Screening of candidate Genes for schizophrenia susceptibility in chromosome 8p12-p21

Evidence from schizophrenia linkage studies, including two genome scans (Blouin et al., 1998); Curling et al., 2001), implicate chromosomal region 8p21 in schizophrenia susceptibility. From 54 multiplex schizophrenia pedigrees exhibiting linkage evidence in the region (P =.0001), we selected probands from 1) families exhibiting allele sharing amongst affected family members for markers in the 8p region, and 2) genome scan families with schizophrenia spectrum disorders diagnosed in relatives (see Pulver et al., 2000, for stratification analyses of chromosome 8 based on diagnoses in first degree relatives). Genes were chosen as candidates based upon their physical location and their function or expression patterns relevant to schizophrenia hypotheses. The positional candidates included adrenergic, cholinergic, and nicotinic receptors, among others. Mutation detection techniques (SSCP, dHPLC, and PTT) were used to analyse DNA from 11 probands for candidates including: ADRA1A,ADRA1C, NEFL, NEF3, GABRR2, GABRR1, LPL, PNOC, CLU, ADRB3-1, ADRB3-2, GFRA2-1 GFRA2-2, SLC18A1, CHRNB3, STC1, and CHRNA2. Aberrant SSCP bands/(heteroduplexes) were then sequenced. No meaningful amino acid changes were found, excluding these candidates for schizophrenia liability in these selected probands.