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EMBL/EMBO Joint Conference 2006

Pierre L. Roubertoux, CNRS – Université de la Méditerranée, Marseille, France

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Pierre L. Roubertoux

Biography

Pierre L. Roubertoux studied both psychology and biology. After completing two post-graduate theses in psychology, he was appointed professor of differential psychology at the University of Paris V, where, two years later, after completing two theses in biology, he took up the position as professor of genetics, specialising in neurogenetics. Roubertoux was chair of the department of neuroscience at the University of Paris V and has served as an expert on national and international committees. He founded the research laboratory on "Genetics, Neurogenetics and Behaviour" at the CNRS in Paris, later transferred to the Institute for Transgenesis, at Orléans, and which he directed for 18 years. He is now at the laboratory of Functional Genomics (CNRS – Université de la Méditerranée, Marseille, France) in Marseilles and has been there since 2001.

Roubertoux has published more than 150 articles in the field of behaviour genetics, and two books: Génétique et Comportement (1975) co-authored with Michèle Carlier, and
Y a-t-il des gènes de comportement? (2004). He received the 2000 Dobzhansky Memorial Award and is now President Elect of the Behavior Genetics Association.

Roubertoux's primary interest is the identification of genes linked to behaviour and the description of neuronal and neurochemical pathways between genes and behaviour. Twenty years ago he mapped the gene first known to be involved in behaviour (the rooting response). His wide genome scan program has focussed on complex traits (behaviour and brain correlates), studying mice, and identified chromosomal regions involved in sensorial and motor development, laterality, cognition and motor behaviour. He proved that the steroid sulfatase gene, located on the X-Y pairing region was involved in spontaneous aggression in mice.

More recently, he showed that mitochondrial polymorphism modulates the anatomy of the brain and cognitive processes, with an age-related increase in the effect. With Michèle Carlier he proved that the uterine and post-natal environments modulated the impact of genes on behavioural processes. Roubertoux and his research group are currently concentrating on two paths: (i) understanding the contribution of the mitochondria to brain development and (ii) deciphering brain and cognitive functions of genes carried in the D21S17-ETS2 region on chromosome 21.

Hobbies: Egyptian art and classical music.

Abstract

From DNA to the Mind: the meaning of the link

Genes modulate brain functioning and behavioural outputs. Replicated studies have uncovered human genes linked with anxiety, cognitive processes and certain psychiatric disorders. Studies of the mouse have found more than 2000 genes to be linked to behavioural phenomena (motor, emotional and social behaviour), and cognitive performance. Given advances in proteomics, and the development of gene targeting, gene over-expression and fine mapping, by 2010, some 10 000 mouse genes will be identified and linked to behavioural traits.

When seen in relation to the findings of genome sequencing, these results present a paradox. There are no more than 30 000 genes in mammalian genomes, and it is generally assumed that no more than 20% of all genes are expressed in the brain; this would mean that 6000 genes could play a role in brain function and behavioural output. It has also been established that half of these 6000 genes code for proteins needed for sensory functions. The logical conclusion is then quite simply that there is no room left for all the genes involved in behaviour. How can this paradox be resolved?

After sequencing the human genome, scientists believed it would be possible to draw up a list of diseases, morphological characteristics and behavioural traits linked to each gene, but the post-genome era has shown that while links between genes and phenotypes, including behavioural phenotypes, do exist, they are more complex than was previously thought. There is no linear connection between genotype and brain and between brain and behaviour; consequently, genomic and behavioural levels of organization are not isomorphous. There is no isomorphism because one gene plays many different roles, which means that the integrative processes needed for the development and functioning of an organism inevitably occur in situations of non-linear multiple causality. Pleiotropy and epistasis, interactions between genes and the environment, alternative splicing and neuronal integration are all crucial mechanisms contributing to the many and varied aspects of brain-related genes.

Post-genomic discoveries have forced us to reconsider approaches establishing links between genes and behavioural phenomena and therefore to revisit the phenomenological classification of behaviour, including psychiatric classifications, "positive and negative" eugenics, and the genetic approach to natural selection.