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pstinard · 06-22-2013, 06:30 AM

Here is a summary of what I found on dilute (Blue Born) color:

DNA testing labs that test for the "D" locus and can determine which dogs are carriers of the "d" (recessive Blue Born) allele:

VetNostic Laboratories - Veterinary Genetic Testing - Yorkshire Terrier testing

D Locus

Recent research article on the association of the dilute (Blue Born) trait with Color Dilution Alopecia (hair loss and skin problems):

I was able to find an excellent review article from 2007 that discusses known coat color genes in dogs. Here is the citation:

"Genes affecting coat colour and pattern in domestic dogs: a review," by S. M. Schmutz and T. G. Berryere. 2007. Animal Genetics 38:539-549.

At that time, they had determined that Color Dilution Alopecia was due to a mutation associated with the MPLH (melanophilin) gene. Interestingly, not all dogs that had a mutation in that gene had alopecia (baldness) and other skin problems, so it might be a particular kind of mutation in that gene, or a mutation in a nearby gene on the same chromosome that is responsible for the skin and hair problems. In other words, the good news is that not all Blue Yorkies will necessarily become bald. On the other hand, at the time time this article had been written, they didn't have everything figured out. Here are some brief quotes from that article, then I have to get back to work. I'll try to find some more recent articles later.:

The melanophilin gene

"Many dog breeds have individuals that are grey or dilute in coat colour (Fig. 1i,j). However, blue is used to denote other phenotypes in various breeds. In some breeds, these blue individuals are born grey, whereas in other breeds individuals take several months to turn from black to grey. The latter characteristic was referred to as ‘progressive greying’ by Little (1957) and attributed to the G locus. In some dog breeds this is called ‘silver’. A few dog breeds have both types of grey occurring. Some Great Danes and all Weimaraners are born blue or dilute whereas Kerry Blue Terriers (Fig. 1k) and Old English Sheepdogs are born black and lighten as they grow into adulthood. Both of these inherited traits cause modification of both eumelanin and phaeomelanin pigmented areas to a paler shade, although the phaeomelanin change is not as dramatic as the eumelanin dilution. Fawn dogs with a melanistic mask (Schmutz et al. 2003a) are easier to observe because their mask is grey instead of black. Dilute fawn dogs have charcoal instead of black nose leather and pads (Fig. 1j). Dogs with an e/e genotype at MC1R (Newton et al. 2000) or clear red phenotype, such as the two Beagles in our previous study (Philipp et al. 2005) were very difficult to detect as dilute. Dogs that are brindle and dilute, such as some Whippets and Greyhounds, have grey stripes on a pale fawn background. Dogs, such as Weimaraners, that have two copies of the mutations in TYRP1 causing brown (Schmutz et al. 2002) and two dilute alleles are a pale brown. The nose leather and pads of such dogs are a similar pale brown. In some breeds such as Chinese Shar-Pei, the dogs are called lilac and in Doberman Pinschers, they are called Isabella."

"Recently, we reported that Doberman Pinschers, German Pinschers, Large Munsterlanders, and Beagles with a dilute phenotype, co-segregated with specific haplotypes of melanophilin (MLPH) (Philipp et al. 2005). A mutation in exon 2 of MLPH causes a splice junction problem in homozygous mice of the leaden phenotype (Matesic et al. 2001). The last seven amino acids of exon 2 are spliced out in leaden mice because a C-to-T transition introduces a premature stop codon. A human infant was reported to have Griscelli Syndrome Type III due to a R35W mutation near the end of exon 2 (Ménaschéet al. 2003). The hair colour of this child was not reported but this syndrome is considered a form of albinism."

