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A Metric to Characterize Differentially Methylated Region Sets Detected from methylation array Data

CURRENT BIOINFORMATICS 2024年第6期19卷 571-583页

作者： Peng, Xiaoqing Cui, Wanxin Zhang, Wenjin Li, Zihao Zhu, Xiaoshu Yuan, Ling Li, Ji Cent South Univ Ctr Med Genet Sch Life Sci Changsha 410083 Peoples R China Cent South Univ Sch Life Sci Hunan Key Lab Med Genet Changsha 410083 Peoples R China Cent South Univ Sch Comp Sci & Engn Hunan Key Lab Bioinformat Changsha 410083 Peoples R China Guilin Univ Elect Technol Guangxi Key Lab Trusted Software Guilin 541004 Guangxi Peoples R China Cent South Univ Xiangya Hosp 2 Dept Hematol Changsha 410012 Peoples R China

Background Identifying differentially methylated region (DMR) is a basic but important task in epigenomics, which can help investigate the mechanisms of diseases and provide methylation biomarkers for screening diseases. A set of methods have been proposed to identify DMRs from methylation array data. However, it lacks effective metrics to characterize different DMR sets and enable a straight way for *** In this study, we introduce a metric, DMRn, to characterize DMR sets detected by different methods from methylation array data. To calculate DMRn, firstly, the methylation differences of DMRs are recalculated by incorporating the correlations between probes and their represented CpGs. Then, DMRn is calculated based on the number of probes and the dense of CpGs in DMRs with methylation differences falling in each *** & Discussion By comparing the DMRn of DMR sets predicted by seven methods on four scenario, the results demonstrate that DMRn can make an efficient guidance for selecting DMR sets, and provide new insights in cancer genomics studies by comparing the DMR sets from the related pathological states. For example, there are many regions with subtle methylation alteration in subtypes of prostate cancer are altered oppositely in the benign state, which may indicate a possible revision mechanism in benign prostate *** Futhermore, when applied to datasets that underwent different runs of batch effect removal, the DMRn can help to visualize the bias introduced by multi-runs of batch effect removal. The tool for calculating DMRn is available in the GitHub repository (https://***/xqpeng/DMRarrayMetric).

关键词： Differentially methylated regions methylation array cancer genomics batch effect

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Identification of differentially methylated candidate genes and their biological significance in IUGR neonates by methylation EPIC array

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JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 2022年第3期35卷 525-533页

作者： Krishna, Rao Gurugubelli Bhat, Ballambattu Vishnu Bobby, Zachariah Papa, Dasari Badhe, Bhawana Kalidoss, Vinoth Kumar Karli, Sreenivasulu All India Inst Med Sci Dept Biochem Mangalagiri Andhra Pradesh India Jawaharlal Inst Postgrad Med Educ & Res Dept Neonatol Pondicherry India AVMC Dept Pediat Pondicherry India JIPMER Dept Biochem Pondicherry India JIPMER Dept Obstet & Gynaecol Pondicherry India JIPMER Dept Pathol Pondicherry India AIIMS Dept CFM Mangalagiri Andhra Pradesh India JIPMER Res Pondicherry 605006 India

Background: Intrauterine growth restriction (IUGR) is a pregnancy-associated disease manifested by decreased growth rate of fetus than the normal genetic growth potential. It is associated with increased susceptibility to metabolic diseases later in life. Although the mechanisms underlying the origin of metabolic diseases are poorly understood, DNA methylation is a crucial investigation for the identification of epigenetic changes. Objectives: To assess the degree of change of DNA methylation in IUGR neonates and compare with that of appropriate for gestational age (AGA) neonates and to explore the differentially methylated candidate genes and their biological significance. Methods: This cohort study was conducted in the Neonatology Department of JIPMER during the period of November 2017 to December 2018. Forty each of IUGR and gestation matched AGA neonates were recruited. Umbilical cord blood samples were collected at birth. DNA was separated from the blood samples;and, using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these neonates was established. Data were expressed as mean +/- standard deviation. methylation EPIC array was performed to identify the differentially methylated candidate genes. David analysis was used to find out the functional annotation chart by KEGG pathway. Results: Genomic DNA methylation varied significantly between IUGR and AGA neonates (IUGR: 3.12 +/- 1.24;AGA: 4.40 +/- 2.03;p value: <.01). A global shift toward hypomethylation was seen in IUGR compared with AGA, targeted to regulatory regions of the genome, and specifically promoters. Pathway analysis identified deregulation of pathways involved in metabolic diseases. Altered methylation of PTPRN2 & HLADQB1 genes leads to dysregulation of T-cells and reactive oxygen species (ROS). These changes may lead to complications later among these neonates subjected to IUGR. Conclusion: Our findings show significant changes in the methylation pattern of genes among IUGR and

