Article thumbnail
Location of Repository

Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs

By Ute Philipp, Henning Hamann, Lars Mecklenburg, Seiji Nishino, Emmanuel Mignot, Anne-Rose Günzel-Apel, Sheila M Schmutz and Tosso Leeb


BACKGROUND: Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH). RESULTS: We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype. CONCLUSION: This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD

Topics: Research Article
Publisher: BioMed Central
Year: 2005
DOI identifier: 10.1186/1471-2156-6-34
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2002). AD: TYRP1 and MC1r genotypes and their effects on coat color in dogs. Mamm Genome
  2. (1998). Black hair follicular dysplasia, an autosomal recessive condition in dogs. Can Vet J
  3. (1990). Canine hereditary black hair follicular dysplasia and color mutant alopecia: Clinical and histopathological aspects. Adv Vet Dermatol
  4. (2002). Carlotti DN: Follicular dysplasia in five Weimaraners. Vet Dermatol
  5. (1998). Coat color in dogs. 2: Clinical significance. Tierärztl Prax Ausg K Kleintiere Heimtiere
  6. (1997). de Saint Basile G: Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-VA gene. Nat Genet
  7. (2003). de Saint Basile G: Griscelli syndrome restricted to hypopigmentation results from melanophilin defect (GS3) or a Myo5A F-exon deletion (GS1).
  8. (2000). de Saint Basile G: Mutations in Rab 27A cause Griscelli Syndrome associated with hemaphagocytic syndrome.
  9. (2001). Galibert F: Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker integrated radiation-hybrid /linkage map of the domestic dog genome to all chromosmes. Genome Res
  10. (2003). Gejman PV: Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet
  11. (2002). JS: Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms.
  12. (2005). Leeb T: Chromosomal assignment of the canine melanophilin gene (MLPH): A candidate gene for coat color dilution in Pinschers. J Hered
  13. (2000). NA: A mutation in Rab27A causes the vesicle transport defects observed in ashen mice. Proc Natl Acad Sci,
  14. (2004). NA: dsu functions in a MYO5A-independent pathway to suppress the coat color of dilute mice. Proc Natl Acad Sci USA
  15. (2001). NA: Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice. Proc Natl Acad Sci USA
  16. (1991). Novel myosins heavy chain encoded by murine dilute coat colour locus. Nature
  17. (1999). PJ: Construction and characterization of an eightfold redundant dog genome bacterial artificial chromosome library. Genomics
  18. Resource Center/Primary Database [ h t t p : /
  19. (2003). The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Mol Cell Biol

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.