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Charla Lambert

Joined Program: 2002
Previous Degrees: M.S., Applied Mathematics, University of Washington; B.S., Mathematics, Massachusetts Institute of Technology
Olson Lab

clambert [ a t ] u.washington.edu

Research:

My current research falls into two main categories of molecular population genetics: 1) Statistical methods for detecting selection from polymorphism data, and 2) The evolutionary history of a human locus, specifically the FY gene (a.k.a., the Duffy blood group locus).

 

Detecting selection. In this part of my project, I study theoretical models of recombination and selection in human DNA sequence evolution. Specifically, I wish to evaluate the influence recombination has on current computational methods for detecting different forms of selection, and vice versa. Many methods for detecting regions of the human genome under selection rely on standard coalescent theory; this involves a critical assumption that no recombination has occurred in the region of interest. Likewise, many methods for detecting and measuring recombination from sequence data rely on the assumption of neutral evolution. An important open question is whether such assumptions bias the resulting estimates of population genetic parameters, and what is needed to create methods incorporating both recombination and selection. To address these questions, I’ve designed and analyzed many simulations generated using the software packages ms and SelSim.

The FY locus. The FY gene encodes the Duffy blood group system in humans. Individuals homozygous for a particular single-base mutation do not express FY protein in their red blood cells and are resistant to malaria caused by the parasite Plasmodium vivax. The so-called Duffy-O mutation has a frequency of nearly 100% in African populations but is nonexistent elsewhere. Because of this unusual geographic distribution, it has long been hypothesized that Duffy-O was the target of positive natural selection caused by the presence of either P. vivax or some similarly harmful agent in prehistoric Africa. In this part of my project, I analyze fully re-sequenced DNA surrounding the site of Duffy-O in chromosomes sampled from different world-wide populations. My goal is to infer possible evolutionary histories for the Duffy-O mutation by analyzing patterns of DNA variation at the locus.