title: Genetic variation in the seven-pass transmembrane cadherin CELSR1: lack of association with schizophrenia.
abstract: OBJECTIVE
  Cadherins play a critical role in morphogenesis and maintenance of neuronal connections in the adult brain. We examined the gene encoding a member of the non-classic seven-pass transmembrane cadherins, CELSR1 for association with schizophrenia. It maps to chromosome 22q13.31, a region in which evidence for linkage to schizophrenia has been reported. The gene has an unusually large first exon of 3544 nucleotides, which encodes the signal peptide and all nine ectodomains in the protein.
  
  
  METHODS
  We screened this exon in 24 schizophrenic patients using denaturing high-performance liquid chromatography followed by sequencing. Genotyping of amino-acid changes was performed with primer extension on a sample of 244 Bulgarian schizophrenic patients from 233 families and all their parents, as well as 180 schizophrenic patients from the UK and 157 controls.
  
  
  RESULTS
  Three amino-acid changes were identified and shown to be in complete linkage disequilibrium: L556 V, S664W and R1126C. There was no preferential transmission of alleles from heterozygous parents to affected offspring. In the UK population the rare alleles were even more common in controls, and this difference almost reached statistical significance for R1126C (chi2=3.63, P=0.057).
  
  
  CONCLUSIONS
  We conclude that variations in the nine ectodomains of CELSR1 do not increase susceptibility to schizophrenia.
authors.affiliation: Department of Medical Genetics, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Georgieva
authors.forename: Ivan
authors.initials: I
authors.lastname: Nikolov
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Poriazova
authors.forename: Gaynor
authors.initials: G
authors.lastname: Jones
authors.forename: Draga
authors.initials: D
authors.lastname: Toncheva
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002031:Bulgaria; D015820:Cadherins / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009679:Nuclear Family; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: C454220:CELSR1 cadherin, human; D015820:Cadherins; D017931:DNA Primers