scholarly journals Karyotype stability and unbiased fractionation in the paleo-allotetraploidCucurbitagenomes

2017 ◽  
Author(s):  
Honghe Sun ◽  
Shan Wu ◽  
Guoyu Zhang ◽  
Chen Jiao ◽  
Shaogui Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Agronomic Traits ◽  
Genetic Distances ◽  
Plant Genome ◽  
Specific Expression ◽  
Important Species ◽  
Allele Specific ◽  
Regulatory Effects ◽  
Karyotype Stability

AbstractTheCucurbitagenus contains several economically important species in the Cucurbitaceae family. Interspecific hybrids betweenC. maximaandC. moschataare widely used as rootstocks for other cucurbit crops. We report high-quality genome sequences ofC. maximaandC. moschataand provide evidence supporting an allotetraploidization event inCucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), and the allotetraploidization happened earlier than 3 Mya, whenC. maximaandC. moschatadiverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization is uncommon in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in theC. maxima×C. moschatainterspecific F1hybrid and the two parents indicates the predominance oftrans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into plant genome evolution and valuable resources for genetic improvement of cucurbit crops.

scholarly journals Genetic influences on cell type specific gene expression and splicing during neurogenesis elucidate regulatory mechanisms of brain traits

2020 ◽  
Author(s):  
Nil Aygün ◽  
Angela L. Elwell ◽  
Dan Liang ◽  
Michael J. Lafferty ◽  
Kerry E. Cheek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Elements ◽  
Regulatory Mechanisms ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Risk Variants ◽  
Allele Specific ◽  
Cell Type Specific ◽  
Regulatory Effects

SummaryInterpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing is mainly performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements of cells present during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs and allele specific expression in primary human neural progenitors (n=85) and their sorted neuronal progeny (n=74). Using colocalization and TWAS, we uncover cell-type specific regulatory mechanisms underlying risk for these traits.

scholarly journals Cis-regulatory divergence in gene expression between two thermally divergent yeast species

2016 ◽  
Author(s):  
Xueying C. Li ◽  
Justin C. Fay
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Binding Sites ◽  
Small Subset ◽  
Regulatory Sequences ◽  
Promoter Regions ◽  
Specific Expression ◽  
Thermal Growth ◽  
Allele Specific ◽  
Regulatory Effects

AbstractGene regulation is a ubiquitous mechanism by which organisms respond to their environment. While organisms are often found to be adapted to the environments they experience, the role of gene regulation in environmental adaptation is not often known. In this study, we examine divergence in cis-regulatory effects between two Saccharomyces species, S. cerevisiae and S. uvarum, that have substantially diverged in their thermal growth profile. We measured allele specific expression (ASE) in the species’ hybrid at three temperatures, the highest of which is lethal to S. uvarum but not the hybrid or S. cerevisiae. We find that S. uvarum alleles can be expressed at the same level as S. cerevisiae alleles at high temperature and most cis-acting differences in gene expression are not dependent on temperature. While a small set of 136 genes show temperature-dependent ASE, we find no indication that signatures of directional cis-regulatory evolution are associated with temperature. Within promoter regions we find binding sites enriched upstream of temperature responsive genes, but only weak correlations between binding site and expression divergence. Our results indicate that temperature divergence between S. cerevisiae and S. uvarum has not caused widespread divergence in cis-regulatory activity, but point to a small subset of genes where the species’ alleles show differences in magnitude or opposite responses to temperature. The difficulty of explaining divergence in cis-regulatory sequences with models of transcription factor binding sites and nucleosome positioning highlights the importance of identifying mutations that underlie cis-regulatory divergence between species.

WED 139 Gene expression regulation in CD4+ t-cell dysfunction in ms

2018 ◽  
Vol 89 (10) ◽  
pp. A16.1-A16
Author(s):  
Hrastelj James ◽  
Bray Nicholas ◽  
Williams Nigel ◽  
Robertson Neil
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Gene Expression Regulation ◽  
Cell Types ◽  
Expression Data ◽  
Specific Expression ◽  
Complex Disorders ◽  
Risk Variants ◽  
Allele Specific ◽  
Regulatory Effects

