Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis

The genes G72/G30 were recently implicated in schizophrenia in both Canadian and Russian populations. We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expe...

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Veröffentlicht in:Biological psychiatry (1969) 2004-08, Vol.56 (3), p.169-176
Hauptverfasser: Korostishevsky, Michael, Kaganovich, Miryam, Cholostoy, Alina, Ashkenazi, Maya, Ratner, Yael, Dahary, Dvir, Bernstein, Jeanne, Bening-Abu-Shach, Ullrike, Ben-Asher, Edna, Lancet, Doron, Ritsner, Michael, Navon, Ruth
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container_issue 3
container_start_page 169
container_title Biological psychiatry (1969)
container_volume 56
creator Korostishevsky, Michael
Kaganovich, Miryam
Cholostoy, Alina
Ashkenazi, Maya
Ratner, Yael
Dahary, Dvir
Bernstein, Jeanne
Bening-Abu-Shach, Ullrike
Ben-Asher, Edna
Lancet, Doron
Ritsner, Michael
Navon, Ruth
description The genes G72/G30 were recently implicated in schizophrenia in both Canadian and Russian populations. We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expected in schizophrenic patients compared with control subjects. Eleven single nucleotide polymorphisms (SNPs) encompassing the G72/G30 genes were typed in the genomic deoxyribonucleic acid (DNA) from 60 schizophrenic patients and 130 matched control subjects of Ashkenazi ethnic origin. Case–control comparisons were based on linkage disequilibrium (LD) and haplotype frequency estimations. Gene expression analysis of G72 and G30 was performed on 88 postmortem dorsolateral prefrontal cortex samples. Linkage disequilibrium analysis revealed two main SNP blocks. Haplotype analysis on block II, containing three SNPs external to the genes, demonstrated an association with schizophrenia. Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. The elevation in expression of the G72 gene coincides with the glutamatergic theory of schizophrenia.
doi_str_mv 10.1016/j.biopsych.2004.04.006
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Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. 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Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. 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Psychiatry</subject><subject>Psychoses</subject><subject>real-time polymerase chain reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>susceptibility genes</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEuLFDEQgIMo7rj6F5Zc9GTP5tHPk8rijgsLXvQcMkn1doZ00qa61Rb875thRvQmFCRVfJVUfYRccbbljNfXh-3exQlXM2wFY-X2GKx-Qja8bWQhSiaekg3LpUIKIS_IC8RDThsh-HNywSvR8KqtNuT3HdJ5ALprxPVOMuqjWZBqxGicnsHSH24eKJrB_YrTkCA4_Y6iCw8eaFiMhzg7C3SKfh1jmgaHI76lg558nNcJ8l0HSx8gAIWfUwJEF0Ouab-iw5fkWa89wqvzeUm-3n78cvOpuP-8u7v5cF8Y2ZVzwU1eseZS86rjJesBSrvnsrEgS9uxnud9dS0q2fa6N3XXVfvKdq0uecWEFkxekjend6cUvy2AsxodGvBeB4gLqrpuZNlykcH6BJoUERP0akpu1GlVnKmjeHVQf8Sro3h1DFbnxqvzD8t-BPu37Ww6A6_PgEajfZ90MA7_4bqmaliZufcnDrKP7w6SQuMgGLAugZmVje5_szwC9tql4Q</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>Korostishevsky, Michael</creator><creator>Kaganovich, Miryam</creator><creator>Cholostoy, Alina</creator><creator>Ashkenazi, Maya</creator><creator>Ratner, Yael</creator><creator>Dahary, Dvir</creator><creator>Bernstein, Jeanne</creator><creator>Bening-Abu-Shach, Ullrike</creator><creator>Ben-Asher, Edna</creator><creator>Lancet, Doron</creator><creator>Ritsner, Michael</creator><creator>Navon, Ruth</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040801</creationdate><title>Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis</title><author>Korostishevsky, Michael ; Kaganovich, Miryam ; Cholostoy, Alina ; Ashkenazi, Maya ; Ratner, Yael ; Dahary, Dvir ; Bernstein, Jeanne ; Bening-Abu-Shach, Ullrike ; Ben-Asher, Edna ; Lancet, Doron ; Ritsner, Michael ; Navon, Ruth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c394t-1c004613a159140fee4db137de34d90f1240a62538fafc6995b5d98a41502a203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Ashkenazi Jews</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Case-Control Studies</topic><topic>dorsolateral prefrontal cortex</topic><topic>European Continental Ancestry Group - ethnology</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Gene Expression - physiology</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Haplotypes - genetics</topic><topic>Humans</topic><topic>Jews - ethnology</topic><topic>Jews - genetics</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Postmortem Changes</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Psychology. 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We hypothesized that 1) polymorphic changes in this gene region might be associated with schizophrenia in the Ashkenazi Jewish population and that 2) changes in G72/G30 gene expression might be expected in schizophrenic patients compared with control subjects. Eleven single nucleotide polymorphisms (SNPs) encompassing the G72/G30 genes were typed in the genomic deoxyribonucleic acid (DNA) from 60 schizophrenic patients and 130 matched control subjects of Ashkenazi ethnic origin. Case–control comparisons were based on linkage disequilibrium (LD) and haplotype frequency estimations. Gene expression analysis of G72 and G30 was performed on 88 postmortem dorsolateral prefrontal cortex samples. Linkage disequilibrium analysis revealed two main SNP blocks. Haplotype analysis on block II, containing three SNPs external to the genes, demonstrated an association with schizophrenia. Gene expression analysis exhibited correlations between expression levels of the G72 and G30 genes, as well as a tendency toward overexpression of the G72 gene in schizophrenic brain samples of 44 schizophrenic patients compared with 44 control subjects. It is likely that the G72/G30 region is involved in susceptibility to schizophrenia in the Ashkenazi population. The elevation in expression of the G72 gene coincides with the glutamatergic theory of schizophrenia.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15271585</pmid><doi>10.1016/j.biopsych.2004.04.006</doi><tpages>8</tpages></addata></record>
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subjects Adolescent
Adult
Adult and adolescent clinical studies
Aged
Ashkenazi Jews
Biological and medical sciences
Carrier Proteins - genetics
Carrier Proteins - metabolism
Case-Control Studies
dorsolateral prefrontal cortex
European Continental Ancestry Group - ethnology
European Continental Ancestry Group - genetics
Female
Gene Expression - physiology
Gene Frequency
Genetic Predisposition to Disease
Haplotypes - genetics
Humans
Jews - ethnology
Jews - genetics
Linkage Disequilibrium
Male
Medical sciences
Middle Aged
Polymorphism, Single Nucleotide
Postmortem Changes
Prefrontal Cortex - metabolism
Proteins - genetics
Proteins - metabolism
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
real-time polymerase chain reaction
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Schizophrenia
Schizophrenia - genetics
susceptibility genes
title Is the G72/G30 locus associated with schizophrenia? single nucleotide polymorphisms, haplotypes, and gene expression analysis
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