The Harris lab will explore why individuals accumulate mutations at different rates and in different genetic locations. The process by which mutations become stamped into the human genome is not entirely random. For example, in my graduate and postdoctoral work, I found that Europeans contain more mutations in the nucleotide sequence “TCC” than do people from Africa or East Asia. Some of this bias may arise from different “mutator alleles”—genetic factors that subtly alter the likelihood a DNA sequence will sustain damage or be efficiently repaired. Now, combining cutting-edge methods in cell and molecular biology and comparative genomics with sophisticated computational and statistical analyses, our group will identify longer sequences that differ in mutability between human populations and assess whether these sequences constitute “landing pads” for specific proteins that may contribute to their damage or impede their repair. In addition, working with strains of inbred mice, we will look for chromosomal regions in which mutator alleles are tightly associated with the mutations they generate—work that could facilitate the discovery of genes that influence mutability, a key factor underlying all heritable human diseases as well as cancer.