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.

项目摘要 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为单倍体 配子（即鸡蛋或精子）。染色体数量不正确的遗传会导致生育 和出生缺陷。但是，染色体错误分析的原因并不总是保守的 在染色体和染色体间差异的原因之间仍然未知。一个钥匙 贡献者似乎是跨越跨越的完全损失，要么是跨界异常的位置。 果蝇Melanogaster是一个强大的模型，可以更好地阐明染色体的调节 特异性交叉以及对染色体分离的影响。在大多数情况下，突变体 跨基因组统一地破坏跨越，使得很难理解如何 发生染色体特异性缺陷。但是，最近确定的一组突变体在部分丧失中 功能突触复合物突变体在配对和重组中表现出根本不同的缺陷 在X染色体和常染色体上。突发型复合体是保守的减数分裂结构 这将同源染色体凝聚在一起，并且对于越过的发生是必要的。长期 该项目的术语目标是研究突发型复合物如何调节染色体 - 隔离所需的特定重组和减数分裂行为。这项工作将调查1） 突发型复合物在调节重组景观中的作用，2） 染色体结构的重要性，告知减数分裂行为。此外，这个项目将 建立一个用于分析单个染色体的新工具包。总体而言，该项目将提供见解 跨越跨界位置和减数分裂染色体生物学的调节。通过研究 单个染色体行为的重要性和重组中的突发性复合物的重要性， 可以在理解发展的生物学发展中取得重大进展 非整倍性。