一种新的基于STR的染色体三体性疾病诊断策略中遗传标记的评估

背景:在此前发表的文章中,我们提出了一种新的基于短串联重复序列(Short Tandem Repeats,STR)的染色体三体性疾病的诊断策略.当应用这种策略来检测特定染色体拷贝数时,需要从人类基因组众多的STR中选择适宜的染色体特异性STR基因座构建一个诊断系统,根据系统中的STR基因座是否检测到三种不同的等位基因产物来判断个体是否为三体患者.目的:本研究拟进一步提出并验证对单个STR基因座及由多个STR基因座构成的诊断系统的评估方法,旨在帮助选择适宜的STR基因座构建一个高效能的诊断系统.方法:我们提出一个新的参数--三等位基因栓出率,并推导出该参数的计算公式,用于定量评估一个STR基因座在这种诊断策略中的效能.在此基础上,推导出另一个数学公式,计算一个非整倍体诊断系统能够在一个三体性患者?哌 检测到三个不同等位基因的概率,根据这个概率的大小来衡量系统诊断效能的高低.最后,我们将所提出的两个公式用于评估我们在先前研究中构建的一个21三体的诊断系统.结果:这个21三体诊断系统由9个21号染色体特异性STR基因座构成.根据我们所提出的两个公式,这些STR基因座的三等位基因检出率在0.203-0.638之间,该系统在21三体患者能够检测到三个不同等位基因的概率大于0.95.结论:我们所提出并验证的公式可以对单个STR基因座和系统的诊断效能进行定量评估,帮助选择适宜的STR遗传标记,并确定一个高效能诊断系统所需的STR基因座的数量,从而为这种诊断策略的广泛应用提供基础.

Evaluation of Genetic Markers in a Novel Diagnostic Strategy for Trisomy Based on Short Tandem Repeats

BackgroundIn the newly published article,we presented a novel STR-based diagnostic strategy for trisomy.When applying the strategy to the detection of the copy number of the selected chromosome,it is necessary at first to construct a multi-marker diagnostic system for trisomy by selecting the optimal chromosome-specific STR markers from numerous STR polymorphisms in human genome.ObjectiveAttempting to provide a reliable method for selecting optimal STR markers to construct a diagnositic system of high efficiency,in this study,we further described the quantitative evaluation of single STR marker and multimarker system during the marker selection.MethodsWe deduced the formulae of three-allele detection rae(TDR)and the probability that three different alleles are observed in a diagnostic system.(P),by which we can quantitatively evaluate efficacy of a STR marker and cumulative efficacy of a multi-marker diagnostic system.Furthermore,we applied them to a multi-marker diagnostic system for trisomy 21 which was constructed in the previous study.ResultsThe TDR values of nine STR markers in our diagnostic system for trisomy 21 ranged from 0.203 to 0.638.The probability that three different alleles are observed in the system is above 0.95.ConclusionThe numerical values obtained from the formulae can provide a basis for the selection of optimal STR markers and the determination of the number of STR markers needed in a system with high efficacy.