High Resolution Mapping QTL Influencing Periodontitis Susceptibility in Collaborative-Cross Mouse

Objectives: Host susceptibility to periodontitis is a complex trait influenced by genetic determinants. Here, we performed a quantitative trait locus (QTL) analysis, associated with host susceptibility to alveolar bone loss induced by perio-pathogens using a unique high genetically diverse mouse reference population (GRP), named, the collaborative cross (CC) mouse.
Methods: 25 different Tau/CC lines were assessed in this study for their susceptibility to alveolar bone loss (as a periodontitis indicator), due to orally co-infection with Porphyromonas Gingivalis and Fusobacterium Nucleatum bacteria. Mice in each assessed line were divided into two groups; infected and control (5 mice on average per group). The alveolar bone loss phenotype was defined as the level of alveolar bone volume of the infected mice, quantified by µCT technique, relatively to the control group. QTL mapping was performed using 77,000 single-nucleotide polymorphisms (SNPs) spread across the mouse genome and the Alveolar bone loss phenotype using Happy-Package on R-Software. Finally, the mapped QTL were refined using the imputation with the catalogue of sequence variation segregating in the CC to suggest potential candidate genes. Genes underlying QTLs and the human orthologous genes were evaluated for their potential involvement using genes annotations database tools.
Results: The assessed phenotype across the different CC lines showed a significant variation (p<0.05) in response to the co-infection; while some lines showed a significant alveolar bone loss due to infection others did not. Two significant QTLs associated with alveolar bone loss on Chromsome1 (Perl3 “Periodontitis Resistant Locus 3”) and chromosome14 (Perl4) were mapped. In total, 54 genes were identified within both QTLs. We suggested candidate genes based on their previously-reported functions in bone biology and immune system.
Conclusions: We have demonstrated, for the first time, novel and high resolution-mapping QTL associated with susceptibility to alveolar bone loss induced by perio-pathogens in the Collaborative-Cross mouse population