From QTL to QTN: candidate gene set approach and a case study in porcine IGF1-FoxO pathway.
Unraveling the genetic background of economic traits is a major goal in modern animal genetics and breeding. Both candidate gene analysis and QTL mapping have previously been used for identifying genes and chromosome regions related to studied traits. However, most of these studies may be limited in their ability to fully consider how multiple genetic factors may influence a particular phenotype of interest. If possible, taking advantage of the combined effect of multiple genetic factors is expected to be more powerful than analyzing single sites, as the joint action of multiple loci within a gene or across multiple genes acting in the same gene set will likely have a greater influence on phenotypic variation. Thus, we proposed a pipeline of gene set analysis that utilized information from multiple loci to improve statistical power. We assessed the performance of this approach by both simulated and a real IGF1-FoxO pathway data set. The results showed that our new method can identify the association between genetic variation and phenotypic variation with higher statistical power and unravel the mechanisms of complex traits in a point of gene set. Additionally, the proposed pipeline is flexible to be extended to model complex genetic structures that include the interactions between different gene sets and between gene sets and environments.
School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Minghui
M
Wang
Qishan
Q
Wang
Yuchun
Y
Pan
D000818:Animals; D003198:Computer Simulation; D030541:Databases, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies / Q000379:methods*; D040582:Inheritance Patterns / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009711:Nucleotides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D034421:Sus scrofa / Q000235:genetics*
D051858:Forkhead Transcription Factors; D009711:Nucleotides; D007334:Insulin-Like Growth Factor I