Navidi W, Arnheim N
Department of Mathematics, University of Southern California, Los Angeles 90089.
Hum Reprod. 1991 Jul;6(6):836-49. doi: 10.1093/oxfordjournals.humrep.a137438.
Preimplantation diagnosis of genetic disease can be accomplished by embryo biopsy or polar body analysis using in-vitro gene amplification (PCR). PCR analysis of single cells is subject to a number of errors which decrease the reliability of the diagnosis. Using realistic assumptions about error rates based on experimental data, we analyse some of the practical consequences to be faced by whose wishing to use this diagnostic procedure. We considered both autosomal dominant and recessive diseases. We calculate the probability of making mistakes in the diagnosis, assuming a realistic range in the magnitude of PCR efficiency, cell transfer, and contamination errors. We conclude that, in general, analysing blastomeres is subject to less mis-diagnosis than polar body analysis, except in the case of dominant diseases which are caused by genes which lie extremely close to the centromere. We also show that typing multiple blastomeres from a single embryo or combining polar body typing with blastomere analysis results in significantly lower levels of mis-diagnosis with unacceptable consequences. The preimplantation diagnosis of X-linked diseases based upon Y chromosome sequence analysis is also discussed.
植入前遗传病诊断可通过胚胎活检或使用体外基因扩增（PCR）的极体分析来完成。单细胞的PCR分析存在一些误差，这会降低诊断的可靠性。基于实验数据对误差率进行实际假设，我们分析了希望使用这种诊断程序的人将面临的一些实际后果。我们考虑了常染色体显性和隐性疾病。假设PCR效率、细胞转移和污染误差幅度处于实际范围内，我们计算了诊断中出错的概率。我们得出结论，一般来说，分析卵裂球比极体分析误诊的可能性小，除非是由极其靠近着丝粒的基因引起的显性疾病。我们还表明，对单个胚胎的多个卵裂球进行分型或将极体分型与卵裂球分析相结合会导致误诊水平显著降低，但后果不可接受。文中还讨论了基于Y染色体序列分析的X连锁疾病的植入前诊断。
