University of Southern California - Departments of Mathematics and Biological Sciences
Huntington's Disease is one of a number of hereditary human diseases associated with a triplet repeat expansion in the region of the gene. The nature of the mutation process that produces repeat number variation in such genes is of considerable interest to molecular biologists. We are using single sperm analysis to study this mechanism. We have amplified the repeat region in sperm from 30 individuals and determined the number of CAG repeats in each of them. These data are used to model paternal instability in repeat number using current molecular ideas about the expansion process. In this talk I will describe a class of stochastic processes that models how the repeats might arise during DNA replication, and illustrate how the sperm typing data can be used to distinguish different molecular mechanisms. Among the issues addressed is the role of paternal age on the distribution of repeat sizes. Some computational problems involved in fitting these models will be discussed, as well as some open problems. The relevant biological background will be explained in the talk.
For some background, see for example E.P. Leeflang, L. Zhang, S. Tavare, R. Hubert, J. Srinidhi, M.E. MacDonald, R.M. Myers, M. de Young, N.S. Wexler, J.F. Gusella, and N. Arnheim. (1995) Single sperm analysis of the trinucleotide repeats in the Huntington's disease.