Towards a comprehensive picture of the genetic landscape of complex traits

• Published in: Briefings in bioinformatics 2014-01, Vol.15 (1), p.30-42
• Main Authors: Wang, Zhong, Wang, Yaqun, Wang, Ningtao, Wang, Jianxin, Wang, Zuoheng, Vallejos, C Eduardo, Wu, Rongling
• Format: Article
• Language: English
• Subjects: Animals; Chromosome Mapping - statistics & numerical data; Computational Biology; Deoxyribonucleic acid; Differential equations; DNA; Epistasis, Genetic; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genetic Association Studies - statistics & numerical data; Genomics; Genotype & phenotype; Humans; Models, Genetic; Polymorphism; Quantitative Trait Loci; Systems Biology
• ISSN: 1467-5463; 1477-4054
• DOI: 10.1093/bib/bbs049

The formation of phenotypic traits, such as biomass production, tumor volume and viral abundance, undergoes a complex process in which interactions between genes and developmental stimuli take place at each level of biological organization from cells to organisms. Traditional studies emphasize the impact of genes by directly linking DNA-based markers with static phenotypic values. Functional mapping, derived to detect genes that control developmental processes using growth equations, has proven powerful for addressing questions about the roles of genes in development. By treating phenotypic formation as a cohesive system using differential equations, a different approach-systems mapping-dissects the system into interconnected elements and then map genes that determine a web of interactions among these elements, facilitating our understanding of the genetic machineries for phenotypic development. Here, we argue that genetic mapping can play a more important role in studying the genotype-phenotype relationship by filling the gaps in the biochemical and regulatory process from DNA to end-point phenotype. We describe a new framework, named network mapping, to study the genetic architecture of complex traits by integrating the regulatory networks that cause a high-order phenotype. Network mapping makes use of a system of differential equations to quantify the rule by which transcriptional, proteomic and metabolomic components interact with each other to organize into a functional whole. The synthesis of functional mapping, systems mapping and network mapping provides a novel avenue to decipher a comprehensive picture of the genetic landscape of complex phenotypes that underlie economically and biomedically important traits.