Lee Sang Hong, van der Werf Julius H J
School of Rural Science and Agriculture, University of New England, Armidale, NSW 2351, Australia.
Genet Sel Evol. 2004 Mar-Apr;36(2):145-61. doi: 10.1186/1297-9686-36-2-145.
In a simulation study, different designs were compared for efficiency of fine-mapping of QTL. The variance component method for fine-mapping of QTL was used to estimate QTL position and variance components. The design of many families with small size gave a higher mapping resolution than a design with few families of large size. However, the difference is small in half sib designs. The proportion of replicates with the QTL positioned within 3 cM of the true position is 0.71 in the best design, and 0.68 in the worst design applied to 128 animals with a phenotypic record and a QTL explaining 25% of the phenotypic variance. The design of two half sib families each of size 64 was further investigated for a hypothetical population with effective size of 1000 simulated for 6000 generations with a marker density of 0.25 cM and with marker mutation rate 4 x10(-4) per generation. In mapping using bi-allelic markers, 42 approximately 55 of replicated simulations could position QTL within 0.75 cM of the true position whereas this was higher for multi allelic markers (48 approximately 76 ). The accuracy was lowest (48%) when mutation age was 100 generations and increased to 68% and 76% for mutation ages of 200 and 500 generations, respectively, after which it was about 70% for mutation ages of 1000 generations and older. When effective size was linearly decreasing in the last 50 generations, the accuracy was decreased (56 to 70%). We show that half sib designs that have often been used for linkage mapping can have sufficient information for fine-mapping of QTL. It is suggested that the same design with the same animals for linkage mapping should be used for fine-mapping so gene mapping can be cost effective in livestock populations.
在一项模拟研究中，对不同设计在QTL精细定位效率方面进行了比较。采用QTL精细定位的方差成分法来估计QTL位置和方差成分。许多小家庭规模的设计比少数大家庭规模的设计具有更高的定位分辨率。然而，在半同胞设计中差异较小。在应用于128只具有表型记录且QTL解释25%表型方差的动物的最佳设计中，QTL定位在真实位置3 cM范围内的重复比例为0.71，在最差设计中为0.68。对于有效大小为1000、模拟6000代、标记密度为0.25 cM且标记突变率为每代4×10(-4)的假设群体，进一步研究了两个大小均为64的半同胞家系的设计。在使用双等位基因标记进行定位时，约42至55次重复模拟可将QTL定位在真实位置0.75 cM范围内，而对于多等位基因标记这一比例更高（约48至76）。当突变年龄为100代时准确性最低（48%），在突变年龄为200代和500代时分别提高到68%和76%，此后在突变年龄为1000代及以上时约为70%。当有效大小在最后50代线性下降时，准确性降低（从56%降至70%）。我们表明，常用于连锁定位的半同胞设计可为QTL精细定位提供足够信息。建议将用于连锁定位的相同动物的相同设计用于精细定位，以便在畜禽群体中基因定位具有成本效益。
