Genomic Rate of Recessive Lethal Mutations in Danio rerio

斑马鱼隐性致死突变的基因组率

• 批准号: 9981445
• 负责人: Amy McCune
• 金额: --
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9981445&HistoricalAwards=false
• 关键词: Genomic; Rate; Recessive; Lethal; Mutations

9981445WhitlockThe goals of this project are to measure in the zebrafish, a vertebrate model organism: (1) the number of recessive lethals (an extreme kind of harmful mutation) in the genome and (2) the rate that such harmful mutations arise. The number of lethal mutations carried in the genome will be estimated by measuring the fraction of lethal-free offspring that are produced using a new technique that makes individuals have only a single copy of the genome and so express all lethal mutations. The rate at which lethal mutations arise will be measured by making individuals in which both copies of the genome are identical (and thus carry no recessive lethals) and then measuring the number of lethals that arise in the next generation. This study will provide the first data in any vertebrate on the genomic rate at which new harmful mutations arise. Among animals, data on the genomic rate of the new appearance of harmful mutations is available only for fruit flies. Knowledge of the rate that harmful mutations arise is essential to understanding evolutionary processes in living organisms, in managing small populations of endangered animals, as well as in assessing health risks in humans. While it is known that an average human newborn carries ~100 de novo mutations, it is not clear what fraction of them are harmful and so might contribute to miscarriage and a variety of hereditary diseases.

9981445Whitlock 该项目的目标是测量斑马鱼（一种脊椎动物模型生物）：（1）基因组中隐性致死（一种极端的有害突变）的数量以及（2）此类有害突变出现的速率。基因组中携带的致命突变的数量将通过测量使用新技术产生的无致命后代的比例来估计，该新技术使个体仅具有基因组的单个副本，因此表达所有致命突变。致命突变发生的速率将通过使个体的两个基因组拷贝相同（因此不携带隐性致死突变）来测量，然后测量下一代中出现的致死突变的数量。 这项研究将提供任何脊椎动物中新的有害突变出现的基因组比率的第一个数据。在动物中，有关有害突变新出现的基因组率的数据仅适用于果蝇。了解有害突变的发生率对于了解生物体的进化过程、管理小群体的濒危动物以及评估人类的健康风险至关重要。虽然已知人类新生儿平均携带约 100 个新生突变，但尚不清楚其中哪些部分是有害的，因此可能导致流产和各种遗传性疾病。