The program is concerned with the detection and analysis of sequence variations in the human genome, particularly those responsible for genetic disease or useful in following those variants. We will depend largely on the system of sequence-defined DNA separations of Fischer and Lerman and extend the system, both in its experimental capability and in theoretical basis of its function. We will also pursue certain structural and thermodynamic questions, particularly those bearing on the relations between sequence and the stability of the helix with respect to melting.