MAPPING AND CHARACTERIZATION OF NOVEL (CAG)(N) REPEAT CDNAS FROM ADULT HUMAN BRAIN-DERIVED BY THE OLIGO CAPTURE METHOD

The expansion of a (CAG)(n) trinucleotide repeat has been associated w ith at least eight neurological disorders in which the repeats code fo r polyglutamine in the protein. To identify additional genes that poss ess (CAG)(n) repeats, single-stranded cDNA clones derived from adult h uman brain were screened using biotinylated oligonucleotide (CAG)(8), and the hybridizing complexes were isolated with strepavidin-coated pa ramagnetic beads. A total of 119 cDNA clones were isolated and initial ly characterized by end sequencing. BLAST homology searches were used to reduce redundancies with overlapping clones and to eliminate those that show sequence identity with previously published cDNAs with tripl et repeats. Only cDNA clones with more than five CAG repeats were purs ued for analysis. A total of 19 novel cDNAs were further characterized by determining chromosomal assignments using the Stanford G3 and Gene bridge radiation-reduced hybrid mapping panels. Transcript sizes and t issue expression patterns were determined by Northern blot analysis. T wo of 19 clones showed specific or high expression in brain. These cDN As are ideal candidate genes for other neurodegenerative disorders, su ch as spinocerebellar ataxia types 5 and 7, and may also be implicated in psychiatric diseases such as bipolar affected disorder and schizop hrenia. (C) 1997 Academic Press.