Severe Combined Immunodeficiency
Severe combined immunodeficiency disease (SCID)
Gene or region: DNAPK
Reference allele: TCTCA
Mutant allele: -
Affected Breeds: Arabian
Research Confidence: High confidence, findings reproduced in multiple studies
What it does:
Severe combined immunodeficiency disease is a condition in which the foal has essentially no immune system, due to a complete absence of certain types of immune cells, specifically B and T lymphocytes. Affected foals are unable to mount an effective immune response after infection and are unable to recover from infections that unaffected foals would easily resist. The disease is universally fatal in horses, usually within 4-6 months of life. It is a recessive trait, meaning that it requires two mutant alleles to manifest; animals carrying just one copy of the mutant allele are completely healthy and are “carriers”, meaning that they can pass the mutation to their offspring. If two carrier horses mate, there is a 25% chance that the foal will have SCID. It has only been detected in horses of Arabian descent, and studies have determined that ~8% of Arabian horses are carriers of the SCID allele.
The particular mutation assessed is a five-nucleotide deletion within the DNAPK gene, leading to a mutant form of the DNA-PK protein that is non-functional. DNA-PK is involved in a process called V(D)J recombination, which leads the development of mature B and T lymphocytes. All known cases of horse SCID arise from this mutation.
Ding et al., DNA-PKcs mutations in dogs and horses: allele frequency and association with neoplasia.” (2002) Gene 283: 263-9. PMID: 11867233
Bernoco, D and Bailey, E, “Frequency of the SCID gene among Arabian horses in the USA.” (1998) Animal Genetics 29: 41-42. PMID: 9682449
Shin et al., “A Kinase-Negative Mutation of DNA-PKcs in Equine SCID Results in Defective Coding and Signal Joint Formation.” (1997) Journal of Immunology 158: 3565-9. PMID: 9103416