Ekstrøm Claus Thorn
Department of Mathematics and Physics, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
Genet Epidemiol. 2004 Apr;26(3):218-30. doi: 10.1002/gepi.10310.
Variance component models form a powerful and flexible tool for multipoint linkage analysis of quantitative traits. Estimates of genetic similarity are needed for the variance component model to detect linkage and to locate genes, and two methods are commonly used to calculate multipoint identity-by-descent (IBD) estimates for autosomes. Fulker et al. ([1995] Am. J. Hum. Genet. 56: 1229-1233) and Almasy and Blangero ([1998] Am. J. Hum. Genet. 62: 119-121) used multiple regression to estimate the IBD sharing along a chromosome, while the approach of Kruglyak and Lander ([1995] Am. J. Hum. Genet. 57: 439-454) is based on a hidden Markov model. In this paper, we modify the variance component model to accommodate sex-chromosomes, and we extend both multipoint IBD estimation methods to accommodate sex-linked loci. Simulation studies demonstrate the power and precision of the variance component model to detect QTLs located on the sex-chromosome. The two multipoint IBD estimation methods have the same accuracy to identify QTL position, but the hidden Markov model yields a larger average maximum LOD score to detect linkage than the regression model. The extension of the multipoint IBD estimation methods and the variance component model to the X chromosome shows that the variance component model is a powerful and flexible tool for linkage analysis of quantitative traits on both autosomes and sex-chromosomes.
方差成分模型构成了用于数量性状多点连锁分析的强大且灵活的工具。方差成分模型检测连锁和定位基因需要遗传相似性估计值，通常使用两种方法来计算常染色体的多点同源状态（IBD）估计值。富尔克等人（[1995]《美国人类遗传学杂志》56: 1229 - 1233）以及阿尔马西和布兰杰罗（[1998]《美国人类遗传学杂志》62: 119 - 121）使用多元回归来估计沿染色体的IBD共享情况，而克鲁格利亚克和兰德（[1995]《美国人类遗传学杂志》57: 439 - 454）的方法基于隐马尔可夫模型。在本文中，我们修改方差成分模型以适应性染色体，并将两种多点IBD估计方法扩展以适应性连锁基因座。模拟研究证明了方差成分模型检测位于性染色体上的数量性状基因座（QTL）的功效和精度。两种多点IBD估计方法在识别QTL位置方面具有相同的准确性，但与回归模型相比，隐马尔可夫模型产生的用于检测连锁的平均最大对数优势（LOD）得分更高。将多点IBD估计方法和方差成分模型扩展到X染色体表明，方差成分模型是用于常染色体和性染色体上数量性状连锁分析的强大且灵活的工具。
