Goldgar D E, Oniki R S
Department of Medical Informatics, University of Utah, Salt Lake City.
Am J Hum Genet. 1992 Mar;50(3):598-606.
We previously developed a method of partitioning genetic variance of a quantitative trait to loci in specific chromosomal regions. In this paper, we compare this method--multipoint IBD (identical by descent) method (MIM)--with parametric multipoint linkage analysis (MLINK). A simulation study was performed comparing the methods for the major-locus, mixed, and two-locus models. The criterion for comparisons between MIM and MLINK was the average lod score from multiple replicates of simulated data sets. The effect of gene frequency, dominance, model misspecification, marker spacing, and informativeness are also considered in a smaller set of simulations. Within the context of the models examined, the MIM approach was found to be comparable in power with parametric multipoint linkage analysis when (a) parental data are unknown, (b) the effect of the major locus is small and there is additional genetic variation, or (c) the parameters of the major-locus model are misspecified. The performance of the MIM method relative to MLINK was markedly lower when the allele frequency at the trait locus was .2 versus .5, particularly for the case when parental data were assumed to be known. Dominance at the trait major locus, as well as marker spacing and heterozygosity, did not appear to have a large effect on the ELOD comparisons.
我们先前开发了一种将数量性状的遗传方差分配到特定染色体区域位点的方法。在本文中，我们将这种方法——多点同源等位基因方法（MIM）——与参数化多点连锁分析（MLINK）进行比较。进行了一项模拟研究，比较了这两种方法在主基因座、混合和双基因座模型中的表现。MIM和MLINK之间比较的标准是模拟数据集多次重复的平均对数优势分数。在一组较小的模拟中，还考虑了基因频率、显性、模型误设、标记间距和信息性的影响。在所研究的模型背景下，当（a）亲本数据未知，（b）主基因座的效应较小且存在额外的遗传变异，或（c）主基因座模型的参数被误设时，发现MIM方法在效能上与参数化多点连锁分析相当。当性状位点的等位基因频率为0.2而非0.5时，尤其是在假设亲本数据已知的情况下，MIM方法相对于MLINK的表现明显较低。性状主基因座的显性以及标记间距和杂合性似乎对平均对数优势比较没有太大影响。
