scholarly journals Integrated epigenome, exome and transcriptome analyses reveal molecular subtypes and homeotic transformation in uterine fibroids

2018 ◽  
Author(s):  
Jitu W. George ◽  
Huihui Fan ◽  
Benjamin K. Johnson ◽  
Anindita Chatterjee ◽  
Amanda L. Patterson ◽  
...  
Keyword(s):  
Epigenetic Modification ◽  
Uterine Fibroids ◽  
Unknown Etiology ◽  
Integrated Analysis ◽  
Homeotic Transformation ◽  
Expression Of Genes ◽  
Whole Exome ◽  
Smooth Muscle Tumors ◽  
The Usa ◽  
Transcriptome Analyses

ABSTRACTUterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, Infinium MethylationEPIC array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria from fibroids, and further separated the fibroids into subtypes marked byMED12mutation,HMGA2activation (HMGA2hi) andHMGA1activation (HMGA1hi). Upregulation ofHMGA2expression inHMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in theHMGA2gene body. Furthermore, we found that expression ofHOXA13was highly upregulated in fibroids and that overexpression ofHOXA13in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.

scholarly journals Integrated Epigenome, Exome, and Transcriptome Analyses Reveal Molecular Subtypes and Homeotic Transformation in Uterine Fibroids

Cell Reports ◽  
2019 ◽  
Vol 29 (12) ◽  
pp. 4069-4085.e6 ◽  
Author(s):  
Jitu Wilson George ◽  
Huihui Fan ◽  
Benjamin Johnson ◽  
Tyler James Carpenter ◽  
Kelly Katherine Foy ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Uterine Fibroids ◽  
Homeotic Transformation ◽  
Transcriptome Analyses

Whole-Exome Sequencing Solved over 2-Decade Kidney Disease Enigma

Nephron ◽  
2021 ◽  
pp. 1-6
Author(s):  
Suramath Isaranuwatchai ◽  
Ankanee Chanakul ◽  
Chupong Ittiwut ◽  
Chalurmpon Srichomthong ◽  
Vorasuk Shotelersuk ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Kidney Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Treatment Plan ◽  
Unknown Etiology ◽  
Pediatric Case ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Whole Exome

Chronic kidney disease of unknown etiology (CKDu) has been a problem in renal practice as indefinite diagnosis may lead to inappropriate management. Here, we report a 54-year-old father diagnosed with CKDu at 33 years old and his 8-year-old son with steroid-resistant nephrotic syndrome. Using whole-exome sequencing, both were found to be heterozygous for c.737G>A (p.Arg246Gln) in LMX1B. The diagnosis of LMX1B-associated nephropathy has led to changes in the treatment plan with appropriate genetic counseling. The previously reported cases with this particular mutation were also reviewed. Most children with LMX1B-associated nephropathy had nonnephrotic proteinuria with normal renal function. Interestingly, our pediatric case presented with steroid-resistant nephrotic syndrome at 8 years old and progressed to ESRD requiring peritoneal dialysis at the age of 15 years. Our report emphasized the need of genetic testing in CKDu for definite diagnosis leading to precise management.

scholarly journals Novel Dominant KCNQ2 Exon 7 Partial In-Frame Duplication in a Complex Epileptic and Neurodevelopmental Delay Syndrome

2020 ◽  
Vol 21 (12) ◽  
pp. 4447
Author(s):  
Pedro A. Lazo ◽  
Juan L. García ◽  
Paulino Gómez-Puertas ◽  
Íñigo Marcos-Alcalde ◽  
Cesar Arjona ◽  
...  
Keyword(s):  
Protein Function ◽  
De Novo ◽  
3D Structure ◽  
Unknown Origin ◽  
Unknown Etiology ◽  
Neurodevelopmental Delay ◽  
Calmodulin Binding ◽  
Whole Exome ◽  
Dynamics Simulations ◽  
Frame Duplication

Complex neurodevelopmental syndromes frequently have an unknown etiology, in which genetic factors play a pathogenic role. This study utilizes whole-exome sequencing (WES) to examine four members of a family with a son presenting, since birth, with epileptic-like crises, combined with cerebral palsy, severe neuromotor and developmental delay, dystonic tetraparexia, axonal motor affectation, and hyper-excitability of unknown origin. The WES study detected within the patient a de novo heterozygous in-frame duplication of thirty-six nucleotides within exon 7 of the human KCNQ2 gene. This insertion duplicates the first twelve amino acids of the calmodulin binding site I. Molecular dynamics simulations of this KCNQ2 peptide duplication, modelled on the 3D structure of the KCNQ2 protein, suggest that the duplication may lead to the dysregulation of calcium inhibition of this protein function.

