Swept under the rug: A systematic analysis of genetic background effects in Drosophila

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。众所周知，DNA序列中的突变可能会产生深远的物理（表型）影响。然而，人们不太清楚的是，这种突变的表型后果不仅仅取决于该基因DNA序列的变化。 虽然DNA的变化很重要，但它们的表型结果可以被环境和拥有突变的个体的遗传组成所改变。换句话说，两个拥有完全相同突变的个体可能不会表现出相同的表型，因为他们经历了不同的环境，而且他们基因组的编码者可能完全不同。他们的基因组之间的差异的后果被称为“遗传背景效应”，虽然在遗传学家中众所周知，但它们很少成为科学研究的焦点。在这个项目中，一组果蝇基因中的一系列突变将被用来解决与生物体遗传背景的影响有关的几个悬而未决的问题。首先，将绘制有助于遗传背景效应的遗传修饰剂，以确定它们如何有助于其他表型。本项目的第二个目标是了解这种遗传背景效应在其他遗传分析中的普遍程度。最后，允许同时检查基因组中所有基因的转录活性的技术将用于比较和测试与遗传背景效应的后果和原因以及所研究的突变强度的变化有关的模型。 这项研究的结果应有助于提供一个框架，以便更广泛地了解某一特定突变以及基因内和基因间的一系列突变的效应谱，该项目的主要智力价值是，它将提供对遗传背景效应后果的系统分析，从而将说明遗传背景效应对遗传研究和分析的重要性。如果计划中的工作证实了初步结果，这项研究可能会改变遗传学的教学方式和遗传分析的执行方式。此外，从事该项目的研究生将接受指导和培训，从而发展遗传学，基因组学和统计学方面的技术分析技能。 为了帮助纠正公众对遗传学的误解，首席研究员为公众开设了一个遗传学教育“博客”。该博客将专注于纠正基因编码性状的误解，而不是影响表型的基因变体（等位基因）。此外，使用最近从文献（genesgonewild.blogspot.com）“翻译”的例子，博客还将讨论突变和等位基因的条件效应，以及这些效应的上下文依赖性（上下文指环境和遗传背景）。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).It is well known that mutations in a sequence of DNA can have profound physical (phenotypic) effects. However, it is less well appreciated that the phenotypic consequences of such mutations depend on more than just the changes in the DNA sequence of that gene. Although the changes in the DNA are important, their phenotypic consequences can be modified both by the environment and by the genetic make-up of the individual possessing the mutation. In other words, two individuals possessing exactly the same mutation may not show the same phenotype, given that they have experienced different environments, and that the remainders of their genomes may be quite different. The consequences of the differences between their genomes are known as "genetic background effects", and while well known among geneticists, they have rarely been the focus of scientific studies. In this project, a series of mutations in a set of Drosophila melanogaster genes will be used to address several outstanding questions pertaining to the effects of an organism's genetic background. First, the genetic modifiers contributing to genetic background effects will be mapped to determine how they contribute to other phenotypes. The second goal of this project is to understand how pervasive such genetic background effects are in other genetic analyses. Finally, technologies that allow for the simultaneous examination of the transcriptional activity of all of the genes in the genome will be used to compare and test models pertaining to the consequences and causes of genetic background effects and variation in the strength of the mutations under study. The results from this research should help to provide a framework for a broader understanding of the spectrum of effects for a given mutation, and for series of mutations within and between genes.The principal intellectual merit of this project is that it will provide a systematic analysis of the consequences of genetic background effects, and thus will address the importance of genetic background effects for genetic studies and analyses. If the planned work confirms the preliminary results, this research could change how genetics is taught and how genetic analyses are performed. In addition, graduate students working on the project will receive mentoring and training, thus developing technical analytical skills in genetics, genomics, and statistics. To help to correct public misconceptions pertaining to genetics, the principal investigator has initiated a "blog" for genetics education for the general public. The blog will focus on correcting the misconception that genes encode traits, rather than variants of genes (alleles) that influence phenotypes. In addition, using recent examples "translated" from the literature (genesgonewild.blogspot.com), the blog will also discuss conditional effects of mutations and alleles, and the context-dependence of these effects (context referring to environment and genetic background).