NOVEL TRANSCRIBED SEQUENCES NEIGHBORING A TRANSLOCATION BREAKPOINT ASSOCIATED WITH SCHIZOPHRENIA

A 1.3Mb chromosome 11-specific yeast artificial chromosome (YAC) that spans a t(1;11) translocation breakpoint associated with major psychos is has been used to enrich cDNAs that are encoded within it and expres sed in the human foetal brain. Database analysis of the selected fragm ents led to the identification of 54 clones matching alpha-tubulin, 4 fragments matching two anonymous human expressed sequence tags (ESTs) and 8 fragments giving no database matches. The clones matching alpha- tubulin led to the identification of a novel alpha-tubulin locus locat ed approximately 250 kb proximal to the translocation breakpoint. Exte nsive sequence and expression analysis of this locus suggests that thi s is a processed pseudogene, although a long open reading frame is mai ntained and the possibility that an abnormally acting protein may be e xpressed in a highly tissue or developmental specific manner cannot be discounted. The novel cDNA fragments map up to 700 kb proximal to the translocation breakpoint and are associated with potential CPG island s, Reverse transcript polymerase chain reaction (RT-PCR) expression an alysis and high resolution genomic mapping suggest that they may compr ise up to three novel genes. No major disruption of the identified fra gments could be detected in the genomic DNA of translocation carriers. The psychosis associated with this translocation may therefore be due to position effects on the transcription of these genes or an involve ment of translocated chromosome 1 sequences. (C) 1997 Wiley-Liss, Inc.