Genomic Rate of Recessive Lethal Mutations in Danio rerio

这个项目的目标是在脊椎动物模式生物斑马鱼中测量：(1)基因组中隐性致死(一种极端的有害突变)的数量和(2)这种有害突变的出现速度。基因组中携带的致命突变的数量将通过测量使用一种新技术产生的非致命后代的比例来估计，这种新技术使个体只有一个基因组副本，从而表达所有致命突变。致命突变出现的速度将通过制造两个基因组副本完全相同的个体(因此没有隐性致死)，然后测量下一代出现的致命突变的数量来衡量。这项研究将提供任何脊椎动物中关于新的有害突变出现的基因组速度的第一个数据。在动物中，关于新出现的有害突变的基因组比率的数据只适用于果蝇。了解有害突变产生的速度对于了解生物的进化过程、管理少量濒危动物以及评估人类的健康风险至关重要。虽然众所周知，一个人类新生儿平均携带100个从头突变，但尚不清楚其中有多少是有害的，因此可能导致流产和各种遗传性疾病。

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.