Walling Grant A, Haley Chris S, Perez-Enciso Miguel, Thompson Robin, Visscher Peter M
Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, UK.
Genet Res. 2002 Feb;79(1):97-106. doi: 10.1017/s0016672301005420.
Previous studies have noted that the estimated positions of a large proportion of mapped quantitative trait loci (QTLs) coincide with marker locations and have suggested that this indicates a bias in the mapping methodology. In this study we predict the expected proportion of QTLs with positions estimated to be at the location of a marker and further examine the problem using simulated data. The results show that the higher proportion of putative QTLs estimated to be at marker positions compared with non-marker positions is an expected consequence of the estimation methods. The study initially focused on a single interval with no QTLs and was extended to include multiple intervals and QTLs of large effect. Further, the study demonstrated that the larger proportion of estimated QTL positions at the location of markers was not unique to linear regression mapping. Maximum likelihood produced similar results, although the accumulation of positional estimates at outermost markers was reduced when regions outside the linkage group were also considered. The bias towards marker positions is greatest under the null hypothesis of no QTLs or when QTL effects are small. This study discusses the impact the findings could have on the calculation of thresholds and confidence intervals produced by bootstrap methods.
以往的研究指出，大部分定位的数量性状基因座（QTL）的估计位置与标记位置重合，并表明这意味着定位方法存在偏差。在本研究中，我们预测了位置估计在标记位置的QTL的预期比例，并使用模拟数据进一步研究了该问题。结果表明，与非标记位置相比，估计在标记位置的假定QTL比例更高是估计方法的预期结果。该研究最初聚焦于无QTL的单个区间，并扩展至包括多个区间和大效应QTL。此外，该研究表明，估计的QTL位置在标记位置的比例更高并非线性回归定位所特有。最大似然法产生了类似结果，不过当也考虑连锁群外区域时，最外侧标记处位置估计的累积有所减少。在无QTL的零假设下或QTL效应较小时，对标记位置的偏差最大。本研究讨论了这些发现可能对通过自助法产生的阈值和置信区间计算所产生的影响。
