Ali A A, Khatkar M S, Kadarmideen H N, Thomson P C
Faculty of Veterinary Science, University of Sydney, Camden, NSW, Australia.
J Anim Breed Genet. 2015 Apr;132(2):187-97. doi: 10.1111/jbg.12147. Epub 2015 Mar 6.
Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems.
全基因组关联研究通常用于识别与感兴趣的性状相关的基因组区域。然而,这忽略了一类重要的基因组关联,即上位性相互作用。使用高密度标记对单核苷酸多态性(SNP)进行全基因组相互作用分析可以检测上位性相互作用,但由于多重检验和计算需求,这是一项艰巨的任务。然而,它对于揭示复杂性状遗传很重要。本研究考虑了检测基因座对之间统计相互作用的分析方法。我们研究了一个三阶段建模程序:(i)一个不包含SNP的模型,用于估计方差成分;(ii)一个包含SNP的模型,使用(i)中的方差成分估计值,从而避免迭代;(iii)使用(ii)中的显著SNP进行全基因组上位性分析。我们将这三个阶段的模型应用于婆罗门牛生长和皮下脂肪厚度超声测量的田间数据。该研究证明了在上位性建模用于复杂性状分析中的有用性,因为它揭示了额外的遗传变异来源,并确定了影响胰岛素样生长因子-1浓度和脂肪深度性状超声扫描测量的潜在候选基因。关于上位性的信息可以增进我们对构成生物系统基本基础的复杂遗传网络的理解。