关键词： Cord blood DNA methylation intrauterine growth restriction methylation array

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methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre

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ACTA NEUROPATHOLOGICA COMMUNICATIONS 2019年第1期7卷 1-18页

作者： Jaunmuktane, Zane Capper, David Jones, David T. W. Schrimpf, Daniel Sill, Martin Dutt, Monika Suraweera, Nirosha Pfister, Stefan M. von Deimling, Andreas Brandner, Sebastian Univ Coll London Hosp NHS Fdn Trust Natl Hosp Neurol & Neurosurg Div Neuropathol Queen Sq London WC1N 3BG England UCL Queen Sq Inst Neurol Dept Clin & Movement Neurosci Queen Sq London WC1N 3BG England Charite Univ Med Berlin Dept Neuropathol Berlin Germany Free Univ Berlin Berlin Germany Humboldt Univ Berlin Germany Berlin Inst Hlth Berlin Germany German Canc Res Ctr German Canc Consortium DKTK Partner Site Berlin Heidelberg Germany Hopp Childrens Canc Ctr Heidelberg KiTZ Heidelberg Germany German Canc Res Ctr Pediat Glioma Res Grp Heidelberg Germany Univ Hosp Heidelberg Dept Neuropathol Heidelberg Germany German Canc Res Ctr Clin Cooperat Unit Neuropathol German Canc Consortium DKTK Heidelberg Germany German Canc Res Ctr Div Pediat Neurooncol Heidelberg Germany Heidelberg Univ Hosp Dept Pediat Oncol Hematol Immunol & Pulmonol Heidelberg Germany UCL Queen Sq Inst Neurol Dept Neurodegenerat Dis Queen Sq London WC1N 3BG England

The introduction of the classification of brain tumours based on their DNA methylation profile has significantly changed the diagnostic approach for cases with ambiguous histology, non-informative or contradictory molecular profiles or for entities where methylation profiling provides useful information for patient risk stratification, for example in medulloblastoma and ependymoma. We present our experience that combines a conventional molecular diagnostic approach with the complementary use of a DNA methylation-based classification tool, for adult brain tumours originating from local as well as national referrals. We report the frequency of IDH mutations in a large cohort of nearly 1550 patients, EGFR amplifications in almost 1900 IDH-wildtype glioblastomas, and histone mutations in 70 adult gliomas. We demonstrate how additional methylation-based classification has changed and improved our diagnostic approach. Of the 325 cases referred for methylome testing, 179 (56%) had a calibrated score of 0.84 and higher and were included in the evaluation. In these 179 samples, the diagnosis was changed in 45 (25%), refined in 86 (48%) and confirmed in 44 cases (25%). In addition, the methylation arrays contain copy number information that usefully complements the methylation profile. For example, EGFR amplification which is 95% concordant with our Real-Time PCR-based copy number assays. We propose here a diagnostic algorithm that integrates histology, conventional molecular tests and methylation arrays.

