Association of CAG repeat loci on chromosome 22 with schizophrenia and bipolar disorder

Chromosome 22 has, been implicated in schizophrenia and bipolar disorder in a number of linkage, association and. cytogenetic studies. Recent evidence has also implicated CAG repeat tract expansion in these diseases. In order to explore the involvement of CAG repeats on chromosome 22 in these diseas es, we have created an integrated map of all CAG repeats greater than or eq ual to5 on this, chromosome together with microsatellite markers associated with these diseases using the recently completed nucleotide sequence of ch romosome 22. Of the 52 GAG repeat loci identified in this, manner, four of the longest repeat stretches in regions previously implicated by linkage an alyses were chosen for further study. Three of the four repeat containing l oci, were found in the coding region with the CAG repeats coding for glutam ine and were expressed In the brain. All. the loci studied showed varying d egrees of polymorphism with one of the loci exhibiting two alleles, of 7 an d 8 CAG repeats. The 8-repeat allele at this locus was significantly overre presented in both schizophrenia and bipolar patient groups when compared to ethnically matched controls, while alleles at the other three loci did not show any such difference. The repeat lies within a gene which shows homolo gy to an androgen receptor related apoptosis protein in rat. We have also i dentified other candidate genes in the vicinity of this locus. Our results suggest that the repeats within this gene or other genes in the vicinity of this locus are, likely to be implicated in bipolar disorder and schizophre nia.