Date of Award


Document Type


Degree Name

Master of Science (MS)



Committee Chair/Advisor

Leigh Anne Clark, PhD

Committee Member

Jennifer M. Mason, PhD

Committee Member

Julia M. George, PhD


The domesticated dog (Canis lupus familiaris) exhibits a unique population structure, with high levels of genetic homogeneity within breeds due to selective breeding. These closed breeding populations can result in breed-specific inherited disorders. Maxillary canine-tooth mesioversion (MCM) is a genetically complex dental anomaly observed nearly exclusively in the small Shetland Sheepdog breed. Here, we utilized a genome-wide approach to discover a locus of major effect on chromosome 9. Using whole-genome resequencing data from a bilaterally affected dog, we identified variants in two genes: FTSJ3, encoding an RNA methyltransferase, and GH1, encoding growth hormone. Independent genome-wide association studies of height and weight revealed that the chromosome 9 locus is also significantly associated with body size in the Shetland Sheepdog. We experimentally determined that a splice-site insertion in GH1 leads to incomplete alternative splicing and predicts a protein previously identified in human pituitary dwarfism. Statistical analyses, however, reveal that a substitution in FTSJ3 is a better predictor of both MCM and reduced body size. Analysis of allele frequencies in 224 breeds revealed that both variants are common in very small breeds and absent from all other breeds. Our findings suggest that linked variants in FTSJ3 and GH1 reduce body growth in the Shetland Sheepdog and other small breeds and confer risk for MCM. We propose that these variants are exerting a pleiotropic effect, where a reduction in body size, specifically the size of the jaw, leads to dental crowding that causes MCM. A genetic test allows Shetland Sheepdog breeders to maintain genetic diversity while reducing the incidence of MCM in their lines.

Author ORCID Identifier


Included in

Genetics Commons



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