Nathaniel Sharp

Credentials: Genetics Department

Position title: Spontaneous mutation rate and spectrum


Phone: 608-263-8003

4124 Genetics and Biotechnology Center
425G Henry Mall
Madison, WI 53706

Headshot of Nathaniel Sharp

lab website:

focus groups:

Molecular & Genome Biology of Microbes; Systems Biology

research description:

Mutation occurs in all organisms and is a major cause of disease, but we are coming to recognize that this fundamental process can be highly variable. I study how the risk of mutation varies across genomic and environmental contexts, recognizing that “mutation” includes a spectrum of single-nucleotide changes, indels and larger chromosomal alterations. For example, I discovered that flies carrying any harmful allele are more likely to use error-prone DSB repair pathways, leading to an increased indel mutation rate. The spatial distribution of mutations throughout the genome is also informative: in yeast I found that haploid cells, but not diploids, are susceptible to mutations in late-replicating DNA, such that ploidy levels will differ in both the location and types of mutations incurred. Going forward, a major focus of my lab will be on characterizing how natural genetic variation influences the spontaneous mutation spectrum, from single-nucleotide changes to aneuploidy, which will lead to new insight into DNA repair processes.


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