"We have now extended our study of MLPH to include approximately 20 dog breeds. Although a mutation that co-segregates with blue in some breeds has been found (unpubl. data), no single mutation has been found that explains the blue in all these breeds. A couple of common mutations occur only in blue dogs (unpubl. data). Our study to identify all the alleles causing blue is ongoing."
-------------------
Diseases associated with pigmentation

"Some (n = 30) of the 119 grey/blue dogs we studied (unpubl. data) showed evidence of hair loss and much more rarely skin problems, symptoms typical of colour dilution alopecia (CDA) and black hair follicular dysplasia (Schmutz et al. 1998; von Bomhard et al. 2006). This was not true of all adult blue dogs however. The symptoms also appeared to vary by breed with the Large Munsterlanders displaying complete hair loss in all grey areas by 12 weeks whereas most dogs of other breeds were a few years old before this degree of hair loss occurred. Several dogs 5 years of age or older were reported to have no hair loss or skin problems. Several of the dogs were pups or <2 years of age or had large areas of white fur and therefore we could not determine whether these dogs had or would develop CDA. Dogs that were blue or blue fawn, male or female, long or short-haired and with or without white spots were affected. There may be a slight tendency for earlier symptoms in dogs with longer hair. CDA was reported in 26 of the 100 dilute dogs with a T/T genotype and four of the 19 dogs that showed a dilute phenotype but did not have a T/T genotype at the synonymous c.106C>T polymorphism in exon 2 of the MLPH gene (unpubl. data)."

"Not all ‘blue’ or genotypically d/d dogs (Fig. 1i,j), have problems associated with CDA and not all dogs that have symptoms develop them at a similar age of onset or with similar severity. For example although all Weimaraners are dilute and all of the eight dogs of this breed we studied had a T/T genotype, not all had CDA. Laffort-Dassot et al. (2002) likewise described variable symptoms in five Weimaraners. Miller (1990) suggested that there were possibly multiple recessive alleles of the dilution gene. Although this may be true, it does not appear that dogs with and without CDA necessarily have different mutations in MLPH. Since MLPH binds to RAB27A in the region (Strom et al. 2002) where we have identified some mutations in MLPH, we wanted to determine if a mutation in RAB27A might interact and cause some dogs to experience symptoms of CDA whereas others did not. We sequenced the entire coding region of RAB27A (GenBank DQ494380) in a Large Munsterlander that had severe symptoms of black hair follicular dysplasia, an Italian Greyhound with CDA symptoms, and a black-and-white Large Munsterlander and a chocolate Labrador Retriever which were not dilute and had no symptoms. No polymorphisms in the RAB27A sequence were detected."

