Characterization of functional/structural constraints operating on the Drosophila genome

果蝇基因组功能/结构限制的表征

• 批准号: 0949365
• 负责人: Jose Ranz
• 金额: $ 13.5万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2012-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0949365&HistoricalAwards=false
• 关键词: Characterization; functional; structural; constraints; operating

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.

染色体是携带基因的细胞实体，由于新构型的破裂和重新分析，其结构可能会改变其结构。 这些破裂并非随机发生：某些染色体区域容易参与染色体重排，而另一些则很少受到影响。 染色体区域之间这些敏感性差异的原因尚不清楚。 当前的概念是合作起作用或具有共同分子需求的基因在尤其是染色体区域聚集。人们认为，如果这些区域被重排干扰，则有机体的生存能力和/或生育能力会受到损害。 在人类中，多种疾病与特定染色体区域的重排相关。 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。 这项赠款为第一个严格的实验测试提供了资金，以了解破坏这些精致，保守的基因组区域的后果。 这项工作将使用果蝇果蝇，这是了解染色体重排后果的最佳模型生物之一。 果蝇染色体具有与脊椎动物相同的精致，超强的区域。 此外，果蝇研究人员还具有分子工具来诱导精确的染色体重排并随后监测其对生物体的影响。 主要研究者计划破坏果蝇的这些特殊染色体区域，以分析后果。 这项研究可能对理解人类遗传疾病有影响。此外，该赠款将培训本科生和博士后研究员，以高级遗传学概念。