Knott S A, Haley C S
Institute of Cell, Animal and Population Biology, University of Edinburgh, Scotland.
Genetics. 1992 Dec;132(4):1211-22. doi: 10.1093/genetics/132.4.1211.
A maximum likelihood method is presented for the detection of quantitative trait loci (QTL) using flanking markers in full-sib families. This method incorporates a random component for common family effects due to additional QTL or the environment. Simulated data have been used to investigate this method. With a fixed total number of full sibs power of detection decreased substantially with decreasing family size. Increasing the number of alleles at the marker loci (i.e., polymorphism information content) and decreasing the interval size about the QTL increased power. Flanking markers were more powerful than single markers. In testing for a linked QTL the test must be made against a model which allows for between family variation (i.e., including an unlinked QTL or a between family variance component) or the test statistic may be grossly inflated. Mean parameter estimates were close to the simulated values in all situations when fitting the full model (including a linked QTL and common family effect). If the common family component was omitted the QTL effect was overestimated in data in which additional genetic variance was simulated and when compared with an unlinked QTL model there was reduced power. The test statistic curves, reflecting the likelihood of the QTL at each position along the chromosome, have discontinuities at the markers caused by adjacent pairs of markers providing different amounts of information. This must be accounted for when using flanking markers to search for a QTL in an outbred population.
提出了一种利用全同胞家系中的侧翼标记检测数量性状基因座(QTL)的最大似然法。该方法纳入了一个随机成分,用于处理由于其他QTL或环境导致的共同家系效应。已使用模拟数据对该方法进行研究。在全同胞总数固定的情况下,检测功效会随着家系规模的减小而大幅下降。增加标记位点的等位基因数量(即多态信息含量)以及减小QTL周围的区间大小会提高功效。侧翼标记比单个标记更具功效。在检测连锁QTL时,必须针对一个允许家系间存在变异的模型进行检验(即包括一个非连锁QTL或家系间方差成分),否则检验统计量可能会被严重夸大。在拟合完整模型(包括一个连锁QTL和共同家系效应)时,所有情况下的平均参数估计值都接近模拟值。如果省略共同家系成分,在模拟了额外遗传方差的数据中,QTL效应会被高估,并且与非连锁QTL模型相比,功效会降低。反映沿染色体每个位置QTL可能性的检验统计量曲线,在标记处存在不连续性,这是由相邻的成对标记提供不同信息量导致的。在远交群体中使用侧翼标记搜索QTL时,必须考虑到这一点。