Comparative and veterinary pharmacogenomics.
Pharmacogenomics is the study of the impact of genetic variation on drug effects, with the ultimate goal of achieving "personalised medicine". Since the completion of the Human Genome Project, great strides have been made towards the goal of personalised dosing of drugs in people, as exemplified by the development of gene-guided dosing of the anticoagulant drug, warfarin. Although the pharmacogenomics of domestic animals is still at an early stage of development, there is great potential for advances in the coming years as the direct result of complete genome sequences currently being derived for many of the species of significance to veterinary and comparative medicine. This sequence information is being used to discover sequence variants in candidate genes associated with altered drug response, as well as to develop whole genome high density single nucleotide polymorphism arrays for genotype-phenotype linkage analysis. This review summarises the current state of veterinary pharmacogenomics research, including drug response variability phenotypes with either known genetic aetiology or strong circumstantial evidence for genetic involvement. Polymorphisms and rarer gene variants affecting drug disposition (pharmacokinetics) and drug effect (pharmacodynamics) are discussed. In addition to providing the veterinary clinician with useful information for the practise of therapeutics, it is envisaged that the increasing knowledge base will also provide a resource for individuals involved in veterinary and comparative biomedical research.
Mosher
Carrie M
CM
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Court
Michael H
MH
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D002415:Cats; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D014644:Genetic Variation; D006736:Horses; D016045:Human Genome Project; D006801:Humans; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics; D013045:Species Specificity; D014730:Veterinary Medicine; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D004364:Pharmaceutical Preparations; D019837:Ryanodine Receptor Calcium Release Channel; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System