title: Copy number variation of the SELENBP1 gene in schizophrenia.
abstract: BACKGROUND
  Schizophrenia is associated with rare copy-number (CN) mutations. Screening for such alleles genome-wide, though comprehensive, cannot study in-depth the causality of particular loci, therefore cannot provide the functional interpretation for the disease etiology. We hypothesized that CN mutations in the SELENBP1 locus could associate with the disorder and that these mutations could alter the gene product's activity in patients.
  
  
  METHODS
  We analyzed SELENBP1 CN variation (CNV) in blood DNA from 49 schizophrenia patients and 49 controls (cohort A). Since CN of genes may vary among tissues, we investigated SELENBP1 CN in age- sex- and postmortem interval-matched cerebellar DNA samples from 14 patients and 14 controls (cohort B). Since CNV may either be de-novo or inherited we analyzed CNV of the SELENBP1 locus in blood DNA from 26 trios of schizophrenia probands and their healthy parents (cohort C). SELENBP1 mRNA levels were measured by real-time PCR.
  
  
  RESULTS
  In cohort A reduced CN of the SELENBP1 locus was found in four patients but in none of the controls. In cohort B we found reduced CN of the SELENBP1 locus in two patients but in none of the controls. In cohort C three patients exhibited drastic CN reduction, not present in their parents, indicating de-novo mutation. A reduction in SELENBP1 mRNA levels in the postmortem cerebellar samples of schizophrenia patients was found.
  
  
  CONCLUSIONS
  We report a focused study of CN mutations in the selenium binding-protein1 (SELENBP1) locus previously linked with schizophrenia. We provide evidence for recurrence of decreased CN of the SELENBP1 locus in three unrelated patients' cohorts but not in controls, raising the possibility of functional involvement of these mutations in the etiology of the disease.
authors.affiliation: Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, and Mental Health Center, Beersheva, Israel.
authors.forename: Shirly
authors.initials: S
authors.lastname: Amar
authors.forename: Ofer
authors.initials: O
authors.lastname: Ovadia
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Richard
authors.initials: R
authors.lastname: Ebstein
authors.forename: R H
authors.initials: RH
authors.lastname: Belmaker
authors.forename: Dan
authors.initials: D
authors.lastname: Mishmar
authors.forename: Galila
authors.initials: G
authors.lastname: Agam
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism*; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010290:Parents; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism*; D051137:Selenium-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins