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 Ouellette; Isabel Fortier; John Raelson; 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; Daniel Cohen

doi:10.1073/pnas.182412499

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 GrelVirginie 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 Ouellette, Isabel Fortier, John Raelson, 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, Daniel Cohen

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Abstract

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.

Original language	English
Pages (from-to)	13675-13680
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	99
Issue number	21
DOIs	https://doi.org/10.1073/pnas.182412499
Publication status	Published - 15 Oct 2002

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Chumakov, I., Blumenfeld, M., Guerassimenko, O., Cavarec, L., Palicio, M., Abderrahim, H., Bougueleret, L., Barry, C., Tanaka, H., La Rosa, P., Puech, A., Tahri, N., Cohen-Akenine, A., Delabrosse, S., Lissarrague, S., Picard, F. P., Maurice, K., Essioux, L., Millasseau, P., ... Cohen, D. (2002). Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 99(21), 13675-13680. https://doi.org/10.1073/pnas.182412499

Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. / Chumakov, Ilya; Blumenfeld, Marta; Guerassimenko, Oxana; Cavarec, Laurent; Palicio, Marta; Abderrahim, Hadi; Bougueleret, Lydie; Barry, Caroline; Tanaka, Hiroaki; La Rosa, Philippe; Puech, Anne; Tahri, Nadia; Cohen-Akenine, Annick; Delabrosse, Sylvain; Lissarrague, Sébastien; Picard, Françoise Pascaline; Maurice, Karelle; Essioux, Laurent; Millasseau, Philippe; Grel, Pascale; Debailleul, Virginie; Simon, Anne Marie; Caterina, Dominique; Dufaure, Isabelle; Malekzadeh, Kattayoun; Belova, Maria; Luan, Jian Jian; Bouillot, Michel; Sambucy, Jean Luc; Primas, Gwenael; Saumier, Martial; Boubkiri, Nadia; Martin-Saumier, Sandrine; Nasroune, Myriam; Peixoto, Hélène; Delaye, Arnaud; Pinchot, Virginie; Bastucci, Mariam; Guillou, Sophie; Chevillon, Magali; Sainz-Fuertes, Ricardo; Meguenni, Said; Aurich-Costa, Joan; Cherif, Dorra; Gimalac, Anne; Van Duijn, Cornelia; Gauvreau, Denis; Ouellette, Gail; Fortier, Isabel; Raelson, John; Sherbatich, Tatiana; Riazanskaia, Nadejda; Rogaev, Evgeny; Raeymaekers, Peter; Aerssens, Jeroen; Konings, Frank; Luyten, Walter; Macciardi, Fabio; Sham, Pak C.; Straub, Richard E.; Weinberger, Daniel R.; Cohen, Nadine; Cohen, Daniel.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 21, 15.10.2002, p. 13675-13680.

Research output: Contribution to journal › Article

Chumakov, I, Blumenfeld, M, Guerassimenko, O, Cavarec, L, Palicio, M, Abderrahim, H, Bougueleret, L, Barry, C, Tanaka, H, La Rosa, P, Puech, A, Tahri, N, Cohen-Akenine, A, Delabrosse, S, Lissarrague, S, Picard, FP, Maurice, K, Essioux, L, Millasseau, P, Grel, P, Debailleul, V, Simon, AM, Caterina, D, Dufaure, I, Malekzadeh, K, Belova, M, Luan, JJ, Bouillot, M, Sambucy, JL, Primas, G, Saumier, M, Boubkiri, N, Martin-Saumier, S, Nasroune, M, Peixoto, H, Delaye, A, Pinchot, V, Bastucci, M, Guillou, S, Chevillon, M, Sainz-Fuertes, R, Meguenni, S, Aurich-Costa, J, Cherif, D, Gimalac, A, Van Duijn, C, Gauvreau, D, Ouellette, G, Fortier, I, Raelson, J, Sherbatich, T, Riazanskaia, N, Rogaev, E, Raeymaekers, P, Aerssens, J, Konings, F, Luyten, W, Macciardi, F, Sham, PC, Straub, RE, Weinberger, DR, Cohen, N & Cohen, D 2002, 'Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 21, pp. 13675-13680. https://doi.org/10.1073/pnas.182412499

