| Other Names: | black coat color, extension locus, red coat color, yellow coat color, ancient red, melanistic mask, cream, grizzle, sable |
|---|---|
| Affected Genes: | MC1R |
| Mutation(s): | e1 = chr5:63694334 (canFam3): C>T (Yellow/Red); e2 = chr5:63695679 (canFam3): C/G (Cream-Australian Cattle Dog Type); e3 = chr5:63694433-63694434 (canFam3): 2 bp deletion (del CT) (White-Alaskan and Siberian Husky Type); eA = chr5:64186743 (canFam4): G/A (Ancient Red-Spitz and Scent Hound Type); Eg = chr5:63695017 (canFam3): G>T (Grizzle-Afghan Hound Type); Eh = chr5:63695000 (canFam3): G/A (Sable-Cocker Spaniel Type); Em = chr5:63694464 (canFam3): G>A (Melanistic mask) |
| Breed(s): | All Breeds |
Testing Summary
The E Locus coat color test reliably determines if a dog has one of the following genotypes at the E locus:
| E/E | This dog carries two copies of E which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 100% of its offspring. Interpretation: Black |
| E/e1 | This dog carries one copy of E and one copy of e1 which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 50% of its offspring and e1 to 50% of its offspring, which can produce a yellow/red coat (including shades of white, cream, yellow, apricot or red) if inherited with another copy of e1, e2, or e3. Interpretation: Black - Carrier (Yellow/Red) |
| E/e2 | This dog carries one copy of E and one copy of e2 which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 50% of its offspring and e2 to 50% of its offspring, which can produce a cream coat in Australian Cattle Dogs if inherited with another copy of e2 or e3. Interpretation:Black - Carrier (Cream- Australian Cattle Dog type) |
| E/e3 | This dog carries one copy of E and one copy of e3 which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 50% of its offspring and e3 to 50% of its offspring, which can produce a white coat in the Alaskan and Siberian Husky if inherited with another copy of e3. Interpretation: Black - Carrier (White-Alaskan and Siberian Husky type) |
| E/eA | This dog carries one copy of E and one copy of eA which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 50% of its offspring and eA to 50% of its offspring, which can produce an ancient red coat color if inherited with another copy of eA, e1, e2, or e3. Interpretation: Black - Carrier (Ancient Red-Spitz and Scent Hound type) |
| E/Eh | This dog carries one copy of E and one copy of Eh which allows for the production of black pigment. However, this dog's coat color is also dependent on the K, A, and B genes. This dog will pass E on to 50% of its offspring and Eh to 50% of its offspring, which can produce a sable coat color if inherited with another copy of Eh, eA, e1, e2, or e3. Interpretation: Black - Carrier (Sable-Cocker Spaniel Type) |
| Em/E | This dog carries one copy of Em and one copy of E which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and E to 50% of its offspring, which can produce black coat color if inherited with another copy of E, eA, e1, e2, or e3. Interpretation: Melanistic Mask - Carrier (Black) |
| Em/Em | This dog carries two copies of Em which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog will pass on Em to 100% of its offspring and will produce only puppies with a melanistic mask. Interpretation: Melanistic Mask |
| Em/Eg | This dog carries one copy of Em and one copy of Eg which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and Eg to 50% of its offspring, which can produce a grizzle coat color pattern if inherited with another copy of Eg, E, Eh, eA, e1, e2, or e3. Interpretation: Melanistic Mask- Carrier (Grizzle-Afghan Hound type) |
| Em/Eh | This dog carries one copy of Em and one copy of Eh which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and Eh to 50% of its offspring, which can produce a sable coat color if inherited with another copy of Eh, eA, e1, e2, or e3. Interpretation: Melanistic Mask- Carrier (Sable-Cocker Spaniel Type) |
| Em/eA | This dog carries one copy of Em and one copy of eA which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and eA to 50% of its offspring, which can produce an ancient red coat color if inherited with another copy of eA, e1, e2, or e3. Interpretation: Melanistic Mask- Carrier (Ancient Red-Spitz and Scent Hound type) |
| Em/e1 | This dog carries one copy of Em and one copy of e1 which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and e1 to 50% of its offspring, which can produce a yellow/red coat (including shades of white, cream, yellow, apricot or red) if inherited with another copy of e1, e2, or e3. Interpretation: Melanistic Mask-Carrier (Yellow/Red) |
| Em/e2 | This dog carries one copy of Em and one copy of e2 which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and e2 to 50% of its offspring, which can produce a cream coat in Australian Cattle Dogs if inherited with another copy of e2or e3. Interpretation: Melanistic Mask- Carrier (Cream-Australian Cattle Dog type) |
