Schlötterer C
Institut für Tierzucht und Genetik, Veterinärmedizinische Universität Wien, Vienna, Austria.
Chromosoma. 2000 Sep;109(6):365-71. doi: 10.1007/s004120000089.
Within the past decade microsatellites have developed into one of the most popular genetic markers. Despite the widespread use of microsatellite analysis, an integral picture of the mutational dynamics of microsatellite DNA is just beginning to emerge. Here, I review both generally agreed and controversial results about the mutational dynamics of microsatellite DNA. Microsatellites are short DNA sequence stretches in which a motif of one to six bases is tandemly repeated. It has been known for some time that these sequences can differ in repeat number among individuals. With the advent of polymerase chain reaction (PCR) technology this property of microsatellite DNA was converted into a highly versatile genetic marker (Litt and Luty 1989; Tautz 1989; Weber and May 1989). Polymerase chain reaction products of different length can be amplified with primers flanking the variable microsatellite region. Due to the availability of high-throughput capillary sequencers or mass spectrography the sizing of alleles is no longer a bottleneck in microsatellite analysis. The almost random distribution of microsatellites and their high level of polymorphism greatly facilitated the construction of genetic maps (Dietrich et al. 1994; Dib et al. 1996) and enabled subsequent positional cloning of several genes. Almost at the same time, microsatellites were established as the marker of choice for the identification of individuals and paternity testing. The high sensitivity of PCR-based microsatellite analysis was not only of great benefit for forensics, but opened completely new research areas, such as the analysis of samples with limited DNA amounts (e.g., many social insects) or degraded DNA (e.g., feces, museum material) (Schlötterer and Pemberton 1998). More recently, microsatellite analysis has also been employed in population genetics (Goldstein and Schlötterer 1999). Compared with allozymes, microsatellites offer the advantage that, in principle, several thousand potentially polymorphic markers are available. Nevertheless, the application of microsatellites to population genetic questions requires a more detailed understanding of the mutation processes of microsatellite DNA as the evolutionary time frames covered in population genetics are often too long to allow novel microsatellite mutations to be ignored. Additional interest in the evolution of microsatellite DNA comes from the discovery that trinucleotide repeats, a special class of microsatellites, are involved in human neurodegenerative diseases (e.g., fragile X and Huntington's disease). A detailed understanding of the processes underlying microsatellite instability is therefore an important contribution toward a better understanding of these human neurodegenerative diseases.
在过去十年中，微卫星已发展成为最受欢迎的遗传标记之一。尽管微卫星分析已被广泛应用，但微卫星DNA突变动态的完整图景才刚刚开始显现。在此，我回顾了关于微卫星DNA突变动态的普遍认可的结果和有争议的结果。微卫星是短的DNA序列片段，其中一到六个碱基的基序串联重复。人们早就知道这些序列在个体之间的重复数可能不同。随着聚合酶链反应（PCR）技术的出现，微卫星DNA的这一特性被转化为一种高度通用的遗传标记（利特和卢蒂，1989；陶茨，1989；韦伯和梅，1989）。可以用位于可变微卫星区域两侧的引物扩增不同长度的聚合酶链反应产物。由于高通量毛细管测序仪或质谱仪的可用性，等位基因大小的测定不再是微卫星分析的瓶颈。微卫星的几乎随机分布及其高度多态性极大地促进了遗传图谱的构建（迪特里希等人，1994；迪布等人，1996），并使得随后能够对多个基因进行定位克隆。几乎与此同时，微卫星被确立为个体识别和亲子鉴定的首选标记。基于PCR的微卫星分析的高灵敏度不仅对法医学有很大益处，而且开辟了全新的研究领域，例如对DNA量有限的样本（如许多社会性昆虫）或降解DNA（如粪便、博物馆标本）的分析（施洛特勒和彭伯顿，1998）。最近，微卫星分析也已应用于群体遗传学（戈尔茨坦和施洛特勒，1999）。与等位酶相比，微卫星的优势在于原则上有数千个潜在的多态性标记可用。然而，将微卫星应用于群体遗传问题需要更详细地了解微卫星DNA的突变过程，因为群体遗传学所涵盖的进化时间框架往往太长，以至于不能忽略新的微卫星突变。对微卫星DNA进化的额外兴趣来自于发现三核苷酸重复序列（一种特殊类型的微卫星）与人类神经退行性疾病（如脆性X综合征和亨廷顿舞蹈症）有关。因此，详细了解微卫星不稳定性背后的过程对于更好地理解这些人类神经退行性疾病具有重要意义。