scholarly journals Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Marta Codina-Solà ◽  
Benjamín Rodríguez-Santiago ◽  
Aïda Homs ◽  
Javier Santoyo ◽  
Maria Rigau ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Transcriptome Profiling ◽  
Autism Spectrum ◽  
Integrated Analysis ◽  
Whole Exome ◽  
Spectrum Disorders

Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Qingwen Zeng ◽  
Yanjie Fan ◽  
Lili Wang ◽  
Zhuo Huang ◽  
Xuefan Gu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Novel Mutation ◽  
Unknown Etiology ◽  
Mendelian Disease ◽  
Atypical Form ◽  
Pathogenic Variants ◽  
Diagnostic Potential ◽  
Whole Exome ◽  
Related Enzyme

AbstractBackground:Mucopolysaccharidosis IIIB (MPS IIIB) is a genetic disease characterized by mutations in theCase presentation:Whole exome sequencing (WES) was conducted and the putative pathogenic variants were validated by Sanger sequencing. The activity of MPS IIIB related enzyme in the patient’s blood serum was assayed. A heterozygous, non-synonymous mutation (c.1562C>T, p.P521L) as well as a novel mutation (c.1705C>A, p.Q569K) were found in theConclusions:Our results describe an atypical form of MPS IIIB and illustrate the diagnostic potential of targeted WES in Mendelian disease with unknown etiology. WES could become a powerful tool for molecular diagnosis of MPS IIIB in clinical setting.

scholarly journals Upregulation of Oxidative Stress Related Genes in a Chronic Kidney Disease Attributed to Specific Geographical Locations of Sri Lanka

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Saravanabavan Sayanthooran ◽  
Dhammika N. Magana-Arachchi ◽  
Lishanthe Gunerathne ◽  
Tilak D. J. Abeysekera ◽  
Suneth S. Sooriyapathirana
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Sri Lanka ◽  
Kidney Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Fibroblast Growth Factor 23 ◽  
Study Groups ◽  
Unknown Etiology ◽  
Pyrin Domain ◽  
Expression Of Genes

Objective.To infer the influence of internal and external oxidative stress in chronic kidney disease patients of unknown etiology (CKDu) in Sri Lanka, by analyzing expression of genes related directly or indirectly to oxidative stress: glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase mu 1 (GSTM1), glucose-6-phosphate dehydrogenase (G6PD), fibroblast growth factor-23 (FGF23), and NLR family pyrin domain containing 3 (NLRP3).Methods.Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was carried out for the selected populations: CKDu patients (n=43), chronic kidney disease patients (CKD;n=14), healthy individuals from a CKDu endemic area (GHI;n=9), and nonendemic area (KHI;n=16). Fold changes were quantified relative to KHI.Results.GCLC had greater than threefold upregulation in all three study groups, with a maximum of 7.27-fold upregulation in GHI (p=0.000). GSTM1 was not expressed in 25.6% of CKDu and 42.9% of CKD patients, but CKDu patients expressing GSTM1 showed upregulation of 2.60-fold (p<0.05). Upregulation of FGF23 and NLRP3 genes in CKD and CKDu was observed (p<0.01), with greater fold changes in CKD.Conclusion.Results suggest higher influence of external sources of oxidative stress in CKDu, possibly owing to environmental conditions.

scholarly journals A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis

2017 ◽  
Vol 214 (11) ◽  
pp. 3449-3466 ◽  
Author(s):  
Alma-Martina Cepika ◽  
Romain Banchereau ◽  
Elodie Segura ◽  
Marina Ohouo ◽  
Brandi Cantarel ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inflammatory Diseases ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Unknown Etiology ◽  
Integrated Analysis ◽  
Cell Phenotype ◽  
Protein Levels ◽  
Aryl Hydrocarbon ◽  
Immune Alterations

The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1β after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.

