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Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

ABSTRACT: There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.

SUBMITTER: Powell JE

PROVIDER: S-EPMC3656157 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

Powell Joseph E JE Henders Anjali K AK McRae Allan F AF Kim Jinhee J Hemani Gibran G Martin Nicholas G NG Dermitzakis Emmanouil T ET Gibson Greg G Montgomery Grant W GW Visscher Peter M PM

PLoS genetics 20130516 5

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twi ...[more]

PMID: 23696747

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Project description:BackgroundPlant domestication is a remarkable example of rapid phenotypic transformation of polygenic traits, such as organ size. Evidence from a handful of study cases suggests this transformation is due to gene regulatory changes that result in non-additive phenotypes. Employing data from published genetic crosses, we estimated the role of non-additive gene action in the modulation of transcriptional landscapes in three domesticated plants: maize, sunflower, and chili pepper. Using A. thaliana, we assessed the correlation between gene regulatory network (GRN) connectivity properties, transcript abundance variation, and gene action. Finally, we investigated the propagation of non-additive gene action in GRNs.ResultsWe compared crosses between domesticated plants and their wild relatives to a set of control crosses that included a pair of subspecies evolving under natural selection and a set of inbred lines evolving under domestication. We found abundance differences on a higher portion of transcripts in crosses between domesticated-wild plants relative to the control crosses. These transcripts showed non-additive gene action more often in crosses of domesticated-wild plants than in our control crosses. This pattern was strong for genes associated with cell cycle and cell fate determination, which control organ size. We found weak but significant negative correlations between the number of targets of trans-acting genes (Out-degree) and both the magnitude of transcript abundance difference a well as the absolute degree of dominance. Likewise, we found that the number of regulators that control a gene's expression (In-degree) is weakly but negatively correlated with the magnitude of transcript abundance differences. We observed that dominant-recessive gene action is highly propagable through GRNs. Finally, we found that transgressive gene action is driven by trans-acting regulators showing additive gene action.ConclusionsOur study highlights the role of non-additive gene action on modulating domestication-related traits, such as organ size via regulatory divergence. We propose that GRNs are shaped by regulatory changes at genes with modest connectivity, which reduces the effects of antagonistic pleiotropy. Finally, we provide empirical evidence of the propagation of non-additive gene action in GRNs, which suggests a transcriptional epistatic model for the control of polygenic traits, such as organ size.

Dataset Information

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

Publications

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.

Similar Datasets

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