Project description:While mammalian genomes are diploid, previous studies extensively investigated the average chromatin architectures without considering the differences between homologous chromosomes. Here we generated Hi-C, ChIP-seq and RNA-seq datasets from CD4 T cells of B6, Cast and hybrid mice, to investigate the diploid chromatin organization and epigenetic regulation. Our data indicate that inter-chromosomal interaction patterns between homologous chromosomes are similar and the similarity is highly correlated with their allelic co-expression levels. Reconstruction of 3D nucleus revealed that distances of the homologous chromosomes to the center of nucleus are almost the same. The inter-chromosomal interactions at centromere-ends are significantly weaker than those at telomere-ends, suggesting that they are located in different regions within the chromosome territories. The majority of A|B compartments or topologically associated domains (TADs) are consistent between B6 and Cast. We found 58% of the haploids in hybrids maintain their parental compartment status at B6/Cast divergent compartments due to cis-effect. About 95% of the trans-effected B6/Cast divergent compartments converge to the same compartment status potentially due to a shared cellular environment. We showed the differentially expressed genes between the two haploids in hybrid were associated with either genetic or epigenetic effects. In summary, our multi-omics data from the hybrid mice provided haploid-specific information on the 3D nuclear architecture and a rich resource for further understanding the epigenetic regulation of haploid-specific gene expression.
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes to alter the transcript accumulation levels in two types of hybrid necrosis-showing plants; one was derived from interspecific crosses of two diploid wheat species Triticum monococcum ssp. aegilopoides and Triticum urartu, and another from intraspecific hybrids of common wheat. Of the up-regulated genes, defense-related and carbohyfrate metabosim-related genes were frequently found, whereas photosythesis-related genes down-regulated in the hybrid necrosis-showing plants. These observations strongly suggests that autoimmune responses might be triggered by Ne1-Ne2 interaction in common wheat and by Ned1-Ned2 interaction in the wild diploid wheat, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in other wheat hybrid necrosis such as type III necrosis in the ABD wheat triploids crossed between tetraploid wheat and Aegilops tauschii. Expression patterns were compared between a wild-type wheat hybrid plant (as a reference) and a hybrid necrosis-showing hybrid plant in each of common and wild diploid wheat. Total RNA samples were isolated from leaf tissues. Two independent experiments were conducted in each expriment.
Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes to alter the transcript accumulation levels in two types of hybrid necrosis-showing plants; one was derived from interspecific crosses of two diploid wheat species Triticum monococcum ssp. aegilopoides and Triticum urartu, and another from intraspecific hybrids of common wheat. Of the up-regulated genes, defense-related and carbohyfrate metabosim-related genes were frequently found, whereas photosythesis-related genes down-regulated in the hybrid necrosis-showing plants. These observations strongly suggests that autoimmune responses might be triggered by Ne1-Ne2 interaction in common wheat and by Ned1-Ned2 interaction in the wild diploid wheat, and that genetically programmed cell death could be regarded as a hypersensitive response-like cell death similar to that observed in other wheat hybrid necrosis such as type III necrosis in the ABD wheat triploids crossed between tetraploid wheat and Aegilops tauschii.
Project description:Heritable differences in gene expression between individuals are an important source of phenotypic variation. The question of how closely the effects of genetic variation on protein levels mirror those on mRNA levels remains open. Here, we addressed this question by using ribosomal footprinting to examine how genetic differences between two strains of the yeast S. cerevisiae affect translation. Strain differences in translation were observed for hundreds of genes, more than half as many as showed genetic differences in mRNA levels. Similarly, allele specific measurements in the diploid hybrid between the two strains found roughly half as many cis-acting effects on translation as were observed for mRNA levels. In both the parents and the hybrid, strong effects on translation were rare, such that the direction of an mRNA difference was typically reflected in a concordant footprint difference. The relative importance of cis and trans acting variation on footprint levels was similar to that for mRNA levels. Across all expressed genes, there was a tendency for translation to more often reinforce than buffer mRNA differences, resulting in footprint differences with greater magnitudes than the mRNA differences. Finally, we catalogued instances of premature translation termination in the two yeast strains. Overall, genetic variation clearly influences translation, but primarily does so by subtly modulating differences in mRNA levels. Translation does not appear to create strong discrepancies between genetic influences on mRNA and protein levels. Ribsosomal footprinting and RNASeq in the two yeast strains BY and RM as well as their diploid hybrid. We generated one library each for the BY and RM parents, and two libraries (biological replicates) for the hybrid data.
Project description:Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin accessibility to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture and evolution of chromatin structure within and between species. We performed Formaldehyde-Assisted Isolation of Regulatory Elements sequencing (FAIRE-Seq) to map chromatin accessibility in two parental haploid yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus and their diploid hybrid. We show that although broad-scale characteristics of the chromatin landscape are well conserved between these species, accessibility is significantly different for 947 regions upstream of genes that are enriched for GO terms such as intracellular transport and protein localization exhibit. We also develop new statistical methods to investigate the genetic architecture of variation in chromatin accessibility between species, and find that cis effects are more common and of greater magnitude than trans effects. Interestingly, we find that cis and trans effects at individual genes are often negatively correlated, suggesting widespread compensatory evolution to stabilize levels of chromatin accessibility. Finally, we demonstrate that the relationship between chromatin accessibility and gene expression levels is complex, and a significant proportion of differences in chromatin accessibility might be functionally benign. There are 20 samples in total. These consist of 10 FAIRE-seq samples, specifically 6 haploid samples, S. cerevisiae strain UWOPS05_217_3 replicates 1 and 2, S. cerevisiae strain DBVPG1373 replicates 1 and 2, and S. paradoxus strain CBS432 replicates 1 and 2. There are also 4 diploid hybrid samples, hybrid between S. cerevisiae strain UWOPS05_217_3 and S. paradoxus strain CBS432 replicates 1 and 2, and the hybrid between S. cerevisiae strain DBVPG1373 and S. paradoxus strain CBS432 replicates 1 and 2. There are also RNA-seq samples for each of these 10 samples.
Project description:Heritable differences in gene expression between individuals are an important source of phenotypic variation. The question of how closely the effects of genetic variation on protein levels mirror those on mRNA levels remains open. Here, we addressed this question by using ribosomal footprinting to examine how genetic differences between two strains of the yeast S. cerevisiae affect translation. Strain differences in translation were observed for hundreds of genes, more than half as many as showed genetic differences in mRNA levels. Similarly, allele specific measurements in the diploid hybrid between the two strains found roughly half as many cis-acting effects on translation as were observed for mRNA levels. In both the parents and the hybrid, strong effects on translation were rare, such that the direction of an mRNA difference was typically reflected in a concordant footprint difference. The relative importance of cis and trans acting variation on footprint levels was similar to that for mRNA levels. Across all expressed genes, there was a tendency for translation to more often reinforce than buffer mRNA differences, resulting in footprint differences with greater magnitudes than the mRNA differences. Finally, we catalogued instances of premature translation termination in the two yeast strains. Overall, genetic variation clearly influences translation, but primarily does so by subtly modulating differences in mRNA levels. Translation does not appear to create strong discrepancies between genetic influences on mRNA and protein levels.
Project description:This study utilizes multi-omic biological data to perform deep immunophenotyping on the major immune cell classes in COVID-19 patients. 10X Genomics Chromium Single Cell Kits were used with Biolegend TotalSeq-C human antibodies to gather single-cell transcriptomic, surface protein, and TCR/BCR sequence information from 254 COVID-19 blood draws (a draw near diagnosis (-BL) and a draw a few days later (-AC)) and 16 healthy donors.