Wow, GENXY making 52 week high today . . . Rick tells me to focus on a few companies, and I'm trying, but this came into my peripheral vision:
>>Published online before print October 3, 2002
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.182412499
Genetics
Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia
Ilya Chumakov *, Marta Blumenfeld *, Oxana Guerassimenko *, Laurent Cavarec *, Marta Palicio *, Hadi Abderrahim *, Lydie Bougueleret *, Caroline Barry *, Hiroaki Tanaka *, Philippe La Rosa *, Anne Puech *, Nadia Tahri *, Annick Cohen-Akenine *, Sylvain Delabrosse *, Sébastien Lissarrague *, Françoise-Pascaline Picard *, Karelle Maurice *, Laurent Essioux *, Philippe Millasseau *, Pascale Grel *, Virginie Debailleul *, Anne-Marie Simon *, Dominique Caterina *, Isabelle Dufaure *, Kattayoun Malekzadeh *, Maria Belova *, Jian-Jian Luan *, Michel Bouillot *, Jean-Luc Sambucy *, Gwenael Primas *, Martial Saumier *, Nadia Boubkiri *, Sandrine Martin-Saumier *, Myriam Nasroune *, Hélène Peixoto *, Arnaud Delaye *, Virginie Pinchot *, Mariam Bastucci *, Sophie Guillou *, Magali Chevillon *, Ricardo Sainz-Fuertes *, Said Meguenni *, Joan Aurich-Costa *, Dorra Cherif *, Anne Gimalac *, Cornelia Van Duijn , Denis Gauvreau , Gail Ouelette , Isabel Fortier , John Realson , Tatiana Sherbatich , Nadejda Riazanskaia , Evgeny Rogaev , Peter Raeymaekers ¶, Jeroen Aerssens ¶, Frank Konings ¶, Walter Luyten ¶, Fabio Macciardi *, Pak C. Sham ||, Richard E. Straub **, Daniel R. Weinberger **, Nadine Cohen ¶, and Daniel Cohen *
*Genset S.A., F-91030 Evry, France; ¶Johnson & Johnson Pharmaceutical Research and Development, B-2340 Beerse, Belgium; Research Center of Mental Health, Academy of Medical Sciences, Moscow 113152, Russia; Signalgene Biotechnologies, Montreal, QC, Canada H2M 2NG; Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands; ||Institute of Psychiatry, London SE5 8AF, United Kingdom; and **National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892
Communicated by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, July 10, 2002 (received for review April 30, 2002)
A map of 191 single-nucleotide polymorphism (SNPs) was built across a 5-Mb segment from chromosome 13q34 that has been genetically linked to schizophrenia. DNA from 213 schizophrenic patients and 241 normal individuals from Canada were genotyped with this marker set. Two 1,400- and 65-kb regions contained markers associated with the disease. Two markers from the 65-kb region were also found to be associated to schizophrenia in a Russian sample. Two overlapping genes G72 and G30 transcribed in brain were experimentally annotated in this 65-kb region. Transfection experiments point to the existence of a 153-aa protein coded by the G72 gene. This protein is rapidly evolving in primates, is localized to endoplasmic reticulum/Golgi in transfected cells, is able to form multimers and specifically binds to carbohydrates. Yeast two-hybrid experiments with the G72 protein identified the enzyme D-amino acid oxidase (DAAO) as an interacting partner. DAAO is expressed in human brain where it oxidizes D-serine, a potent activator of N-methyl-D-aspartate type glutamate receptor. The interaction between G72 and DAAO was confirmed in vitro and resulted in activation of DAAO. Four SNP markers from DAAO were found to be associated with schizophrenia in the Canadian samples. Logistic regression revealed genetic interaction between associated SNPs in vicinity of two genes. The association of both DAAO and a new gene G72 from 13q34 with schizophrenia together with activation of DAAO activity by a G72 protein product points to the involvement of this N-methyl-D-aspartate receptor regulation pathway in schizophrenia.<<
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Cheers, Tuck |
