Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S153. doi: 10.1186/1471-2156-6-S1-S153.
Errors while genotyping are inevitable and can reduce the power to detect linkage. However, does genotyping error have the same impact on linkage results for single-nucleotide polymorphism (SNP) and microsatellite (MS) marker maps? To evaluate this question we detected genotyping errors that are consistent with Mendelian inheritance using large changes in multipoint identity-by-descent sharing in neighboring markers. Only a small fraction of Mendelian consistent errors were detectable (e.g., 18% of MS and 2.4% of SNP genotyping errors). More SNP genotyping errors are Mendelian consistent compared to MS genotyping errors, so genotyping error may have a greater impact on linkage results using SNP marker maps. We also evaluated the effect of genotyping error on the power and type I error rate using simulated nuclear families with missing parents under 0, 0.14, and 2.8% genotyping error rates. In the presence of genotyping error, we found that the power to detect a true linkage signal was greater for SNP (75%) than MS (67%) marker maps, although there were also slightly more false-positive signals using SNP marker maps (5 compared with 3 for MS). Finally, we evaluated the usefulness of accounting for genotyping error in the SNP data using a likelihood-based approach, which restores some of the power that is lost when genotyping error is introduced.
基因分型过程中难免会出现错误，这可能会降低检测连锁的能力。然而，基因分型错误对于单核苷酸多态性（SNP）和微卫星（MS）标记图谱的连锁结果是否具有相同的影响呢？为了评估这个问题，我们利用相邻标记间多点亲缘关系共享的大幅变化，检测了符合孟德尔遗传规律的基因分型错误。只有一小部分孟德尔一致性错误是可检测到的（例如，MS 中有 18%，SNP 中有 2.4%）。与 MS 基因分型错误相比，SNP 基因分型错误中有更多的孟德尔一致性错误，因此基因分型错误可能对使用 SNP 标记图谱的连锁结果产生更大的影响。我们还使用缺失父母的模拟核家庭，在 0、0.14 和 2.8%的基因分型错误率下，评估了基因分型错误对连锁分析效能和Ⅰ型错误率的影响。在存在基因分型错误的情况下，我们发现 SNP（75%）标记图谱比 MS（67%）标记图谱更能检测到真实的连锁信号，尽管 SNP 标记图谱也会产生稍微多一些的假阳性信号（MS 为 3 个，而 SNP 为 5 个）。最后，我们使用基于似然的方法评估了在 SNP 数据中考虑基因分型错误的有用性，该方法可以恢复引入基因分型错误时失去的部分效能。
