Vol 6 n° 1 - Predictors of Response to Treatment in Neuropsychiatry
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iomedical research and practice is in the midst of a profound transformation that is being driven by two primary factors: the massive increase in the amount of DNA sequence information; and the development of technologies to apply the new information.The principal aim of the Human Genome Project, namely the elucida- tion of the approximately 3 billion base pairs (bps) of the entire genome, has almost been achieved. In February 2001, the analysis of the first draft of the sequence was published,1 and this analysis provided the first great sur- prise:  the  total  number  of  protein-coding  genes  was nearer to 35 000 than the previously estimated 100 000.2 The finished sequence of five entire human chromosomes (chromosomes 22, 21, 20, 14, and Y) has been published,3-7 and for the 50th anniversary of the publication of the structure of DNA by Watson and Crick8 in April 2003, the finished DNA sequence of the entire genome was made available  to  the  public  by  the  International  Human Genome Sequencing Consortium (IHGSC) on the inter- net. Over the past few years, more than 30 organisms have  had  their  genomes  completely  sequenced, with another 100 in progress9,10 and an at least partial DNA sequence has been obtained for thousands of mouse and rat genes. Consequently, we find ourselves at a time at which new types of experiments are possible, and obser- vations, analyses, and discoveries are being made on an unprecedented scale. It can be expected that genetic con- siderations will become important in all aspects of dis- ease, be they diagnosis, treatment, or prevention. Unfortunately, the billions of bases of DNA sequence do not tell us what all the genes do, how cells work, how we B a s i c   r e s e a r c h 2 7 The future of genetic testing for drug response Deborah J. Morris-Rosendahl, PhD; Bernd L. Fiebich, PhD Keywords: genetics; drug response; single nucleotide polymorphism; DNA Author   affiliations:   Institute   for   Human   Genetics   and Anthropology, University  of  Freiburg,  Freiburg,  Germany  (Deborah  J.  Morris-Rosendahl); Department of Psychiatry, University of Freiburg, Freiburg, Germany (Bernd L. Fiebich) Address for correspondence: Deborah J. Morris-Rosendahl, PhD, Institute for   Human   Genetics   and   Anthropology,   University   of   Freiburg, Breisacherstrasse 33, D-79106 Freiburg, Germany   (e-mail: morrisro@ukl.uni-freiburg.de) B The effect of variation in genes coding for drug targets and for the enzymes involved in drug metabolism has highlighted the genetic component of drug response. Drug response can be likened to a complex, multifacto- rial genetic trait, and the study of its genetic variation, termed pharmacogenetics, is analogous to the study of complex genetic disease in terms of the questions posed and the analytical possibilities. Just as DNA variants are associated with specific disease predispositions, so will they be associated with individual response to certain drugs. The testing for drug response is following the same route as the genetic testing for inherited disorders, and has reached the stage where genome-wide analy- sis, as opposed to the analysis of single genes, is a real- ity. In this article, we will discuss some of the technical advances that facilitate such analyses, leading to faster and more extensive diagnostic capabilities. © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:27-37. Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org