Phenotype: Base coat colors are lightened (diluted) to paler shades. For example, black becomes a gray-blue color (often called "blue" by breeders) and chocolate brown becomes a pale silvery red (in some breeds, this can be called "lilac"; in the French Bulldog, this is typically referred to as "isabella" - other breeds may have different names for this dilution).
Dogs with D/D genotype are not expected to display dilute coat colors; they have no known dilution variants. They cannot produce dilute offspring or transmit any of the known dilution variants to their offspring.
Dogs with D/d1, D/d2, or D/d3 genotype are not expected to display dilute coat colors, but they are carriers of dilution variants. They will transmit the dilution variant they carry to 50% of their offspring. Matings between two carriers of dilute variants are expected to produce 25% puppies with dilute coat colors.
Dogs with d1/d1, d2/d2, d3/d3, d1/d2, d1/d3, or d2/d3 genotype are expected to display dilute coat colors. They will transmit a dilution variant to all of their offspring.
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
A recessive mutation d1, previously named d, in the melanophilin (MLPH) gene (g.48121642G>A, c.-22G>A) was identified as the cause of color dilution phenotypes in several dog breeds (Drögemüller et al. 2007). However, this mutation alone does not account for all dilute color phenotypes. In 2018, Bauer et al. identified a second dilution in MLPH,variant d2 (c.705G>C, p.Gln235His) in the Sloughi, Chow Chow, and Thai Ridgeback dogs. Analysis at the Veterinary Genetics Laboratory (VGL) determined that the d2 variant is present at a frequency of less than 1% in phenotypically dilute French Bulldogs, thus suggesting that additional variants also cause this phenotype. Subsequent research at the VGL identified a third, very rare dilution variant d3 (c.667_668insC, p.His223Profs*41). The d3 variant has been detected in the Italian Greyhound, Chihuahua, Mudi, Pumi, Shih Tzu, Pekingese, Tibetan Mastiff, Yorkshire Terrier, Shetland Sheepdog, indigenous dogs, and wolf-dog hybrids (Van Buren et al. 2020).
Two copies of any of the three dilution variants, or any combination of two of these variants, are necessary to lighten the color. The d1 mutation is known to cause a reduction in the amount of full-length protein product, thus producing less pigment. The effect of the d2 mutation on the resultant protein is unknown, although in the homozygous state it dilutes color. The phenotype produced by two copies of the d3 variant is unknown, but this mutation is predicted to shorten the MLPH protein and likely disrupt function. Dogs that are compound heterozygotes d1/d2, d2/d3, or d1/d3 have a dilute phenotype. This diagnostic DNA test can detect all three known variants of the MLPH gene.
Note: The known variants d1, d2, and d3 do not account for all color dilution in some breeds such as Doberman Pinscher, French Bulldog, Italian Greyhound, and English Bulldog. This means that there are still unknown mutations that dilute color which need to be investigated. In these breeds, and likely others, some dogs may carry one known and one unknown dilution mutation and present a dilute phenotype.
Drögemüller, C., Philipp, U., Haase, B., Günzel-Apel, A-R., & Leeb, T. (2007). A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs. Journal of Heredity,98(5), 468-473. doi: 10.1093/jhered/esm021
Bauer, A., Kehl, A., Jagannathan, V., & Leeb, T. (2018). A novel MLPH variant in dogs with coat colour dilution. Animal Genetics,49(1), 94-97. doi: 10.1111/age.12632
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. (2020). A Third MLPH Variant Causing Coat Color Dilution in Dogs. Genes, 11(6), 639. doi: 10.3390/genes11060639