PeakSeeker: a program for interpreting genotypes of mononucleotide repeats.
PeakSeeker: a program for interpreting genotypes of mononucleotide repeats.
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DOI：
10.1186/1756-0500-2-17
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发表时间：
2009-02-03
影响因子：
1.8
通讯作者：
Salipante, Stephen J
中科院分区：
文献类型：
--
作者：
Thompson, James M;Salipante, Stephen J
单核苷酸重复序列微卫星是一种丰富的、高度多态的DNA序列，具有作为有价值的遗传标记的潜力。单核苷酸多态性微卫星的使用受到限制，因为它们倾向于产生“口吃”，混淆PCR过程中发生的单核苷酸多态性片段内插入和缺失的信号，这通过掩盖等位基因的真实位置而使基因型的解释复杂化。因此，使用具有较大重复亚基（二核苷酸和三核苷酸基序）的微卫星，其产生较少的口吃，但遗传异质性较小，信息量较小。一种解释单核苷酸重复序列基因型的方法将允许在遗传研究中广泛使用这些高信息量的微卫星。我们已经开发了一种方法来解释基因型的monopoltide重复使用的软件程序，名为PeakSeeker。PeakSeeker将实验电泳图解释为最有可能是来自单个等位基因的信号的产物。由于单核苷酸序列显示了位点特异性的断续峰模式，因此这种方法需要为每个标记定义来自单个等位基因的基因型模式，这可以通过对单个DNA分子或纯合子进行基因分型来近似。我们已经评估了该程序的能力，区分各种类型的纯合和杂合单核苷酸多态性位点使用模拟和实验数据。单核苷酸序列比传统上用于遗传研究的二核苷酸和三核苷酸微卫星标记具有显著的优势。PeakSeeker算法提供了一种高通量的方法，使用传统的和广泛实施的片段长度多态性基因分型来分型单核苷酸片段。此外，PeakSeeker算法可能会被修改，以改善，也许是标准化，传统的微卫星基因型的分析。
Mononucleotide repeat microsatellites are abundant, highly polymorphic DNA sequences, having the potential to serve as valuable genetic markers. Use of mononucleotide microsatellites has been limited by their tendency to produce "stutter", confounding signals from insertions and deletions within the mononucleotide tract that occur during PCR, which complicates interpretation of genotypes by masking the true position of alleles. Consequently, microsatellites with larger repeating subunits (dinucleotide and trinucleotide motifs) are used, which produce less stutter but are less genetically heterogeneous and less informative. A method to interpret the genotypes of mononucleotide repeats would permit the widespread use of those highly informative microsatellites in genetic research. We have developed an approach to interpret genotypes of mononucleotide repeats using a software program, named PeakSeeker. PeakSeeker interprets experimental electropherograms as the most likely product of signals from individual alleles. Because mononucleotide tracts demonstrate locus-specific patterns of stutter peaks, this approach requires that the genotype pattern from a single allele is defined for each marker, which can be approximated by genotyping single DNA molecules or homozygotes. We have evaluated the program's ability to discriminate various types of homozygous and heterozygous mononucleotide loci using simulated and experimental data. Mononucleotide tracts offer significant advantages over di- and tri-nucleotide microsatellite markers traditionally employed in genetic research. The PeakSeeker algorithm provides a high-throughput means to type mononucleotide tracts using conventional and widely implemented fragment length polymorphism genotyping. Furthermore, the PeakSeeker algorithm could potentially be adapted to improve, and perhaps to standardize, the analysis of conventional microsatellite genotypes.