Spinocerebellar ataxia type 1 (SCA1) is a brain disease that results in loss of coordination and balance. It is caused by a change in the DNA containing the information for a gene called ataxin 1. People who develop SCA1 have a larger segment of DNA in this gene than normal, caused by more copies of a repeated sequence of DNA (called a CAG repeat after the DNA code that it contains – reading CAGCAGCAGCAGCAG etcetera). This particular DNA codes for an amino acid called Glutamine, and so these repeats are often referred to as polyglutamine repeats (a similar mutation causes Huntington’s disease). Geneticists noticed several years ago that not all CAG repeats were perfect, in fact the majority of normal-sized repeats contain the DNA sequence CAT, which codes for the amino acid Histidine. In this study Dr Suran Nethisinghe and Dr Paola Giunti from the UCL Institute of Neurology, along with collaborators from the MRC National Institute of Medical Research, examined how these CAT interruptions impact on the disease caused by the CAG repeats. It has been known for sometime that the longer the CAG repeat sequence in a patient, the earlier the ataxia in that patient starts. What Suran and Paola found was that the age at which the disease starts, or age at onset, is not linked to how many CAG repeats there are in total, but how many continuous CAG repeats there are (that is, repeats not interrupted by a CAT sequence). This is important for a number of reasons. First of all, it helps to make predictions of age at onset better for people who have these CAG repeat mutations. Secondly, it sheds light on some of the molecular events that cause brain cells in people with SCA1 to die – leading to disease. Finally, the researchers have shown that the interruptions slow down the toxic process that leads to cell death.
Read more about this research in Suran and Paola’s paper in PLoS Genetics: