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Significance Through the study of a dental anomaly we identified a locus strongly associated with body size in the Shetland Sheepdog. Within this locus are variants in two genes: a substitution inFtsJ RNA 2′-O-Methyltransferase 3 (FTSJ3 ) and a splice donor insertion inGrowth Hormone 1 (GH1 ). We demonstrated that theGH1 variant causes an abnormal splicing pattern that is also observed in dominant forms of human pituitary dwarfism. Interestingly, theFTSJ3 variant is estimated to have the greatest impact on height and weight and this gene has not been previously characterized in body size traits. Both derived alleles are found in high frequencies in very small “toy” breeds but are entirely absent from larger breeds.

Variants in FtsJ RNA 2′-O-Methyltransferase 3 and Growth Hormone 1 are associated with small body size and a dental anomaly in dogs