回文序列介导的人类精子中染色体新突变发生规律初探

发布时间：2018-05-05 14:57

本文选题：染色体易位 + 精子质量　；参考：《中国医科大学》2006年硕士论文

【摘要】：前言近年来,人类精子质量的快速下降正日益引起人们的关注,这不仅成为男性不育的又一重要病因,还可导致出生缺陷的比率升高。虽然辅助生殖技术可以帮助低生育能力者获得自己的后代,但是已有证据证明,卵泡浆内单精子注射(Intracytoplasmic sperm injection,ICSI)可将遗传缺陷传递给下一代,从而影响人口的优生优育。因此,研究精子发生的遗传学规律,评估精子的质量,并且对辅助受孕者进行植入前遗传学诊断(PGD Preimplantation Genertic Diagnosis)就显得尤其重要。既往对精子质量的评价主要依靠显微镜下对精子细胞形态学进行观察所得出的数据(如精液密度、活率、形态等)。随着分子生物学的发展,越来越多的研究者开始对精子发生机制的研究,尽管目前这一机制尚未阐明,但人们已经发现了某些遗传缺陷,如基因突变或染色体异常等,与无精症和严重少精症的发生密切相关。其中研究最为详细的是Y染色体无精子因子AZF(azoospermia factor)区域的微缺失,常见的大Y染色体以及性染色体非整倍性(Klinefelter综合征)等。然而,目前对于导致无精症、少精症或习惯性流产的常染色体间相互易位的机制研究尚少。t(11;22)(q23;q11)[以下简称t(11;22)]易位是最为常见的非罗伯逊染色体易位。2001年,Kurahashi与Emanuel意外发现,t(11;22)易位的连接片段在精子标本中广泛存在且具有非常高的发生率(1.24-9.46×10~5),并且该易位是由两个染色体上各自一段对称的回文序列介导的。2002年,随着整个Y染色体测序的完成,研究者还发现部分AZF区域的微缺失断裂点位于回文序列中。提示回文序列在基因组中广泛存在,并可能导致基因组不稳定性,其介导的染色体易位是一种较为常见的染色体畸变机理。为了进一步了解回文序列介导的染色体易位发生规律及其对精子质量产生的影响,我们对28例少精子症与32例正常男性志愿者精液标本进行了研究。本实验中,利用巢式
[Abstract]:Preface In recent years, the rapid decline in the quality of human sperm is attracting more and more attention, which not only becomes another important cause of male infertility, but also leads to an increase in the rate of birth defects. Although assisted reproductive technology can help people with low fertility to obtain their own offspring, it has been shown that intracytoplasmic sperm injection (ICSI) can transfer genetic defects to the next generation, thus affecting the population's fertility. Therefore, it is very important to study the genetic law of spermatogenesis, evaluate the quality of spermatozoa, and make a preimplantation genetic diagnosis of PGD Preimplantation Genertic diagnosis. In the past, the evaluation of sperm quality mainly depended on the observation of sperm cell morphology under microscope (such as semen density, viability, morphology, etc.) With the development of molecular biology, more and more researchers have begun to study the mechanism of spermatogenesis. Although this mechanism has not been clarified, some genetic defects, such as gene mutation or chromosome abnormality, have been discovered. It is closely related to the occurrence of azoospermia and severe oligozoospermia. The microdeletions in the azoospermia factor AZF(azoospermia factor region of Y chromosome, the common large Y chromosome and sex chromosome aneuploidy Klinefelter syndrome were studied in detail. However, in the present case of azoospermia, The mechanism of autosomal transposition between autosomes in oligozoospermia or habitual abortion is less than that of Q23Q11). The translocation of non-Robertson chromosomes is the most common. It is widely present and has a very high incidence rate of 1.24-9.46 脳 10 ~ (5) and the translocation is mediated by a symmetrical palindromic sequence on each of the two chromosomes. With the completion of the whole Y chromosome sequencing, the researchers also found that the microdeletion breakpoints of some AZF regions were located in palindromes. It is suggested that palindromes exist widely in the genome and may lead to genomic instability. The chromosomal translocation mediated by palindromes is a common mechanism of chromosome aberration. In order to further understand the regularity of chromosome translocation mediated by palindromes and its effect on sperm quality, we studied the semen samples of 28 oligozoospermia and 32 normal male volunteers. In this experiment, nesting is used
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R321

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