Dissertation Research: Population Genetic Processes Underlying a Common Disease Allele in Humans

University Of Chicago, Chicago IL

Investigators

Abstract

0073297 Kreitman & Toomajian This project studies the broad question of why certain DNA mutations that lead to inherited diseases are so common in the present human population. The study focuses on one particular disease, hereditary hemochromatosis, which is caused primarily by the mutation of a single DNA base carried by about 1 in 10 individuals of Northern European descent. The collection of the DNA differences that exist within and between human populations for a region of DNA surrounding the hemochromatosis mutation allows the inference of details about the history of this mutation and the gene in which it occurs. The goal of this work is to compare competing models for hemochromatosis' prevalence that take into account the role of natural selection and demographic history to the actual genetic variation found at this locus to determine which models best fit the data. Because mutations that affect the function of genes and lead to inherited disease make up an appreciable proportion of human genetic variation, the study of the factors affecting their prevalence is relevant for understanding both human genetic diversity and health. These detrimental mutations affect all other forms of life, but their study in humans is powerful because modern medicine excels at detecting the minor effects of these naturally occurring mutations.