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

• DOI: 10.1073/pnas.2009500117
• Publication Date: 2020-09-22T00:41:41Z
• Authors: Sydney R. Abrams; Alexandra L. Hawks; Jacquelyn M. Evans; Thomas R. Famula; Mary Mahaffey; Gary S. Johnson; Jennifer M. Mason; Leigh Anne Clark
• Keywords: 0301 basic medicine; GH1; Genotype; IGF1; Body Weight; 610; weight; Single Nucleotide; Exons; Methyltransferases; Breeding; Polymorphism, Single Nucleotide; 630; 03 medical and health sciences; Dogs; Haplotypes; FTSJ3; Growth Hormone; Animals; Body Size; Polymorphism; Alleles; height; Genome-Wide Association Study

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 in FtsJ RNA 2′-O-Methyltransferase 3 ( FTSJ3 ) and a splice donor insertion in Growth Hormone 1 ( GH1 ). We demonstrated that the GH1 variant causes an abnormal splicing pattern that is also observed in dominant forms of human pituitary dwarfism. Interestingly, the FTSJ3 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.