locus The gene at the B locus is known as tyrosinase related protein 1 (TYRP1). This gene affects the color of the eumelanin pigment produced, making it either black or brown. TYRP1 is an enzyme involved in the synthesis of eumelanin. Each of the known mutations appears to eliminate or significantly reduce TYRP1 enzymatic activity. This modifies the shape of the final eumelanin molecule, changing the pigment from a black to a brown color. Color is affected in coat and skin (including the nose and paw pads). There are four known alleles that occur at the B locus: B = Black eumelanin. An animal that has at least one copy of the B allele will have a black nose, paw pads and eye rims and (usually) dark brown eyes. b = Brown eumelanin - such as chocolate or liver (includes several alleles - bs, bd and bc). An animal with any matched or unmatched pair of the b alleles will have brown, rather than black, hair, a liver nose, paw pads and eye rims, and hazel eyes. Phaeomelanin color is unaffected. Only one of the alleles is present in the English Setter (bs), Doberman Pinscher (bd) and Italian Greyhound (bc), but in most breeds with any brown allele two or all three are present. It is unknown whether the different brown alleles cause specific shades or hues of brown. B is dominant to b. D (dilute) locus The melanophilin gene (MLPH) at the D locus causes a dilution mainly of eumelanin, while phaeomelanin is less affected. This dilution gene determines the intensity of pigmentation. MLPH codes for a protein involved in the distribution of melanin - it is part of the melanosome transport complex. Defective MLPH prevents normal pigment distribution, resulting in a paler colored coat. There are two common alleles: D (normal, wild-type MLPH), and d (defective MLPH) that occur in many breeds. But recently the research group of Tosso Leeb has identified additional alleles in other breeds. D = Not diluted. Black or brown eumelanin (as determined by Brown locus), reddish or orangish tan phaeomelanin. d = Diluted. Diluted fur color: black eumelanin (B/-) diluted to bluish grey (ranging from light blue-grey to dark steel); brown eumelanin (b/b) diluted to taupe or "Isabella". Phaeomelanin is diluted from red to yellowish tan; this phaeomelanin dilution is not as dramatic as the eumelanin color shift. Slight to moderate dilution of