title: Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18.
abstract: Both the long and short arms of chromosome 18 have been consistently identified as potential locations for schizophrenia and bipolar affective disorder susceptibility genes. We previously described the identification of two independent pericentric inversions of chromosome 18 [inv(18)(p11.31;q21.2) and inv(18)(p11.31;q21.1)] occurring in two small families in which carriers have been diagnosed with schizophrenia and bipolar affective disorder, respectively. Using fluorescence in situ hybridization on patient metaphase chromosomes we have identified the locations of all four chromosome breakpoints in the inversion carriers. Neither pericentric inversion results in a direct gene disruption. However, each inversion breakpoint has the potential to perturb local gene expression by position effect or by the separation of important regulatory (enhancer) sequences from the core gene sequences. Five genes in the localities of the breakpoints have been identified as good candidates for the genetic basis of psychiatric illness in these families; TTMA, a novel membrane spanning protein; TCF4, a basic helix-loop-helix transcription factor; DLGAP1, an interactor of the PSD-95 synaptic protein; and ARKL1 and ARKL2, novel members of the ubiquitin ligase gene family.
authors.affiliation: Department of Medical Genetics, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. ben.pickard@ed.ac.uk
authors.forename: Ben S
authors.initials: BS
authors.lastname: Pickard
authors.forename: M Pat
authors.initials: MP
authors.lastname: Malloy
authors.forename: Leanne
authors.initials: L
authors.lastname: Clark
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lehellard
authors.forename: Henrik L
authors.initials: HL
authors.lastname: Ewald
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Douglas H R
authors.initials: DH
authors.lastname: Blackwood
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Muir
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002353:Carrier State; D007446:Chromosome Inversion / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D016384:Consensus Sequence; D017931:DNA Primers; D005190:Family; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D011618:Psychotic Disorders / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers