Do Intermediate-Frequency or Rare Alleles Contribute to the Bulk of Standing Phenotypic Variation?

复杂性状的稳定变异是几个基因和环境协同作用的结果。复杂性状的例子有人类的心脏病和身高，以及家禽的产蛋。我们对这些性状变异的遗传基础知之甚少。对于这种变异的起源和维持，以及我们操纵致病基因的能力来说，一个核心问题是：导致这些特征变异的等位基因通常是罕见的还是频率居中的？这项提议的实验将使用一种新的果蝇遗传图谱方案来区分这些相互竞争的假说。对于复杂特征变异的遗传基础是什么这个问题，答案有许多潜在的影响。无论贡献等位基因的频率通常是低还是高，都表明克隆致病基因的策略将是最有利可图的。最佳的克隆策略将通过设计药物和/或复杂疾病的诊断来影响人类的健康和福利。复杂性状的等位基因频率将使我们最终了解我们通常观察到的复杂性状的表型变异在允许物种适应环境变化方面的作用。

Standing variation in complex traits is the results of the concerted action of several genes and the environment. Examples of complex traits are heart disease and height in humans, and egg production in poultry. We know very little about the genetic basis of variation in such traits. A question central to the origin and maintenance of such variation, as well as our ability to manipulate causative genes, is: are the alleles which contribute to variation in these traits generally rare or more intermediate in frequency? The experiments of this proposal will use a novel genetic mapping scheme in Drosophila to distinguish between these competing hypotheses.The answer to the question, what is the genetic basis of variation in complex traits, has many potential repercussions. Whether contributing alleles are generally at low or high frequency suggests strategies that will most profitably be employed in order to clone causative genes. Optimal cloning strategies will impact human health and welfare via designer drugs and/or diagnostics for complex disease. The frequency of alleles contributing to complex traits will allow us to ultimately understand the role of the phenotypic variation we commonly observe for complex traits in allowing species to adapt to environmental change.