Effect of Normal Polyglutamine Polymorphism on Huntington Disease Protein Function.

Huntington Disease (HD) is a progressive neurodegenerative disorder that causes deterioration of specific brain cells- leading to uncontrolled movement, emotional disturbance, and ultimately death. HD results from a mutation in the DNA encoding the protein huntingtin- a large protein of unknown fiinction ubiquitously expressed throughout all tissues of the human body. Interestingly, huntingtin contains a polyglutamine (polyQ) tract near its NH2-terminus that is normally polymorphic within the human population (Qe- Qss), but that increases in size well beyond its normal range to cause disease. It is unclear what consequence normal polyQ polymorphism has on huntingtin function within cells- thus we are deriving a series of HD constructs differing in polyQ tract length (to go along with the huntingtin constructs 23, 45, 55, and 86 glutamines currently in the lab). These new normal range constructs will ultimately be used to perform protein localization experiments within tissue culture cells to elucidate how normal polyQ tract length polymorphism affects huntingtin intracellular localization