Comparative and veterinary pharmacogenomics.
Abstract: 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.
Publication Date: 2010-03-06 PubMed ID: 20204583DOI: 10.1007/978-3-642-10324-7_3Google Scholar: Lookup
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- Journal Article
- Review
Summary
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This research article elaborates on the field of pharmacogenomics – the science of understanding how genetic variation influences drug effects – with a focus on its applications in the context of veterinary and comparative medicine. The paper reviews current research in the area and discusses how variations in genes can impact drug metabolism and efficacy in animals.
Background of Pharmacogenomics
- The article begins by defining pharmacogenomics as a branch of medical science focusing on how a person’s unique genetic makeup can impact their body’s response to drugs. The ultimate aim of this field is to enable “personalised medicine,” tailoring medical treatment to each individual’s genetic code.
- Great progress has been made in this field with humans, particularly with the development of gene-guided dosing of drugs like Warfarin, a commonly prescribed anticoagulant.
Progress in Veterinary Pharmacogenomics
- The article then turns its focus to pharmacogenomics in domestic animals, which is still in the early stages of development, but shows immense potential for advancement in the future, largely due to the ongoing efforts to sequence the genomes of many animal species.
- Genome sequence information is used to identify sequence variants in genes associated with different responses to drugs. This information is also used for developing high-density single nucleotide polymorphism arrays (groups of genetic variants), which can then be used in genotypic-phenotypic analysis.
Current State of Veterinary Pharmacogenomics Research
- The article then presents a summary of the current state of research in veterinary pharmacogenomics, particularly concerning drug response variability phenotypes – observable traits influenced by the interaction between an organism’s genetic makeup and its environment – with either a known genetic aetiology (cause) or strong circumstantial evidence for a genetic connection.
Impact of Polymorphisms and Rarer Gene Variants
- The article also discusses how different types of polymorphisms (variations in the DNA sequence at a particular location on a chromosome) and less common gene variants can affect drug disposition (pharmacokinetics) and the effects of drugs (pharmacodynamics) on the organism.
Implications of Pharmacogenomics for Veterinary Practice and Research
- Finally, the article states that besides offering valuable insights for veterinary practitioners in terms of drug prescription and therapeutic intervention, the growing knowledge and research in the field of veterinary pharmacogenomics will serve as a valuable resource for individuals engaged in veterinary and comparative biomedical research.
Cite This Article
APA
Mosher CM, Court MH.
(2010).
Comparative and veterinary pharmacogenomics.
Handb Exp Pharmacol(199), 49-77.
https://doi.org/10.1007/978-3-642-10324-7_3 Publication
Researcher Affiliations
- Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
MeSH Terms
- Animals
- Anticoagulants / therapeutic use
- Cats
- Cytochrome P-450 Enzyme System / genetics
- Cytochrome P-450 Enzyme System / metabolism
- Dogs
- Genetic Variation
- Horses
- Human Genome Project
- Humans
- Mice
- Pharmaceutical Preparations / metabolism
- Pharmacogenetics / methods
- Polymorphism, Genetic
- Rats
- Ryanodine Receptor Calcium Release Channel / chemistry
- Ryanodine Receptor Calcium Release Channel / genetics
- Species Specificity
- Veterinary Medicine
- Warfarin / therapeutic use
Citations
This article has been cited 5 times.- Samadi M, Beigi L, Yadegari F, Ansari AM, Majidzadeh-A K, Eskordi M, Farahmand L. Recognition of functional genetic polymorphism using ESE motif definition: a conservative evolutionary approach to CYP2D6/CYP2C19 gene variants.. Genetica 2022 Oct;150(5):289-297.
- Martinez SE, Andresen MC, Zhu Z, Papageorgiou I, Court MH. Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization.. Sci Rep 2020 Jan 9;10(1):69.
- Lavergne SN. In Vitro Research Tools in the Field of Human Immediate Drug Hypersensitivity and Their Present Use in Small Animal Veterinary Medicine.. Vet Sci 2016 Dec 22;4(1).
- Mizukami K, Yabuki A, Chang HS, Uddin MM, Rahman MM, Kushida K, Kohyama M, Yamato O. High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs.. Dis Markers 2013;35(6):669-72.
- Court MH. Canine cytochrome P-450 pharmacogenetics.. Vet Clin North Am Small Anim Pract 2013 Sep;43(5):1027-38.
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