Addiction and Genes: Animal Models


Genes influence susceptibility to alcohol and drug dependence. The sequence of a gene may differ among individuals, and each gene form (or allele) may produce a different product (i.e. a different form of a protein, such as an enzyme, receptor or hormone). Differences in gene sequence or polymorphisms are one source of individual differences in risk for addiction. In addition, individuals with the same form of a gene may express the gene product in different amounts, and this may be another source of differential risk. Genetic animal models are used to study genetic influence and identify addiction‐relevant genes. These include classical genetic models, such as standard inbred strains and selected lines, and newer era genetic models and techniques such as transgenics, knockouts, microarray analysis, next generation sequencing and optogenetics. These genetic models are important tools used to identify factors that influence risk for addiction and mechanisms that could lead to novel treatments.

Key Concepts:

  • Addiction is not a single gene trait (also known as a Mendelian trait) like Huntington's disease or sickle‐cell anaemia.

  • Each gene that influences addiction may have a relatively small influence but together can account for a significant amount of the variation among people in risk for addiction.

  • The newest tools used to explore the genetics of addiction have benefited from the complete sequencing of the human genome and the genome of several other species.

  • Successful selective breeding indicates that there is genetic influence on the measured trait.

  • Bidirectional genetic research occurs when animal studies lead to investigation of similar genetic factors in humans and vice versa.

  • Optogenetics is a relatively new and exciting procedure for controlling brain activity with light using specific genetic manipulations.

Keywords: gene mapping; mutagenesis; gene expression; quantitative trait locus (QTL); RNAseq; optogenetics; selected line; congenic strain

Figure 1.

Schematic representation of one chromosome pair from an interval specific congenic strain panel used to narrow a chromosomal region thought to harbour a quantitative trait locus (QTL). Each set of vertical bars represents a single chromosome pair. Each pair is from one of seven congenic strains. Each strain is genetically identical to the Control strain across all chromosome pairs, including this one, except for the segment shown in grey. All congenics and the control strain are tested for the trait of interest. The result of comparing the trait magnitude of a congenic to that of the control is indicated as NO (not different) or YES (different). These data permit isolation of a chromosomal segment, indicated by the two horizontal lines, as the location where the influential QTL(s) must reside, based on the strain differences. This is the only region of overlap for the grey segment in those strains that differed from the control strain. The black circles indicate the end of the chromosome (the centromere).



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Further Reading

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Phillips, Tamara J, and Gubner, Noah R(Mar 2013) Addiction and Genes: Animal Models. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005914.pub2]