MEIOSIS IN MEN AND RISKS ASSOCIATED WITH ICSI

描述：（改编自申请人摘要）减数分裂是一种特殊类型 通过一个复杂的途径产生单倍体配子， 需要数百个基因，其中一些是特定的减数分裂细胞， 另一些则在表达中无处不在。在不同的生物体中， 酵母到小鼠，许多基因的突变可能导致减数分裂特异性缺陷， 导致与体细胞缺陷相关减数分裂缺陷， 由DNA修复缺陷引起的肿瘤虽然减数分裂很可能是 在整个进化过程中，减数分裂的遗传学知之甚少 在人类中，尽管与染色体畸变相关的减数分裂停滞可能 无精子症（不产生精子）或少精子症（产生 小于100万个精子/ml）可能是常见的。这一观察促使 Reijo博士回答了以下问题：1）有些男性的精子数量很低或没有精子吗？ 计算AZoospermia基因缺失的嵌合体， 与减数分裂的进程有关吗2)一些数字很低的人 精子在重组或DNA修复方面有缺陷？如果是，这些缺陷 在诊所里宣传儿童的努力中被忽视， 其他有害影响，可能会出现在以后的生活？在这项工作中，他们 总的假设是参与减数分裂的基因，如DAZ， 而那些重组和DNA修复所需的蛋白质则可能导致减数分裂停滞 (at粗线素I检查点），就像这些基因的缺陷会导致 其他生物的减数分裂停滞。他们过去四年的研究 确定了许多男性不育的病例是遗传的， 不孕症可以通过目前的临床实践从父亲传给儿子。 最近，他们收集的初步数据表明，DNA修复 减数分裂阻滞的不育男性比正常男性更容易出现缺陷。 有生育能力的男人他们建议扩展他们的发现并使用他们的新技术 在人类生殖遗传学中，通过使用单精子PCR来检测 不育男性生殖细胞DAZ缺失和DNA修复缺陷， 重组

DESCRIPTION: (Adapted from the applicant's abstract) Meiosis is a special type of cell division that yields haploid gametes via a complex pathway that likely requires hundreds of genes, some of which are specified to meiotic cells and others which are ubiquitous in their expression. In diverse organisms from yeast to mice, mutations in many genes may lead to meiosis-specific defects or lead to defects in meiosis that are associated with somatic cell defects such as tumors caused by defective DNA repair. Although it is likely that meiosis is conserved throughout evolution, little is known about the genetics of meiosis in humans even though it is likely that meiotic arrest associated with azoospermia (the production of no sperm) or oligospermia (the production of less that one million sperm/ml) may be common. This observation has prompted Dr. Reijo to address the questions: 1) Are some men with very low or no sperm counts mosaic for deletions of the Deleted in AZoospermia genes which are implicated in progression through meiosis? 2) Do some men with very low numbers of sperm have a defect in recombination or DNA repair? If so, are these defects being bypassed in efforts to propagate children in the clinic without regard to other deleterious effects that may present later in life? In this work, their overall hypothesis is that defects in genes involved in meiosis, such as DAZ, and those required for recombination and DNA repair may cause meiotic arrest (at a pachytene I checkpoint) in men just as defects in these genes cause meiotic arrest in other organisms. Their research over the last four years established that many cases of infertility in men are genetic and that infertility can be passed from father to son via current clinical practice. More recently they have collected preliminary data that suggest that DNA repair defects occur more frequently in infertile men with meiotic arrest than in fertile men. They propose to extend their findings and use their new technology in the genetics of human reproduction by using single sperm PCR to examine the germ cells of infertile men for DAZ deletions and defects in DNA repair and recombination.