A NOVEL LONG AND UNSTABLE CAG CTG TRINUCLEOTIDE REPEAT ON CHROMOSOME 17Q/

Using the direct identification of repeat expansion and cloning techni que, we cloned a novel long CAG/ CTG trinucleotide repeat on chromosom e 17. Using radiation hybrid panels, the CAG/CTG repeat was mapped to chromosome 17q. The CAG/CTG repeat is highly polymorphic, with a heter ozygosity of 85%, and exhibits a bimodal distribution (allele S, 10-26 repeat units, and allele L, 50-92 repeat units). The CAG/CTG repeat o f allele L exhibited intergenerational instabilities, which are more p rominent in maternal transmission than in paternal transmission. Analy ses of Northern blot and RT-PCR indicate that the repeat is transcribe d. Although the size of the CAG/CTG repeat of allele L is within the r ange of the expanded CAG repeat of disease-causing genes, we did not d etect any association of allele L with various neurodegenerative disea ses, including frontotemporal dementia and parkinsonism, mapped to 17q 21-q23. (C) 1998 Academic Press.