scholarly journals Cloudy with a Chance of Insights: Context Dependent Gene Regulation and Implications for the Evolution of Gene Expression

2019 ◽  
Author(s):  
Elisa Buchberger ◽  
Micael Reis ◽  
Ting-Hsuan Lu ◽  
Nico Posnien
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Evolutionary Biology ◽  
Expression Data ◽  
Regulatory Evolution ◽  
Specific Expression ◽  
Genome Wide ◽  
Key Driver ◽  
Context Dependent ◽  
Genome Wide Expression

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic variation. An exceptional contribution of cis-regulatory evolution has for instance been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and developmental stage-specific expression. We argue that the regulatory context must be considered when studying evolution of gene expression.

scholarly journals Cloudy with a Chance of Insights: Context Dependent Gene Regulation and Implications for Evolutionary Studies

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 492 ◽  
Author(s):  
Buchberger ◽  
Reis ◽  
Lu ◽  
Posnien
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Evolutionary Biology ◽  
Phenotypic Evolution ◽  
Specific Expression ◽  
Expression Studies ◽  
Genome Wide ◽  
Key Driver ◽  
Context Dependent ◽  
Genome Wide Expression

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic evolution. An exceptional contribution of cis-regulatory divergence has been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and stage-specific expression. We argue that the regulatory context must be considered in comparative expression studies.

scholarly journals Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution

Science ◽  
2019 ◽  
Vol 363 (6434) ◽  
pp. 1463-1467 ◽  
Author(s):  
Samuel G. Rodriques ◽  
Robert R. Stickels ◽  
Aleksandrina Goeva ◽  
Carly A. Martin ◽  
Evan Murray ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Spatial Resolution ◽  
Expression Patterns ◽  
Cell Types ◽  
Expression Data ◽  
Tissue Sections ◽  
Spatially Resolved ◽  
Genome Wide ◽  
Cell Type Specific ◽  
Genome Wide Expression

Spatial positions of cells in tissues strongly influence function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. We developed Slide-seq, a method for transferring RNA from tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the locations of the RNA to be inferred by sequencing. Using Slide-seq, we localized cell types identified by single-cell RNA sequencing datasets within the cerebellum and hippocampus, characterized spatial gene expression patterns in the Purkinje layer of mouse cerebellum, and defined the temporal evolution of cell type–specific responses in a mouse model of traumatic brain injury. These studies highlight how Slide-seq provides a scalable method for obtaining spatially resolved gene expression data at resolutions comparable to the sizes of individual cells.

scholarly journals Sex Chromosome Dosage Effects On Gene Expression In Humans

2017 ◽  
Author(s):  
Armin Raznahan ◽  
Neelroop Parikshak ◽  
Vijayendran Chandran ◽  
Jonathan Blumenthal ◽  
Liv Clasen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
X Chromosome ◽  
Gene Networks ◽  
Sex Chromosome ◽  
Autosomal Gene ◽  
Expression Data ◽  
Systematic Map ◽  
Genome Wide ◽  
Genome Wide Expression

ABSTRACTA fundamental question in the biology of sex-differences has eluded direct study in humans: how does sex chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex chromosome aneuploidies (XO, XXX, XXY, XYY, XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity amongst evolutionarily preserved X-Y homologs, and update prevailing theoretical models for SCD compensation by detecting X-linked genes whose expression increases with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex chromosome genes regulate specific co-expression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. Our findings detail wide-ranging effects of SCD on genome function with implications for human phenotypic variation.SIGNIFICANCE STATEMENTSex chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex chromosome aneuploidy syndromes, but challenging to study given the co-segregation of SCD and gonadal status. We address this obstacle by systematically modelling SCD effects on genome wide expression data from a large and rare cohort of individuals with diverse SCDs (XO, XX, XXX, XXXX, XY, XXY, XYY, XXYY, XXXXY). Our findings update current models of sex chromosome biology by (i) pinpointing a core set of X- and Y-linked genes with “obligate” SCD sensitivity, (ii) discovering several non-canonical modes of X-chromosome dosage compensation, and (iii) dissecting complex regulatory effects of X-chromosome dosage on large autosomal gene networks with key roles in cellular functioning.

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

scholarly journals Identification of unique venous thromboembolism-susceptibility variants in African-Americans

2017 ◽  
Vol 117 (04) ◽  
pp. 758-768 ◽  
Author(s):  
Sebastian Armasu ◽  
Bryan McCauley ◽  
Iftikhar Kullo ◽  
Hugues Sicotte ◽  
Jyotishman Pathak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Venous Thromboembolism ◽  
African Americans ◽  
Differential Expression ◽  
White Women ◽  
Genome Wide Association Study ◽  
Expression Data ◽  
Significant Differential Expression ◽  
Genome Wide ◽  
A Genome

SummaryTo identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.Supplementary Material to this article is available online at www.thrombosis-online.com.

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.

FRI0309 The genome-wide expression of human osteoarthritic cartilage shows different GENE-expression profiles OA-related

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 418.3-418
Author(s):  
J. Fernandez-Tajes ◽  
A. Soto-Hermida ◽  
M. Fernandez-Moreno ◽  
M.E. Vazquez-Mosquera ◽  
N. Oreiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Osteoarthritic Cartilage ◽  
Genome Wide ◽  
Genome Wide Expression
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