APPARENT HETEROZYGOTE DEFICIENCIES OBSERVED IN DNA TYPING DATA AND THEIR IMPLICATIONS IN FORENSIC APPLICATIONS
APPARENT HETEROZYGOTE DEFICIENCIES OBSERVED IN DNA TYPING DATA AND THEIR IMPLICATIONS IN FORENSIC APPLICATIONS
复制标题
DOI：
10.1111/j.1469-1809.1992.tb01128.x
复制
发表时间：
1992-01-01
影响因子：
1.9
通讯作者：
BUDOWLE, B
中科院分区：
文献类型：
--
作者：
CHAKRABORTY, R;DEANDRADE, M;BUDOWLE, B
利用Southern blot技术进行限制性内切片段长度多态性（RFLP）分析，可以识别人类基因组多个区域内保守核心序列可变数串联重复序列（VNTR）的拷贝数变化。这类新的多态性揭示了高度的遗传变异，有助于个体识别。针对此类DNA分型数据的法医应用的批评包括采用Hardy-Weinberg基因型频率期望的局限性，因为一些调查表明，与Hardy-Weinberg期望相比，杂合性明显不足（或过度纯合）。本研究假设了表观杂合性缺乏的另一种解释，这是由于Southern凝胶电泳的敏感性导致无法检测到极小的等位基因（称为“不可检测的”等位基因）。我们表明，“不可检测”等位基因的存在可以产生伪纯合子，其频率可以从观察到的比例杂合子缺乏症中预测出来。此外，在这种“不可检测”等位基因的隐蔽存在下，我们表明基因计数方法提供了样本群体中等位基因频率的高估，因此Hardy-Weinberg对基因型频率的预测避免了在DNA分型数据的法医应用中对嫌疑人的错误偏见。将这一理论应用于美国白种人和美国黑人的6个VNTR位点的种群数据表明，“不可检测”等位基因的存在可能是明显杂合子缺陷的主要原因，目前预测特定DNA表型的种群频率的方法在法庭上应用DNA分型数据时几乎不存在可能的错误偏差。
Restriction fragment length polymorphisms (RFLP) analysis using the Southern blot technique can be used to recognize copy number variation of variable number of tandem repeats (VNTR) of conserved core sequences at several regions of the human genome. This new class of polymorphisms reveals a high degree of genetic variation, useful for individual identification purposes. Criticisms against forensic applications of such DNA typing data include the limitation of employing Hardy-Weinberg expectation of genotype frequencies, since several surveys indicate apparent deficiency of heterozygosity (or excess homozygosity) in comparison with Hardy-Weinberg expectations. This research postulates an alternative explanation of deficiency of apparent heterozygosity which is caused by the inability to detect extremely small-sized alleles (called 'non-detectable' alleles) due to the sensitivity of Southern gel electrophoresis. We show that the presence of 'non-detectable' alleles can produce pseudo-homozygosity and their frequencies can be predicted from the observed proportional heterozygote deficiency. Furthermore, in the covert presence of such 'non-detectable' alleles, we show that the gene-count method provides over-estimates of allele frequencies in the sample population, and hence the Hardy-Weinberg predictions of genotype frequencies avoid wrongful bias against suspects in forensic applications of DNA typing data. Applications of this theory to population data on six VNTR loci in US Caucasians and US Blacks suggest that the presence of 'non-detectable' alleles could be the major cause of apparent heterozygote deficiency, and the current approaches of predicting the population frequency of specific DNA phenotypes are practically free of the possible wrongful bias in courtroom applications of DNA typing data.