ANALYSIS OF POLYGLUTAMINE-CODING REPEATS IN THE TATA-BINDING PROTEIN IN DIFFERENT HUMAN-POPULATIONS AND IN PATIENTS WITH SCHIZOPHRENIA AND BIPOLAR AFFECTIVE-DISORDER

A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expa nsions of CAG trinucleotides in the coding regions of genes, In all of these diseases the CAG repeats are thought to be translated into poly glutamine tracts, There is accumulating evidence arguing for CAG trinu cleotide expansions as one of the causative disease mutations in schiz ophrenia and bipolar affective disorder, We and others believe that th e TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of gluta mine codons, which are close to the threshold length where the polyglu tamine tracts start to be associated with disease, Thus, we examined t he lengths of this polyglutamine repeat in normal unrelated East Angli ans, South African Blacks, sub-Saharan Africans mainly from Nigeria, a nd Asian Indians, We also examined 43 bipolar affective disorder patie nts and 65 schizophrenic patients, The range of polyglutamine tract-le ngths that we found in humans was from 26-42 codons, No patients with bipolar affective disorder and schizophrenia had abnormal expansions a t this locus. (C) 1996 Wiley-Liss, Inc.