Extensive Placental Methylation Profiling in Normal Pregnancies

The placental methylation pattern is crucial for the regulation of genes involved in trophoblast invasion and placental development, both key events for fetal growth. We investigated LINE-1 methylation and methylome profiling using a methylation EPIC array and the targeted methylation sequencing of 154 normal, full-term pregnancies, stratified by birth weight percentiles. LINE-1 methylation showed evidence of a more pronounced hypomethylation in small neonates compared with normal and large for gestational age. Genome-wide methylation, performed in two subsets of pregnancies, showed very similar methylation profiles among cord blood samples while placentae from different pregnancies appeared very variable. A unique methylation profile emerged in each placenta, which could represent the sum of adjustments that the placenta made during the pregnancy to preserve the epigenetic homeostasis of the fetus. Investigations into the 1000 most variable sites between cord blood and the placenta showed that promoters and gene bodies that are hypermethylated in the placenta are associated with blood-specific functions, whereas those that are hypomethylated belong mainly to pathways involved in cancer. These features support the functional analogies between a placenta and cancer. Our results, which provide a comprehensive analysis of DNA methylation profiling in the human placenta, suggest that its peculiar dynamicity can be relevant for understanding placental plasticity in response to the environment.

Download Full-text

GENE-23. GENOME-WIDE DNA METHYLATION PROFILES DISTINGUISH SILENT FROM NON-SILENT ACTH ADENOMAS

Neuro-Oncology ◽

10.1093/neuonc/noz175.425 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi102-vi102

Author(s):

Franz Ricklefs ◽

Krys Fita ◽

Roman Rotermund ◽

Manfred Westphal ◽

Ulrich Schüller ◽

...

Keyword(s):

Dna Methylation ◽

Sanger Sequencing ◽

Gene Locus ◽

Cushing Disease ◽

Strong Expression ◽

Genome Wide ◽

Corticotroph Adenomas ◽

Epic Array ◽

Methylation Profiling ◽

Transsphenoidal Resection

Abstract BACKGROUND Corticotroph adenomas are immunopositive for adrenocorticotrophic hormone (ACTH) associated with elevated blood ACTH levels leading to Cushing disease (CD). Yet silent ACTH adenomas (SCA) immunostain for ACTH but do not cause hypercortisolism. SCA have consistently been shown to have a more aggressive postoperative course, then nonfunctioning and ACTH adenomas. Here we show that genome-wide methylation profiles can be used to distinguish ACTH adenomas from SCA. METHODS16 SCA patients and 19 CD patients that underwent transsphenoidal resection were included. Tumor size was measured by MRI. Tumor histology was proven by immunstain for ACTH and routine histopathology. Sanger sequencing was performed to analyse mutational burden within the ACTH locus (n=3). Genome-wide DNA methylation profiling was performed using a 850k Illumina EPIC array and classified by the DKFZ brain tumor classifier as well as PCA analysis using R (n=17). RESULTS Mean age was 55,4 and 46,2 for SCA and CD patients, respectively. Patients with SCA had significantly larger tumors (SCA: 12,56±3,07ccm; CD: 1,9±1,2ccm p< 0.01). Both SCA and CD tumors showed strong expression of ACTH as proven by immunohistochemistry. Sanger sequencing revealed no mutations within the ACTH gene locus in SCA. Both, SCA and CD tumors classified as ACTH adenomas by genome-wide methylation profiling. Further PCA of DNA methylation profiles allowed subtype tumor classification into SCA and CD adenomas. CONCLUSION SCA show a strong expression of ACTH without causing hypercortisolism. The reason for this is not yet known. Our data suggest that SCA do not harbor specific mutations within the ACTH gene locus. However genome wide methylation profiles allows subgrouping of SCA and CD adenomas.

Download Full-text

Abstract #91: Comparison of Cord Blood Insulin in Large-for-Gestational-Age Infants and Appropriate-for-Age Filipino Infants of Nondiabetic Mothers: A Pilot Study

Endocrine Practice ◽

10.1016/s1530-891x(20)46363-3 ◽

2004 ◽

Vol 10 ◽

pp. 31

Author(s):

Florence M. Amorado-Santos ◽

Maria Honolina S. Gomez ◽

Maria Victoria R. Olivares ◽

Zayda N. Gamilla

Keyword(s):

Pilot Study ◽

Cord Blood ◽

Gestational Age ◽

Large For Gestational Age ◽

Blood Insulin

Download Full-text

X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

Genetics ◽

10.1093/genetics/iyab043 ◽

2021 ◽

Author(s):

Thomas D Brekke ◽

Emily C Moore ◽

Shane C Campbell-Staton ◽

Colin M Callahan ◽

Zachary A Cheviron ◽

...

