TRANSLOCATIONS/GENES ASSOCIATED WITH PREMATURE OVARIAN FAILURE

大约1%-3%的女性经历了早熟绝经，要么从未经历过月经初潮，要么在35岁左右停止月经，而不是在大约50岁时达到标准的生育寿命。此类早发性卵巢早衰(POF)中的一小部分是遗传的。3号染色体上的一个单基因座与几个家系和几个有易位或缺失的孤立个体有关，这些易位或缺失导致该区域的DNA中断。据报道，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。在这里，我们已经表明，基于我们构建的物理图谱，至少有35个不同的X染色体座位可以产生POF。为了了解相关易位是否通过参与卵泡形成或稳定的特定基因的中断而导致POF，我们已经开始对跨越易位断裂点的序列进行进一步的分子分析。对于3号染色体和两个X染色体，断裂点被定位在200kb以内，并选择了底物克隆进行长距离测序分析。计算机辅助序列分析和cdna搜索的组合被用来寻找可以决定女性生殖寿命的候选基因。-更年期；X染色体断裂点；图谱；序列分析；胎儿发育；X-失活

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