关键词： IDH1 IDH2 BRAF Histone mutation H3 K27M methylation array Illumina array DKFZ classifier methylation classifier Molecular diagnostics Glioma Ependymoma Brain tumour classification Adult brain tumours

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methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern

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CLINICAL EPIGENETICS 2014年第1期6卷 1-6页

作者： Philibert, Robert A. Terry, Nicolas Erwin, Cheryl Philibert, Winter J. Beach, Steven R. H. Brody, Gene H. Univ Iowa Dept Psychiat Iowa City IA 52242 USA Behav Diagnost Inc Iowa City IA 52244 USA Indiana Univ Robert H McKinney Sch Law Indianapolis IN 46202 USA Texas Tech Univ Hlth Sci Ctr Dept Med Educ Lubbock TX 79430 USA Texas Tech Univ Hlth Sci Ctr Dept Psychiat Lubbock TX 79430 USA Univ Georgia Ctr Family Res Athens GA 30602 USA Univ Georgia Dept Psychol Athens GA 30602 USA

Background: Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. Results: In this communication, we analyze methylation data from the Illumina Humanmethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. Conclusions: We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification.

关键词： Genetics DNA methylation Ethics methylation array Confidentiality

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Testing Meningiomas With methylation arrays: Insights and Recommendations From a Large Single-Centre Study

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NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY 2025年第3期51卷 e70018页

作者： Ruiz, Fernanda Rispoli, Rossella Jaunmuktane, Zane Merve, Ashirwad D'Antona, Linda Dutt, Monika Sahm, Felix Brandner, Sebastian Univ Coll NHS Fdn Trust Natl Hosp Neurol & Neurosurg Div Neuropathol London England UCL Queen Sq Inst Neurol Dept Neurodegenerat Dis London England UCL Queen Sq Inst Neurol Dept Clin & Movement Neurosci London England Great Ormond St Hosp Sick Children Dept Histopathol London England Univ Coll Hosp NHS Fdn Trust Natl Hosp Neurol & Neurosurg Div Neurosurg London England Univ Hosp Heidelberg Dept Neuropathol Heidelberg Germany German Canc Res Ctr German Consortium Translat Canc Res DKTK CCU Neuropathol Heidelberg Germany

AimsMeningiomas are common primary CNS tumours, and their morphological diagnosis is usually straightforward. Their histological grading according to CNS WHO criteria alone provides limited information on recurrence risk. Risk stratification of meningiomas combining WHO grade, methylation class and copy number profile improves prediction of the risk of early recurrence. Because of the frequency of meningiomas in diagnostic practice, applying this prediction algorithm to all meningiomas is financially not viable in most healthcare *** analysed a retrospective dataset of over 1000 meningiomas from a single centre with methylation arrays to provide guidance on which meningiomas to prioritise for integrated molecular testing and to understand how WHO grades resolve into risk *** 90% of CNS WHO Grade 1 meningiomas were allocated into the methylation class 'benign' and also into a low-risk group. Grade 2 meningiomas were allocated almost equally to either the low-risk (39%) or intermediate-risk groups (46%) but occasionally also to the high-risk group (15%). All grading criteria for CNS WHO Grade 2 meningiomas (brain invasion, mitotic count, cytoarchitectural atypia and histological type) showed a similar risk score distribution as the entire group. Grade 3 meningiomas were allocated to intermediate- (26%) or high-risk groups (74%).ConclusionOur data suggest that Grade 2 and 3 meningiomas should be prioritised for methylation profiling. A small proportion of Grade 1 meningiomas may also benefit from integrated molecular analysis, and further research is needed to explore if those histologically benign meningiomas with a predicted increased recurrence risk are associated with distinct demographic or histological characteristics.

关键词： CNS WHO grading meningioma methylation array model score prognostication

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Comprehensive molecular analysis to predict the efficacy ofchemotherapy containing bevacizumab in patients with metastaticcolorectal cancer

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Oncology Research 2023年第6期31卷 855-866页

作者： SUNG HEE LIM HEE JIN CHO KYOUNG-MEE KIM HO YEONG LIM WON KI KANG JEEYUN LEE YOUNG SUK PARK HEE CHEOL KIM SEUNG TAE KIM Division of Hematology/Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea Precision Medicine Research Institute Samsung Medical CenterGangnam-guSeoul06351Korea Department of Biomedical Convergence Science and Technology Kyungpook National UniversityDaegu41566Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul06351Korea Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineGangnam-guSeoul06351Korea

Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been ***:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing *** molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient ***:Genomic and molecularcharacterization was successfully conducted in 103 *** of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite *** those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to *** the four SRCCs,two were CMS1,one was CMS4,and the other was *** status was a significantly enriched factor in responders to bevacizumab *** growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in ***,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX ***),thesignificance of the molecular pathways varied according to the backbone ***:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing *** need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic oppor

关键词： Bevacizumab Whole-exome sequencing Ribonucleic acid sequencing methylation array Colorectal cancer

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Medulloblastoma in adults: evaluation of the Dutch society for neuro-oncology treatment protocol

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JOURNAL OF NEURO-ONCOLOGY 2023年第1期162卷 225-235页

作者： Bleeker, L. Kouwenhoven, M. C. M. de Heer, I. Lissenberg-Witte, B. I. Gijsbers, A. H. Dubbink, H. J. Kros, J. M. Gijtenbeek, J. M. M. Kurt, E. van der Rijt, C. C. D. Swaak-Kragten, A. T. de Vos, F. Y. van der Weide, H. L. French, P. J. van den Bent, M. J. Wesseling, P. Bromberg, J. E. C. Amsterdam UMC Brain Tumor Ctr Amsterdam Dept Neurol Amsterdam Netherlands Erasmus MC Canc Inst Brain Tumor Ctr Dept Neurol Rotterdam Netherlands Amsterdam UMC Dept Epidemiol & Data Sci Amsterdam Netherlands Nationwide Network Registry Histopathol & Cytopath Houten Netherlands Erasmus MC Canc Inst Brain Tumor Ctr Dept Pathol Rotterdam Netherlands Radboud Univ Nijmegen Med Ctr Dept Neurol Nijmegen Netherlands Radboud Univ Nijmegen Med Ctr Dept Neurosurg Nijmegen Netherlands Erasmus MC Canc Inst Dept Med Oncol Rotterdam Netherlands Erasmus MC Canc Inst Dept Radiat Oncol Rotterdam Netherlands Univ Med Ctr Utrecht Canc Ctr Dept Med Oncol Utrecht Netherlands Univ Groningen Univ Med Ctr Groningen Dept Radiat Oncol Groningen Netherlands Univ Amsterdam Med Ctr VUmc Dept Pathol Amsterdam Netherlands Princess Maxima Ctr Pediat Oncol Lab Childhood Canc Pathol Utrecht Netherlands

PurposeMedulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma *** medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were ***-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn't statistically *** chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival.

关键词： Medulloblastoma Adults Treatment methylation array Toxicity

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The complex search for the cause of gastroschisis

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BIRTH DEFECTS RESEARCH 2022年第19期114卷 1291-1297页

作者： de Freitas, Amanda Brasil Vieira Francisco, Rossana Pulcineli Hoshida, Mara Sandra De Oliveira, Yanca Gasparini Kulikowski, Leslie Domenici Brizot, Maria de Lourdes Univ Sao Paulo FMUSP Dept Obstet & Gynecol Fac Med Sao Paulo Brazil Univ Sao Paulo FMUSP Dept Pathol Cytogen Lab Fac Med Sao Paulo Brazil Univ Sao Paulo Hosp Clin Lab Obstetr Physiol LIM57 Sao Paulo Brazil

Background To reveal the complex etiology of gastroschisis through two independent cases. Cases Case 1 involves gastroschisis recurrence in a consanguineous marriage, and Case 2 concerns a fetus with gastroschisis whose mother had undergone gastroplasty. methylation array was carried out in both cases (two fetuses with gastroschisis, their two mothers, one father from the consanguineous marriage), and in 16 controls (fetuses and their respective mothers). Conclusion The two cases presented different noninherited methylation profiles.

