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

Author

Chumakov, I. (Ilya), Blumenfeld, M. (Marta), Guerassimenko, O. (Oxana), Cavarec, L. (Laurent), Palicio, M. (Marta), Abderrahim, H. (Hadi), Bougueleret, L. (Lydie), Barry, C. (Caroline), Tanaka, H. (Hiroaki), Rosa, P. (Philippe) La, Puech, A. (Anne), Tahri, N. (Nadia), Cohen-Akenine, A. (Annick), Delabrosse, S. (Sylvain), Lissarrague, S. (Sébastien), Picard, F.P., Maurice, K. (Karelle), Essioux, L. (Laurent), Millasseau, P. (Philippe), Grel, P. (Pascale), Debailleul, V. (Virginie), Simon, A-M. (Anne-Marie), Caterina, D. (Dominique), Dufaure, I. (Isabelle), Malekzadeh, K. (Kattayoun), Belova, M. (Maria), Luan, J.J., Bouillot, M. (Michel), Sambucy, J.L., Primas, G. (Gwenael), Saumier, M. (Martial), Boubkiri, N. (Nadia), Martin-Saumier, S. (Sandrine), Nasroune, M. (Myriam), Peixoto, H. (Hélène), Delaye, A. (Arnaud), Pinchot, V. (Virginie), Bastucci, M. (Mariam), Guillou, S. (Sophie), Chevillon, M. (Magali), Sainz-Fuertes, R. (Ricardo), Meguenni, S. (Said), Aurich-Costa, J. (Joan), Cherif, D. (Dorra), Gimalac, A. (Anne), Duijn, C.M. (Cornelia) van, Gauvreau, D. (Denis), Ouelette, G., Fortier, I. (Isabel), Realson, J., Sherbatich, T. (Tatiana), Riazanskaia, N. (Nadejda), Rogaev, E. (Evgeny), Raeymaekers, P. (Peter), Aerssens, J. (Jeroen), Konings, F. (Frank), Luyten, W. (Walter), Macciardi, F. (Fabio), Sham, P.C. (Pak), Straub, R.E. (Richard), Weinberger, D.R. (Daniel), Cohen, N. (Nadine), Cohen, D. (Daniel), Chumakov, I. (Ilya), Blumenfeld, M. (Marta), Guerassimenko, O. (Oxana), Cavarec, L. (Laurent), Palicio, M. (Marta), Abderrahim, H. (Hadi), Bougueleret, L. (Lydie), Barry, C. (Caroline), Tanaka, H. (Hiroaki), Rosa, P. (Philippe) La, Puech, A. (Anne), Tahri, N. (Nadia), Cohen-Akenine, A. (Annick), Delabrosse, S. (Sylvain), Lissarrague, S. (Sébastien), Picard, F.P., Maurice, K. (Karelle), Essioux, L. (Laurent), Millasseau, P. (Philippe), Grel, P. (Pascale), Debailleul, V. (Virginie), Simon, A-M. (Anne-Marie), Caterina, D. (Dominique), Dufaure, I. (Isabelle), Malekzadeh, K. (Kattayoun), Belova, M. (Maria), Luan, J.J., Bouillot, M. (Michel), Sambucy, J.L., Primas, G. (Gwenael), Saumier, M. (Martial), Boubkiri, N. (Nadia), Martin-Saumier, S. (Sandrine), Nasroune, M. (Myriam), Peixoto, H. (Hélène), Delaye, A. (Arnaud), Pinchot, V. (Virginie), Bastucci, M. (Mariam), Guillou, S. (Sophie), Chevillon, M. (Magali), Sainz-Fuertes, R. (Ricardo), Meguenni, S. (Said), Aurich-Costa, J. (Joan), Cherif, D. (Dorra), Gimalac, A. (Anne), Duijn, C.M. (Cornelia) van, Gauvreau, D. (Denis), Ouelette, G., Fortier, I. (Isabel), Realson, J., Sherbatich, T. (Tatiana), Riazanskaia, N. (Nadejda), Rogaev, E. (Evgeny), Raeymaekers, P. (Peter), Aerssens, J. (Jeroen), Konings, F. (Frank), Luyten, W. (Walter), Macciardi, F. (Fabio), Sham, P.C. (Pak), Straub, R.E. (Richard), Weinberger, D.R. (Daniel), Cohen, N. (Nadine), and Cohen, D. (Daniel)

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.

Published
2002
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4. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia

Author

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, Duijn, Cornelia, 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, and Duijn, Cornelia

Published
2002

8. Human mucin genes MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 express stable and extremely large mRNAs and exhibit a variable length polymorphism. An improved method to analyze large mRNAs.

