No CAG or CCG repeats within 18Q21.33-q23 involved in bipolar disorder

Bipolar (BP) disorder is reported to show clinical anticipation, a characteristic shared with neurological diseases caused by triplet repeat expansions. To investigate the involvement of triplet repeats in BP disorder, we isolated and analyzed all CAG/CTG and CCG/CGG repeats present in the chromosome 18q21.33-q23 BP candidate region. Hereto we applied the triplet repeat YAC fragmentation method on three YACs spanning the region. CAG/CTG YAC fragmentation resulted in four CAG/CTG repeats, none of which were expanded in BP patients nor associated with BP disorder in a case control sample. CCG/CGG YAC fragmentation resulted in one CCG/CGG repeat, also not involved in BP pathogenesis linked to chromosome 18. Analysis of the fragmented YACs showed that besides CCG/CGG repeats, also CpG islands are isolated using this method. Three sequences with a high GC content (75 to 80 %) and a high CpG content (10 to 17 CpGs in 100 bp) were identified, all three predicted by Proscan to have a potential promoter activity. Based on these results, we concluded that neither CAG/CTG nor CCG/CGG repeats are implicated in BP disorder linked to 18q21.33-q23.