title: Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia.
abstract: Accumulating evidence suggests that the pathologic lesions of schizophrenia may in part be due to the altered cytoskeletal architecture of neurons. Microtubule-associated proteins (MAPs) that bind to cytoskeletal microtubules to stabilize their assembly are prominently expressed in neurons. Of the MAPs, MAP6 (STOP) has a particular relevance to schizophrenia pathology, since mice deficient in the gene display neuroleptic-responsive behavioral defects. Here we examined the genetic contribution of MAP6 to schizophrenia in a case (n = 570) -control (n = 570) study, using dense single nucleotide polymorphism (SNP) markers. We detected nominal allelic (p = 0.0291) and haplotypic (global p = 0.0343 for 2 SNP-window, global p = 0.0138 for 3 SNP-window) associations between the 3' genomic interval of the gene and schizophrenia. MAP6 transcripts are expressed as two isoforms. A postmortem brain expression study showed up-regulation of mRNA isoform 2 in the prefrontal cortex (Brodmann's area 46) of patients with schizophrenia. These data suggest that the contribution of MAP6 to the processes that lead to schizophrenia should be further investigated.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Kauhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakajima
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
chemical_list: C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger