Key issues in contemporary behavioral genetics
Introduction
Behavior genetics is the study of the inheritance of behavioral phenotypes. Many different species have been studied, especially rodents (mice and rats), fruit flies (Drosophila melanogaster), worms (Caenorhabditis elegans), and humans, with zebrafish (Danio rerio) currently catching up swiftly. Especially in the last few decades, progress has been rapid and many new genetic techniques are helping elucidate the role of genetics in the causation of behavior. Many of these advances will be addressed in the other reviews in this issue. In this review I will focus on a few key issues facing contemporary behavior genetics.
Behavior genetics is, in principle, not very different from other subfields of genetics: It is strongly multidisciplinary and interdisciplinary, with contributions from ethology, psychology, neuroscience, ecology, psychiatry, etc., and focuses on a specific class of phenotypes: behavior. Therein, however, also lays its greatest distinction with most other genetics disciplines. Behavior is a phenotype that often is very malleable by factors in an organism's environment and almost invariably is influenced by the actions of multiple genes. Exceptions are some, usually rather severe disorders, such as Huntington's chorea and Fragile X Syndrome, which are caused by mutations in a single crucial gene or genomic region. Needless to say that, apart from these exceptions, the genetic analysis of behavior is made much harder by its complex nature. After all, behavior is the output of the brain, by many magnitudes the most complex structure known.
Section snippets
Looking back: A brief history of behavior genetics
Behavior genetics has a long history. This may sound surprising to many younger colleagues who cannot remember the time that we did not have genetically modified animals or genome-wide association studies (GWAS) and who may think that this is a relatively young field. As a matter of fact, the first research into the inheritance of behavior already took place in the 19th century, with Charles Darwin writing about selective breeding for animal behavior [1] and his cousin Francis Galton working on
Human behavior genetics
While in the early days most behavior geneticists often studied many different species and switched rather freely between animal species and humans, the field has become more fragmented over time. Not only has it become rare for researchers to switch between species, but the field of human behavior genetics has effectively separated into two: one investigates the inheritance of normal behavior and the other studies the genetics of pathologies (a subfield nowadays generally called psychiatric
Animal behavior genetics
In principle, of course, there is not really any reason to divide behavior genetics into human and animal studies. In practice, however, the ability to manipulate populations and to carry out directed breeding means that the field has advanced much farther in animal species. Other articles in this issue will present results obtained with fruit flies, worms, and fish. Here I concentrate on mouse studies. As in humans, animal behavior genetics used to be heavily oriented towards quantitative
Defining phenotypes
Ever since the landmark study of Crabbe et al. was published in 1999 [48••], researchers have worried about the replicability of behavioral data obtained with genetically defined animals in standardized tests. Crabbe and colleagues tested a number of inbred strains, as well as one KO mutant, simultaneously in three different laboratories on a battery of carefully standardized behavioral tests. The results came as a shock to many in the field: large differences were found between the results
Looking forward: the future
From the above it becomes apparent that the sophistication of our genetic methodologies and tools is not matched by a similar understanding of the behavior of our subjects. It should be obvious that many failures to replicate behavioral results or gene localizations can be traced back to the problems outlined above. For example, if two research groups report conflicting results for the effect of a certain KO mutation on, say, depressive behavior, this is not necessarily because of a lack of
Conclusions
The long history of the field of behavior genetics has greatly enriched our understanding of the inheritance of behavior. New methodologies promise to facilitate gene localization and identification. One serious problem faced by both animal and human behavioral geneticists is the need to increase our understanding of the phenotypes that we study. The behavioral constructs supposedly underlying the test batteries that we use are in urgent need of validation and, in psychiatric genetics, disease
Conflict of interest
Nothing declared.
Acknowledgements
I thank Drs. Richard Brown (Dalhousie University, Halifax, NS, Canada), John Crabbe (VA, Portland, OR, USA), Douglas Wahlsten (Salt Spring Island, BC, Canada), and Frank Peyré (Bordeaux) for many stimulating discussions over the years about the ideas presented in this article.
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