title: Translational Safety Genetics.
abstract: The emerging field of translational safety genetics is providing new opportunities to enhance drug discovery and development. Genetic variation in therapeutic drug targets, off-target interactors and relevant drug metabolism/disposition pathways can contribute to diverse drug pharmacologic and toxicologic responses between different animal species, strains and geographic origins. Recent advances in the sequencing of rodent, canine, nonhuman primate, and minipig genomes have dramatically improved the ability to select the most appropriate animal species for preclinical drug toxicity studies based on genotypic characterization of drug targets/pathways and drug metabolism and/or disposition, thus avoiding inconclusive or misleading animal studies, consistent with the principles of the 3Rs (replacement, reduction and refinement). The genetic background of individual animals should also be taken into consideration when interpreting phenotypic outcomes from toxicity studies and susceptibilities to spontaneous safety-relevant background findings.
authors.affiliation: 1 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Priyasma
authors.initials: P
authors.lastname: Bhoumik
authors.affiliation: 1 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Del Rio-Espinola
authors.affiliation: 1 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Hahne
authors.affiliation: 1 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moggs
authors.affiliation: 1 Preclinical Safety, Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Grenet
mesh_terms: D000818:Animals; D000830:Animals, Laboratory / Q000235:genetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D014644:Genetic Variation; D017408:Guidelines as Topic; D012107:Research Design; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods*; D057170:Translational Research, Biomedical / Q000379:methods*
keywords: animal species; cynomolgus monkey; genetic variation; genome; safety genetics; sequencing; toxicology