scholarly journals Integrated analysis of the methylome and transcriptome of twin almonds (Prunus dulcis [Mill.] D.A.Webb) reveals genomic features associated with non-infectious bud failure

2021 ◽  
Author(s):  
Katherine M. D’Amico-Willman ◽  
Chad E. Niederhuth ◽  
Matthew R. Willman ◽  
Thomas M. Gradziel ◽  
Wilburforce Z. Ouma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Monozygotic Twin ◽  
Prunus Dulcis ◽  
Integrated Analysis ◽  
Related Disorder ◽  
Genomic Features ◽  
Genetic Components ◽  
Age Related ◽  
Genome Wide

I.SummaryAlmond (Prunus dulcis [Mill.] D.A.Webb) exhibits an age-related disorder called non-infectious bud-failure (BF) affecting vegetative bud development and nut yield. The underlying cause of BF remains unknown but is hypothesized to be associated with heritable epigenetic mechanisms. To address this disorder and its epigenetic components, we utilized a monozygotic twin study model profiling genome-wide DNA methylation and gene expression in two sets of twin almonds discordant for BF-exhibition. Analysis of DNA methylation patterns show that BF-exhibition and methylation, namely hypomethylation, are not independent phenomena. Transcriptomic data generated from the twin pairs also shows genome-wide differential gene expression associated with BF-exhibition. After identifying differentially methylated regions (DMRs) in each twin pair, a comparison revealed 170 shared DMRs between the two twin pairs. These DMRs and the associated genetic components may play a role in BF-exhibition. A subset of 52 shared DMRs are in close proximity to genes involved in meristem maintenance, cell cycle regulation, and response to heat stress. Annotation of specific genes included involvement in processes like cell wall development, calcium ion signaling, and DNA methylation. Results of this work support the hypothesis that BF-exhibition is associated with hypomethylation in almond, and identified DMRs and differentially expressed genes can serve as potential biomarkers to assess BF-potential in almond germplasm. Our results contribute to an understanding of the contribution of epigenetic disorders in agricultural performance and biological fitness of perennials.II.SignificanceThis study examines epigenetic components underlying noninfectious bud failure, an aging-related disorder affecting almond. Results from this work contribute to our understanding of the implications of DNA methylation on agricultural production, namely perennial fruit and nut production, due to effects on growth, development, and reproduction. Describing the methylome of discordant, monozygotic twin almonds enables the study of genomic features underlying noninfectious bud failure in this economically important crop.

Genome Wide DNA Methylation and Transcriptome Analysis in HSC Aging

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2367-2367
Author(s):  
Mira Jeong ◽  
Deqiang Sun ◽  
Min Luo ◽  
Aysegul Ergen ◽  
Hongcang Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed ◽  
Mouse Bone Marrow ◽  
Rna Seq ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Exon Arrays ◽  
Age Related ◽  
Genome Wide