Chumakov, Ilya ; Blumenfeld, Marta ; Guerassimenko, Oxana ; Cavarec, Laurent ; Palicio, Marta ; Abderrahim, Hadi ; Bougueleret, Lydie ; Barry, Caroline ; Tanaka, Hiroaki ; La Rosa, Philippe ; Puech, Anne ; Tahri, Nadia ; Cohen-Akenine, Annick ; Delabrosse, Sylvain ; Lissarrague, Sébastien ; Picard, Françoise Pascaline ; Maurice, Karelle ; Essioux, Laurent ; Millasseau, Philippe ; Grel, Pascale ; Debailleul, Virginie ; Simon, Anne Marie ; Caterina, Dominique ; Dufaure, Isabelle ; Malekzadeh, Kattayoun ; Belova, Maria ; Luan, Jian Jian ; Bouillot, Michel ; Sambucy, Jean Luc ; Primas, Gwenael ; Saumier, Martial ; Boubkiri, Nadia ; Martin-Saumier, Sandrine ; Nasroune, Myriam ; Peixoto, Hélène ; Delaye, Arnaud ; Pinchot, Virginie ; Bastucci, Mariam ; Guillou, Sophie ; Chevillon, Magali ; Sainz-Fuertes, Ricardo ; Meguenni, Said ; Aurich-Costa, Joan ; Cherif, Dorra ; Gimalac, Anne ; Van Duijn, Cornelia ; Gauvreau, Denis ; Ouellette, Gail ; Fortier, Isabel ; Raelson, John ; Sherbatich, Tatiana ; Riazanskaia, Nadejda ; Rogaev, Evgeny ; Raeymaekers, Peter ; Aerssens, Jeroen ; Konings, Frank ; Luyten, Walter ; Macciardi, Fabio ; Sham, Pak C. ; Straub, Richard E. ; Weinberger, Daniel R. ; Cohen, Nadine ; Cohen, Daniel. / Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 21. pp. 13675-13680.

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title = "Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia",

abstract = "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.",

author = "Ilya Chumakov and Marta Blumenfeld and Oxana Guerassimenko and Laurent Cavarec and Marta Palicio and Hadi Abderrahim and Lydie Bougueleret and Caroline Barry and Hiroaki Tanaka and {La Rosa}, Philippe and Anne Puech and Nadia Tahri and Annick Cohen-Akenine and Sylvain Delabrosse and S{\'e}bastien Lissarrague and Picard, {Fran{\c c}oise Pascaline} and Karelle Maurice and Laurent Essioux and Philippe Millasseau and Pascale Grel and Virginie Debailleul and Simon, {Anne Marie} and Dominique Caterina and Isabelle Dufaure and Kattayoun Malekzadeh and Maria Belova and Luan, {Jian Jian} and Michel Bouillot and Sambucy, {Jean Luc} and Gwenael Primas and Martial Saumier and Nadia Boubkiri and Sandrine Martin-Saumier and Myriam Nasroune and H{\'e}l{\`e}ne Peixoto and Arnaud Delaye and Virginie Pinchot and Mariam Bastucci and Sophie Guillou and Magali Chevillon and Ricardo Sainz-Fuertes and Said Meguenni and Joan Aurich-Costa and Dorra Cherif and Anne Gimalac and {Van Duijn}, Cornelia and Denis Gauvreau and Gail Ouellette and Isabel Fortier and John Raelson and Tatiana Sherbatich and Nadejda Riazanskaia and Evgeny Rogaev and Peter Raeymaekers and Jeroen Aerssens and Frank Konings and Walter Luyten and Fabio Macciardi and Sham, {Pak C.} and Straub, {Richard E.} and Weinberger, {Daniel R.} and Nadine Cohen and Daniel Cohen",

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T1 - Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia

AU - Chumakov, Ilya

AU - Blumenfeld, Marta

AU - Guerassimenko, Oxana

AU - Cavarec, Laurent

AU - Palicio, Marta

AU - Abderrahim, Hadi

AU - Bougueleret, Lydie

AU - Barry, Caroline

AU - Tanaka, Hiroaki

AU - La Rosa, Philippe

AU - Puech, Anne

AU - Tahri, Nadia

AU - Cohen-Akenine, Annick

AU - Delabrosse, Sylvain

AU - Lissarrague, Sébastien

AU - Picard, Françoise Pascaline

AU - Maurice, Karelle

AU - Essioux, Laurent

AU - Millasseau, Philippe

AU - Grel, Pascale

AU - Debailleul, Virginie

AU - Simon, Anne Marie

AU - Caterina, Dominique

AU - Dufaure, Isabelle

AU - Malekzadeh, Kattayoun

AU - Belova, Maria

AU - Luan, Jian Jian

AU - Bouillot, Michel

AU - Sambucy, Jean Luc

AU - Primas, Gwenael

AU - Saumier, Martial

AU - Boubkiri, Nadia

AU - Martin-Saumier, Sandrine

AU - Nasroune, Myriam

AU - Peixoto, Hélène

AU - Delaye, Arnaud

AU - Pinchot, Virginie

AU - Bastucci, Mariam

AU - Guillou, Sophie

AU - Chevillon, Magali

AU - Sainz-Fuertes, Ricardo

AU - Meguenni, Said

AU - Aurich-Costa, Joan

AU - Cherif, Dorra

AU - Gimalac, Anne

AU - Van Duijn, Cornelia

AU - Gauvreau, Denis

AU - Ouellette, Gail

AU - Fortier, Isabel

AU - Raelson, John

AU - Sherbatich, Tatiana

AU - Riazanskaia, Nadejda

AU - Rogaev, Evgeny

AU - Raeymaekers, Peter

AU - Aerssens, Jeroen

AU - Konings, Frank

AU - Luyten, Walter

AU - Macciardi, Fabio

AU - Sham, Pak C.

AU - Straub, Richard E.

AU - Weinberger, Daniel R.

AU - Cohen, Nadine

AU - Cohen, Daniel

PY - 2002/10/15

Y1 - 2002/10/15

N2 - 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.

AB - 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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10.1073/pnas.182412499