Dissecting genetic networks underlying complex phenotypes: The theoretical framework

Fan Zhang, Hu Qu Zhai, Andrew H. Paterson, Jian Long Xu, Yong Ming Gao, Tian Qing Zheng, Rong Ling Wu, Bin Ying Fu, Jauhar Ali, Zhi Kang Li

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Great progress has been made in genetic dissection of quantitative trait variation during the past two decades, but many studies still reveal only a small fraction of quantitative trait loci (QTLs), and epistasis remains elusive. We integrate contemporary knowledge of signal transduction pathways with principles of quantitative and population genetics to characterize genetic networks underlying complex traits, using a model founded upon one-way functional dependency of downstream genes on upstream regulators (the principle of hierarchy) and mutual functional dependency among related genes (functional genetic units, FGU). Both simulated and real data suggest that complementary epistasis contributes greatly to quantitative trait variation, and obscures the phenotypic effects of many 'downstream' loci in pathways. The mathematical relationships between the main effects and epistatic effects of genes acting at different levels of signaling pathways were established using the quantitative and population genetic parameters. Both loss of function and ''co-adapted'' gene complexes formed by multiple alleles with differentiated functions (effects) are predicted to be frequent types of allelic diversity at loci that contribute to the genetic variation of complex traits in populations. Downstream FGUs appear to be more vulnerable to loss of function than their upstream regulators, but this vulnerability is apparently compensated by different FGUs of similar functions. Other predictions from the model may account for puzzling results regarding responses to selection, genotype by environment interaction, and the genetic basis of heterosis.

Original languageEnglish (US)
Article numbere14541
JournalPloS one
Volume6
Issue number1
DOIs
StatePublished - Feb 3 2011

Fingerprint

Complex networks
Genes
Population Genetics
Phenotype
phenotype
epistasis
quantitative genetics
Genetic Epistasis
quantitative traits
Hybrid Vigor
population genetics
genes
Quantitative Trait Loci
Dissection
Signal transduction
loci
Signal Transduction
heterosis
Alleles
Genotype

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zhang, F., Zhai, H. Q., Paterson, A. H., Xu, J. L., Gao, Y. M., Zheng, T. Q., ... Li, Z. K. (2011). Dissecting genetic networks underlying complex phenotypes: The theoretical framework. PloS one, 6(1), [e14541]. https://doi.org/10.1371/journal.pone.0014541
Zhang, Fan ; Zhai, Hu Qu ; Paterson, Andrew H. ; Xu, Jian Long ; Gao, Yong Ming ; Zheng, Tian Qing ; Wu, Rong Ling ; Fu, Bin Ying ; Ali, Jauhar ; Li, Zhi Kang. / Dissecting genetic networks underlying complex phenotypes : The theoretical framework. In: PloS one. 2011 ; Vol. 6, No. 1.
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Zhang, F, Zhai, HQ, Paterson, AH, Xu, JL, Gao, YM, Zheng, TQ, Wu, RL, Fu, BY, Ali, J & Li, ZK 2011, 'Dissecting genetic networks underlying complex phenotypes: The theoretical framework', PloS one, vol. 6, no. 1, e14541. https://doi.org/10.1371/journal.pone.0014541

Dissecting genetic networks underlying complex phenotypes : The theoretical framework. / Zhang, Fan; Zhai, Hu Qu; Paterson, Andrew H.; Xu, Jian Long; Gao, Yong Ming; Zheng, Tian Qing; Wu, Rong Ling; Fu, Bin Ying; Ali, Jauhar; Li, Zhi Kang.

In: PloS one, Vol. 6, No. 1, e14541, 03.02.2011.

Research output: Contribution to journalArticle

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Zhang F, Zhai HQ, Paterson AH, Xu JL, Gao YM, Zheng TQ et al. Dissecting genetic networks underlying complex phenotypes: The theoretical framework. PloS one. 2011 Feb 3;6(1). e14541. https://doi.org/10.1371/journal.pone.0014541