Phenotype: Horses with foal immunodeficiency syndrome (FIS) appear normal at birth but develop anemia and signs of infection typically within the first 3-6 weeks of age. Symptoms of the syndrome include coughing, diarrhea, and failure to suckle. Foals may initially respond to treatment, but infections persist due to the immune system’s inability to generate a response, and FIS-affected foals die or are humanely euthanized within the first 1-3 months of life.
Breeds appropriate for testing: Dales Pony, Fell Pony
Explanation of Results:
Horses with N/N genotype do not have the variant associated with Foal Immunodeficiency Syndrome (FIS).
Horses with N/FIS genotype are carriers of the Foal Immunodeficiency Syndrome variant but will not show signs of the disease. Horses with this genotype can transmit the disease variant to approximately 50% of their offspring. Matings between two carriers have a 25% chance of producing an affected foal.
Horses with FIS/FIS genotype are homozygous for the Foal Immunodeficiency Syndrome variant and will develop FIS, an invariably fatal condition.
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
Foal Immunodeficiency Syndrome (FIS) is an inherited immunodeficiency found in the Fell and Dales, two rare, related pony breeds native to the UK. Affected foals appear normal at birth but develop anemia and signs of infection within the first weeks of life, typically by 3-6 weeks of age. This corresponds to the natural decline in maternally derived antibodies from the mother’s first milk (colostrum). Affected foals are unable to generate their own adaptive immune response due to a B-lymphocyte immunodeficiency associated with reduced antibody levels. Consequently, the foals develop infections often marked by coughing, diarrhea, and failure to suckle, and they also develop a severe, progressive anemia. Though foals may initially respond to treatment, infections persist due to inherent immunodeficiency and this syndrome invariably leads to death or humane euthanasia within the first 1-3 months of life.
A singe nucleotide polymorphism (SNP) in the in the sodium/myo-inositol cotransporter gene (SLC5A3) was found to be perfectly correlated with FIS. This change of one nucleotide in the DNA sequence (c.1337G>T), is a missense variant, meaning it causes an altered protein product by replacing the amino acid proline with leucine at position 446 (p.P446L). The mechanism by which this amino acid substitution translates into the immune system phenotypes of FIS-affected foals is not yet fully understood but may be related to partial loss of function or alteration of function of SLC5A3, which is involved in osmotic stress response.
FIS is inherited in an autosomal recessive fashion, meaning two copies of the disease-associated variant must be present for the disease to manifest, and both sexes are affected equally.
Researchers identifying the variant associated with FIS determined that up to 10% of Fell foals and 1% of Dales foals were affected by FIS (2011). Since affected animals do not survive to breeding age, FIS foals are produced by matings between carriers. Testing for this disease variant helps breeders identify carriers among breeding stock. To reduce the risk of producing affected foals matings between carriers should be avoided. Mating carriers to N/N ponies or N/N ponies to each other will not produce affected animals and may help to gradually reduce the number of carriers in the population, over several generations, while still maintaining as much genetic diversity as possible.
Normal. No copies of the variant associated with Foal Immunodeficiency Syndrome detected.
Carrier. One copy of the Foal Immunodeficiency Syndrome associated variant detected.
Affected. Two copies Foal Immunodeficiency Syndrome associated variant detected. Foal will likely die or need to be euthanized.
Fox-Clipsham, L.Y., Carter, S.D., Goodhead, I., Hall, N., Knottenbelt, D.C., May, P.D.F., Ollier, W.E., & Swinburne, J.E. (2011). Identification of a Mutation Associated with Fatal Foal Immunodeficiency Syndrome in the Fell and Dales Pony. PLOS Genetics, 7(7), e1002133. doi: 10.1371/journal.pgen.1002133