Cui Yuehua, Li Shaoyu, Li Gengxin
Department of Statistics & Probability, Michigan State University, East Lansing, MI 48824, USA.
Theor Biol Med Model. 2008 Mar 17;5:6. doi: 10.1186/1742-4682-5-6.
Genomic imprinting, a phenomenon referring to nonequivalent expression of alleles depending on their parental origins, has been widely observed in nature. It has been shown recently that the epigenetic modification of an imprinted gene can be detected through a genetic mapping approach. Such an approach is developed based on traditional quantitative trait loci (QTL) mapping focusing on single trait analysis. Recent studies have shown that most imprinted genes in mammals play an important role in controlling embryonic growth and post-natal development. For a developmental character such as growth, current approach is less efficient in dissecting the dynamic genetic effect of imprinted genes during individual ontology.
Functional mapping has been emerging as a powerful framework for mapping quantitative trait loci underlying complex traits showing developmental characteristics. To understand the genetic architecture of dynamic imprinted traits, we propose a mapping strategy by integrating the functional mapping approach with genomic imprinting. We demonstrate the approach through mapping imprinted QTL controlling growth trajectories in an inbred F2 population. The statistical behavior of the approach is shown through simulation studies, in which the parameters can be estimated with reasonable precision under different simulation scenarios. The utility of the approach is illustrated through real data analysis in an F2 family derived from LG/J and SM/J mouse stains. Three maternally imprinted QTLs are identified as regulating the growth trajectory of mouse body weight.
The functional iQTL mapping approach developed here provides a quantitative and testable framework for assessing the interplay between imprinted genes and a developmental process, and will have important implications for elucidating the genetic architecture of imprinted traits.
基因组印记是指等位基因根据其亲本来源进行非等效表达的现象，在自然界中已被广泛观察到。最近的研究表明，印记基因的表观遗传修饰可以通过基因定位方法检测到。这种方法是在传统的数量性状位点（QTL）定位基础上发展而来的，主要侧重于单一性状分析。最近的研究表明，哺乳动物中的大多数印记基因在控制胚胎生长和出生后发育中起着重要作用。对于像生长这样的发育性状，目前的方法在剖析个体发育过程中印记基因的动态遗传效应方面效率较低。
功能定位已成为一种强大的框架，用于定位具有发育特征的复杂性状的数量性状位点。为了理解动态印记性状的遗传结构，我们提出了一种将功能定位方法与基因组印记相结合的定位策略。我们通过在近交F2群体中定位控制生长轨迹的印记QTL来展示该方法。通过模拟研究展示了该方法的统计行为，在不同的模拟场景下，参数能够以合理的精度进行估计。通过对来自LG/J和SM/J小鼠品系的F2家系的实际数据分析说明了该方法的实用性。鉴定出三个母源印记QTL调控小鼠体重的生长轨迹。
本文开发的功能性印记QTL定位方法为评估印记基因与发育过程之间的相互作用提供了一个定量且可检验的框架，对于阐明印记性状的遗传结构具有重要意义。
