权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Understanding how developmental systems compensate for and are affected by change

了解发展系统如何补偿变化并受变化影响

基本信息

批准号：
8532934
负责人：
Susan E Lott
金额：
$ 23.26万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-11 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532934
关键词：
Accounting Adult Affect Aneuploidy Animals Autistic Disorder Behavior Biochemical Buffers California Complex Congenital Abnormality Congenital Disorders Data Development Developmental Process Diploidy Disease Dissection Dosage Compensation (Genetics)Dose Drosophila genus Drosophila melanogaster Embryo Female Financial compensation Gene Dosage Gene Expression Gene Transfer Techniques Genes Genetic Genetic Variation Genome Genomics Growth Human Lead Link Measures Mentorship Messenger RNA Methods Modeling Molecular Morphology Organism Outcome Pattern Phenotype Play Process Proteins Research Research Personnel Role Severities Sex Chromosomes Source Spontaneous abortion Staging Stereotyping System Techniques Testing Time Transgenic Organisms Universities Variant Y Chromosome abstracting base dosage follow-up male mutant programs response sex skills

项目摘要

Project Abstract Animal development is remarkably robust to variation, be it of genetic, environmental, or stochastic origin. It is widely believed that complex systems have evolved to buffer against variation because the consequences of uncompensated variation are severely deleterious to the organism, as in the myriad human congenital disorders that arise because of genetic or environmental perturbations in development. Despite the importance of the systems that make development robust, they remain poorly understood. Little is known, for example, about relationship between the level of robustness and the severity of the phenotype were the robustness to fail. Arguably the most common form of large-scale genetic variation encountered in animal development is sex chromosome dosage. In my research, I use the consequences of and response to differences in sex chromosome dose between males and females of Drosophila melanogaster as a general model for understanding how variation in the gene dose can affect development. I recently developed methods to sequence the mRNA from single Drosophila embryos, which allowed me to discover that many X-linked genes that play an important role in patterning the Drosophila embryo are expressed at nearly identical levels before the canonical Drosophila dosage compensation system is activated. This demonstrated the existence of an uncharacterized, yet widely used, system of dosage compensation in the early embryo. Moving forward, I will A.1) determine the mechanism of early zygotic dosage compensation, A.2) characterize dosage compensation in a species with recently derived sex chromosomes to identify genes with a strong requirement for compensation, and A.3) manipulate gene dose in transgenic D. melanogaster to characterize how variation in early development affects adult phenotypes. The last aim will allow dissection of how variation is propagated or suppressed during development, and form the basis of the independent stage of my research program.

项目摘要