| Em/e3 | This dog carries one copy of Em and one copy of e3 which allows for the production of black pigment with a melanistic mask on the muzzle of the dog. However, a melanistic mask may be unrecognizable on a dog with a dark coat color. This dog's coat color is also dependent on the K, A, and B genes. This dog will pass Em on to 50% of its offspring and e3 to 50% of its offspring, which can produce a white coat in the Alaskan and Siberian Husky if inherited with another copy of e3. Interpretation: Melanistic Mask- Carrier (White-Alaskan and Siberian Husky type) |
| Eg/E | This dog carries one copy of Eg and one copy of E which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and E to 50% of its offspring, which can produce a black coat if inherited with another copy of E, Eh, eA, e1, e2, or e3. Interpretation: Grizzle (Afghan Hound type)- Carrier (Black) |
| Eg/Eg | This dog carries two copies of Eg which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 100% of its offspring. Interpretation: Grizzle (Afghan Hound type) |
| Eg/Eh | This dog carries one copy of Eg and one copy of Eh which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and Eh to 50% of its offspring, which can produce a sable coat color if inherited with another copy of Eh, eA, e1, e2, or e3. Interpretation: Grizzle (Afghan Hound Type)- Carrier (Sable-Cocker Spaniel Type) |
| Eg/eA | This dog carries one copy of Eg and one copy of Eh which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and eA to 50% of its offspring, which can produce an ancient red coat color if inherited with another copy of eA, e1, e2, or e3. Interpretation: Grizzle (Afghan Hound Type)- Carrier Ancient Red (Spitz and Scent Hound type) |
| Eg/e1 | This dog carries one copy of Eg and one copy of Eh which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and e1 to 50% of its offspring, which can produce a yellow/red coat (including shades of white, cream, yellow, apricot or red) if inherited with another copy of e1, e2, or e3. Interpretation:Grizzle (Afghan Hound type)- Carrier (Yellow/Red) |
| Eg/e2 | This dog carries one copy of Eg and one copy of Eh which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and e2 to 50% of its offspring, which can produce a cream coat in Australian Cattle Dogs if inherited with another copy of e2 or e3. Interpretation: Grizzle (Afghan Hound type)- Carrier (Cream- Australian Cattle Dog type) |
| Eg/e3 | This dog carries one copy of Eg and one copy of Eh which allows for the production of black pigment with a grizzle coat color pattern. However, this dog’s coat color is also dependent on the K, A, and B genes. This dog will pass on Eg to 50% of its offspring and e3 to 50% of its offspring, which can produce a white coat in the Alaskan and Siberian Husky if inherited with another copy of e3. Interpretation: Grizzle (Afghan Hound type)- Carrier (White-Alaskan and Siberian Husky type) |
| Eh/Eh | This dog carries two copies of Eh which which allows for the production of black pigment with the sable coat color. However, this dog’s coat color is also dependent on the K, A, and B genes. A sable pattern can be seen in this dog if it is KB/KB or KB/ky at the K locus. This dog will pass one copy of Eh to 100% of its offspring. Interpretation: Sable (Cocker Spaniel Type) |
| Eh/eA | This dog carries one copy of Eh and one copy of eA which which allows for the production of black pigment with the sable coat color. However, this dog’s coat color is also dependent on the K, A, and B genes. A sable pattern can be seen in this dog if it is KB/KB or KB/ky at the K locus. This dog will pass one copy of Eh to 50% of its offspring and eA to 50% of its offspring, which can produce an ancient red coat color if inherited with another copy of eA, e1, e2, or e3. Interpretation: Sable (Cocker Spaniel Type)- Carrier Ancient Red (Spitz and Scent Hound type) |
| Eh/e1 | This dog carries one copy of Eh and one copy of e1 which which allows for the production of black pigment with the sable coat color. However, this dog’s coat color is also dependent on the K, A, and B genes. A sable pattern can be seen in this dog if it is KB/KB or KB/ky at the K locus. This dog will pass one copy of Eh to 50% of its offspring and e1 to 50% of its offspring, which can produce a yellow/red coat (including shades of white, cream, yellow, apricot or red) if inherited with another copy of e1, e2, or e3. Interpretation: Sable (Cocker Spaniel Type)- Carrier (Yellow/Red) |
| Eh/e2 | This dog carries one copy of Eh and one copy of e2 which which allows for the production of black pigment with the sable coat color. However, this dog’s coat color is also dependent on the K, A, and B genes. A sable pattern can be seen in this dog if it is KB/KB or KB/ky at the K locus. This dog will pass one copy of Eh to 50% of its offspring and e2 to 50% of its offspring, which can produce a cream coat in Australian Cattle Dogs if inherited with another copy of e2 or e3. Interpretation: Sable (Cocker Spaniel Type)- Carrier (Cream- Australian Cattle Dog type) |
