OMIA 000031-9615 : Coat colour, dilution, MLPH-related in Canis lupus familiaris

In other species: domestic cat , cattle , sheep , rabbit , American mink

Possibly relevant human trait(s) and/or gene(s) (MIM number): 609227

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: FN acknowledges invaluable feedback from Cord Drögemüller that has led to the name of this phene being changed from "Coat colour, diluted" to "Coat colour, dilution, MLPH-related". At the same time, a new phene "Coat colour, dilution, generic" was created.

Species-specific name: Colour mutant alopecia; Color dilution alopecia; Colour dilution alopecia

Mapping: Philipp et al. (2005) mapped a very likely comparative candidate gene (based on a similar dilute mutant in mice, namely Mlph), to canine chromosome CFA25q24.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous phenotype in humans and mice), namely MLPH, Drögemüller et al. (2007) identified a causal mutation as an "an A/G SNP located at the last nucleotide of the untranslated exon 1 (c.-22G>A)" which "affects a conserved nucleotide of the splice donor recognition motif". As a result of the "reduction of splicing efficiency", the authors reported that "the mutant A-allele is predicted to reduce splicing efficiency 8-fold".

Bauer et al. (2018) "investigated dilute coloured Chow Chows whose coat colour could not be explained by their genotype at the previously known MLPH: c.–22G>A variant [allele d^1]. Whole genome sequencing of such a dilute Chow Chow revealed another variant in the MLPH gene: MLPH:c.705G>C [allele d^2] . . . Although relatively rare overall, this d2 allele is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai Ridgebacks".

Van Buren et al. (2020) reported a third variant "(c.667_668insC) (d^3), which leads to a frameshift and premature stop codon (p.His223Profs*41)".

Prevalence: Van Buren et al. (2020): "The d^3 allele is found at low frequency in multiple dog breeds, as well as in wolves, wolf-dog hybrids, and indigenous dogs.The d3 allele was found in a wide spectrum of breeds and other canids, minimally including the Hungarian pumi, Hungarian mudi, Chihuahua, Pekingese, Italian greyhound, Shih Tzu, Tibetan mastiff, Yorkshire terrier, and Shetland sheepdog, as well as indigenous dogs, wolves, and wolf-dog hybrids. The wolf-dog hybrids in this study that carry the d3 variant have recent ancestry behind them, including wolf, Alaskan Malamute, German shepherd dog, Siberian husky, and collie. The presence of the d3 variant in village dogs and wolves may indicate that this variant represents an ancient mutation, persisting at a low frequency across some breeds, while being lost in others. However, given that this variant is a single nucleotide insertion in an 8 bp poly C stretch, the possibility that d3 is identical by state, at least in some breeds, must be considered."

Genetic testing: Van Buren et al. (2020): "As this newly identified c.667_668insC d3 variant does not resolve all MLPH genotype/phenotype inconsistencies, additional variants are likely. This fact must be taken under consideration when performing genetic testing and counseling."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MLPH melanophilin Canis lupus familiaris 25 NC_006607.3 (48121499..48167535) MLPH 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
Chihuahua Hungarian mudi Hungarian pumi Italian Greyhound Pekingese Shetland Sheepdog Shih-Tzu Tibetan Mastiff Yorkshire Terrier Dilute MLPH d^3 insertion, small (<=20) CanFam3.1 25 g.48,150,749_50insC c.667_668insC p.(His223Profs*41) "(NM_001103219.2: c.667_668insC or chr25: g.48150749_50insC" (van Buren et al. (2020) 2020 32531980
American Staffordshire terrier Beagle Doberman Pinscher German Pinscher Large Munster-lander Miniature Pinscher Rhodesian Ridgeback Dilute MLPH d^1 splicing CanFam3.1 25 g.48121642G>A c.-22G>A 2007 17519392 Variant coordinates obtained from or confirmed by EBI's Variant Effect Predictor (VEP) tool
Chow Chow Sloughi Thai Ridgeback Dilute MLPH d^2 missense CanFam3.1 25 g.48150787G>C c.705G>C p.Gln235His 2018 29349785

