Cheverud James M, Hager Reinmar, Roseman Charles, Fawcett Gloria, Wang Bing, Wolf Jason B
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4253-8. doi: 10.1073/pnas.0706562105. Epub 2008 Mar 12.
Genomic imprinting results in the differential expression of genes, depending on which allele is inherited from the mother and which from the father. The effects of such differential gene expression are reflected in phenotypic differences between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes have been identified and play a key role in development, little is known about the contribution of imprinting to quantitative variation in trait expression. Here, we examine this problem by mapping imprinting effects on adult body composition traits in the F(3) generation of an intercross between the Large (LG/J) and Small (SM/J) inbred mouse strains. We identified eight pleiotropic imprinted quantitative trait loci (iQTL) located throughout the genome. Most iQTL are in novel locations that have not previously been associated with imprinting effects, but those on chromosomes 7, 12, and centromeric 18 lie in regions previously identified as containing imprinted genes. Our results show that the effects of genomic imprinting are relatively small, with reciprocal heterozygotes differing by approximately 0.25 standard deviation units and the effects at each locus accounting for 1% to 4% of the phenotypic variance. We detected a variety of imprinting patterns, with paternal expression being the most common. These results indicate that genomic imprinting has small, but detectable, effects on the normal variation of complex traits in adults and is likely to be more common than usually thought.
基因组印记导致基因的差异表达,这取决于基因是从母亲还是父亲那里遗传而来。这种基因差异表达的影响反映在正反交杂合子(Aa与aA)之间的表型差异上。尽管已经鉴定出许多印记基因,并且它们在发育过程中起着关键作用,但关于印记对性状表达的数量变异的贡献却知之甚少。在这里,我们通过在大型(LG/J)和小型(SM/J)近交系小鼠品系杂交产生的F(3)代中,绘制印记对成年体组成性状的影响来研究这个问题。我们在整个基因组中鉴定出八个多效性印记数量性状基因座(iQTL)。大多数iQTL位于以前与印记效应无关的新位置,但位于7号、12号染色体以及18号染色体着丝粒区域的那些iQTL位于以前鉴定为含有印记基因的区域。我们的结果表明,基因组印记的影响相对较小,正反交杂合子之间的差异约为0.25个标准差单位,每个基因座的效应占表型变异的1%至4%。我们检测到了多种印记模式,其中父本表达最为常见。这些结果表明,基因组印记对成年复杂性状的正常变异有微小但可检测到的影响,并且可能比通常认为的更为普遍。