Schizophrenia is a complexly inherited disorder involving multiple genes of small effect influencing numerous central nervous system trait deficits.¹ Two genes in the chromosome 1q42 region—disrupted-in-schizophrenia 1 (DISC1) and translin-associated factor X (TRAX)—represent particularly good candidate loci based on positional and functional considerations. Although the evidence for linkage of this region to schizophrenia has been negligible in some studies,² the translocation break point that cosegregates with schizophrenia in a Scottish pedigree³^,4 and the peak linkage signal in the 1q42 region within the Finnish population⁵^-7 are intragenic to DISC1, with several other linkage and association findings also pointing to this region.⁸^-15 The DISC1 gene is expressed in neurons and glia and is translated to a protein that has an impact on neurodevelopmental and neurochemical processes thought to be involved in the pathophysiology of schizophrenia, including neuritic outgrowth, neuronal migration, synaptogenesis, and glutamatergic transmission.¹⁶^-19 Recently, 2 haplotypes incorporating different blocks of single-nucleotide polymorphic (SNP) markers in the DISC1 gene were found to be associated with schizophrenia (one undertransmitted and the other overtransmitted to affected cases) in a study of multiplex families from Finland.⁶ How these genetic variations influence central nervous system trait components associated with schizophrenia remains to be determined, although it is notable that carriers of the (1;11)(q42;q14.3) translocation show deficits in the amplitude of the P300 electrophysiological response.¹² Another locus affected by the balanced translocation in the Scottish pedigree DISC2 is not known to form a protein but is thought to act through its RNA as a regulator of DISC1.³

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