Research Interests Unusual DNA structures and human hereditary neurological diseases Dr. Wells is interested in the role of DNA structure in triplet repeat diseases. Recent investigations since 1991 have revealed that approximately 15 human hereditary neurological diseases are caused by the non-Mendelian expansion of simple triplet repeat sequences (CTGoCAG, CGGoCCG, and GAAoTTC). Some of these diseases are myotonic dystrophy, Huntington's disease, and Friedreich's ataxia. The clinical observation termed "anticipation" refers to the earlier age of onset and increased severity of the disease through a human pedigree. This non- Mendelian behavior is correlated with an increase in length of the triplet repeat sequences and is caused by the non-Mendelian expansion process. This laboratory is investigating the molecular mechanisms of the genetic instabilities that give rise to the disease etiology in well-defined genetic systems such as Escherichia coli. In addition, studies are underway on the DNA synthetic enzymes (polymerases and topoisomerases) that carry out the expansion process. DNA structural investigations have revealed the presence of a new, unusual conformation (flexible and writhed DNA) which is an intrinsic property of the CTGoCAG and CGGoCCG repeat sequences.