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 (pharmaco-
dynamics) 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.
KeywordsCytochrome P450 Drug metabolismMalignant hyperthermia
N-acetyltransferaseP-glycoproteinPharmacogenomicsThiopurine methyl-
transferaseUDP-glucuronosyltransferase
1 Introduction
Pharmacogenomics is the study of the impact of genetic variation on drug pharma-
cokinetics and pharmacodynamics, and is concerned with understanding interac-
tions between drugs and the entire set of genes in an organism (i.e. the genome)
(Court 2007 ). Pharmacogenomics is a relatively new discipline that arose less than
15 years ago from the field of pharmacogenetics (a term first coined in 1956 by
Carson et al. ( 1956 )), which typically addresses a single, or relatively few, genes.
The two terms are often used interchangeably, and for the purposes of this discus-
sion, pharmacogenomics will be used inclusively. As pointed out in a recent review
article (Court 2007 ), over the last 15 years, there has been almost exponential
growth in the volume of published pharmacogenomics research. The initial driving
force behind this growth was likely the Human Genome Project, initiated in 1990
and culminating in 2003 with the publication of the complete human genome
sequence (www.ornl.gov/sci/techresources/Human_Genome/home.shtml). A direct
outcome of the Human Genome Project was the International Hapmap Project
(2003–2008), which recently completed mapping the common patterns of genetic
variation in four different human populations (www.hapmap.org). Currently, the
1000 Genomes Project (2008-onwards) proposes to provide a high resolution map
of human genetic variation through sequencing the entire genomes of approxi-
mately 1,200 individuals from around the world (www.1000genomes.org).
Unfortunately, research into the pharmacogenomics of non-human species has
lagged significantly behind that of human research. However, the recent release of
genome sequences for a number of domestic animal species of direct relevance to
veterinary clinical medicine and comparative animal research now provides a
scaffold on which veterinary pharmacogenomics research can be constructed,
hopefully at a more rapid pace. At the time of this writing (April, 2009), complete
genome sequences have been deposited in the US National Center for Biotechnol-
ogy Information (NCBI) Genbank database for the human and mouse, while draft
sequence assemblies (in various stages of completeness) are available for a further
50 C.M. Mosher and M.H. Court