06-22-2013, 06:30 AM	#8
pstinard YT 3000 Club Member Join Date: Apr 2013 Location: Urbana, IL USA Posts: 3,648	dilute (Blue Born) coat color information Here is a summary of what I found on dilute (Blue Born) color: DNA testing labs that test for the "D" locus and can determine which dogs are carriers of the "d" (recessive Blue Born) allele: VetNostic Laboratories - Veterinary Genetic Testing - Yorkshire Terrier testing D Locus Recent research article on the association of the dilute (Blue Born) trait with Color Dilution Alopecia (hair loss and skin problems): I was able to find an excellent review article from 2007 that discusses known coat color genes in dogs. Here is the citation: "Genes affecting coat colour and pattern in domestic dogs: a review," by S. M. Schmutz and T. G. Berryere. 2007. Animal Genetics 38:539-549. At that time, they had determined that Color Dilution Alopecia was due to a mutation associated with the MPLH (melanophilin) gene. Interestingly, not all dogs that had a mutation in that gene had alopecia (baldness) and other skin problems, so it might be a particular kind of mutation in that gene, or a mutation in a nearby gene on the same chromosome that is responsible for the skin and hair problems. In other words, the good news is that not all Blue Yorkies will necessarily become bald. On the other hand, at the time time this article had been written, they didn't have everything figured out. Here are some brief quotes from that article, then I have to get back to work. I'll try to find some more recent articles later.: The melanophilin gene "Many dog breeds have individuals that are grey or dilute in coat colour (Fig. 1i,j). However, blue is used to denote other phenotypes in various breeds. In some breeds, these blue individuals are born grey, whereas in other breeds individuals take several months to turn from black to grey. The latter characteristic was referred to as ‘progressive greying’ by Little (1957) and attributed to the G locus. In some dog breeds this is called ‘silver’. A few dog breeds have both types of grey occurring. Some Great Danes and all Weimaraners are born blue or dilute whereas Kerry Blue Terriers (Fig. 1k) and Old English Sheepdogs are born black and lighten as they grow into adulthood. Both of these inherited traits cause modification of both eumelanin and phaeomelanin pigmented areas to a paler shade, although the phaeomelanin change is not as dramatic as the eumelanin dilution. Fawn dogs with a melanistic mask (Schmutz et al. 2003a) are easier to observe because their mask is grey instead of black. Dilute fawn dogs have charcoal instead of black nose leather and pads (Fig. 1j). Dogs with an e/e genotype at MC1R (Newton et al. 2000) or clear red phenotype, such as the two Beagles in our previous study (Philipp et al. 2005) were very difficult to detect as dilute. Dogs that are brindle and dilute, such as some Whippets and Greyhounds, have grey stripes on a pale fawn background. Dogs, such as Weimaraners, that have two copies of the mutations in TYRP1 causing brown (Schmutz et al. 2002) and two dilute alleles are a pale brown. The nose leather and pads of such dogs are a similar pale brown. In some breeds such as Chinese Shar-Pei, the dogs are called lilac and in Doberman Pinschers, they are called Isabella." "Recently, we reported that Doberman Pinschers, German Pinschers, Large Munsterlanders, and Beagles with a dilute phenotype, co-segregated with specific haplotypes of melanophilin (MLPH) (Philipp et al. 2005). A mutation in exon 2 of MLPH causes a splice junction problem in homozygous mice of the leaden phenotype (Matesic et al. 2001). The last seven amino acids of exon 2 are spliced out in leaden mice because a C-to-T transition introduces a premature stop codon. A human infant was reported to have Griscelli Syndrome Type III due to a R35W mutation near the end of exon 2 (Ménaschéet al. 2003). The hair colour of this child was not reported but this syndrome is considered a form of albinism." "We have now extended our study of MLPH to include approximately 20 dog breeds. Although a mutation that co-segregates with blue in some breeds has been found (unpubl. data), no single mutation has been found that explains the blue in all these breeds. A couple of common mutations occur only in blue dogs (unpubl. data). Our study to identify all the alleles causing blue is ongoing." ------------------- Diseases associated with pigmentation "Some (n = 30) of the 119 grey/blue dogs we studied (unpubl. data) showed evidence of hair loss and much more rarely skin problems, symptoms typical of colour dilution alopecia (CDA) and black hair follicular dysplasia (Schmutz et al. 1998; von Bomhard et al. 2006). This was not true of all adult blue dogs however. The symptoms also appeared to vary by breed with the Large Munsterlanders displaying complete hair loss in all grey areas by 12 weeks whereas most dogs of other breeds were a few years old before this degree of hair loss occurred. Several dogs 5 years of age or older were reported to have no hair loss or skin problems. Several of the dogs were pups or <2 years of age or had large areas of white fur and therefore we could not determine whether these dogs had or would develop CDA. Dogs that were blue or blue fawn, male or female, long or short-haired and with or without white spots were affected. There may be a slight tendency for earlier symptoms in dogs with longer hair. CDA was reported in 26 of the 100 dilute dogs with a T/T genotype and four of the 19 dogs that showed a dilute phenotype but did not have a T/T genotype at the synonymous c.106C>T polymorphism in exon 2 of the MLPH gene (unpubl. data)." "Not all ‘blue’ or genotypically d/d dogs (Fig. 1i,j), have problems associated with CDA and not all dogs that have symptoms develop them at a similar age of onset or with similar severity. For example although all Weimaraners are dilute and all of the eight dogs of this breed we studied had a T/T genotype, not all had CDA. Laffort-Dassot et al. (2002) likewise described variable symptoms in five Weimaraners. Miller (1990) suggested that there were possibly multiple recessive alleles of the dilution gene. Although this may be true, it does not appear that dogs with and without CDA necessarily have different mutations in MLPH. Since MLPH binds to RAB27A in the region (Strom et al. 2002) where we have identified some mutations in MLPH, we wanted to determine if a mutation in RAB27A might interact and cause some dogs to experience symptoms of CDA whereas others did not. We sequenced the entire coding region of RAB27A (GenBank DQ494380) in a Large Munsterlander that had severe symptoms of black hair follicular dysplasia, an Italian Greyhound with CDA symptoms, and a black-and-white Large Munsterlander and a chocolate Labrador Retriever which were not dilute and had no symptoms. No polymorphisms in the RAB27A sequence were detected."