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 | |
| Publication status | Published - 15 Oct 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Genetics
- General
Cite this
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
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=0037108758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037108758&partnerID=8YFLogxK
U2 - 10.1073/pnas.182412499
DO - 10.1073/pnas.182412499
M3 - Article
VL - 99
SP - 13675
EP - 13680
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 21
ER -