Smith Jason, Liu Fang, Beyer Barbara, Morales Krista, Reilly Andrew, Cole Richard, Herron Bruce J
1 Wadsworth Center, New York State Department of Health, Albany, New York, USA; and 2 Department of Biomedical Sciences, School of Public Health, State University of New York at Albany, Albany, New York, USA.
J Biomol Tech. 2015 Jul;26(2):45-53. doi: 10.7171/jbt.15-2602-002.
Identification of genetic factors that modify complex traits is often complicated by gene-environment interactions that contribute to the observed phenotype. In model systems, the phenotypic outcomes quantified are typically traits that maximize observed variance, which in turn, should maximize the detection of quantitative trait loci (QTL) in subsequent mapping studies. However, when the observed trait is dependent on multiple interacting factors, it can complicate genetic analysis, reducing the likelihood that the modifying mutation will ultimately be found. Alternatively, by focusing on intermediate phenotypes of a larger condition, we can reduce a model's complexity, which will, in turn, limit the number of QTL that contribute to variance. We used a novel method to follow angiogenesis in mice that reduces environmental variance by measuring endothelial cell growth from culture of isolated skin biopsies that varies depending on the genetic source of the tissue. This method, in combination with a backcross breeding strategy, is intended to reduce genetic complexity and limit the phenotypic effects to fewer modifier loci. We determined that our approach was an efficient means to generate recombinant progeny and used this cohort to map a novel s.c. angiogenesis QTL to proximal mouse chromosome (Chr.) 8 with suggestive QTL on Chr. 2 and 7. Global mRNA expression analysis of samples from parental reference strains revealed β-defensins as potential candidate genes for future study.
修饰复杂性状的遗传因素的鉴定常常因基因与环境的相互作用而变得复杂，这些相互作用会影响所观察到的表型。在模型系统中，量化的表型结果通常是使观察到的方差最大化的性状，这反过来又应能在后续的定位研究中最大限度地检测到数量性状位点（QTL）。然而，当观察到的性状依赖于多个相互作用的因素时，遗传分析就会变得复杂，降低最终发现修饰突变的可能性。另外，通过关注较大病症的中间表型，我们可以降低模型的复杂性，这反过来又会限制对方差有贡献的QTL的数量。我们使用了一种新方法来跟踪小鼠的血管生成，该方法通过测量从分离的皮肤活检组织培养物中内皮细胞的生长来减少环境方差，而这种生长因组织的遗传来源而异。这种方法与回交育种策略相结合，旨在降低遗传复杂性，并将表型效应限制在较少的修饰位点上。我们确定我们的方法是产生重组后代的有效手段，并利用这一群组将一个新的皮下血管生成QTL定位到小鼠近端8号染色体（Chr.）上，在2号和7号染色体上有暗示性的QTL。对亲本参考品系样本的全局mRNA表达分析显示，β-防御素是未来研究的潜在候选基因。