Abstract Abstract 2367 Hematopoietic stem cell (HSC) Aging is a complex process linked to number of changes in gene expression and functional decline of self-renewal and differentiation potential. While epigenetic changes have been implicated in HSC aging, little direct evidence has been generated. DNA methylation is one of the major underlying mechanisms associated with the regulation of gene expression, but changes in DNA methylation patterns with HSC aging have not been characterized. We hypothesize that revealing the genome-wide DNA methylation and transcriptome signatures will lead to a greater understanding of HSC aging. Here, we report the first genome-scale study of epigenomic dynamics during normal mouse HSC aging. We isolated SP-KSL-CD150+ HSC populations from 4, 12, 24 month-old mouse bone marrow and carried out genome-wide reduced representative bisulfite sequencing (RRBS) and identified aging-associated differentially methylated CpGs. Three biological samples were sequenced from each aging group and we obtained 30–40 million high-quality reads with over 30X total coverage on ∼1.1M CpG sites which gives us adequate statistical power to infer methylation ratios. Bisulfite conversion rate of non-CpG cytosines was >99%. We analyzed a variety of genomic features to find that CpG island promoters, gene bodies, 5'UTRs, and 3'UTRs generally were associated with hypermethylation in aging HSCs. Overall, out of 1,777 differentially methylated CpGs, 92.8% showed age-related hypermethylation and 7.2% showed age-related hypomethylation. Gene ontology analyses have revealed that differentially methylated CpGs were significantly enriched near genes associated with alternative splicing, DNA binding, RNA-binding, transcription regulation, Wnt signaling and pathways in cancer. Most interestingly, over 579 splice variants were detected as candidates for age-related hypermethylation (86%) and hypomethylation (14%) including Dnmt3a, Runx1, Pbx1 and Cdkn2a. To quantify differentially expressed RNA-transcripts across the entire transcriptome, we performed RNA-seq and analyzed exon arrays. The Spearman's correlation between two different methods was good (r=0.80). From exon arrays, we identified 586 genes that were down regulated and 363 gene were up regulated with aging (p<0.001). Most interestingly, overall expression of DNA methyl transferases Dnmt1, Dnmt3a, Dnmt3b were down regulated with aging. We also found that Dnmt3a2, the short isoform of Dnmt3a, which lacks the N-terminal region of Dnmt3a and represents the major isoform in ES cells, is more expressed in young HSC. For the RNA-seq analysis, we focused first on annotated transcripts derived from cloned mRNAs and we found 307 genes were down regulated and 1015 gene were up regulated with aging (p<0.05). Secondly, we sought to identify differentially expressed isoforms and also novel transcribed regions (antisense and novel genes). To characterize the genes showing differential regulation, we analyzed their functional associations and observed that the highest scoring annotation cluster was enriched in genes associated with translation, the immune network and hematopoietic cell lineage. We expect that the results of these experiments will reveal the global effect of DNA methylation on transcript stability and the translational state of target genes. Our findings will lend insight into the molecular mechanisms responsible for the pathologic changes associated with aging in HSCs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1510
Author(s):  
Mathis Hildonen ◽  
Amanda M. Levy ◽  
Christine Søholm Hansen ◽  
Jonas Bybjerg-Grauholm ◽  
Axel Skytthe ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Neuropsychiatric Disorders ◽  
Monozygotic Twin ◽  
Mtor Pathway ◽  
Spectrum Disorder ◽  
Genetic Components ◽  
Genome Wide ◽  
Chronic Tic Disorder ◽  
Mtor Signalling

Tic spectrum disorder (TSD) is an umbrella term which includes Gilles de la Tourette syndrome (GTS) and chronic tic disorder (CTD). They are considered highly heritable, yet the genetic components remain largely unknown. In this study we aimed to investigate disease-associated DNA methylation differences to identify genes and pathways which may be implicated in TSD aetiology. For this purpose, we performed an exploratory analysis of the genome-wide DNA methylation patterns in whole blood samples of 16 monozygotic twin pairs, of which eight were discordant and six concordant for TSD, while two pairs were asymptomatic. Although no sites reached genome-wide significance, we identified several sites and regions with a suggestive significance, which were located within or in the vicinity of genes with biological functions associated with neuropsychiatric disorders. The two top genes identified (TSC1 and CRYZ/TYW3) and the enriched pathways and components (phosphoinosides and PTEN pathways, and insulin receptor substrate binding) are related to, or have been associated with, the PI3K/AKT/mTOR pathway. Genes in this pathway have previously been associated with GTS, and mTOR signalling has been implicated in a range of neuropsychiatric disorders. It is thus possible that altered mTOR signalling plays a role in the complex pathogenesis of TSD.

scholarly journals Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs

AGE ◽  
2014 ◽  
Vol 36 (3) ◽  
Author(s):  
Wilma T. Steegenga ◽  
Mark V. Boekschoten ◽  
Carolien Lute ◽  
Guido J. Hooiveld ◽  
Philip J. de Groot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Human Pbmcs ◽  
Age Related ◽  
Genome Wide ◽  
Age Related Changes

scholarly journals Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Shasha Su ◽  
Wenjie Kong ◽  
Jing Zhang ◽  
Xinguo Wang ◽  
Hongmei Guo
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Dna Methylation ◽  
Expression Profiles ◽  
Osteoclast Differentiation ◽  
Functional Enrichment ◽  
Functional Network ◽  
Integrated Analysis ◽  
Genome Wide ◽  
Potential Biomarker

Abstract Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

scholarly journals Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 62547-62558 ◽  
Author(s):  
Jiufeng Wei ◽  
Guodong Li ◽  
Jinning Zhang ◽  
Yuhui Zhou ◽  
Shuwei Dang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rectal Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Integrated Analysis ◽  
Genome Wide ◽  
Novel Biomarkers
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