Keyword(s):

Gene Expression ◽

X Chromosome ◽

Regulatory Networks ◽

Mammalian Species ◽

Strongly Correlated ◽

Placental Development ◽

Substitution Lines ◽

Genome Wide ◽

Highly Sensitive ◽

First And Second Generation

AbstractEmbryonic development in mammals is highly sensitive to changes in gene expression within the placenta. The placenta is also highly enriched for genes showing parent-of-origin or imprinted expression, which is predicted to evolve rapidly in response to parental conflict. However, little is known about the evolution of placental gene expression, or if divergence of placental gene expression plays an important role in mammalian speciation. We used crosses between two species of dwarf hamsters (Phodopus sungorus and Phodopus campbelli) to examine the genetic and regulatory underpinnings of severe placental overgrowth in their hybrids. Using quantitative genetic mapping and mitochondrial substitution lines, we show that overgrowth of hybrid placentas was primarily caused by genetic differences on the maternally inherited P. sungorus X chromosome. Mitochondrial interactions did not contribute to abnormal hybrid placental development, and there was only weak correspondence between placental disruption and embryonic growth. Genome-wide analyses of placental transcriptomes from the parental species and first- and second-generation hybrids revealed a central group of co-expressed X-linked and autosomal genes that were highly enriched for maternally biased expression. Expression of this gene network was strongly correlated with placental size and showed widespread misexpression dependent on epistatic interactions with X-linked hybrid incompatibilities. Collectively, our results indicate that the X chromosome is likely to play a prominent role in the evolution of placental gene expression and the accumulation of hybrid developmental barriers between mammalian species.

Download Full-text

Comprehensive analysis of CCCH-type zinc finger gene family in citrus (Clementine mandarin) by genome-wide characterization

Molecular Genetics and Genomics ◽

10.1007/s00438-014-0858-9 ◽

2014 ◽

Vol 289 (5) ◽

pp. 855-872 ◽

Cited By ~ 13

Author(s):

Shengrui Liu ◽

Muhammad Rehman Gul Khan ◽

Yongping Li ◽

Jinzhi Zhang ◽

Chungen Hu

Keyword(s):

Gene Family ◽

Zinc Finger ◽

Comprehensive Analysis ◽

Zinc Finger Gene ◽

Genome Wide

Download Full-text

Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots

Clinical Epigenetics ◽

10.1186/s13148-016-0242-1 ◽

2016 ◽

Vol 8 (1) ◽

Cited By ~ 22

Author(s):

Nicklas H. Staunstrup ◽

Anna Starnawska ◽

Mette Nyegaard ◽

Lene Christiansen ◽

Anders L. Nielsen ◽

...

Keyword(s):

Dna Methylation ◽

Dried Blood Spots ◽

Blood Spots ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

Download Full-text

Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis

Gut ◽

10.1136/gutjnl-2020-322983 ◽

2021 ◽

pp. gutjnl-2020-322983

Author(s):

Benjamin Goeppert ◽

Damian Stichel ◽

Reka Toth ◽

Sarah Fritzsche ◽

Moritz Anton Loeffler ◽

...

Keyword(s):

Treatment Options ◽

Genetic Alterations ◽

Integrative Analysis ◽

Intermediate Form ◽

Precursor Lesions ◽

Molecular Alterations ◽

Genome Wide ◽

Cells Of Origin ◽

Sample Set ◽

Methylation Profiling

ObjectiveA detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options.DesignWe analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor lesions of the biliary tract and correlated the results with an independent non-IPNB/ITPN associated CCA cohort (n=294). The triplet sample set of non-neoplastic biliary epithelium, precursor and invasive CCA was analysed by next generation sequencing, DNA copy number and genome-wide methylation profiling.ResultsPatients with invasive CCA arising from IPNB/ITPN had better prognosis than patients with CCA not associated with IPNB/ITPN. ITPN was localised mostly intrahepatic, whereas IPNB was mostly of extrahepatic origin. IPNB/ITPN were equally associated with small-duct and large-duct type intrahepatic CCA. IPNB exhibited mutational profiles of extrahepatic CCA, while ITPN had significantly fewer mutations. Most mutations were shared between precursor lesions and corresponding invasive CCA but ROBO2 mutations occurred exclusively in invasive CCA and CTNNB1 mutations were mainly present in precursor lesions. In addition, IPNB and ITPN differed in their DNA methylation profiles and analyses of latent methylation components suggested that IPNB and ITPN may have different cells-of-origin.ConclusionIntegrative analysis revealed that IPNB and ITPN harbour distinct early genetic alterations, IPNB are enriched in mutations typical for extrahepatic CCA, whereas ITPN exhibited few genetic alterations and showed distinct epigenetic profiles. In conclusion, IPNB/ITPN may represent a distinctive, intermediate form of intrahepatic and extrahepatic cholangiocarcinogenesis.