| Eh/e3 | This dog carries one copy of Eh and one copy of e3 which which allows for the production of black pigment with the sable coat color. However, this dog’s coat color is also dependent on the K, A, and B genes. A sable pattern can be seen in this dog if it is KB/KB or KB/ky at the K locus. This dog will pass one copy of Eh to 50% of its offspring and e3 to 50% of its offspring, which can produce a white coat in the Alaskan and Siberian Husky if inherited with another copy of e3. Interpretation: Sable (Cocker Spaniel Type)- Carrier (White-Alaskan and Siberian Husky type) |
| eA/eA | This dog carries two copies of eA which can result in an ancient red coat color. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B loci among others. This dog will pass one copy of eA to 100% of its offspring. Interpretation: Ancient Red (Spitz and Scent Hound type) |
| eA/e1 | This dog carries one copy of eA and one copy of e1 which can result in an ancient red coat color. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B loci among others. This dog will pass one copy of eA to 50% of its offspring and e1 to 50% of its offspring, which can produce a yellow/red coat (including shades of white, cream, yellow, apricot or red) if inherited with another copy of e1, e2, or e3. Interpretation:Ancient Red (Spitz and Scent Hound type)- Carrier (Yellow/Red) |
| eA/e2 | This dog carries one copy of eA and one copy of e2 which can result in an ancient red coat color. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B loci among others. This dog will pass one copy of eA to 50% of its offspring and e2 to 50% of its offspring, which can produce a cream coat in Australian Cattle Dogs if inherited with another copy of e2 or e3. Interpretation: Ancient Red (Spitz and Scent Hound type)- Carrier (cream- Australian Cattle Dog Type) |
| eA/e3 | This dog carries one copy of eA and one copy of e3 which can result in an ancient red coat color. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B loci among others. This dog will pass one copy of eA to 50% of its offspring and e3 to 50% of its offspring, which can produce a white coat in the Alaskan and Siberian Husky if inherited with another copy of e3. Interpretation: Ancient Red (Spitz and Scent Hound type)- Carrier (White-Alaskan and Siberian Husky type) |
| e1/e1 | This dog carries two copies of e1 which inhibits production of black pigment. The coat color of this dog will be yellow/red (including shades of white, cream, yellow, apricot or red). This dog will pass e1 on to 100% of its offspring. Interpretation: Yellow/red |
| e1/e2 | This dog carries one copy of e1 and one copy of e2 which inhibits production of black pigment. The coat color of this dog will be yellow/red (including shades of white, cream, yellow, apricot or red). This dog will pass e1 on to 50% of its offspring and e2 to 50% of its offspring. Interpretation: Yellow/Red - Carrier (Cream-Australian Cattle Dog Type) |
| e1/e3 | This dog carries one copy of e1 and one copy of e2 which inhibits production of black pigment. The coat color of this dog will be yellow/red (including shades of white, cream, yellow, apricot or red). This dog will pass e1 on to 50% of its offspring and e3 to 50% of its offspring. Interpretation: Yellow/Red - Carrier (White-Alaskan and Siberian Husky Type) |
| e2/e2 | This dog carries two copies of e2 which results in a cream coat color in Australian Cattle Dogs. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B genes among others. This dog will pass one copy of e2 to 100% of its offspring. Interpretation: Cream (Australian Cattle Dog Type) |
| e2/e3 | This dog carries one copy of e2 and one copy of e3 which results in a cream coat color in Australian Cattle Dogs. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B genes among others. This dog will pass one copy of e2 to50% of its offspring and e3 to 50% of its offspring. Interpretation: Cream (Australian Cattle Dog Type) - Carrier (White-Alaskan and Siberian Husky Type) |
| e3/e3 | This dog carries two copies of e3 which results in a white coat color in the Alaskan and Siberian Husky. However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B genes among others. This dog will pass one copy of e3 to 100% of its offspring. Interpretation: White (Alaskan and Siberian Husky Type) |
Detailed Summary
The two major pigments that impact canine coat color are eumelanin (black pigment) and phaeomelanin (yellow/red pigment). These pigments are produced within specialized cells called melanocytes located in the canine epidermis and hair follicles. Within the melanocyte, the pigments are made in tiny organelles called melanosomes. The melanosomes are continually being transferred from the melanocytes to the surrounding keratinocyte cells that make up the hair and skin, thereby giving the skin and hair specific color based on the type of pigment they contain. The MC1R gene, also known as the extension (E) Locus, controls the production of eumelanin (black pigment) in the melanocytes. However, DNA variants in the MC1R gene can prevent production of eumelanin in the melanocytes leaving only the production of pheomelanin. Variants of MC1R follow the following order of dominance: Em (melanistic mask) > Eg (grizzle/domino) > E (wild-type) > Eh (sable) > eA (ancient red) > e1-3 (recessive apricot/yellow/red, cream, white).
