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Gray Collie Syndrome (GCS) – Cyclic Neutropenia
| Acronym: | GCS, CN |
| Gene: | AP3B1 |
| Mutation: | c.2407_2408insA |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Gray Collie Syndrome (GCS) is a form of canine cyclic neutropenia affecting the Collie breed. Cyclic neutropenia is a form of neutropenia, a condition of abnormally low concentrations of neutrophils in the blood. It has been recognized in humans and dogs. Neutrophils are a form of white blood cells or granulocytes that are the most numerous white blood cells in mammals. They are produced in the bone marrow and formed from stem cells, undifferentiated biological cells. Neutrophils are highly mobile and they can enter parts of tissue where other cells are not able to. They are also a type of phagocytes and have an important role in defense against various types of infection. They are the first responders of inflammatory cells that migrate towards the location of inflammation caused by bacterial infection, environmental exposure, or some cancers. Neutropenia is a term for low neutrophil counts. It can be hereditary or it can be developed during life, as a form of aplastic anemia or some kinds of leukemia, but it can also be a side effect of medication such as chemotherapy. Gray Collie Syndrome is a form of neutropenia that is hereditary and it is caused by a defect in the bone marrow stem cells. GCS is characterized by a sudden fall in neutrophil levels every 10 to 12 days, after which it rebounds. With the important role of neutrophils in the immune system, this sudden drop has a severe negative impact on a dog’s overall health.
Affected cubs appear to be weaker and can be recognized by their greyer or light-colored fur in any color compared to the fur of other, healthy cubs. Due to immunity problems caused by low neutrophil count, affected dogs suffer from gastrointestinal problems, fever, bleeding, blood poisoning, and bacterial infections of the eye, respiratory system, or skin. The life expectancy of Collie with cyclic neutropenia is usually less than three years. Canine cyclic neutropenia, or Gray Collie Syndrome, is caused by a mutation in the canine AP3B1 gene. Gray Collie Syndrome is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of cyclic neutropenia. At conception, when mating two carrier dogs, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Weiden PL, Robinett B, Graham TC, Adamson J, Storb R. (1974): Canine Cyclic Neutropenia: A STEM CELL DEFECT. Journal of Clinical Investigation. 1974;53(3):950-953.
Yanay, O. et al. (2003.): Treatment of canine cyclic neutropenia by lentivirus-mediated G-CSF delivery. Blood. 2003 Sep 15;102(6):2046-52. Epub 2003 May 15.
Benson, F. K. et al. (2004.): Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes as a consequence of transcriptional infidelity through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia. Nucleic Acids Research, 2004, Vol. 32, No. 21 6327–6333