短串联重复序列多态性及在造血干细胞移植中的应用

发布时间：2018-04-18 00:24

本文选题：短串联重复序列 + 多态性　；参考：《郑州大学》2006年硕士论文

【摘要】：背景：短串联重复序列(short tandem repeat，，STR)是近年来发现的，广泛存在于基因组中的DNA长度多态性片段，它由2～6个碱基构成一个在长度上呈串联重复排列的核心序列。STR因具有分布广泛、信息量大、高度多态性、高杂合度、低突变率、检测简便、快捷并遵循孟德尔共显性遗传规律等优点，成为继RFLP之后理想的第二代DNA遗传标记，被广泛应用于基因作图、连锁分析、基因诊断与产前诊断、遗传学、人类学及法医学个体识别和亲权鉴定、器官移植等领域。STR位点在不同的种族和地区有很大的差异，河南地处中原、是众多民族的汇聚地，而其中又以汉族人群居多，因此，河南汉族群体的遗传学特征对中国汉族人群有较好的代表性。 20世纪90年代以来，造血干细胞移植(hematopoietic stem cell transplantation，HSCT)技术取得飞速发展，现已成为治疗恶性血液病、遗传性疾病等的主要手段之一。随着HSCT应用范围的扩大，移植效果日益得到重视，移植后的检测也将成为HSCT研究中不可缺少的一部分。有学者将STR应用于HSCT后植入证据的检测，结果显示STR基因位点检测可用于判断移植效果、预防复发、实行临床早期干预治疗等，但定期反复检测需长期保留受者移植前的血样和供者血样。本实验首次对河南汉族人群的D7S3048、D4S2639、D14S306、D18S535基因座的多态性分布情况进行调查，获得河南汉族人群D7S3048、D4S2639、D14S306、D18S535基因座的遗传学数据；并将该4个STR位点与我室前期筛选的F13A01、FESFPS、vWA、CSF1PO、TPOX、TH01等位点联合应用于HSCT后的监测，对其应用价值进行评价和验证；用受者口腔黏膜DNA代替移植前外周血淋巴细胞DNA，比较患者移植后外周血与口腔粘膜DNA的基因型，以解决需多次采集或长期保存供者样本的困难，建立一种简便、准确、早期监测外源基因植入效果的技术，推广应用于临床。
[Abstract]:Background: short tandem repeat (short tandem repeat STR) is a polymorphic fragment of DNA length found in recent years. It consists of 2 ~ 6 bases to form a core sequence. STR has a wide distribution.Because of its advantages of large amount of information, high polymorphism, high heterozygosity, low mutation rate, simple, fast detection and following Mendelian codominant inheritance, it has become an ideal second generation DNA genetic marker after RFLP, and has been widely used in gene mapping.Linkage analysis, gene diagnosis and prenatal diagnosis, genetics, individual identification and paternity identification in anthropology and forensic medicine, organ transplantation and other fields have great differences in different races and regions. Henan Province is located in the Central Plains.It is the gathering place of many nationalities, and the Han population is the majority among them. Therefore, the genetic characteristics of Henan Han population have a better representation to the Chinese Han population.Since the 1990s, hematopoietic stem cell transplants (HSCTs) have developed rapidly, and have become one of the main methods for the treatment of malignant hematological diseases and hereditary diseases.With the expansion of HSCT application scope, transplantation effect has been paid more and more attention, and post-transplant detection will become an indispensable part of HSCT research.Some scholars used STR to detect the evidence of HSCT implantation. The results showed that the detection of STR gene locus could be used to judge the effect of transplantation, prevent recurrence, and carry out early clinical intervention, etc.But regular repeated tests require long-term retention of pre-transplant and donor blood samples.The polymorphism distribution of D7S3048 / D4S2639 / D14S306/ D18S535 locus in Henan Han population was investigated for the first time, and genetic data of D7S3048 / D4S2639 / D14S306D18S535 locus were obtained.The four STR loci were combined with F13A01FESFPSvWAA CSF1POTPOXT01 to monitor the HSCT, and the application value was evaluated and verified.The peripheral blood lymphocyte DNA was replaced by oral mucosal DNA of recipient before transplantation. The genotypes of DNA in peripheral blood and oral mucosa of patients were compared in order to solve the difficulty of collecting or preserving donor samples for many times, and to establish a simple and accurate method.The technique of early monitoring the effect of exogenous gene implantation was popularized and applied in clinic.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R394

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