e1, e2, and e3: The dominant form of the MC1R gene (E) allows for normal production of eumelanin in the melanocytes. However, a DNA variant in the MC1R gene (e) shuts down production of eumelanin (black pigment) in the melanocytes leaving only the production of phaeomelanin (yellow/red pigment) in the melanocytes. Because e1, e2, and e3 are recessive to the E variants (E, Em, Eg, Eh), two copies of an MC1R e variant must be present to express these coat colors. e1 is the common variant responsible for various shades of red in many breeds, whereas e2 and e3 have been found primarily in the Australian Cattle Dog and Alaskan and Siberian Husky respectively.
eA: The ancient red Allele (eA) can impact the coat color of dogs in different ways depending on the breed and the K (dominant black) and A (agouti) locus genotypes of the dog. First, when a dog is ky/ky at the K locus (which allows for agouti expression), the ancient red allele can alter the agouti patterning, typically by increasing the amount of pheomelanin (yellow/red pigment) and reducing the amount of eumelanin (black pigment) that is expressed in the coat. Dogs that are ky/ky at the K locus and have an ancient red genotype (eA/eA or eA/e) show an increase in agouti expression that varies depending on the breed and the A locus genotype. Dogs that have an ancient red genotype (eA/eA or eA/e) and are also fawn with minimal to no eumelanin expression at the A locus (Ay), have coats that appear similar to recessive apricot/yellow/red, cream, or white (e1-3/e1-3). For example, in breeds like the Berger d’Auvergne where Ay typically produces a fawn colored coat with minimal eumelanin, the coat becomes almost cream in dogs with an ancient red genotype. Alternatively, dogs like the Finnish Lapphund that have an ancient red genotype and are also heavily shaded sable/fawn with some eumelanin expression at the A locus (Ay), have coats that appear to have a "domino" pattern with greater pheomelanin expression around the muzzle, eyes, and body. Likewise, dogs that have an ancient red genotype and are wolf sable at the A locus (aw) can also have a "domino" pattern that is often found in Alaskan Malamutes and Siberian Huskies. Dogs that have an ancient red genotype and are tan pointed at the A locus (at) can show an increase in the size of the tan points or have more "tan" (pheomelanin) interspersed with the dark (eumelanin) hairs. This is referred to as "grizzle" in Chihuahuas or "pied" in Beagles. Lastly, dogs that have an ancient red genotype and are recessive black at the A locus (a/a), can express some pheomelanin similar to domino, wolf sable, or tan points depending on the breed.
Second, when a dog is dominant black (KB/KB or KB/ky) at the K locus (which typically blocks agouti expression), the ancient red allele can bypass the K locus block and allow agouti (A locus) expression (i.e., sable/fawn, wolf sable, or tan points). Thus, dogs with one or two copies of the ancient red allele (eA/eA or eA/e) will show some amount of the agouti patterning (depending on the A locus genotype) even if they are KB/KB or KB/ky (dominant black) at the K locus. Ancient red may, therefore, account for what is sometimes referred to as a "leaky K allele" when a dog displays some atypical agouti patterning even in the presence of one or two copies of KB (dominant black).
