A Novel Long and Unstable CAG/CTG Trinucleotide Repeat on Chromosome 17q

• Published in: Genomics (San Diego, Calif.) Calif.), 1998-04, Vol.49 (2), p.321-326
• Main Authors: Ikeuchi, Takeshi, Sanpei, Kazuhiro, Takano, Hiroki, Sasaki, Hidenao, Tashiro, Kunio, Cancel, Géraldine, Brice, Alexis, Bird, Thomas D., Schellenberg, Gerry D., Pericak-Vance, Margaret A., Welsh-Bohmer, Kathleen A., Clark, Lorraine N., Wilhelmsen, Kirk, Tsuji, Shoji
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Chromosome Mapping - methods; Chromosomes, Human, Pair 17 - genetics; Classical genetics, quantitative genetics, hybrids; Fundamental and applied biological sciences. Psychology; Genes, Dominant; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; Molecular Sequence Data; Polymorphism, Genetic - genetics; Spinocerebellar Degenerations - genetics; Trinucleotide Repeats - genetics
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1998.5266

Using the direct identification of repeat expansion and cloning technique, we cloned a novel long CAG/CTG trinucleotide repeat on chromosome 17. Using radiation hybrid panels, the CAG/CTG repeat was mapped to chromosome 17q. The CAG/CTG repeat is highly polymorphic, with a heterozygosity of 85%, and exhibits a bimodal distribution (allele S, 10–26 repeat units, and allele L, 50–92 repeat units). The CAG/CTG repeat of allele L exhibited intergenerational instabilities, which are more prominent in maternal transmission than in paternal transmission. Analyses of Northern blot and RT-PCR indicate that the repeat is transcribed. Although the size of the CAG/CTG repeat of allele L is within the range of the expanded CAG repeat of disease-causing genes, we did not detect any association of allele L with various neurodegenerative diseases, including frontotemporal dementia and parkinsonism, mapped to 17q21–q23.