Characterization of functional/structural constraints operating on the Drosophila genome

染色体是携带基因的细胞实体，由于断裂和重新附着在新的结构中，它们的结构可能会发生变化。这些断裂不是随机发生的：一些染色体区域容易参与染色体重排，而其他区域很少受到影响。染色体区域间易感性差异的原因尚不清楚。目前的观点是，协同工作或具有共同分子需求的基因聚集在特定的染色体区域。据认为，如果这些区域被重排破坏，生物体的生存能力和/或生育力可能会受损。在人类中，多种疾病与特定染色体区域的重排有关。有趣的是，这些染色体区域在健康个体中是完整的，这一观察结果也适用于其他脊椎动物物种。这笔拨款资助了第一个严格的实验测试，以了解破坏这些微妙的、超保守的基因组区域的后果。这项工作将使用果蝇，这是了解染色体重排后果的最佳模式生物之一。果蝇的染色体拥有和脊椎动物一样的精致、超保守的区域。此外，果蝇研究人员有分子工具来诱导精确的染色体重排，并随后监测它们对生物体的影响。首席研究员计划破坏果蝇的这些特殊染色体区域，以便分析其后果。这项研究可能会对理解人类遗传疾病产生影响。此外，这项资助将培养本科生和博士后在先进的遗传学概念。

Chromosomes, the cellular entities that carry genes, can suffer modifications in their structure due to breakages and reattachments in new configurations. These breakages do not occur at random: some chromosome regions are prone to participate in chromosomal rearrangements while others are seldom affected. The reasons for these differences in susceptibility among chromosome regions are unclear. The current notion is that genes that work cooperatively or that have common molecular requirements are clustered in particular chromosome regions. It is thought that the viability and/or fertility of the organism can be impaired if these regions are disrupted by rearrangements. In humans, multiple diseases correlate with rearrangements of particular chromosome regions. Interestingly, those chromosome regions are intact in healthy individuals, an observation that also applies to other vertebrate species. This grant funds the first rigorous experimental test to understand the consequences of disrupting these delicate, ultra-conserved genomic regions. The work will use the fruit fly Drosophila, which is one of the best model organisms to understand the consequences of chromosomal rearrangements. Drosophila chromosomes possess the same kind of delicate, ultra-conserved regions as vertebrates do. In addition, Drosophila researchers have molecular tools to induce precise chromosomal rearrangements and to subsequently monitor their effects on the organism. The principal investigator plans to disrupt these special chromosome regions of Drosophila in order to analyze the consequences. The research is likely to have implications for understanding human genetic diseases. Furthermore, this grant will train undergraduate students and postdoctoral fellows in advanced concepts of genetics.