Uncovering mechanisms controlling chromosome-specific behaviors during meiosis

揭示减数分裂过程中控制染色体特异性行为的机制

• 批准号: 10039230
• 负责人: Katherine Elisabeth Billmyre
• 金额: $ 10万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10039230
• 关键词: Address; Affect; Aneuploidy; Animal Model; Behavior; Biological; Biology; Cells; Cellular biology; Centromere; Chromosome Pairing; Chromosome Segregation; Chromosome Structures; Chromosomes; Congenital Abnormality; Cytology; DNA; Defect; Development; Developmental Biology; Diploidy; Drosophila genus; Drosophila melanogaster; Embryo; Etiology; Event; Exhibits; Failure; Female; Fertility Disorders; GTP-Binding Protein alpha Subunits, Gs; Genetic; Genetic Crossing Over; Genetic Nondisjunction; Genetic Recombination; Genome; Germ Cells; Goals; Haploidy; Human; In Situ Hybridization; Individual; Infertility; Location; Meiosis; Meiotic Recombination; Modeling; Molecular; Oocytes; Organism; Pattern; Process; Proteins; Recombinant DNA; Regulation; Research; Resolution; Role; Sampling; Sterility; Structure; Synaptonemal Complex; System; Techniques; Time; Training Support; Work; X Chromosome; arm; autosome; chromosome missegregation; egg; experience; genome sequencing; high resolution imaging; insight; loss of function; mutant; novel; offspring; programs; segregation; sperm cell; whole genome

Project Summary Meiosis is a tightly controlled process during which the diploid genome must segregate into haploid gametes (i.e. eggs or sperm). Inheritance of the incorrect number of chromosomes causes fertility and birth defects. However, the causes of chromosome missegregation are not always conserved between chromosomes and the reasons for inter-chromosomal differences are still unknown. One key contributor appears to be either a complete loss of crossing over or abnormal crossover placement. Drosophila melanogaster is a powerful model to better elucidate the regulation of chromosome- specific crossing over and the effects on chromosome segregation. In most cases, mutants that disrupt crossing over do so uniformly across the genome making it difficult to understand how chromosome-specific defects occur. However, a recently identified set of mutants in a partial loss-of- function synaptonemal complex mutant exhibit substantially different defects in pairing and recombination on the X chromosome and the autosomes. The synaptonemal complex is a conserved meiotic structure that holds homologous chromosomes together and is necessary for crossing over to occur. The long- term goal of this project is to investigate how the synaptonemal complex regulates chromosome- specific recombination and meiotic behaviors necessary for segregation. This work will investigate 1) the role of the synaptonemal complex in regulating the recombination landscape and 2) the importance of chromosome structure informing meiotic behaviors. Furthermore, this project will establish a new toolkit for analyzing individual chromosomes. Overall, this project will provide insights into both the regulation of crossover location and meiotic chromosome biology. By studying the importance of individual chromosome behaviors and the synaptonemal complex in recombination, substantial advances can be made in understand the biology underlying the development of aneuploidies.

项目概要 减数分裂是一个严格控制的过程，在此过程中二倍体基因组必须分离成单倍体 配子（即卵子或精子）。遗传错误的染色体数量会导致生育能力 和出生缺陷。然而，染色体错误分离的原因并不总是保守的 染色体之间的差异以及染色体间差异的原因仍然未知。一键 贡献者似乎是交叉完全丢失或交叉放置异常。 黑腹果蝇是一个强大的模型，可以更好地阐明染色体调控 特异性交换和对染色体分离的影响。在大多数情况下，突变体 破坏交叉在整个基因组中统一进行，因此很难理解如何进行 发生染色体特异性缺陷。然而，最近发现的一组突变体部分丧失- 功能联会复合体突变体在配对和重组方面表现出截然不同的缺陷 位于 X 染色体和常染色体上。联会复合体是一种保守的减数分裂结构 它将同源染色体固定在一起，并且是交换发生所必需的。长- 该项目的长期目标是研究联会复合体如何调节染色体 分离所需的特定重组和减数分裂行为。这项工作将调查 1) 联会复合体在调节重组景观中的作用以及2） 染色体结构对减数分裂行为的重要性。此外，该项目将 建立一个用于分析个体染色体的新工具包。总体而言，该项目将提供见解 交叉位置的调节和减数分裂染色体生物学。通过研究 个体染色体行为和联会复合体在重组中的重要性， 在理解发育背后的生物学方面可以取得实质性进展 非整倍体。