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

该项目研究了一个广泛的问题，即为什么某些导致遗传性疾病的DNA突变在当前人群中如此普遍。这项研究的重点是一种特殊的疾病，遗传性血色素沉着症，这主要是由大约十分之一的北欧人携带的单个DNA碱基突变引起的。在血色素沉着症突变周围的DNA区域中，收集存在于人群内部和人群之间的DNA差异，可以推断出这种突变的历史和发生这种突变的基因的细节。这项工作的目的是比较血色素沉着病流行的竞争模型，这些模型考虑了自然选择和人口统计学历史的作用，以及在该位点发现的实际遗传变异，以确定哪种模型最适合数据。由于影响基因功能并导致遗传疾病的突变在人类遗传变异中占相当大的比例，因此研究影响其流行的因素对于理解人类遗传多样性和健康都是相关的。这些有害的突变会影响所有其他形式的生命，但它们在人类身上的研究是强有力的，因为现代医学擅长检测这些自然发生的突变的轻微影响。

0073297Kreitman & ToomajianThis 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.