Göring Harald H H, Williams Jeff T, Dyer Thomas D, Blangero John
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S72. doi: 10.1186/1471-2156-4-S1-S72.
An empirical comparison between three different methods for estimation of pair-wise identity-by-descent (IBD) sharing at marker loci was conducted in order to quantify the resulting differences in power and localization precision in variance components-based linkage analysis. On the examined simulated, error-free data set, it was found that an increase in accuracy of allele sharing calculation resulted in an increase in power to detect linkage. Linkage analysis based on approximate multi-marker IBD matrices computed by a Markov chain Monte Carlo approach was much more powerful than linkage analysis based on exact single-marker IBD probabilities. A "multiple two-point" approximation to true "multipoint" IBD computation was found to be roughly intermediate in power. Both multi-marker approaches were similar to each other in accuracy of localization of the quantitative trait locus and far superior to the single-marker approach. The overall conclusions of this study with respect to power are expected to also hold for different data structures and situations, even though the degree of superiority of one approach over another depends on the specific circumstances. It should be kept in mind, however, that an increase in computational accuracy is expected to go hand in hand with a decrease in robustness to various sources of errors.
为了量化基于方差成分的连锁分析中三种不同方法在估计标记位点上成对的同源等位基因(IBD)共享时所产生的功效和定位精度差异,我们对这三种方法进行了实证比较。在所检验的无误差模拟数据集上,发现等位基因共享计算精度的提高会导致检测连锁的功效增加。基于马尔可夫链蒙特卡罗方法计算的近似多标记IBD矩阵进行的连锁分析,比基于精确单标记IBD概率的连锁分析功效要强得多。对于真实“多点”IBD计算的“多重两点”近似法,其功效大致处于中间水平。两种多标记方法在数量性状位点定位精度方面彼此相似,且远优于单标记方法。尽管一种方法相对于另一种方法的优势程度取决于具体情况,但预计本研究关于功效的总体结论对于不同的数据结构和情况也同样适用。然而,应该记住的是,计算精度的提高预计会与对各种误差源的稳健性降低同时出现。