STRUCTURE AND EXPRESSION OF THE GENE RESPONSIBLE FOR THE TRIPLET REPEAT DISORDER, DENTATORUBRAL AND PALLIDOLUYSIAN ATROPHY (DRPLA)

Dentatorubral and pallidoluysian atrophy is associated with expansion of an unstable CAG repeat on chromosome 12p. We have determined the nu cleotide sequences of overlapping cDNA clones and deduced the gene str ucture. The gene is ubiquitously expressed to form a single 4.5 kb tra nscript and encoded by an open reading frame of 1184 amino acids (aa), in which a polyglutamine track with variable length starts at aa 484. Although the predicted amino acid sequence does not reveal any functi on, it does contain several interesting motifs consisting of a simple repeated amino acid sequence, a homo-proline track, two stretches of a rginine-glutamic acid dipeptides and a stretch of alternative histidin e residues. These results provide clues toward understanding neurodege nerative diseases associated with triplet repeat expansion.