BackgroundGenetic risk variants for complex disorders such as multiple sclerosis (MS) rarely encode protein. Growing evidence suggests risk variants regulate gene expression in specific disease-relevant cells by altering regulatory genetic sequences. This can be explored by correlating genotype at risk loci with expression of nearby genes (cis-regulation), with greatest sensitivity demonstrated in the most relevant cell types. Identifying genes under regulation by the MS risk variants could be a crucial step in identifying novel therapeutic targets.Aims1) Interrogate MS risk loci for cis-regulatory effects using allele-specific expression (ASE) analysis. 2) Establish a publicly available resource of genome-wide RNA-seq expression data in CSF-derived CD4 +T lymphocytes. 3) Correlate gene expression data with longitudinal clinical data to seek biomarkers of prognosis.Method and progressWe have extracted RNA from FACS-sorted CSF-derived CD4 +T lymphocytes from over 100 individuals. cDNA library preparation and sequencing for each sample is underway.Data analysisASE analysis makes use of a pre-selected transcribed SNP to differentiate maternal and paternal transcripts of each gene of interest. When an individual is heterozygous at an additional functional regulatory locus the ratio of maternal: paternal expression will deviate from 1:1. Each MS risk locus will be interrogated for this effect.

scholarly journals Behavior-dependent cis regulation reveals genes and pathways associated with bower building in cichlid fishes

2018 ◽  
Vol 115 (47) ◽  
pp. E11081-E11090 ◽  
Author(s):  
Ryan A. York ◽  
Chinar Patil ◽  
Kawther Abdilleh ◽  
Zachary V. Johnson ◽  
Matthew A. Conte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Plasticity ◽  
Genetic Basis ◽  
Specific Expression ◽  
Preferential Expression ◽  
Cichlid Fishes ◽  
Brain Gene Expression ◽  
Genome Wide ◽  
Allele Specific ◽  
Genomic Regions

Many behaviors are associated with heritable genetic variation [Kendler and Greenspan (2006) Am J Psychiatry 163:1683–1694]. Genetic mapping has revealed genomic regions or, in a few cases, specific genes explaining part of this variation [Bendesky and Bargmann (2011) Nat Rev Gen 12:809–820]. However, the genetic basis of behavioral evolution remains unclear. Here we investigate the evolution of an innate extended phenotype, bower building, among cichlid fishes of Lake Malawi. Males build bowers of two types, pits or castles, to attract females for mating. We performed comparative genome-wide analyses of 20 bower-building species and found that these phenotypes have evolved multiple times with thousands of genetic variants strongly associated with this behavior, suggesting a polygenic architecture. Remarkably, F1 hybrids of a pit-digging and a castle-building species perform sequential construction of first a pit and then a castle bower. Analysis of brain gene expression in these hybrids showed that genes near behavior-associated variants display behavior-dependent allele-specific expression with preferential expression of the pit-digging species allele during pit digging and of the castle-building species allele during castle building. These genes are highly enriched for functions related to neurodevelopment and neural plasticity. Our results suggest that natural behaviors are associated with complex genetic architectures that alter behavior via cis-regulatory differences whose effects on gene expression are specific to the behavior itself.

Allele-Specific Expression and Evolution of Gene Regulation Underlying Acute Heat Stress Response and Local Adaptation in the Copepod Tigriopus californicus

2020 ◽  
Vol 111 (6) ◽  
pp. 539-547
Author(s):  
Sumaetee Tangwancharoen ◽  
Brice X Semmens ◽  
Ronald S Burton
Keyword(s):  
Gene Expression ◽  
Heat Stress ◽  
Stress Response ◽  
Local Adaptation ◽  
F1 Hybrids ◽  
Specific Expression ◽  
Heat Stress Response ◽  
Acute Heat Stress ◽  
Number Of Genes ◽  
Allele Specific

Abstract Geographic variation in environmental temperature can select for local adaptation among conspecific populations. Divergence in gene expression across the transcriptome is a key mechanism for evolution of local thermal adaptation in many systems, yet the genetic mechanisms underlying this regulatory evolution remain poorly understood. Here we examine gene expression in 2 locally adapted Tigriopus californicus populations (heat tolerant San Diego, SD, and less tolerant Santa Cruz, SC) and their F1 hybrids during acute heat stress response. Allele-specific expression (ASE) in F1 hybrids was used to determine cis-regulatory divergence. We found that the number of genes showing significant allelic imbalance increased under heat stress compared to unstressed controls. This suggests that there is significant population divergence in cis-regulatory elements underlying heat stress response. Specifically, the number of genes showing an excess of transcripts from the more thermal tolerant (SD) population increased with heat stress while that number of genes with an SC excess was similar in both treatments. Inheritance patterns of gene expression also revealed that genes displaying SD-dominant expression phenotypes increase in number in response to heat stress; that is, across loci, gene expression in F1’s following heat stress showed more similarity to SD than SC, a pattern that was absent in the control treatment. The observed patterns of ASE and inheritance of gene expression provide insight into the complex processes underlying local adaptation and thermal stress response.

scholarly journals Interactions between genetic variation and cellular environment in skeletal muscle gene expression

2017 ◽  
Author(s):  
D. Leland Taylor ◽  
David A. Knowles ◽  
Laura J. Scott ◽  
Andrea H. Ramirez ◽  
Franceso Paolo Casale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Genetic Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Specific Expression ◽  
Muscle Gene Expression ◽  
Cellular Environment ◽  
Allele Specific ◽  
Muscle Gene

AbstractFrom whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discovercisacting genotype-environment interactions (GxE) - genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate interaction quantitative trait loci (iQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.

scholarly journals Large structural variations in the haplotype-resolved African cassava genome.

