Genetic analysis of morphological traits in cavefish, Astyanax mexicanus.

描述（由申请人提供）：在过去的十年中，基因组资源已经开发并成功地用于帮助定义传统模型系统中性状的遗传基础。然而，这些资源尚未被广泛应用于自然群体的性状研究。许多新兴的模式系统，包括洞穴鱼Astyanax mexicanus，是特别有利的生物体，用于研究许多鲜为人知的发育过程。具体来说，在过去的1万年里，对洞穴微环境的适应导致了各种退化特征的积累，例如，眼睛和色素完全丧失。一个表面河流居住，种内成员的本属的持久性，使这些鱼杂交，创造杂交种。Tabin实验室开发了一个基于重组的连锁图，使用数百个微卫星标记来促进数量性状位点（QTL）的研究。由于洞穴鱼是密切的系统发育亲属的研究鱼类，斑马鱼，他们共享一个显着水平的基因组同线性。这些鱼的地质和自然历史深深植根于相当数量的古典和当代文献中。此外，居住在多个洞穴内的墨西哥中部的Sierra de El Abra地区的洞穴鱼的几个人口，允许分析的平行进化和收敛的表型性状在不同的Astyanax人口已经从地质隔离的洞穴人口。最后，洞穴鱼是强壮的生物，很容易在塔宾实验室中维持和繁殖。为了更好地了解退化形态的遗传基础Astyanax，提出了一个三重策略。首先，由Tabin实验室先前构建和出版的全基因组连锁图，包括数百个微卫星标记，将分析它们在Astyanax最近的亲属中的同线位置，斑马鱼Danio rerio。这项工作的目的是锚定的洞穴鱼类连锁图的斑马鱼的物理地图。第二，利用QTL分析，我将确定与四个性状的发展相关的候选基因的位置：视觉系统退化，黑色素产生细胞的损失，肋骨数量和形态的变异，以及面部骨骼发育不全。第三，将对与上述QTL紧密连锁的基因进行功能测定，以了解和表征它们在这些特征丧失中的潜在作用。在Astyanax的洞穴形式中存在的几种退行性特征可能在人类退行性疾病中具有等同或平行的基础。因此，在本研究中提出的QTL中获得的结果也可能对更好地表征导致类似人类临床疾病的遗传事件具有意义

DESCRIPTION (provided by applicant): Genomic resources have been developed and used successfully over the past decade to help define the genetic basis for traits in traditional model systems. These resources, however, have not been applied widely to the study of traits in natural populations. Many emerging model systems, including the cavefish Astyanax mexicanus, are especially favorable organisms for the study of numerous poorly-understood developmental processes. Specifically, adaptation to the cave microenviroment in the past 10,000 years has resulted in the accumulation of a variety of degenerate traits, e.g., complete loss of eyes and pigmentation. The persistence of a surface river-dwelling, intraspecific member of this genus has allowed these fish to be interbred to create hybrids. The Tabin lab has developed a recombination-based linkage map using hundreds of microsatellite markers to facilitate quantitative trait locus (QTL) studies. Since cavefish are close phylogenetic relatives of the well-studied fish, Danio rerio, they share a remarkable level of genomic synteny. The geological and natural history of these fish are well-rooted in a sizeable classical and contemporary literature. In addition, several populations of cavefish residing in multiple caves within the Sierra de El Abra region of central Mexico, allow for analyses of parallel evolution and the convergence of phenotypic traits in different populations of Astyanax having evolved from geologically-isolated cave populations. Finally, cavefish are robust organisms that are easily maintained and bred in the Tabin laboratory. To better understand the genetic basis for degenerate morphologies in Astyanax, a three-fold strategy is proposed. First, a genome-wide linkage map, previously constructed and published by the Tabin laboratory, comprised of hundreds of microsatellite markers will be analyzed for their syntenic positions in the closest relative of Astyanax with a sequenced genome, the zebrafish Danio rerio. This work will be aimed at anchoring the cavefish linkage map to the zebrafish physical map. Second, utilizing QTL analyses, I will identify the location of candidate genes associated with the development of four traits: visual system degeneration, loss of melanin-producing cells, variability in rib number and morphology, and facial bone dysgenesis. Third, genes closely linked to the QTL described above will be subjected to functional assays to understand and characterize their potential role(s) in the loss of these characteristics. Several of the degenerative traits present in the cave-form of Astyanax may have equivalent or parallel bases in human degenerative disorders. Thus, results obtained in the QTLs proposed in this study may also have implications for better characterizing genetic events leading to analogous human clinical diseases