Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18

Ben S. Pickard, M. Pat Malloy, Leanne Clark, Stéphanie Lehellard, Henrik L. Ewald, Ole Mors, David J. Porteous, Douglas H. R. Blackwood, Walter J. Muir

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.
LanguageEnglish
Pages37-44
Number of pages8
JournalPsychiatric Genetics
Volume15
Issue number1
Publication statusPublished - Mar 2005

Fingerprint

Psychiatry
Genes
Mood Disorders
Bipolar Disorder
Schizophrenia
Chromosome Breakpoints
Basic Helix-Loop-Helix Transcription Factors
Chromosomes, Human, Pair 18
Gene Order
Metaphase
Ligases
Ubiquitin
Fluorescence In Situ Hybridization
Membrane Proteins
Chromosomes
Chromosome 18 Pericentric Inversion
Gene Expression
Proteins

Keywords

  • sequence carrier
  • chromosome 18
  • amino acid
  • molecular sequence data
  • psychotic disorders
  • schizophrenia
  • bipolar disorder
  • gene disruption

Cite this

Pickard, B. S., Malloy, M. P., Clark, L., Lehellard, S., Ewald, H. L., Mors, O., ... Muir, W. J. (2005). Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18. Psychiatric Genetics, 15(1), 37-44.
Pickard, Ben S. ; Malloy, M. Pat ; Clark, Leanne ; Lehellard, Stéphanie ; Ewald, Henrik L. ; Mors, Ole ; Porteous, David J. ; Blackwood, Douglas H. R. ; Muir, Walter J. / Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18. In: Psychiatric Genetics. 2005 ; Vol. 15, No. 1. pp. 37-44.
@article{e30aa3eb5a4645c6b4bb3a7353759f35,
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.",
keywords = "sequence carrier, chromosome 18, amino acid, molecular sequence data, psychotic disorders, schizophrenia, bipolar disorder, gene disruption",
author = "Pickard, {Ben S.} and Malloy, {M. Pat} and Leanne Clark and St{\'e}phanie Lehellard and Ewald, {Henrik L.} and Ole Mors and Porteous, {David J.} and Blackwood, {Douglas H. R.} and Muir, {Walter J.}",
year = "2005",
month = "3",
language = "English",
volume = "15",
pages = "37--44",
journal = "Psychiatric Genetics",
issn = "0955-8829",
number = "1",

}

Pickard, BS, Malloy, MP, Clark, L, Lehellard, S, Ewald, HL, Mors, O, Porteous, DJ, Blackwood, DHR & Muir, WJ 2005, 'Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18' Psychiatric Genetics, vol. 15, no. 1, pp. 37-44.

Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18. / Pickard, Ben S.; Malloy, M. Pat; Clark, Leanne; Lehellard, Stéphanie; Ewald, Henrik L.; Mors, Ole; Porteous, David J.; Blackwood, Douglas H. R.; Muir, Walter J.

In: Psychiatric Genetics, Vol. 15, No. 1, 03.2005, p. 37-44.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18

AU - Pickard, Ben S.

AU - Malloy, M. Pat

AU - Clark, Leanne

AU - Lehellard, Stéphanie

AU - Ewald, Henrik L.

AU - Mors, Ole

AU - Porteous, David J.

AU - Blackwood, Douglas H. R.

AU - Muir, Walter J.

PY - 2005/3

Y1 - 2005/3

N2 - 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.

AB - 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.

KW - sequence carrier

KW - chromosome 18

KW - amino acid

KW - molecular sequence data

KW - psychotic disorders

KW - schizophrenia

KW - bipolar disorder

KW - gene disruption

UR - http://journals.lww.com/psychgenetics/toc/2005/03000

M3 - Article

VL - 15

SP - 37

EP - 44

JO - Psychiatric Genetics

T2 - Psychiatric Genetics

JF - Psychiatric Genetics

SN - 0955-8829

IS - 1

ER -