2021 ◽  
Author(s):  
Ben N Mansfeld ◽  
Adam Boyher ◽  
Jeffrey C Berry ◽  
Mark Wilson ◽  
Shujun Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Load ◽  
Specific Gene ◽  
Stem Cuttings ◽  
Structural Variations ◽  
Manihot Esculenta Crantz ◽  
Specific Expression ◽  
Global Food Security ◽  
Allele Specific ◽  
Two Phases

Cassava (Manihot esculenta Crantz, 2n=36) is a global food security crop. Cassava has a highly heterozygous genome, high genetic load, and genotype-dependent asynchronous flowering. It is typically propagated by stem cuttings and any genetic variation between haplotypes, including large structural variations, is preserved by such clonal propagation. Traditional genome assembly approaches generate a collapsed haplotype representation of the genome. In highly heterozygous plants, this results in artifacts and an oversimplification of heterozygous regions. We used a combination of Pacific Biosciences (PacBio), Illumina, and Hi-C to resolve each haplotype of the genome of a farmer-preferred cassava line, TME7 (Oko-iyawo). PacBio reads were assembled using the FALCON suite. Phase switch errors were corrected using FALCON-Phase and Hi-C read data. The ultra-long-range information from Hi-C sequencing was also used for scaffolding. Comparison of the two phases revealed more than 5,000 large haplotype-specific structural variants affecting over 8 Mb, including insertions and deletions spanning thousands of base pairs. The potential of these variants to affect allele specific expression was further explored. RNA-seq data from 11 different tissue types were mapped against the scaffolded haploid assembly and gene expression data are incorporated into our existing easy-to-use web-based interface to facilitate use by the broader plant science community. These two assemblies provide an excellent means to study the effects of heterozygosity, haplotype-specific structural variation, gene hemizygosity, and allele specific gene expression contributing to important agricultural traits and further our understanding of the genetics and domestication of cassava.

scholarly journals Transcriptome variation in human tissues revealed by long-read sequencing

2021 ◽  
Author(s):  
Dafni A Glinos ◽  
Garrett Garborcauskas ◽  
Paul Hoffman ◽  
Nava Ehsan ◽  
Lihua Jiang ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rare Variants ◽  
Similar Proportion ◽  
Specific Expression ◽  
Sequencing Technologies ◽  
Cellular Environment ◽  
Long Read ◽  
Allele Specific ◽  
Transcript Structure ◽  
Regulatory Effects

SummaryRegulation of transcript structure generates transcript diversity and plays an important role in human disease. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure. In this paper, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from GTEx tissues and cell lines, complementing the GTEx resource. We identified just under 100,000 new transcripts for annotated genes, and validated the protein expression of a similar proportion of novel and annotated transcripts. We developed a new computational package, LORALS, to analyze genetic effects of rare and common variants on the transcriptome via allele-specific analysis of long reads. We called allele-specific expression and transcript structure events, providing novel insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we use this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.

scholarly journals Spatially varying cis-regulatory divergence inDrosophilaembryos elucidates cis-regulatory logic

2017 ◽  
Author(s):  
Peter A. Combs ◽  
Hunter B. Fraser
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Raw Material ◽  
Spatial Patterning ◽  
Rna Seq ◽  
Specific Expression ◽  
Complex Interactions ◽  
Allele Specific ◽  
Spatially Varying ◽  
Cis And Trans

AbstractSpatial patterning of gene expression is a key process in development—responsible for the incredible diversity of animal body plans—yet how it evolves is still poorly understood. Both cis- and trans-acting changes could accumulate and participate in complex interactions, so to isolate the cis-regulatory component of patterning evolution, we measured allele-specific spatial gene expression patterns inD. melanogaster×D. simulanshybrid embryos. RNA-seq of cryosectioned slices revealed 55 genes with strong spatially varying allele-specific expression, and several hundred more with weaker but significant spatial divergence. For example, we found thathunchback (hb), a major regulator of developmental patterning, had reduced expression specifically in the anterior tip ofD. simulansembryos. Mathematical modeling ofhbcis-regulation suggested that a mutation in a Bicoid binding site was responsible, which we verified using CRISPR-Cas9 genome editing. In sum, even comparing morphologically near-identical species we identified a substantial amount of spatial variation in gene expression, suggesting that development is robust to many such changes, but also that natural selection may have ample raw material for evolving new body plans via cis-regulatory divergence.

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