Linkage disequilibrium mapping and candidate gene screening of the VCFS deleted region for mutations associated with schizophrenia

N. M. Williams, G. Spurlock, H. Williams, Nadine Norton, A. Walters, R. Saunders, A. G. Cardno, G. McCarthy, M. C. O'Donovan, M. J. Owen

Research output: Contribution to journalArticle

Abstract

Velo-cardio-facial syndrome (VCFS) is associated with small interstitial deletions of chromosome 22q11. Patients with VCFS have a high risk of developing schizophrenia. Kimber and colleagues have deleted a 150kb fragment from the region on murine chromosome 16 syntenic to the VCFS critical region. Interestingly, mice heterozygous for this deletion displayed an increase in prepulse inhibition (PPI) of the startle response which is considered by some to model aspects of the schizophrenia phenotype. This suggests that the genes that map within this 150kb fragment should be considered strong candidate genes for psychosis. We have now screened the human homologues of the 6 genes contained within the murine 150kb deletion (Znf741, DGCR2, Stk22a, DGSI, GscI, and Slc25A1) for sequence variants using DHPLC and sequencing. Non- synonymous SNP's have been genotyped in a stage one association sample of 174 DSM-IV schizophrenic patients and 174 matched controls together with a further 81 subjects that had been ranked according to their PPI measurement. In addition we have used both microsatellites and SNP's to perform LD mapping across the VCFS deleted region in an attempt to refine the location of a schizophrenia susceptibility locus.

Original languageEnglish (US)
Pages (from-to)475
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume96
Issue number4
StatePublished - Aug 7 2000
Externally publishedYes

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DiGeorge Syndrome
Chromosome Mapping
Linkage Disequilibrium
Schizophrenia
Mutation
Genes
Single Nucleotide Polymorphism
Startle Reflex
Chromosomes, Human, Pair 16
Chromosome Deletion
Diagnostic and Statistical Manual of Mental Disorders
Psychotic Disorders
Microsatellite Repeats
Phenotype
Prepulse Inhibition

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

Cite this

Linkage disequilibrium mapping and candidate gene screening of the VCFS deleted region for mutations associated with schizophrenia. / Williams, N. M.; Spurlock, G.; Williams, H.; Norton, Nadine; Walters, A.; Saunders, R.; Cardno, A. G.; McCarthy, G.; O'Donovan, M. C.; Owen, M. J.

In: American Journal of Medical Genetics - Neuropsychiatric Genetics, Vol. 96, No. 4, 07.08.2000, p. 475.

Research output: Contribution to journalArticle

Williams, NM, Spurlock, G, Williams, H, Norton, N, Walters, A, Saunders, R, Cardno, AG, McCarthy, G, O'Donovan, MC & Owen, MJ 2000, 'Linkage disequilibrium mapping and candidate gene screening of the VCFS deleted region for mutations associated with schizophrenia', American Journal of Medical Genetics - Neuropsychiatric Genetics, vol. 96, no. 4, pp. 475.
Williams, N. M. ; Spurlock, G. ; Williams, H. ; Norton, Nadine ; Walters, A. ; Saunders, R. ; Cardno, A. G. ; McCarthy, G. ; O'Donovan, M. C. ; Owen, M. J. / Linkage disequilibrium mapping and candidate gene screening of the VCFS deleted region for mutations associated with schizophrenia. In: American Journal of Medical Genetics - Neuropsychiatric Genetics. 2000 ; Vol. 96, No. 4. pp. 475.
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