Eg: The Eg variant of the MC1R gene produces a characteristic coat color pattern consisting of a black pigmented widow's peak on the head of the dog with other black tipped hairs on the back of the dog similar to some sable or saddle tan colorations. The grizzle coat color pattern has only been observed in the saluki, Afghan hound (referred to as "domino" in this breed) and the borzoi (referred to as "sable" in this breed). Although the Eg variant of the MC1R gene is dominant to E and e, it is recessive to Em (melanistic mask). Therefore, the grizzle coat color pattern is only expressed if the dog does not have an Em variant (i.e., does not have a melanistic mask) and is also ky/ky for the K Locus and at/at for the A locus.
Eh: The Eh variant of the MC1R gene has been associated with the ‘sable’ appearance in Cocker Spaniels. This specific sable coat color is not caused by the A locus as seen in most breeds including the Cocker Spaniel, but is a variant of the E locus. This sable coat color/pattern shows a darker brown or black pigment on the head and neck of the dog which lightens to a cream/tan pigment down the body of the dog and muzzle. This Mutation is recessive to the E Allele (which allows dark pigment) and dominant to the e allele (red/apricot/cream) that is tested through the E locus test (E>Eh>e).
Dogs with Eh/Eh or Eh/e genotypes typically have a pattern of dark pigment on their head and lighter pigment on their body. However, there are other genes that influence the final coat color and pattern of the dog. A dog must have at least one copy of KB at the K locus (KB/KB or KB/ky) to express this sable pattern and dogs that inherit two copies of ky (ky/ky) will instead display lighter red hair with darker tips. Dogs that carry at least one copy of Eh can produce sable dogs if bred to another dog that carries at least one copy of sable (Eh/Eh, E/Eh or Eh/e) or carries at least one copy of red/cream (E/e or e/e).
Em: The Em variant of the MC1R gene results in the localized distribution of eumelanin (black pigment) on the muzzle of the dog which resembles a dark "mask" on dogs with lighter colored coats. Although the Em variant produces a black melanistic mask, the final color of a dog's mask is dependent on other DNA variants such as the B and D loci that modify the production or appearance of the eumelanin (black pigment) in the dog. For example, dogs that are b/b at the B locus will have brown masks due to the disruption of eumelanin synthesis that results in the conversion of black pigmented areas to brown.
Testing Tips
The E Locus coat color test provides a comprehensive evaluation of the eight variants at the MC1R gene (e1, e2, e3, eA, E, Eg, Eh, and Em) to determine a dog’s overall E locus genotype. Variants of MC1R follow the following order of dominance: Em (melanistic mask) > Eg (grizzle/domino) > E (wild-type) > Eh (sable) > eA (ancient red) > e1-3 (recessive apricot/yellow/red, cream, white). However, the dog’s coat color is also dependent on the dog’s genotypes at the K, A, and B genes among others. Normal results do not exclude inherited mutations not tested in these or other genes that may also contribute to coat colors and traits in dogs.
Disclaimer:
There may be other causes of these color patterns in dogs and a normal result does not exclude a different Mutation in this gene or any other gene that may result in a similar genetic trait.
References
- Anderson H, Honkanen L, Ruotanen P, Mathlin J, Donner J. Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog. Canine Med Genet. 2020 Nov 5;7(1):16. [PubMed: 33292722]
- Dreger DL, Schmutz SM. A new mutation in MC1R explains a coat color phenotype in 2 "old" breeds: Saluki and Afghan hound. J Here. 2010 Sep-Oct; 101(5):644-49. [PubMed: 20525767]
- Dürig N, Letko A, Lepori V, Hadji Rasouliha S, Loechel R, Kehl A, Hytönen MK, Lohi H, Mauri N, Dietrich J, Wiedmer M, Drögemüller M, Jagannathan V, Schmutz SM, Leeb T. Two MC1R loss-of-function alleles in cream-coloured Australian Cattle Dogs and white Huskies. Anim Genet. 2018 Aug;49(4):284-290. [PubMed: 29932470]
- Everts RE, Rothuizen J, van Oost BA. Identification of a premature stop codon in the melanocyte-stimulating hormone receptor gene (MC1R) in Labrador and Golden retrievers with yellow coat color. Animal Genetics. 2000 Jun; 31(3):194-99. [PubMed: 10895310]
- Schmutz SM, Berryere TG, Ellinwood NM, Kerns JA, Barsh GS. MC1R studies in dogs with melanistic mask or brindle patterns. J Hered. 2003 Jan-Feb; 94(1):69-73. [PubMed: 12692165]