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.
2020 Van Buren, S.L., Minor, K.M., Grahn, R.A., Mickelson, J.R., Grahn, J.C., Malvick, J., Colangelo, J.R., Mueller, E., Kuehnlein, P., Kehl, A. :
A Third <i>MLPH</i> Variant Causing Coat Color Dilution in Dogs. Genes (Basel) 11:, 2020. Pubmed reference: 32531980. DOI: 10.3390/genes11060639.
2018 Bauer, A., Kehl, A., Jagannathan, V., Leeb, T. :
A novel MLPH variant in dogs with coat colour dilution. Anim Genet 49:94-97, 2018. Pubmed reference: 29349785. DOI: 10.1111/age.12632.
2009 Perego, R., Proverbio, D., Roccabianca, P., Spada, E. :
Color dilution alopecia in a blue Doberman pinscher crossbreed. Can Vet J 50:511-4, 2009. Pubmed reference: 19436637.
Welle, M., Philipp, U., Rüfenacht, S., Roosje, P., Scharfenstein, M., Schuetz, E., Brenig, B., Linek, M., Mecklenburg, L., Grest, P., Drögemüller, M., Haase, B., Leeb, T., Drögemüller, C. :
MLPH genotype melanin phenotype correlation in dilute dogs. Journal of Heredity 100:S75–S79, 2009.
2007 Drögemüller, C., Philipp, U., Haase, B., Günzel-Apel, A.R., Leeb, T. :
A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. J Hered 98:468-73, 2007. Pubmed reference: 17519392. DOI: 10.1093/jhered/esm021.
2005 Kim, JH., Kang, KI., Sohn, HJ., Woo, GH., Jean, YH., Hwang, EK. :
Color-dilution alopecia in dogs. J Vet Sci 6:259-61, 2005. Pubmed reference: 16131833.
Philipp, U., Hamann, H., Mecklenburg, L., Nishino, S., Mignot, E., Gunzel-Apel, AR., Schmutz, SM., Leeb, T. :
Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs. BMC Genet 6:34, 2005. Pubmed reference: 15960853. DOI: 10.1186/1471-2156-6-34.
Philipp, U., Quignon, P., Scott, A., Andre, C., Breen, M., Leeb, T. :
Chromosomal Assignment of the Canine Melanophilin Gene (MLPH): A Candidate Gene for Coat Color Dilution in Pinschers. J Hered 96:774-6, 2005. Pubmed reference: 15958794. DOI: 10.1093/jhered/esi079.
2002 Laffort-Dassot, C., Beco, L., Carlotti, D.N. :
Follicular dysplasia in five Weimaraners Veterinary Dermatology 13:253-260, 2002. Pubmed reference: 12358609.
1999 Castellano, M.C., Idiart, J.R. :
Colour dilution alopecia in a German Shepherd dog Canine Practice 24:6-7, 1999.
1998 Rothstein, E., Scott, D.W., Miller, W.H., Bagladi, M.S. :
A retrospective study of dysplastic hair follicles and abnormal melanization in dogs with follicular dysplasia syndromes or endocrine skin disease Veterinary Dermatology 9:235-241, 1998.
1997 Madewell, B.R., Ihrke, P.J., Griffey, S.M. :
Multiple skin tumours in a Doberman Pinscher with colour dilution alopecia Veterinary Dermatology 8:59-61, 1997.
1996 Beco, L., Fontaine, J., Gross, T.L., Charlier, G. :
Colour dilution alopecia in seven Dachshunds - a clinical study and the hereditary, microscopical and ultrastructural aspect of the disease Veterinary Dermatology 7:91-97, 1996.
1995 Lowenstein, C. :
Color mutant alopecia in a yorkshire terrier [German] Kleintierpraxis 40:781 ff., 1995.
Roperto, F., Cerundolo, R., Restucci, B., Vincensi, M.R., Decaprariis, D., Devico, G., Maiolino, P. :
Colour dilution alopecia (cda) in ten yorkshire terriers Veterinary Dermatology 6:171-178, 1995.
1993 Finnie, J.W., Tham, V.L. :
Colour Mutant Alopecia in a Kelpie X Border Collie Dog Australian Veterinary Journal 70:388-389, 1993. Pubmed reference: 8257319.

Edit History


  • Created by Frank Nicholas on 28 Aug 2006
  • Changed by Frank Nicholas on 10 Aug 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 17 Oct 2012
  • Changed by Frank Nicholas on 22 Jan 2018
  • Changed by Frank Nicholas on 23 Jan 2018
  • Changed by Frank Nicholas on 15 Jun 2020