scholarly journals HEALTHY AND PATHOLOGICAL CHANGES OF MYOMETRIUM: PREGNANT MYOMETRIUM, UTERINE FIBROIDS AND LEIOMYOSARCOMA. Cambios normales y patológicos del miometrio: miometrio del embarazo, fibrosis uterina y leiomiosarcoma

2016 ◽  
Vol 4 (1) ◽  
pp. 7-13
Author(s):  
Pasquapina Ciarmela ◽  
Soriful Islam ◽  
Pasquale Lamanna ◽  
Andrea Tranquilli ◽  
Mario Castellucci
Keyword(s):  
Smooth Muscle ◽  
Uterine Fibroids ◽  
Present Review ◽  
Benign Tumors ◽  
Pathological Changes ◽  
Uterine Smooth Muscle ◽  
Smooth Muscle Tumors ◽  
In Pregnancy

El miometrio, la pared muscular del útero, puede modificar su misma masa y las propiedades celulares en el embarazo y también en los tumores como el leiomioma y el leiomiosarcoma. El leiomioma, dicho también fibroma, es un tumor benigno del útero y se considera como  una de las causas más frecuentes de infertilità en el período reproductivo femenino. El leiomiosarcoma, en cambio, es un tumor maligno y agresivo de la musculatura lisa uterina. La presente revisión discute las características generales del leiomioma y el leiomiosarcoma y los relativos tratamientos clínicos actualmente usados y además describe las características del miometrio normal en el embarazo.  The myometrium, the muscular wall of the uterus, can modify its mass and cellular properties in pregnancy as well as in tumor conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumors of the uterus, considered to be one of the most frequent causes of infertility in reproductive years of women. Leiomyosarcomas in turn, are rare aggressive malignant uterine smooth-muscle tumors. The present review is discussing the general features of leiomyoma and leiomyosarcoma with their current treatments and also discussing the characteristics of normal pregnant myometrium and compare with leiomyoma.

scholarly journals Integrated analysis of whole exome and RNA sequencing for Neo-epitope peptide prediction in buccal cancer

2017 ◽  
Vol 1 (Special Issue-Supplement) ◽  
pp. 245-245
Author(s):  
Coral Karunakaran ◽  
Jisha Elias ◽  
Nitin Mandoli ◽  
Anand K. Maurya ◽  
Rajesh Kantharia ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Integrated Analysis ◽  
Epitope Peptide ◽  
Whole Exome ◽  
Peptide Prediction

scholarly journals No effect of acute exercise on the dynamic change in the expression of genes involved in epigenetic modification in professional athletes

2021 ◽  
Author(s):  
Witold Józef Światowy ◽  
Jacek Zieliński ◽  
Maria Aleksandra Osielska ◽  
Krzysztof Kusy ◽  
Dariusz Wieliński ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Exercise ◽  
Epigenetic Modification ◽  
Dynamic Change ◽  
Epigenetic Modifications ◽  
Professional Athletes ◽  
Peak Exercise ◽  
Gene Transcript ◽  
Interesting Phenomenon ◽  
Expression Of Genes

Abstract Background:The adaptation of the organism to exercise in the context of gene expression profile is an interesting phenomenon. Exercise can change the expression of individual genes due to changes in the degree of DNA methylation, changes in miRNA expression, or through methylation or acetylation of histones.Hypothesis:Acute exercise increases the expression of genes such as HDAC1, DNMT1, and JHDM1D that can affect epigenetic modifications in PBMCs.Methods:The aim of this study was to determine whether there was a change in gene expression in the blood cells during acute exercise and after a 1-hour recovery. The transcriptions of genes involved in epigenetic modifications (HDAC1, HDAC1 and JHDM1D) were examined in 9 professional athletes at rest, during consecutive stages of a treadmill exercise until exhaustion, and following recovery.Results:No significant differences in the level of transcript were observed in the course of the experiment in the tested PBMC cells. On the other hand, a significant (p = 0.007) correlation was observed in the level of the JHDM1D gene transcript and the number of monocytes in the samples obtained after reaching peak exercise intensity, but in the initial samples this correlation was not significant (p = 0.053).Conclusion:Acute physical exercise does not rapidly alter the transcript levels of the JHDM1D, DNMT1 and HDAC1 genes in PBMCs. The observed correlation between the level of JHDM1D mRNA and the level of monocytes and HDAC1 with lymphocytes requires further investigation.

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