Understanding Autosomal Recessive Conditions in Dogs

Introduction to Autosomal Recessive 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 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 recessive conditions in dogs are genetic disorders that occur when a dog inherits two copies of a variant associated with that disease, one from each parent. The disease-associated variant is located on one of the autosomes (non-sex chromosomes). Because these conditions are recessive, both parents need to pass the defective gene to their offspring for the condition to manifest. If a dog has only one copy of the variant associated with disease, then that dog is a carrier and does not show clinical signs of the disease. The same principles can also be applied to recessive traits, such as coat colors.

Autosomal Recessive Inheritance

To demonstrate the inheritance of autosomal recessive conditions, Progressive Retinal Atrophy, Progressive Rod-Cone Degeneration (PRA-prcd) will be used as an example. PRA-prcd is a well-known autosomal recessive genetic condition in dogs that leads to blindness, typically later in life. When making breeding decisions to manage this and similar autosomal recessive conditions, it is important to understand the genetic status of both potential breeding partners. DNA testing can be used to determine a dog’s genotype and help make smart breeding decisions. Knowing a dog’s genotype can identify dogs who will develop PRA from this genetic variant, prior to the development of clinical signs.

Key Terms

• • Normal (Clear) (WT/WT): Two normal alleles, also known as “wildtype

• • Carrier (WT/M): One normal (wildtype) allele and one allele associated with a disease, sometimes called “mutant” or “mutated allele”

• • At-Risk/Affected (M/M): Two alleles associated with disease. In this case, a dog will go on to develop the genetic disease. Sometimes these diseases are present at birth, but other times they can develop later in life. In other words, a dog could have two copies of a variant that is associated with disease, but not actually have the disease at a certain time. However, the presence of the two copies related to the disease predicts that the dog will develop the disease at some point in its life. For example, PRA-prcd typically develops later in life, so a dog likely will have normal eyes during puppyhood and young adulthood.

Determining Possible Outcomes of Puppies

Punnett 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.

The following breeding scenarios are possible for PRA-prcd:

1. Normal (WT/WT) x Normal (WT/WT)

• Outcome: All offspring are genetically normal.

2. Normal (WT/WT) x Carrier (WT/M)

• Outcome: Every puppy in a litter has a 50% chance of being normal and a 50% chance of being a carrier.
• • It is important to note that each box for the offspring represents a liklihood of each individual puppy having that genotype. This liklihood does not mean that in a litter of 8 puppies, 4 will have the normal variants and 4 will be carriers of PRA-prcd. 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 carry PRA-prcd, or 2 puppies that carry PRA-prcd and 6 normal puppies. Any combination is possible.

3. Normal (WT/WT) x At-Risk/Affected (M/M)

• Outcome: All offspring are carriers.

4. Carrier (WT/M) x Carrier (WT/M)

• Outcome: Every puppy in a litter has a 25% chance of being normal, 50% chance of being a carrier, and a 25% chance of being at-risk/affected.

5. Carrier (WT/M) x At-Risk/Affected (M/M)

• Outcome: Every puppy in a litter has 50% chance of being a carrier and a 50% chance of being at-risk/affected.

6. At-Risk/Affected (M/M) x At-Risk/Affected (M/M)

• Outcome: All offspring are at-risk/affected.

Management Strategies

• • • 1. Genetic Diversity: Maintaining a diverse gene pool is crucial to avoid other genetic problems. Breeding only clear dogs might lead to a loss of genetic diversity, so carriers may be used judiciously.
      2. Gradual Reduction: For recessive conditions related to disease, aim to reduce the number of carriers without drastically narrowing the gene pool. This can be achieved by breeding carriers to normal dogs and selecting normal offspring for future breeding. Other recessive traits, such as coat colors, may be desirable to maintain in a breed.
      3. Education and Collaboration: Breeders should work together and share information to make informed decisions. Educating new breeders about genetic conditions and testing is essential.

Conclusion

Autosomal recessive conditions present significant challenges to dog breeders, but understanding the mode of inheritance helps select for certain traits or decrease the risk of producing unhealthy dogs. Diligent genetic testing can also be used as a tool to mitigate these risks.

If you are interested in learning more about DNA, please visit the AKC DNA Resource Center.

Citations:

• • • Dostal J, Hrdlicova A, Horak P. Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression. Veterinarni Medicina. 2011 Jun; 56(5):243-47. [Not In PubMed]
    • Kohyama M1, Tada N, Mitsui H, Tomioka H, Tsutsui T, Yabuki A, Rahman MM, Kushida K, Mizukami K, Yamato O. Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan. J Vet Med Sci. 2015 Nov 6. [PubMed: 26549343]
    • Moody JA, Famula TR, Sampson RC, Murphy KE. Identification of microsatellite markers linked progressive retinal atrophy in American Eskimo Dogs. Am J Vet Res. 2005 Nov;66(11):1900-2. [PubMed: 16334947]
    • Zangerl B, Goldstein O, Philp AR, Lindauer SJ, Pearce-Kelling SE, Mullins RF, Graphodatsky AS, Ripoll D, Felix JS, Stone EM, Acland GM, Aguirre GD. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans. Genomics. 2006 Nov; 88(5):551-63. [PubMed: 16938425]