EDGE CMT: deleterious recessive variation - from experimental data to predictive models

在群体样本中，低频率的隐性分离变异很大程度上是无法研究的。 这个项目使用了一个实验系统，在这个系统中，罕见的等位基因已经变得常见，即隐性的 等位基因可以根据需要进行纯合，并累积大量小效变异的影响 可以不偏不倚地衡量。该项目以贝氏线虫为中心，该线虫 拥有线虫的所有实验优点，但交配系统和种群生物学使 它更适合于解决一般的遗传多样性问题，尤其是隐性变异问题。这 该项目将测量特定性别的竞争适合度和特定性别和等位基因的转录丰度 在C.becei的一个特别设计的小组中，揭示了分离隐性变异和 它的分子特征。这些数据将解决进化生物学中的基本问题，同时 生成可推广的基因和变量尺度模型，预测变异体是否可能具有 隐性效应。

In population samples, segregating recessive variants at low frequency are largely inaccessible to study. This project uses an experimental system in which rare alleles have been made common, recessive alleles can be homozygosed on demand, and cumulative effects of large numbers of small-effect variants can be measured in an unbiased way. The project centers on the nematode Caenorhabditis becei, which has all the experimental virtues of C. elegans but with a mating system and population biology that make it better suited to questions about genetic diversity in general and recessive variation in particular. This project will measure sex-specific competitive fitnesses and sex- and allele-specific transcript abundances in a specially designed panel of C. becei to reveal the architecture of segregating recessive variation and its molecular characteristics. The data will address basic questions in evolutionary biology while generating generalizable gene- and variant-scale models that predict whether variants are likely to have recessive effects.