Download Full-text

EPCO-17. METHYLATION ANALYSIS OF MATCHED PRIMARY AND RECURRENT IDHmt ASTROCYTOMA; AN UPDATE FROM THE GLIOMA LONGITUDINAL ANALYSIS NL (GLASS-NL) CONSORTIUM

Neuro-Oncology ◽

10.1093/neuonc/noab196.016 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi5-vi5

Author(s):

Wies Vallentgoed ◽

Anneke Niers ◽

Karin van Garderen ◽

Martin van den Bent ◽

Kaspar Draaisma ◽

...

Keyword(s):

Dna Methylation ◽

Surgical Resection ◽

Molecular Mechanisms ◽

Relative Proportion ◽

Low Grade ◽

High Grade ◽

Primary Tumors ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

Abstract The GLASS-NL consortium, was initiated to gain insight into the molecular mechanisms underlying glioma evolution and to identify markers of progression in IDH-mutant astrocytomas. Here, we present the first results of genome-wide DNA-methylation profiling of GLASS-NL samples. 110 adult patients were identified with an IDH-mutant astrocytoma at first diagnosis. All patients underwent a surgical resection of the tumor at least twice, separated by at least 6 months (median 40.9 months (IQR: 24.0, 64.7). In 37% and 18% of the cases, patients were treated with radiotherapy or chemotherapy respectively, before surgical resection of the recurrent tumor. DNA-methylation profiling was done on 235 samples from 103 patients (102 1st, 101 2nd, 29 3rd, and 3 4th resection). Copy number variations were also extracted from these data. Methylation classes were determined according to Capper et al. Overall survival (OS) was measured from date of first surgery. Of all primary tumors, the methylation-classifier assigned 85 (87%) to the low grade subclass and 10 (10%) to the high grade subclass. The relative proportion of high grade tumors increased ~three-fold at tumor recurrence (32/101, 32%) and even further in the second recurrence (15/29, 52%). Methylation classes were prognostic, both in primary and recurrent tumors. The overall DNA-methylation levels of recurrent samples was lower than that of primary samples. This difference is explained by the increased number of high grade samples at recurrence, since near identical DNA-methylation levels were observed in samples that remained low grade. In an unsupervised analysis, DNA-methylation data derived from primary and first recurrence samples of individual patients mostly (79%) cluster together. Recurrent samples that do not cluster with their primary tumor, form a separate group with relatively low genome-wide DNA-methylation. Our data demonstrate that methylation profiling identifies a shift towards a higher grade at tumor progression coinciding with reduced genome-wide DNA-methylation levels.

Download Full-text

Genome-wide DNA methylation profiling shows a distinct epigenetic signature associated with lung macrophages in cystic fibrosis

Clinical Epigenetics ◽

10.1186/s13148-018-0580-2 ◽

2018 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Youdinghuan Chen ◽

David A. Armstrong ◽

Lucas A. Salas ◽

Haley F. Hazlett ◽

Amanda B. Nymon ◽

...

Keyword(s):

Cystic Fibrosis ◽

Dna Methylation ◽

Lung Macrophages ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

Download Full-text

Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates

Frontiers in Genetics ◽

10.3389/fgene.2021.696840 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zongzhi Liu ◽

Wei Chen ◽

Zilong Zhang ◽

Junyun Wang ◽

Yi-Kun Yang ◽

...

Keyword(s):

Dna Methylation ◽

Immune System ◽

Cord Blood ◽

Genetic Model ◽

Housekeeping Genes ◽

Normal Pregnancy ◽

Methylation Pattern ◽

Whole Genome ◽

Maternal Cell ◽

Dna Methylation Pattern

The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns’ heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.

Download Full-text

Genome-Wide Essentiality Analysis of Mycobacterium abscessus by Saturated Transposon Mutagenesis and Deep Sequencing

mBio ◽

10.1128/mbio.01049-21 ◽

2021 ◽

Author(s):

Dalin Rifat ◽

Liang Chen ◽

Barry N. Kreiswirth ◽

Eric L. Nuermberger

Keyword(s):

Deep Sequencing ◽

Mycobacterium Abscessus ◽

Transposon Mutagenesis ◽

Comprehensive Analysis ◽

Data Sets ◽

Similar Data ◽

Intrinsic Resistance ◽

Effective Strategies ◽

Genome Wide

Limited knowledge regarding Mycobacterium abscessus pathogenesis and intrinsic resistance to most classes of antibiotics is a major obstacle to developing more effective strategies to prevent and mitigate disease. Using optimized procedures for Himar1 transposon mutagenesis and deep sequencing, we performed a comprehensive analysis to identify M. abscessus genetic elements essential for in vitro growth and compare them to similar data sets for M. tuberculosis and M. avium subsp. hominissuis .

Download Full-text