Introduction to Autosomal Dominant Conditions
Dogs have 78 chromosomes, or 39 pairs in each cell. Genes are located on these chromosomes, and they can have different genetic variants related to genes, known as alleles. Each gene also typically has 2 copies, one from the dam and one from the sire. The dam and sire randomly contribute one of their two alleles for each gene, giving each allele a 50% chance of being passed on. The combination of the two alleles is known as a “genotype,” and the expression of the alleles determines “phenotype,” which is an observable trait in a dog.
Autosomal dominant conditions in dogs are genetic disorders that occur due to a variant in a single copy of a gene located on one of the autosomes (non-sex chromosomes). Because these conditions are dominant, only one parent needs to pass the defective gene to their offspring for the condition to manifest. This can make managing these conditions in breeding programs particularly challenging, but with informed decisions, breeders can mitigate risks and promote healthier canine populations.
Autosomal Dominant Inheritance
To demonstrate the inheritance of autosomal dominant, Progressive Retinal Atrophy (Bullmastiff/Mastiff Type), a specific genetic variant, will be used as an example.
Progressive Retinal Atrophy (Bullmastiff/Mastiff Type)
Progressive retinal atrophy (PRA) is an eye disease that leads to blindness. The rod type of photoreceptor cells of the retina degenerate over time. Multiple genetic variants can cause this disease with various ages of onset. This specific genetic variant has been identified in Bullmastiffs and Mastiffs, results in clinical signs by about 18 months. Affected dogs start with vision loss in dim light or at night, and loss of peripheral vision. The disease gradually progresses to complete blindness. This genetic variant is a SNP (single nucleotide polymorphism) in the RHO gene. Dogs with one copy of this variant develop PRA, and dogs with 2 copies have a more rapid progression to vision loss.
Determining Possible Outcomes of Puppies
Punnet squares are useful tools to demonstrate the inheritance of genetic diseases. This tool helps breeders evaluate the genotypes of the dam and sire and assess risk of producing puppies with certain genotypes.
A simple table, or square, is used to help demonstrate possible genetic combinations. The genotype of the sire it put on columns, and the genotype of the dam is put on rows. Offspring will inherit randomly one copy of a gene from the sire and one from the dam, so this chart helps show all the possible genotypes of the offspring. The four possible genotypes add up to 100%, with each square contributing 25%. Similar genotypes are added together to determine an overall liklihood of a genotype for a specific puppy.
For example, in the first picture, the sire is affected with this form of PRA and has 2 copies of the variant allele (also known as “mutant”). This is denoted as a genotype of “M/M.” The dam does not have this type of PRA, and her genotype is denoted as “WT/WT” to show she has the “wild type,” or normal, allele. The 4 boxes in the middle represent all the possible genotypes of the offspring. With this mating, all puppies have 100% chance of inheriting an “M” from the sire and a “WT” from the dam, meaning that all puppies will theoretically develop this form of PRA.
This next example shows an affected sire with only 1 copy of the disease-associated genetic variant. With this combination, each puppy has a 50% chance of inheriting the abnormal allele and developing PRA and a 50% chance of inheriting the normal allele.
It is important to note that each box for the offspring represents a likelihood of each individual puppy having that genotype. This likelihood does not mean that in a litter of 8 puppies, 4 will have the normal variants and 4 will go on to develop PRA. Rather, each puppy has a 50% chance of not having this genetic variant and a 50% chance of inheriting the abnormal genetic variant. For example, this mating could result in a litter of 8 with 8 puppies that will go on to have PRA, or 1 puppy that will develop PRA and 7 normal puppies. Any combination is possible.
Conclusion
Autosomal dominant conditions present significant challenges to dog breeders, but with diligent genetic testing, careful pedigree analysis, and ethical breeding practices, it is possible to mitigate these risks. By prioritizing the health of the breed and making informed breeding decisions, breeders can contribute to the long-term well-being and sustainability of their breeds.
Citations:
- Kijas JW, Cideciyan AV, Aleman TS, Pianta MJ, Pearce-Kelling SE, Miller BJ, Jacobson SG, Aguirre GD, Acland GM. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. Proc Natl Acad Sci U S A. 2002 Apr 30; 99(9):6328-33.[11972042]
- Kijas JW, Miller BJ, Pearce-Kelling SE, Aguirre GD, Acland GM. Canine models of ocular disease: outcross breedings define a dominant disorder present in the English mastiff and bull mastiff dog breeds. J Hered. 2003 Jan-Feb; 94(1):27-30.[12692159]