关键词： gastroplasty gastroschisis methylation array recurrence

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The d3GHR carrier epigenome in Druze clan longevity

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SCIENTIFIC REPORTS 2024年第1期14卷 1-12页

作者： Falah, Ghadeer Kurolap, Alina Paperna, Tamar Ekhilevitch, Nina Moustafa, Nivin Damouny-Naoum, Nadine Amir, Yam Sharvit, Lital Moghrabi, Rihan Hassoun, Gamal Fares, Fuad Baris Feldman, Hagit Atzmon, Gil Univ Haifa Fac Nat Sci Dept Human Biol Haifa Israel Tel Aviv Sourasky Med Ctr Genet Inst Tel Aviv Israel Tel Aviv Sourasky Med Ctr Genom Ctr Tel Aviv Israel Rambam Hlth Care Campus Genet Inst H_efa Israel Rambam Hlth Care Campus Inst Allergy Clin Immunol & AIDS H_efa Israel Tel Aviv Univ Fac Med & Hlth Sci Sch Med Tel Aviv Israel Albert Einstein Coll Med Dept Med & Genet Bronx NY 10461 USA

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health.

关键词： DNA methylation Epigenetics methylation array GHR D3GHR

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Do assisted reproductive technologies and in vitro embryo culture influence the epigenetic control of imprinted genes and transposable elements in children?

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HUMAN REPRODUCTION 2021年第2期36卷 479-492页

作者： Barberet, J. Binquet, C. Guilleman, M. Doukani, A. Choux, C. Bruno, C. Bourredjem, A. Chapusot, C. Bourc'his, D. Duffourd, Y. Fauque, P. Univ Bourgogne Franche Equipe Genet Anomalies Dev GAD INSERM UMR 1231 Dijon France CHU Dijon Bourgogne Lab Biol Reprod CECOS Dijon France CHU Dijon Bourgogne Ctr Invest Clin Module Epidemiol Clin Essais Clin CIC EC Dijon France INSERM Module Epidemiol Clin CIC1432 Dijon France Sorbonne Univ Site Pitie Salpetriere Fac Med Paris France CHU Dijon Bourgogne Serv Gynecol Obstet Dijon France CHU Dijon Bourgogne Plateforme Genet Canc Bourgogne Dijon France PSL Univ Inst Curie INSERM CNRS Paris France

STUDY QUESTION: Do assisted reproductive technologies (ART) and in vitro embryo culture influence the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) in children? SUMMARY ANSWER: Significant differences in the DNA methylation of IGs or transposon families were reported between ART and naturally conceived children, but there was no difference between culture media. WHAT IS KNOWN ALREADY: There is concern that ART may play a role in increasing the incidence of adverse health outcomes in children, probably through epigenetic mechanisms. It is crucial to assess epigenetic control, especially following non-optimal in vitro culture conditions and to compare epigenetic analyses from ART-conceived and naturally conceived children. STUDY DESIGN, SIZE, DURATION: This follow-up study was based on an earlier randomized study comparing in vitro fertilization outcomes following the use of two distinct culture media. We compared the epigenetic profiles of children from the initial randomized study according to the mode of conception [i.e. ART singletons compared with those of a cohort of naturally conceived singleton children (CTL)], the type of embryo culture medium used [global medium (LifeGlobal) and single step medium (Irvine Scientific)] and the mode of in vitro fertilization (i.e. IVF versus ICSI). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 57 buccal smears were collected from 7- to 8-year-old children. The DNA methylation profiles of four differentially methylated regions (DMRs) of IGs (H19/IGF2: IG-DMR, KCNQ1OT1: TSS-DMR, SNURF: TSS-DMR, and PEG3: TSS-DMR) and two TEs (AluYa5 and LINE-1) were first assessed by pyrosequencing. We further explored IGs and TEs' methylation changes through methylation array (Human methylationEPIC BeadChip referred as EPIC array, Illumina). MAIN RESULTS AND THE ROLE OF CHANCE: Changes in the IGs' DNA methylation levels were found in ART children compared to controls. DNA methylation levels of H19/IGF2 DMR w

关键词： assisted reproduction children DNA methylation imprinted genes methylation array transposable elements

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