Shifman Sagiv, Darvasi Ariel
The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Genetics. 2005 Feb;169(2):849-54. doi: 10.1534/genetics.104.032474. Epub 2004 Nov 1.
The shared ancestry of mouse inbred strains, together with the availability of sequence and phenotype information, is a resource that can be used to map quantitative trait loci (QTL). The difficulty in using only sequence information lies in the fact that in most instances the allelic state of the QTL cannot be unambiguously determined in a given strain. To overcome this difficulty, the performance of multiple crosses between various inbred strains has been proposed. Here we suggest and evaluate a general approach, which consists of crossing the two strains used initially to map the QTL and any new strain. We have termed these crosses "yin-yang," because they are complementary in nature as shown by the fact that the QTL will necessarily segregate in only one of the crosses. We used the publicly available SNP database of chromosome 16 to evaluate the mapping resolution achievable through this approach. Although on average the improvement of mapping resolution using only four inbred strains was relatively small (i.e., reduction of the QTL-containing interval by half at most), we found a great degree of variability among different regions of chromosome 16 with regard to mapping resolution. This suggests that with a large number of strains in hand, selecting a small number of strains may provide a significant contribution to the fine mapping of QTL.
小鼠近交系的共同祖先，以及序列和表型信息的可用性，是一种可用于定位数量性状基因座（QTL）的资源。仅使用序列信息的困难在于，在大多数情况下，无法在给定品系中明确确定QTL的等位基因状态。为了克服这一困难，有人提出在各种近交系之间进行多次杂交。在此，我们提出并评估一种通用方法，该方法包括将最初用于定位QTL的两个品系与任何新的品系进行杂交。我们将这些杂交称为“阴阳杂交”，因为它们本质上是互补的，这一点从QTL必然只在其中一个杂交中分离这一事实可以看出。我们使用公开可用的16号染色体单核苷酸多态性（SNP）数据库来评估通过这种方法可实现的定位分辨率。虽然平均而言，仅使用四个近交系时定位分辨率的提高相对较小（即含QTL区间最多减半），但我们发现16号染色体的不同区域在定位分辨率方面存在很大差异。这表明，手头有大量品系时，选择少数品系可能对QTL的精细定位有显著贡献。
