The influence of short indel heterozygosity on local nucleotide mutation rate

短插入缺失杂合度对局部核苷酸突变率的影响

• 批准号: 1011475
• 负责人: Charles Baer
• 金额: $ 1.49万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1011475&HistoricalAwards=false
• 关键词: influence; short; indel; heterozygosity; local

All organisms' genomes mutate, but do some mutate more than others? For example, are individuals with differing lengths of repetitive DNA at a given site in their genome more likely to mutate? To examine this question, next-generation DNA sequencing technology will be used to compare the mutational properties at genomic sites that differ in length in 16 individuals from an experimental population of nematode worms. The DNA sequencing information will be used to test whether 1) sites that differ by short stretches of DNA mutate more than sites that do not and 2) if there is a greater number of single DNA base mutations in the regions flanking the sites that differ in length.Understanding how differences in mutational properties differ between and within species has implications beyond pure academic interests. Most people who live in an industrialized society will die of diseases with a complex genetic basis; for example, there are a multitude of subtle genetic causes that lead to cancers. If genomic mutation rates differ significantly among individuals within a species, this would have a significant effect on how to best approach the study of such complex diseases. In particular, the understanding of the "rare variant/common variant" conceptual framework that motivates association studies of human diseases would need to be re-evaluated in light of a greater appreciation of the role of rare variants in the human population. If individuals with differing lengths of repetitive DNA at a given site are predisposed to mutation, this will indeed be the case.

所有生物体的基因组都会发生突变，但是否有一些比其他的突变更多？例如，在基因组中某一特定位点上具有不同长度重复DNA的个体是否更容易发生突变？为了研究这个问题，下一代DNA测序技术将用于比较来自线虫实验种群的16个个体的基因组长度不同位点的突变特性。DNA测序信息将被用来测试是否1)短段DNA不同的位点比短段DNA不同的位点发生更多的突变，2)在长度不同的位点两侧的区域是否有更多的单DNA碱基突变。了解物种之间和物种内部的突变特性差异的意义超越了纯粹的学术兴趣。生活在工业化社会中的大多数人将死于具有复杂遗传基础的疾病；例如，有许多微妙的遗传因素导致癌症。如果同一物种内不同个体的基因组突变率有显著差异，这将对如何最好地研究此类复杂疾病产生重大影响。特别是，对推动人类疾病关联研究的“罕见变异/常见变异”概念框架的理解需要根据对罕见变异在人类群体中的作用的更大认识进行重新评价。如果在一个特定位点上具有不同长度的重复DNA的个体易发生突变，情况确实如此。