Sex-Specific Regulation of Meiotic Recombination Hotspots

减数分裂重组热点的性别特异性调控

基本信息

批准号：
8836550
负责人：
Petko M Petkov
金额：
$ 35.44万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8836550
关键词：
Address Affect Alleles Aneuploidy Animals Behavior Biological Assay Biological Process Chromosome Mapping Chromosome Segregation Chromosomes Chromosomes, Human, Pair 1 Congenital Abnormality DNA Development Disease Dominant Genes Event Female Frequencies Gene Dosage Gene Order Genes Genetic Genetic Crosses Genetic Recombination Genetic Structures Genetic Variation Genome Genomic Instability Germ Cells Goals Hereditary Disease High-Throughput Nucleotide Sequencing Human Individual Infertility Length Malignant Neoplasms Maps Massive Parallel Sequencing Measurement Meiosis Meiotic Recombination Mouse Strains Pathway interactions Pattern Predisposition Process Production Recessive Genes Regulation Reporting Sex Behavior Sex Characteristics Specificity Spontaneous abortion Sterility System Telomere Shortening Testing Trans-Activators Work dosage egg genetic resource genome-wide human disease improved male research study sex sperm cell telomere

项目摘要

DESCRIPTION (provided by applicant): Meiotic recombination events are distributed unevenly along the chromosomes and are regulated by genetic background and sex. The goal of this project is to determine the factors regulating sex specificity of meiotic recombination, boh its regional distribution along the chromosomes and the activity of sex-specific recombination hotspots. We will search for both dominant and recessive trans-acting genes that differ between two mouse strains and affect sex specificity of hotspots Esrrg-1 and Tmem182. Hotspot Esrrg-1 has the same activity in females, but is two-fold more active in male B6xCAST than in WSBxCAST. Hotspot Tmem182 is dependent on PWD genetic background and is two-fold more active in female B6xPWD compared to WSBxPWD, but the reverse is true in males. We will use genetic crosses that will allow us to assess dominance issues and dosage effects separately, for which we will create new genetic resources by developing two new mouse strains on a B6 genetic background combining knockin alleles of the recombination positioning gene Prdm9 created for this study with CAST or PWD sequences on Chr1. We will test for hotspot activity in sperm and eggs of individual animals using a newly developed massive parallel sequencing assay. We will also characterize in detail the sex-specific effect of mTert(-/-) telomere shortenin on genome-wide, regional and local recombination rates by comparing two genetic crosses on the same genetic background but differing in their telomeric lengths.

描述（由申请人提供）：减数分裂重组事件沿染色体不均匀地分布，并由遗传背景和性别调节。该项目的目的是确定调节减数分裂重组的性别特异性的因素，BOH沿染色体的区域分布以及性别特异性重组热点的活性。我们将搜索两种小鼠菌株之间不同并影响热点ESRRG-1和TMEM182的性别特异性的显性和隐性反式作用基因。热点ESRRG-1在女性中具有相同的活动，但在男性B6Xcast中比WSBXcast高两个。热点TMEM182取决于PWD遗传背景，与WSBXPWD相比，女性B6XPWD的活性更高，但在男性中，这种反向是正确的。我们将使用遗传十字架，使我们能够分别评估优势问题和剂量效应，为此，我们将通过在B6遗传背景上开发两个新的鼠标菌株，结合了重组定位基因PRDM9的敲除等位基因，为这项研究创建在CHR1上使用铸造或PWD序列。我们将使用新开发的大量平行测序测定法测试精子和单个动物卵的热点活性。我们还将详细介绍MTERT（ - / - ）端粒的性别特异性作用，通过比较两个遗传背景上的两个遗传杂交，但其端粒长度有所不同，从而对全基因组，区域和局部重组率进行了特定的性别影响。