This chapter discusses DNA structure and genetic instabilities associated with on spinocerebellar ataxia type 10 (ATTCT)n ·(AGAAT)n repeats. SCA10 is associated with expansion from a normal range of 10 to 22 10 (ATTCT)n·(AGAAT)n pentanucleotide repeats to as many as 4,500 repeats that forms an unpaired region, which then extends into adjacent A + T-rich flanking sequences. For plasmids containing 29 repeats, above the normal human size range, a locally condensed structure formed at high superhelical densities. Although the structure is "condensed," the bases remained unpaired. The pentanucleotide repeat exhibits unusual characteristics when grown in E coli. The (ATTCT)n ·(AGAAT)n repeats do not undergo deletion at a high rate, and unlike trinucleotide repeats that are rapidly deleted in E. coli, (ATTCT)n ·(AGAAT)n repeats undergo expansion associated with a complex mutational event upon prolonged growth in E. coli. The complex mutations involved both plasmid dimerization and inversion of a part of the repeat tract forms an inverted repeat. The results are consistent with a high frequency of primer-template misalignment during DNA replication.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)