Author

Debailleul, V, Laine, A, Huet, G, Mathon, P, d'Hooghe, M C, Aubert, J P, and Porchet, N

Abstract

Of the nine mucin genes that have been characterized, only MUC1 and MUC7 have been fully sequenced, and their transcripts can be detected as distinct bands of predicted size by Northern blot analysis. In contrast, the RNA patterns observed for each of the other MUC genes have usually shown a very high degree of polydispersity. This polydispersity has been believed to be one of the typical features of the mucin mRNAs, but until now, its origin has remained unexplained. In the work described in the present paper, we investigated two possible kinds of explanation for this phenomenon: namely that the extensive polydispersity results from a biological mechanism or that it is artifactual in origin. The data obtained, as a result of improving the purification and blotting methods, allowed us to show that in all of the tissues analyzed, each of the genes, MUC2-6, expresses mRNAs that are stable and are of an unusually large size to be found in eukaryotes (14-24 kilobases). Moreover, allelic variations in length of these mucin transcripts were observed. We demonstrate that these variations are directly related to the variable number of tandem repeat polymorphisms seen at the DNA level.

Published
1998

9. MGAT5 alters the severity of multiple sclerosis

Author

Filippo Martinelli-Boneschi, Federica Esposito, V. Debailleul, Jérôme Wojcik, Hadi Abderrahim, Gilles Edan, Giacomo P. Comi, J. Yaouanq, Boel Brynedal, Jan Hillert, Brynedal, B, Wojcik, J, Esposito, F, Debailleul, V, Yaouanq, J, MARTINELLI BONESCHI, F, Edan, G, Comi, Giancarlo, Hillert, J, and Abderrahim, H.

Subjects
Adult, Genetic Markers, Male, Glycosylation, Multiple Sclerosis, Genotype, DNA Mutational Analysis, Immunology, Population, Central nervous system, Nerve Tissue Proteins, Biology, N-Acetylglucosaminyltransferases, Severity of Illness Index, Genome, Cohort Studies, Disability Evaluation, Immune system, medicine, Demyelinating disease, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Genetic Testing, education, Gene, Oligonucleotide Array Sequence Analysis, Genetic association, education.field_of_study, Multiple sclerosis, Genetic Variation, medicine.disease, Europe, medicine.anatomical_structure, Neurology, Female, Neurology (clinical), Genome-Wide Association Study
Abstract

Multiple Sclerosis (MS) is a genetically complex immune mediated, demyelinating disease of the central nervous system. To date no genetic variants have been unambiguously linked to disease severity. We have conducted a genome wide screen, using Affymetrix Genechip® 500K technology, for severity in 1040 MS patients. Two markers within MGAT5 , a gene coding for a glycosylation enzyme, were found to be significantly associated with outcome in the screening as well as in an independent population (combined p -values: 2.8 × 10 − 6 and 1.5 × 10 − 7 ).

Published
2010
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10. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia.

Author

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, and Cohen D

Subjects
Amino Acid Sequence, Case-Control Studies, Chromosome Mapping, Chromosomes, Artificial, Bacterial genetics, Chromosomes, Human, Pair 13 genetics, Cloning, Molecular, D-Amino-Acid Oxidase metabolism, Enzyme Activation, Genetic Markers, Humans, In Vitro Techniques, Molecular Sequence Data, Polymorphism, Single Nucleotide, Receptors, N-Methyl-D-Aspartate genetics, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, D-Amino-Acid Oxidase genetics, Schizophrenia genetics, Schizophrenia physiopathology
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.

Published
2002
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11. Abnormalities in mucin gene expression in Crohn's disease.

Author

Buisine MP, Desreumaux P, Debailleul V, Gambiez L, Geboes K, Ectors N, Delescaut MP, Degand P, Aubert JP, Colombel JF, and Porchet N

Subjects
Adolescent, Adult, Aged, Biopsy, Needle, Humans, Ileum chemistry, Ileum pathology, Intestinal Mucosa chemistry, Intestinal Mucosa pathology, Male, Middle Aged, RNA, Messenger analysis, Reference Values, Sensitivity and Specificity, Statistics, Nonparametric, Crohn Disease genetics, Gene Expression Regulation, Mucins genetics
Abstract

Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.

Published
1999
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13. [A disease not to be forgotten...peritoneal tuberculosis].

Author

Debailleul V, Herbin H, Barbieux H, Hazard C, and Florin M

Subjects
Adult, Aged, Humans, Male, Middle Aged, Peritonitis, Tuberculous drug therapy, Peritonitis, Tuberculous pathology, Peritonitis, Tuberculous diagnosis
Published
1982

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