This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To follow a group of individuals at risk for Huntington's Disease (HD) longitudinally (1) to establish how many individuals develop signs of the disease over the study period, (2) to identify the earliest signs of the illness and the age at which they begin, (3) to examine the accuracy of current clinical measures used in detecting the onset of HD, (4) to ascertain possible factors such as potential environmental modifiers and personal beliefs and attitudes influencing age of onset and clinical precursors predictive of onset of manifest HD, and (5) to examine the specificity and sensitivity of markers of DNA and RNA damage as potential state biomarkers for HD.