Project description:Epialleles are meiotically inherited variations in expression states that are not linked to changes in DNA sequence. Although they are well documented to persist in plant genomes, their molecular origins are unknown. Here, we show using a variety of mutant and experimental populations that epialleles in Arabidopsis thaliana result from feedback regulation of pathways that primarily function to maintain DNA methylation at heterochromatin. Perturbations to maintenance of heterochromatin methylation leads to feedback regulation of DNA methylation in genes, with a preference for genes with pre-existing DNA methylation. Using epigenetic recombinant inbred lines (epiRIL), we show that epiallelic variation is enriched in euchromatin, yet, associated with QTL primarily located in heterochromatin. Mapping three-dimensional chromatin contacts reveals that genes that are hotspots for epiallelic variation have increased contact frequencies with regions possessing H3K9me2. Altogether, these data show that feedback regulation of pathways that evolved to maintain heterochromatin silencing leads to the origins of spontaneous epialleles.
Project description:Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. To map gene regulatory pathways, we used microarray-derived gene expression measurements in 60 individuals of an F2 sample segregating for diabetes. We performed correlation analysis among ~40,000 expression traits. By combining correlation among expression traits and linkage mapping information, we were able to identify regulatory networks, make functional predictions to uncharacterized genes, and characterize novel members of known pathways. Using 36 seed traits, we found evidence of coordinate regulation of 160 G-protein coupled receptor (GPCR) pathway expression traits. Of the 160 traits, 50 had their major LOD peak within 8 cM of a locus on chromosome 2, and 81 others had a secondary peak in this region. A previously uncharacterized Riken cDNA clone, which showed strong correlation with stearoyl CoA desaturase 1 expression, was experimentally validated to be responsive to conditions that regulate lipid metabolism. Using linkage mapping, we identified multiple genes whose expression is under the control of transcription regulatory loci. Trait-correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we only studied mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping only. References: Kendziorski C., M. Chen, M. Yuan, H. Lan, and A.D. Attie. Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping. Biometrics, to appear, 2005. Lan H, Chen M, Flowers JB, Yandell BS, Stapleton DS, et al. (2006) Combined Expression Trait Correlations and Expression Quantitative Trait Locus Mapping. PLoS Genet 2(1): e6. Keywords: Genetics of gene expression
Project description:This data originates from an expression quantitative trait locus analysis of liver in an advanced intercross of Red Jungefowl and White Leghorn chickens. The aim of the study was to map the genetic basis of growth traits and transcript abundance traits in the liver, and use the latter to search for candidate causative genes for chicken growth.
Project description:This data originates from an expression quantitative trait locus analysis of cerebrum in an advanced intercross of Red Jungefowl and White Leghorn chickens. The aim of the study was to map the genetic basis of cerebrum and body mass, and idenifiy transcriptional differences within the intercross to assess any candidate genes for cerebrum and body mass.
Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the ‘biological signature’ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Keywords: rat, hypertension, genetics, polygenic trait, microarray, gene expression
Project description:We performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium.
Project description:Plants bearing a sulfurea epiallele (TAB2sulf) were crossed with nrpe1 (largest polV subunit) mutants in Solanum Lycopersicum. 7 plants of a F3 progeny expected to be 100% TAB2sulf and segregating for the nrpe1 mutation were sequenced. 4 plants bear the nrpe1 mutation and 3 plants have NRPE1 WT alleles. The aim of the experiment was to compare sRNA accumulation between nrpe1 and WT F3 plants with particular interest on SlTAB2 (Solyc02g005200) which has been previously associated with paramutation in the sulfurea background. Both WT and nrpe1 F3 plants had methylation levels consistent with the TAB2sulf epiallele. nrpe1 and sulfurea parental controls are added in single replicates and a WT cv M82 plant is also sequenced as control. More replicates of WT and M82 are sequenced in a related experiment.