GENETIC AND EPIGENETIC CONTROL OF EYE GROWTH

描述(改编自申请者摘要)：近视是一种极端 普遍的视力异常，通常是由过度生长引起的 眼睛的后部相对于角膜的光学能量和 镜头。近视及其治疗的累积成本是巨大的。发病时间和 近视的发展受环境因素的强烈影响，但 近视的风险显然受基因的影响。这样做的中心目的是 工作是确定正常情况下哪些基因和分子调节细胞的生长 哺乳动物眼睛的不同部位，然后评估其中是否 同样的基因也会导致人类的视觉异常。 这个项目的第一个目标是系统地定位选择性地 影响小鼠眼睛、晶状体、角膜和视网膜的生长。 利用新的数量性状基因座(QTL)区间定位方法，超过 选择性影响眼睛不同部位生长的10个基因座 将与F2杂交组合作图。作为第二个目标的一部分，这些QTL将 使用更高的精度(1&2厘米的临界区域)绘制地图 特殊作图资源&高级杂交与正反交同源 台词。然后将使用互补的方法来评估最有希望的 与特定QTL连锁的候选基因。第三个目标是发展 几个重要品系的眼球生长动因研究，以及 特别设计的同源基因菌株。这项工作将测试关于如何 基因和环境因素影响眼睛的光学发育。 了解不同的QTL如何影响眼睛的不同部位 最终有助于更好地理解分子和 与人类眼睛发育相关的发育机制。

DESCRIPTION (Adapted from applicant's abstract): Myopia is an extremely pervasive abnormality of vision that is usually caused by excessive growth of the posterior part of the eye relative to the optical power of the cornea and lens. The cumulative cost of myopia and its treatment is huge. The onset and progression of myopia are strongly influenced by environmental factors, but the risk of becoming myopic is clearly influenced by genes. The central aim of this work is to determine what genes and molecules normally regulate the growth of different parts of the mammalian eye and to then assess whether any of these same genes contribute to optical abnormality in humans. The first aim of this project is to systematically map genes that selectively influence the growth of the eye, the lens, the cornea, and the retina of mice. Using novel quantitative trait locus (QTL) interval mapping methods, more than 10 gene loci that selectively affect the growth of different parts of the eye will be mapped with F2 intercrosses. As part of the second aim, these QTLs will be mapped with far greater precision (a critical region of 1‑2 cM) using special mapping resources‑advanced intercrosses and reciprocal congenic lines. Complementary methods will then be used to evaluate the most promising candidate genes linked with particular QTLs. The third aim is a developmental study of the mekics of eye growth in several important strains, and in specially engineered congenic strains. This work will test ideas about how genes and environmental factors affect the optics of eye development. Understanding how different QTLs affect different parts of the eye will ultimately contribute to a far better understanding of molecular and developmental mechanisms associated with eye growth in humans.