Physiological and genetic mechanisms underlying variation in growth within species

在所有物种中，许多特征在个体之间表现出连续的变化（例如，体重），而不是离散的一个或另一个状态（例如，血型）。连续性状是由环境和潜在的大量基因共同决定的。我的研究计划的目标是了解物种内生长变化的生理和遗传因素。我将通过研究特定的生理途径和将生理变化与小鼠体型变化（例如，质量，骨长等）联系起来来实现这一目标。我的计划的重点是健康个体之间自然发生的变异，而不是人工基因修饰的影响。这一领域的大量工作是对近亲繁殖的小鼠进行研究。尽管近亲繁殖的动物从遗传角度来看具有优势，但尚不清楚它们在“现实世界”中的代表性如何。因此，我将在实验室中研究近亲繁殖和近亲繁殖的老鼠种群，然后利用这项工作产生假设，我将在啮齿类动物的自然种群中进行测试。这将把遗传和生理结果置于生态环境中（例如，遗传和生理变异对动物生存和繁殖能力的影响是什么？）我的研究将深入了解遗传变异与整个动物特征（如体型）变异之间的关系。这些信息对于理解为什么有些人比其他人更容易患上某种疾病至关重要。例如，我打算研究的一条生理途径会影响骨矿物质密度，因此这条途径的变化可能会影响骨质疏松症的易感性。了解物种内变异的机制对于预测自然种群如何应对不断变化的环境也很重要，因为遗传变异是实现适应的原材料。

Within all species, many traits show continuous variation between individuals (e.g., body mass) rather than discrete one-or-the-other states (e.g., blood type).  Continuous traits are determined by both the environment and a potentially large number of genes.  The goal of my research programme is to understand the physiological and genetic factors underlying within-species variation in growth.  I will achieve this by studying specific physiological pathways and relating physiological variation to variation in body size (e.g., mass, bone length, etc) in mice.  The focus of my programme will be on naturally-occurring variation among healthy individuals, and not on the effects of artificial genetic modifications.      A great deal of work in this field has examined inbred mice.  Although inbred animals offer advantages from a genetic perspective, it is not clear how representative they are of the 'real world'.  I will therefore study both inbred and outbred populations of mice in the laboratory, and then use this work to generate hypotheses which I will test in natural populations of rodents.  This will put the genetic and physiological results in an ecological context (e.g., what are the consequences of genetic and physiological variation for an animal's ability to survive and reproduce?).      My research will yield insight into the pathways through which genetic variation is related to variation in whole-animal traits such as body size.  Such information is crucial to understanding why some people are more susceptible to a particular disease than others.  For example, one of the physiological pathways I intend to study influences bone mineral density, and so variation in this pathway may affect susceptibility to osteoporosis.  Understanding the mechanisms responsible for within-species variation is also important to predicting how natural populations will respond to a changing environment, since genetic variation is the raw material by which adaptation may be achieved.