Genetic Screen for Postembryonic Development in the Zebrafish (&ITDanio rerio&IT): Dominant Mutations Affecting Adult Form
Genetic Screen for Postembryonic Development in the Zebrafish (&ITDanio rerio&IT): Dominant Mutations Affecting Adult Form
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DOI：
10.1534/genetics.117.300187
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发表时间：
2017-10-01
期刊：
影响因子：
3.3
通讯作者：
Harris, Matthew P.
中科院分区：
文献类型：
--
作者：
Henke, Katrin;Daane, Jacob M.;Harris, Matthew P.
大规模的正向基因筛查有助于识别调节发育、内稳态和再生的基因，以及疾病的机制。斑马鱼Danio rerio是一种成熟的遗传和发育模型，用于基因筛查，以揭示早期发育所需的基因。然而，对胚胎后发育的调控受到的关注较少，因为这些筛查更劳动密集型，需要广泛的资源。缺乏对后期发育的系统询问，使得成虫形态和生理的遗传调节的很大方面没有得到解决。为了了解胚胎后发育的遗传控制，我们对影响成年斑马鱼的表型进行了显性筛选。在我们的筛选中，我们鉴定了72个成年可存活突变体，显示出骨骼形状的变化以及色素沉着的缺陷。为了对这些突变体进行有效的定位和突变鉴定，我们设计了一种新的基于突变体特定单倍型鉴定的定位策略。使用这种方法与候选基因方法相结合，我们能够在所分析的25个突变体中识别出22个连锁突变。总的来说，我们的突变分析表明，存在与后期发育相关的关键基因和途径。这些途径中的许多与人类共享，并在各种疾病条件下受到影响，这表明可能导致成人形态变化的遗传途径受到限制。综上所述，这些结果表明，显性筛选是识别突变的一种可行和有效的手段，可以进一步了解基因在胚胎后发育和疾病中的功能。
Large-scale forward genetic screens have been Instrumental for Identifying genes that regulate development, homeostasis, and regeneration, as well as the mechanisms of disease. The zebrafish, Danio rerio, Is an established genetic and developmental model used In genetic screens to uncover genes necessary for early development. However, the regulation of postembryonic development has received less attention as these screens are more labor Intensive and require extensive resources. The lack of systematic Interrogation of late development leaves large aspects of the genetic regulation of adult form and physiology unresolved. To understand the genetic control of postembryonic development, we performed a dominant screen for phenotypes affecting the adult zebrafish. In our screen, we Identified 72 adult viable mutants showing changes In the shape of the skeleton as well as defects In pigmentation. For efficient mapping of these mutants and mutation Identification, we devised a new mapping strategy based on Identification of mutant-specific haplotypes. Using this method In combination with a candidate gene approach, we were able to Identify linked mutations for 22 out of 25 mutants analyzed. Broadly, our mutational analysis suggests that there are key genes and pathways associated with late development. Many of these pathways are shared with humans and are affected In various disease conditions, suggesting constraint In the genetic pathways that can lead to change In adult form. Taken together, these results show that dominant screens are a feasible and productive means to Identify mutations that can further our understanding of gene function during postembryonic development and In disease.