scholarly journals Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair

2021 ◽  
Vol 22 (18) ◽  
pp. 9740
Author(s):  
Alessia Russo ◽  
Clara Viberti ◽  
Katia Mareschi ◽  
Elisabetta Casalone ◽  
Simonetta Guarrera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Twin Pair ◽  
Expression Profiles ◽  
Monozygotic Twin ◽  
Lymphocytic Leukemia ◽  
Nras Mutation ◽  
Monozygotic Twin Pair

The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant KMT2A/AFF1-rearranged infant monozygotic twin pair and their parents, and they were compared to three independent KMT2A/AFF1-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated. A de novo Q61H NRAS mutation was detected in the affected twin at diagnosis and backtracked in both twins at birth. The KMT2A/AFF1 rearrangement was absent at birth in both twins. Genetic analyses conducted at birth gave more insights into the timing of the mutation hit. We identified correlations between DNA methylation and gene expression changes for 32 genes in the three independent affected versus remitted patients. The strongest correlations were observed for the RAB32, PDK4, CXCL3, RANBP17, and MACROD2 genes. This epigenetic signature could be a putative target for the development of novel epigenetic-based therapies and could help in explaining the molecular mechanisms characterizing ALL infants with KMT2A/AFF1 fusions.

Study of Gene Expression Profiles and Biological Mechanism of Cerebral Palsy Using a Monozygotic Twin Pair

2007 ◽  
Vol 10 (3) ◽  
pp. 496-507 ◽  
Author(s):  
Tiane Zhang ◽  
Miqu Wang ◽  
Ling Pan ◽  
Weijun Ding ◽  
J.G. Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Palsy ◽  
Differentially Expressed Genes ◽  
Twin Pair ◽  
Expression Profiles ◽  
Monozygotic Twin ◽  
Differentially Expressed ◽  
Cell Junction ◽  
Biological Databases ◽  
Monozygotic Twin Pair

AbstractThe gene expression profile of a normal-suffering monozygotic twin pair is investigated to explore biological mechanisms of spastic type cerebral palsy. Main works include following three aspects: First, a cDNA microarray test is carried out to get the differentially expressed genes of the patient with cerebral palsy compared to her monozygotic twin sister. Second, these differentially expressed genes are searched for their bioinformation within 4 biological databases: FatiGO, FatiGOPlus, KEGG, and SOURCE. Third, a set of special genes and gene families are screened out from the spastic type cerebral palsy patient. These biological analyses reveal that those genes for cell junction are mostly down-regulated, while those genes for metabolism are mostly up-regulated. The individual genes, gene family, and their associated biological functions can reflect the pathological and physiological characteristics of the cerebral palsy.

scholarly journals De novo deletion in MECP2 in a monozygotic twin pair: a case report

2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Kirti Mittal ◽  
Madhulika Kabra ◽  
Ramesh Juyal ◽  
Thelma BK
Keyword(s):  
Case Report ◽  
De Novo ◽  
Twin Pair ◽  
Monozygotic Twin ◽  
Monozygotic Twin Pair

Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylationThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (4) ◽  
pp. 463-466 ◽  
Author(s):  
Ana C. D’Alessio ◽  
Moshe Szyf
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
De Novo ◽  
Peer Review Process ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Transformation ◽  
Genetic Alterations ◽  
Covalent Modification ◽  
Associated Proteins

The epigenome, which comprises chromatin, associated proteins, and the pattern of covalent modification of DNA by methylation, sets up and maintains gene expression programs. It was originally believed that DNA methylation was the dominant reaction in determining the chromatin structure. However, emerging data suggest that chromatin can affect DNA methylation in both directions, triggering either de novo DNA methylation or demethylation. These events are particularly important for the understanding of cellular transformation, which requires a coordinated change in gene expression profiles. While genetic alterations can explain some of the changes, the important role of epigenetic reprogramming is becoming more and more evident. Cancer cells exhibit a paradoxical coexistence of global loss of DNA methylation with regional hypermethylation.

scholarly journals Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

2014 ◽  
Vol 51 (7) ◽  
pp. 455-459 ◽  
Author(s):  
Gülşah M Dal ◽  
Bekir Ergüner ◽  
Mahmut S Sağıroğlu ◽  
Bayram Yüksel ◽  
Onur Emre Onat ◽  
...  
Keyword(s):  
De Novo ◽  
Twin Pair ◽  
Monozygotic Twin ◽  
Monozygotic Twin Pair ◽  
Postzygotic Mutations

scholarly journals Intra-Monozygotic Twin Pair Discordance and Longitudinal Variation of Whole-Genome Scale DNA Methylation in Adults

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135022 ◽  
Author(s):  
Na Zhang ◽  
Shumin Zhao ◽  
Su-Hua Zhang ◽  
Jinzhong Chen ◽  
Daru Lu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Twin Pair ◽  
Monozygotic Twin ◽  
Whole Genome ◽  
Longitudinal Variation ◽  
Monozygotic Twin Pair ◽  
Genome Scale

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome

2010 ◽  
Vol 79 (6) ◽  
pp. 546-553 ◽  
Author(s):  
S Tierling ◽  
NY Souren ◽  
S Reither ◽  
KD Zang ◽  
J Meng-Hentschel ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Twin Pair ◽  
Monozygotic Twin ◽  
Monozygotic Twin Pair

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals Copy number-dependent DNA methylation of the Pyricularia oryzae MAGGY retrotransposon is triggered by DNA damage

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ba Van Vu ◽  
Quyet Nguyen ◽  
Yuki Kondo-Takeoka ◽  
Toshiki Murata ◽  
Naoki Kadotani ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Copy Number ◽  
Rna Silencing ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Pyricularia Oryzae ◽  
Transcriptional Gene Silencing ◽  
Physical Interaction ◽  
Uncharacterized Protein ◽  
Form Complex

AbstractTransposable elements are common targets for transcriptional and post-transcriptional gene silencing in eukaryotic genomes. However, the molecular mechanisms responsible for sensing such repeated sequences in the genome remain largely unknown. Here, we show that machinery of homologous recombination (HR) and RNA silencing play cooperative roles in copy number-dependent de novo DNA methylation of the retrotransposon MAGGY in the fungusPyricularia oryzae. Genetic and physical interaction studies revealed thatRecAdomain-containing proteins, includingP. oryzaehomologs ofRad51, Rad55, andRad57, together with an uncharacterized protein, Ddnm1, form complex(es) and mediate either the overall level or the copy number-dependence of de novo MAGGY DNA methylation, likely in conjunction with DNA repair. Interestingly,P. oryzaemutants of specific RNA silencing components (MoDCL1andMoAGO2)were impaired in copy number-dependence of MAGGY methylation. Co-immunoprecipitation of MoAGO2 and HR components suggested a physical interaction between the HR and RNA silencing machinery in the process.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

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