Environmental factors affecting heritable mutation frequencies in vertibrates

我研究计划的总体目标是了解导致脊椎动物遗传（种系）突变率变异的过程。我提出了两个主要的研究方向：(1)实验诱导小鼠的生殖系突变和开发新的突变标记用于野外和实验室研究；(2)定量暴露于环境污染物的鸟类自然种群的生殖系突变频率。对于第一部分，我将研究小鼠种系中重复DNA序列突变。我的项目将侧重于描述由诱变剂暴露引起的雌性小鼠卵子中的突变诱导，并开发实验室技术，使用最先进的遗传学设备对突变频率进行可靠的量化。这些新的标记将有助于未来对野生小鼠的研究，野生小鼠是污染物暴露的有用哨兵物种。在我项目的第二部分，我将开发新的遗传标记来检测鸟类的突变，并应用这些标记来量化自然种群的种系突变率。我将把重点放在种群规模大、地理范围广的物种上，其中一些将用于突变率变异的基础研究，另一些将作为有毒环境因素影响的哨兵。这种方法将使我能够解决有关种系突变率差异的问题，这是由于：(a)来自各种来源的污染暴露，(b)种群之间的遗传差异，以及(c)哨兵物种之间的敏感性差异。

The overall goal of my research program is to understand processes that contribute to variance in the heritable (germline) mutation rates of vertebrates. I propose two major lines of investigation: (1) experimental induction of germline mutations in mice and development of new mutation markers for field and laboratory studies, and (2) quantification of germline mutation frequencies in natural populations of birds exposed to environmental contaminants. For part (1) I will study repetitive DNA sequence mutations in the germline of mice. My program will focus on characterizing mutation induction in the eggs of female mice caused by mutagen exposure, and developing laboratory techniques that will enable reliable quantification of mutation frequencies using the most up to date genetics equipment. These new markers will facilitate future studies of feral mice, a useful sentinel species for contaminant exposures. For part (2) of my program I will develop new genetic markers for detecting mutations in birds and apply these to quantify germline mutation rates in natural populations. I will focus on species that have large population sizes and broad geographic ranges, some of which will be used for basic studies of variance in mutation rates, and others as sentinels for the effects of toxic environmental agents. This approach will enable me to address questions regarding variance in germline mutation rates due to: (a) pollution exposure from a variety of sources, (b) genetic differences among populations, and (c) sensitivity differences among sentinel species.