :61-85, 2001.
1984 Carver, E.A. :
Coat colour genetics of the German shepherd dog Journal of Heredity 75:247-252, 1984. DOI: 10.1093/oxfordjournals.jhered.a109926.
1941 Iljin, N.A. :
Wolf-dog genetics Journal of Genetics 42:359-414, 1941. DOI: 10.1007/BF02982879.
1932 Iljin, N.A. :
Genetics and Breeding of the Dog. Seljskohozgiz, Moscow :, 1932.

Edit History


  • Created by Frank Nicholas on 23 May 2019
  • Changed by Frank Nicholas on 23 May 2019
  • Changed by Frank Nicholas on 24 May 2019
  • Changed by Frank Nicholas on 28 May 2019