Gingival enlargement (GE) is dental disease characterized by overgrowth of the gums that leads to periodontal disease, impaired mastication, and mucosal ulceration. A generalized form of GE occurs in multiple breeds but has greatest incidence and severity in Boxers. The precise etiology and genetic basis of GE in the Boxer is unknown, and diagnosis is typically made well after sexual maturity, making the disease difficult to eliminate. Our hypothesis is that generalized GE in Boxers is mediated by genetic risk factors. The aims are to identify (1) genes and pathways dysregulated in GE and (2) candidate causal variants. In aim 1, we will generate transcriptome sequencing of gingival tissue from 20 affected and healthy dogs and matched histopathology to further characterize features of Boxer GE. In aim 2, we will undertake low-pass whole genome sequencing (1X coverage) followed by imputation and genome-wide association analysis. To create a reference panel for genotype imputation from low-pass sequence, we will select 5 cases and 5 controls for high coverage (30X) sequencing and incorporate these data with over 2000 public dog genomes. This approach has the potential to reveal causal mutations. Top associated variants will be investigated for predicted functional impact and association with GE in a broader cohort. The results of this comprehensive genomic and transcriptomic investigation will be candidate causal variants and genetic pathways underlying GE. This will lead to a genetic test to produce dogs at low risk for GE and improved diagnosis and treatment.