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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Primate-Accelerated Evolutionary Genes: Novel Routes to Drug Discovery in Psychiatric Disorders

Author(s): J. -M. Moalic, Y. Le Strat, A. -M. Lepagnol-Bestel, N. Ramoz, Y. Loe-Mie, G. Maussion, P. Gorwood and M. Simonneau

Volume 17 , Issue 13 , 2010

Page: [1300 - 1316] Pages: 17

DOI: 10.2174/092986710790936338

Price: $65


Novel molecular genetic approaches, at genome-scale in different species allowed characterizing genes that have undergone recent selection. The interest in this research field is not limited to the natural curiosity about our evolutionary past, but it is also to identify novel susceptibility genes for neuropsychiatic disorders by pointing specific human traits, such as behavioral and cognitive abilities. Hypotheses have been proposed to relate specific psychiatric disorders to the origin of modern humans, as evidenced by the theory of Crow about schizophrenia. In the present review, we will focus on genes that underwent positive selection in humans or displayed a human specific evolutionary pattern and which were reported as associated with psychiatric disorders. This will include the (1) DRD4 gene associated with attentiondeficit/ hyperactivity disorder, located in a locus that underwent a positive selection; the (2) GABRB2 gene, a gene associated with schizophrenia and recently reported as the target of a positive selection; (3) MARK1, a candidate gene for autism that was reported as displaying a signature of adaptative evolution in the human lineage, and (4) the ADH and ALDH2 genes which are associated with alcoholism, and for which evidence of positive selection was identified in the human lineage since the divergence between humans and chimpanzees. Identification of novel candidate genes based on recent evolution selection, coupled to genome-wide strategies designed to detect rare structural variants, could lead to a better knowledge of the molecular mechanisms of neurodevelopmental disorders and might therefore help to develop new medical chemistry.

Keywords: Psychiatric diseases, schizophrenia, alcoholism, autism, primate-accelerated evolution, positive selection, synaptic transmission, drugable targets

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