SEARCH FOR UNSTABLE DNA IN SCHIZOPHRENIA FAMILIES WITH EVIDENCE FOR GENETIC ANTICIPATION

Evidence for genetic anticipation has recently become an important sub ject of research in clinical psychiatric genetics. Renewed interest in anticipation was evoked by molecular genetic findings of a novel type of mutation termed ''unstable DNA.'' The unstable DNA model can be co nstrued as the ''best fit'' for schizophrenia twin and family epidemio logical data. We have performed a large-scale Southern blot hybridizat ion, asymmetrical PCR-based, and repeat expansion-detection screening for (CAG)(n)/(CTG)(n) and (CCG)(n)/(CGG)(n) expansions in eastern Cana dian schizophrenia multiplex families demonstrating genetic anticipati on. There were no differences in (CAG)(n)/(CTG)(n), and (CCG)(n)/(CGG) (n) pattern distribution either between affected and unaffected indivi duals or across generations. Our findings do not support the hypothesi s that large (CAG)(n)/(CTG)(n) or (CCG)(n)/(CGG)(n) expansions are the major etiologic factor in schizophrenia. A separate set of experiment s directed to the analysis of small (30-130 trinucleotides), Huntingto n disease-type expansions in individual genes is required in order to fully exclude the presence of (CAG)(n)/(CTG)(n)- or (CCG)(n)/(CGG)(n)- type unstable mutation.