Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylation profiles across different brain regions in Alzheimer disease mice models

ABSTRACT: Genome wide DNA methylation profiling of normal and disease samples from different mice models. A custom Illumina Golden Gate DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 800 CpGs. Bisulphite converted DNA from the 35 samples were hybridised to the Illumina custom golden gate DNA methylation array.

ORGANISM(S): Mus musculus

SUBMITTER: Antonio Gómez

PROVIDER: E-GEOD-47036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease.

Sanchez-Mut Jose V JV Aso Ester E Panayotis Nicolas N Lott Ira I Dierssen Mara M Rabano Alberto A Urdinguio Rocio G RG Fernandez Agustin F AF Astudillo Aurora A Martin-Subero Jose I JI Balint Balazs B Fraga Mario F MF Gomez Antonio A Gurnot Cecile C Roux Jean-Christophe JC Avila Jesus J Hensch Takao K TK Ferrer Isidre I Esteller Manel M

Brain : a journal of neurology 20130911 Pt 10

The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional activity, and aberrations in the distribution of this epigenetic mark may be involved in many neurological disorders, such as Alzheimer's disease. Herein, we have analysed 12 distinct mouse brain regions according to their CpG 5'-end gene methylation patterns and observed their unique epigenetic landscapes ...[more]

PMID: 24030951

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Project description:Background: Patient-derived tumour xenografts are an attractive model for preclinical testing of anti-cancer drugs. Insights into tumour biology and biomarkers predictive of responses to chemotherapeutic drugs can also be gained from investigating xenograft models. As a first step towards examining the equivalence of epigenetic profiles between xenografts and primary tumours in paediatric leukaemia, we performed genome-scale DNA methylation and gene expression profiling on a panel of 10 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone response. Results: We found high correlations in DNA methylation and gene expression profiles between matching primary and xenograft tumour samples with Pearson’s correlation coefficients ranging between 0.85 and 0.98. In order to demonstrate the potential utility of epigenetic analyses in BCPALL xenografts, we identified DNA methylation biomarkers that correlated with prednisolone responsiveness of the original tumour samples. Differential methylation of CAPS2, ARHGAP21, ARX and HOXB6 were confirmed by locus specific analysis. We identified 20 genes showing an inverse relationship between DNA methylation and gene expression in association with prednisolone response. Pathway analysis of these genes implicated apoptosis, cell signalling and cell structure networks in prednisolone responsiveness. Conclusions: The findings of this study confirm the stability of epigenetic and gene expression profiles of paediatric BCP-ALL propagated in mouse xenograft models. Further, our preliminary investigation of prednisolone sensitivity highlights the utility of mouse xenograft models for preclinical development of novel drug regimens with parallel investigation of underlying gene expression and epigenetic responses associated with novel drug responses. 20 samples were analysed using Illumina Infinium HM27K Bead arrays. This consisted of 10 matched primary tumour and low passage xenografts. Of which, 5 were prednisolone good responders and 5 were prednisolone poor responders

Project description:Preeclampsia is one of the leading causes of maternal death worldwide. While the root cause is still unknown, the underlying biology of the disorder is becoming more clear. We recently published a study showing large, significant differences in DNA methylation in 3rd trimester placental samples associated with early-onset preeclampsia (EOPET) compared to controls. In this study, to identify DNA methylation differences associated with preeclampsia that occur early in pregnancy and to further delineate common EOPET-associated differences, we utilized a genetic defect, trisomy 16 (T16), that is predisposing to preeclampsia. We ran T16 placental samples from the 1st trimester (n=5) and 3rd trimester (n=10) against gestational age matched controls on the Illumina Infinium HumanMethylation450 BeadChip. Third trimester samples were from pregnancies with T16 confined to the placenta (confined placental mosaicism 16;CPM16), and consisted of samples that were and were not associated with EOPET (n=5 each). We identified a large number of DNA methylation differences in CPM16 samples compared to controls using stringent criteria (n=2254;False Discovery Rate <0.01, ->0.15). Several of these differences (11%) overlapped differences observed in chromosomally normal EOPET using similarly stringent criteria (FDR<0.01;->0.125). Isolating EOPET-associated probes produced a similar - distribution amongst CPM16 samples, although samples associated with EOPET showed a tendency towards larger DNA methylation differences. We also identified 262 DNA methylation differences between 1st trimester T16 and 1st trimester controls. Of these, 77 overlapped differences seen in 3rd trimester CPM16. Investigating these 77 T16/CPM16 specific DNA methylation differences, we identified three probes near two genes (ARGHEF37 and JUNB) that were also present as EOPET-associated methylation differences. In summary, we identified significant overlapping DNA methylation profiles of placentas with T16 and chromosomally normal placentas associated with EOPET. Specific DNA methylation marks within these profiles may be of future clinical utility in early identification of pregnancies susceptible to EOPET. Bisulfite converted DNA from 5 1st trimester trisomy 16 placentas, 5 chromosomally normal 1st trimester placentas, 10 third trimester placentas from confined placental mosaicism placentas and 10 chromosomally normal 3rd trimester placentas

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Dataset Information

DNA methylation profiles across different brain regions in Alzheimer disease mice models

Publications

DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease.

Similar Datasets

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