Wu Rongling, Ma Chang-Xing, Hou Wei, Corva Pablo, Medrano Juan F
Department of Statistics, University of Florida, Gainesville 32611, USA.
Genetics. 2005 Sep;171(1):239-49. doi: 10.1534/genetics.104.040162. Epub 2005 Jun 18.
The high growth (hg) mutation increases body size in mice by 30-50%. Given the complexity of the genetic regulation of animal growth, it is likely that the effect of this major locus is mediated by other quantitative trait loci (QTL) with smaller effects within a web of gene interactions. In this article, we extend our functional mapping model to characterize modifier QTL that interact with the hg locus during ontogenetic growth. Our model is derived within the maximum-likelihood context, incorporated by mathematical aspects of growth laws and implemented with the EM algorithm. In an F2 population founded by a congenic high growth (HG) line and non-HG line, a highly additive effect due to the hg gene was detected on growth trajectories. Three QTL located on chromosomes 2 and X were identified to trigger significant additive and/or dominant effects on the process of growth. The most significant finding made from our model is that these QTL interact with the hg locus to affect the shapes of the growth process. Our model provides a powerful means for understanding the genetic architecture and regulation of growth rate and body size in mammals.
高生长（hg）突变使小鼠体型增大30%至50%。鉴于动物生长的遗传调控十分复杂，该主效基因座的效应很可能是由基因相互作用网络中其他效应较小的数量性状基因座（QTL）介导的。在本文中，我们扩展了功能定位模型，以表征在个体发育生长过程中与hg基因座相互作用的修饰QTL。我们的模型是在最大似然框架下推导出来的，结合了生长规律的数学方面，并通过期望最大化（EM）算法实现。在由一个同源高生长（HG）品系和非HG品系建立的F2群体中，检测到hg基因对生长轨迹有高度加性效应。在2号染色体和X染色体上定位到的三个QTL被确定对生长过程有显著的加性和/或显性效应。我们的模型得出的最显著发现是，这些QTL与hg基因座相互作用，影响生长过程的形状。我们的模型为理解哺乳动物生长速率和体型的遗传结构及调控提供了一种有力手段。
