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

论文研究：人类常见疾病等位基因的群体遗传过程

• 批准号: 0073297
• 负责人: Martin Kreitman
• 金额: $ 1万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0073297&HistoricalAwards=false
• 关键词: Dissertation; Research; Population; Genetic; Processes

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.

0073297Kreitman & Toomajian 该项目研究了一个广泛的问题，即为什么导致遗传性疾病的某些 DNA 突变在当前人群中如此常见。 该研究重点关注一种特殊疾病——遗传性血色素沉着病，这种疾病主要是由北欧血统的大约十分之一的个体携带的单个 DNA 碱基突变引起的。收集人群内部和人群之间存在的血色素沉着病突变周围 DNA 区域的 DNA 差异，可以推断出有关该突变的历史和发生该突变的基因的详细信息。 这项工作的目标是比较血色素沉着病患病率的竞争模型，考虑到自然选择和人口历史与在该位点发现的实际遗传变异的作用，以确定哪些模型最适合数据。由于影响基因功能并导致遗传性疾病的突变在人类遗传变异中占相当大的比例，因此对影响其患病率的因素的研究对于了解人类遗传多样性和健康都具有重要意义。 这些有害的突变影响所有其他形式的生命，但它们在人类身上的研究是强大的，因为现代医学擅长检测这些自然发生的突变的微小影响。