Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Genetics. 2010 Jul;185(3):1059-68. doi: 10.1534/genetics.110.116087. Epub 2010 May 3.
By treating the transcript abundance as a quantitative trait, gene expression can be mapped to local or distant genomic regions relative to the gene encoding the transcript. Local expression quantitative trait loci (eQTL) generally act in cis (that is, control the expression of only the contiguous structural gene), whereas distal eQTL act in trans. Distal eQTL are more difficult to identify with certainty due to the fact that significant thresholds are very high since all regions of the genome must be tested, and confounding factors such as batch effects can produce false positives. Here, we compare findings from two large genetic crosses between mouse strains C3H/HeJ and C57BL/6J to evaluate the reliability of distal eQTL detection, including "hotspots" influencing the expression of multiple genes in trans. We found that >63% of local eQTL and >18% of distal eQTL were replicable at a threshold of LOD > 4.3 between crosses and 76% of local and >24% of distal eQTL at a threshold of LOD > 6. Additionally, at LOD > 4.3 four tissues studied (adipose, brain, liver, and muscle) exhibited >50% preservation of local eQTL and >17% preservation of distal eQTL. We observed replicated distal eQTL hotspots between the crosses on chromosomes 9 and 17. Finally, >69% of local eQTL and >10% of distal eQTL were preserved in most tissues between sexes. We conclude that most local eQTL are highly replicable between mouse crosses, tissues, and sex as compared to distal eQTL, which exhibited modest replicability.
通过将转录丰度视为定量性状，可以相对于转录本编码基因将基因表达映射到局部或远程基因组区域。局部表达数量性状位点 (eQTL) 通常在顺式作用（即，仅控制相邻结构基因的表达），而远程 eQTL 在反式作用。由于必须测试基因组的所有区域，因此显著阈值非常高，因此很难确定远程 eQTL，并且批次效应等混杂因素会产生假阳性。在这里，我们比较了两个大型遗传杂交实验（即 C3H/HeJ 和 C57BL/6J 两个小鼠品系之间的杂交实验）的结果，以评估远程 eQTL 检测的可靠性，包括影响多个基因表达的“热点”。我们发现，在两个杂交实验之间的 LOD > 4.3 阈值下，超过 63%的局部 eQTL 和超过 18%的远程 eQTL 是可复制的，在 LOD > 6 的阈值下，63%的局部和超过 24%的远程 eQTL 是可复制的。此外，在 LOD > 4.3 时，我们研究的四个组织（脂肪、大脑、肝脏和肌肉）中的超过 50%的局部 eQTL 和超过 17%的远程 eQTL 得以保留。我们观察到在两个杂交实验的第 9 和第 17 号染色体上存在复制的远程 eQTL 热点。最后，在 LOD > 4.3 时，超过 69%的局部 eQTL 和超过 10%的远程 eQTL 在大多数组织中在性别之间得以保留。我们得出的结论是，与远程 eQTL 相比，大多数局部 eQTL 在小鼠杂交、组织和性别之间具有高度的可重复性，而远程 eQTL 的可重复性则适中。
