TRANSLOCATIONS/GENES ASSOCIATED WITH PREMATURE OVARIAN FAILURE

与卵巢早衰相关的易位/基因

• 批准号: 6288732
• 负责人: Ramaiah Nagaraja
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6288732
• 关键词: chromosome translocation; computer assisted sequence analysis; gene deletion mutation; gene expression; genetic mapping; graafian follicles; human genetic material tag; human tissue; molecular cloning; molecular genetics; nucleic acid sequence; ovary disorder; sex chromosomes

About 1-3% of all women undergo precocious menopause, either never going through menarche or stopping menstruation by the mid-30s, rather than reaching the standard reproductive lifespan at about 50. A fraction of such instances of early-onset premature ovarian failure (POF) is genetic. A single locus on chromosome 3 is implicated in several families and in several isolated individuals with translocations or deletions that interrupt the DNA in that region. A much larger group of translocations have been reported on the X chromosome, centering on a critical region of the long arm. There we have shown that based on the physical map we had constructed, there are at least 35 distinct X chromosome loci at which translocations can produce POF. To see if the associated translocations cause POF by the interruption of specific genes involved in follicle formation or stability, we have begun further molecular analyses of the sequences spanning translocation breakpoints. For the chromosome 3 locus and for two X chromosome loci, breakpoints have been localized to within 200 kb, and substrate clones have been chosen for long-range sequencing analysis. A combination of computer-aided sequence analysis and cDNA searches is being used to look for gene candidates that can be determining for female reproductive lifespan. - Menopause; X chromosome breakpoints; mapping; sequence analysis; fetal development; X- inactivation

大约1-3%的女性经历过早的更年期，要么从未经历月经初潮，要么在30多岁时停止月经，而不是在50岁左右达到标准的生殖寿命。早发性卵巢早衰（POF）的一小部分是遗传性的。3号染色体上的一个单一基因座与几个家庭和几个孤立的个体有关，这些个体具有中断该区域DNA的易位或缺失。据报道，在X染色体上有一组更大的易位，集中在长臂的一个关键区域，根据我们构建的物理图谱，至少有35个不同的X染色体位点，易位可以产生POF。为了了解相关的易位是否通过中断参与卵泡形成或稳定性的特定基因而导致POF，我们已经开始对跨越易位断点的序列进行进一步的分子分析。对于3号染色体基因座和两个X染色体基因座，断裂点已定位在200 kb内，并已选择底物克隆进行长距离测序分析。计算机辅助序列分析和cDNA搜索的结合正在被用来寻找可以决定女性生殖寿命的候选基因。- 更年期; X染色体断点;定位;序列分析;胎儿发育; X染色体失活