October 30, 2017

The effect of genetic bottlenecks and inbreeding on the incidence of two major autoimmune diseases in standard poodles, sebaceous adenitis and Addison’s disease

In this study by Pedersen, Brucker, Tessier, Liu, Penedo, Hughes, Oberbauer, and Sacks discuss the commonality of sebaceous adenitis (SA) and Addison’s disease (AD) found in the standard poodle. Sebaceous adenitis is an autoimmune disease that affects the skin glands of dogs causing an inflammatory reaction. Addison’s disease is an autoimmune disease that affect the adrenal gland and affects the secretion of hormones that help with metabolism. The study asks the question of what led to the increase in SA and AD in the standard poodle. The scientists hypothesize that through inbreeding in the mid-twentieth century, in the positive selection for specific phenotypes, there has been the inadvertent selection for AD and SA.

The study of 3 different bottlenecks and historical events led to the loss of bloodlines, resulting in an increase inbreeding. There was the Midcentury Bottleneck (MCB), Wycliffe, and Old English apricot (OEA). The MCB is when there was a decrease in diversity due to the use of show winning dog breed lines in order to obtain a specific look. The Wycliffe bottleneck first occurred with the mating between Annsown Gay Knight to Wycliffe Jacqueline. Knight and Wycliffe produced show winning puppies and these puppies were then sent around the world, thus spreading their genes to different regions. The OEA is a minor bottleneck, where there was the positive selection for poodles with an apricot coat in order to improve the quality of the coat. Some events that wiped out bloodlines by creating artificial bottlenecks were when poodle’s ancestors went from wild to domesticated by remaining with humans, the implementation in England of the breed registry, poodle size limits, World War II, and the Iron Curtain. These events decreased genetic diversity, thus increasing inbreeding in poodles.

This study uses different methods in order to prove the lack of diversity between standard poodles as well as address the gene causing AD and SA. Short tandem repeat (STR) frequencies were used in order to determine the internal relatedness in the standard poodle population as well as for comparisons of internal relatedness between healthy standard poodles and standard poodles with AD or SA. The STRs are part of noncoding regions, which allows for great variety and differences between individuals. Principal coordinate analysis (PCoA) were used to also show the genetic similarities of the standard poodle, miniature poodle, and standard/miniature poodle crosses based on 33 genomic STRs. DLA (Dog Leukocyte Antigen) plays a role in the immune system response and class I and II are regions and are involved with the regulations of antigens in the immune system. DLA class I and II haplotype frequencies were used in order to determine which, if any, haplotypes were associated with AD and SA.

The results show that their hypothesis was proven to be correct.  In conclusion, bottlenecks and the selection for certain phenotypes led to an increase in inbreeding, leading to an increase in AD and SA. This was shown through the %MCB, %Wycliffe and %OEA. %MCB and %Wycliffe correlated to the increase and decrease in incidence of AD and SA throughout the history. The PCoA plot with standard poodles, miniature poodles, and standard/miniature poodle crosses from different regions shows that throughout the poodle breed population, independent of region, there appears to be significant genetic similarities across the breed. The PCoA plot of healthy, SA, and AD standard poodles, also shows great genetic similarities, but the outliers were mainly SA and AD free, showing they were more genetically diverse poodles. Another discovery made through the DLA class I and II haplotypes was that haplotype 1003 was the only haplotype significantly related to both AD and SA.

Pedersen et al. 2015. The effect of genetic bottlenecks and inbreeding on the incidence of two major autoimmune diseases in standard poodles, sebaceous adenitis and Addison's disease. Canine Genetics and Epidemiology. 2(14):1-18

Original Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579369/pdf/40575_2015_Article_26.pdf

Reviewed by Hannah Cohen