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Meiotic Pairing in Male Drosophila

雄性果蝇的减数分裂配对

基本信息

批准号：
9231619
负责人：
JOHN E TOMKIEL DEAN
金额：
$ 43.65万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-08 至 2022-03-31
项目状态：
已结题

项目摘要

The pairing of homologous chromosomes at meiosis I is an essential step in the production of euploid gametes. Failures in pairing lead to chromosome missegregation events (nondisjunction), a leading cause of human genetic syndromes. A novel pairing assay has been developed in the male fruit fly, Drosophila melanogaster, that allows one to assay for the ability of selected sequences to facilitate sex chromosome meiotic pairing (i.e. act as pairing sites). The assay employs an X chromosome that is deleted for the endogenous meiotic pairing sites and a partner Y chromosome into which X chromosome euchromatin has been inserted. Genetic tests of sex chromosome transmission indicate that these “synthetic” pairing sites are capable of all steps required for proper XY segregation, including homolog recognition, adhesion, orientation and disjunction. Molecularly defined CRISPR-mediated deletions of putative pairing sites will be created to identify sequence, position and/or size-specific requirements for pairing sites. Confocal microscopy will be used to examine in situ hybridization of probes to putative pairing sites, and in combination with genetic tests of chromosome transmission, will determine if there are different requirements for pairing versus homolog adhesion versus disjunction. Mutations in genes encoding the putative adhesion complex proteins Tef, MNM and SMN will be tested to define the roles of these genes in effecting adhesion between X euchromatin sequences. As male fly lack recombination, these studies may reveal insights into potentially conserved aspects of homology recognition and pairing that are independent of recombination-associated processes.

在减数分裂I中同源染色体的配对是减数分裂的重要步骤。整倍体配子的产生。配对失败导致染色体错误分离事件（不分离），人类遗传综合征的主要原因。一个新的配对已经在雄性果蝇黑腹果蝇中开发了一种检测方法，该方法允许一种用于测定所选序列促进性染色体减数分裂的能力配对（即充当配对位点）。该检测采用了一个X染色体，对于内源性减数分裂配对位点和伴侣Y染色体，X 染色体常染色质被插入。性染色体的基因检测传输表明这些“合成”配对位点能够进行所有步骤，适当的XY分离所需的，包括同系物识别，粘附，定向和分离分子定义的CRISPR介导的推定的基因缺失将产生配对位点以鉴定序列、位置和/或大小特异性配对网站的要求。共聚焦显微镜将用于原位检查探针与推定的配对位点的杂交，以及与以下基因检测的组合：染色体传递，将决定是否有不同的配对要求与同源粘附与分离的比较。编码假定的粘附复合物蛋白Tef，MNM和SMN将被测试，以确定这些基因影响X常染色质序列之间的粘附。由于雄蝇缺乏重组，这些研究可能揭示了潜在的保守方面的见解，同源性识别和配对不依赖于重组相关流程.