Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF).
Tetralogy of Fallot (TOF) is the most common Critical Congenital Heart Defect (CCHD). The etiology of TOF is unknown in most cases. Preliminary data from our group and others suggest that epigenetic changes may play an important role in CHD. Epidemiologically, a significant percentage of CHD includi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6136787?pdf=render |
| _version_ | 1818067344904159232 |
|---|---|
| author | Uppala Radhakrishna Sangeetha Vishweswaraiah Avinash M Veerappa Rita Zafra Samet Albayrak Prajna H Sitharam Nazia M Saiyed Nitish K Mishra Chittibabu Guda Ray Bahado-Singh |
| author_facet | Uppala Radhakrishna Sangeetha Vishweswaraiah Avinash M Veerappa Rita Zafra Samet Albayrak Prajna H Sitharam Nazia M Saiyed Nitish K Mishra Chittibabu Guda Ray Bahado-Singh |
| author_sort | Uppala Radhakrishna |
| collection | DOAJ |
| description | Tetralogy of Fallot (TOF) is the most common Critical Congenital Heart Defect (CCHD). The etiology of TOF is unknown in most cases. Preliminary data from our group and others suggest that epigenetic changes may play an important role in CHD. Epidemiologically, a significant percentage of CHD including TOF fail to be diagnosed in the prenatal and early newborn period which can negatively affect health outcomes. We performed genome-wide methylation assay in newborn blood in 24 non-syndromic TOF cases and 24 unaffected matched controls using Illumina Infinium HumanMethylation450 BeadChips. We identified 64 significantly differentially methylated CpG sites in TOF cases, of which 25 CpG sites had high predictive accuracy for TOF, based on the area under the receiver operating characteristics curve (AUC ROC) ≥ 0.90). The CpG methylation difference between TOF and controls was ≥10% in 51 CpG targets suggesting biological significance. Gene ontology analysis identified significant biological processes and functions related to these differentially methylated genes, including: CHD development, cardiomyopathy, diabetes, immunological, inflammation and other plausible pathways in CHD development. Multiple genes known or plausibly linked to heart development and post-natal heart disease were found to be differentially methylated in the blood DNA of newborns with TOF including: ABCB1, PPP2R5C, TLR1, SELL, SCN3A, CREM, RUNX and LHX9. We generated novel and highly accurate putative molecular markers for TOF detection using leucocyte DNA and thus provided information on pathogenesis of TOF. |
| first_indexed | 2024-12-10T15:22:12Z |
| format | Article |
| id | doaj.art-2dcee422c29642fabbb659704358d1ff |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T15:22:12Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2dcee422c29642fabbb659704358d1ff2022-12-22T01:43:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e020389310.1371/journal.pone.0203893Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF).Uppala RadhakrishnaSangeetha VishweswaraiahAvinash M VeerappaRita ZafraSamet AlbayrakPrajna H SitharamNazia M SaiyedNitish K MishraChittibabu GudaRay Bahado-SinghTetralogy of Fallot (TOF) is the most common Critical Congenital Heart Defect (CCHD). The etiology of TOF is unknown in most cases. Preliminary data from our group and others suggest that epigenetic changes may play an important role in CHD. Epidemiologically, a significant percentage of CHD including TOF fail to be diagnosed in the prenatal and early newborn period which can negatively affect health outcomes. We performed genome-wide methylation assay in newborn blood in 24 non-syndromic TOF cases and 24 unaffected matched controls using Illumina Infinium HumanMethylation450 BeadChips. We identified 64 significantly differentially methylated CpG sites in TOF cases, of which 25 CpG sites had high predictive accuracy for TOF, based on the area under the receiver operating characteristics curve (AUC ROC) ≥ 0.90). The CpG methylation difference between TOF and controls was ≥10% in 51 CpG targets suggesting biological significance. Gene ontology analysis identified significant biological processes and functions related to these differentially methylated genes, including: CHD development, cardiomyopathy, diabetes, immunological, inflammation and other plausible pathways in CHD development. Multiple genes known or plausibly linked to heart development and post-natal heart disease were found to be differentially methylated in the blood DNA of newborns with TOF including: ABCB1, PPP2R5C, TLR1, SELL, SCN3A, CREM, RUNX and LHX9. We generated novel and highly accurate putative molecular markers for TOF detection using leucocyte DNA and thus provided information on pathogenesis of TOF.http://europepmc.org/articles/PMC6136787?pdf=render |
| spellingShingle | Uppala Radhakrishna Sangeetha Vishweswaraiah Avinash M Veerappa Rita Zafra Samet Albayrak Prajna H Sitharam Nazia M Saiyed Nitish K Mishra Chittibabu Guda Ray Bahado-Singh Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). PLoS ONE |
| title | Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). |
| title_full | Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). |
| title_fullStr | Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). |
| title_full_unstemmed | Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). |
| title_short | Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF). |
| title_sort | newborn blood dna epigenetic variations and signaling pathway genes associated with tetralogy of fallot tof |
| url | http://europepmc.org/articles/PMC6136787?pdf=render |
| work_keys_str_mv | AT uppalaradhakrishna newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT sangeethavishweswaraiah newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT avinashmveerappa newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT ritazafra newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT sametalbayrak newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT prajnahsitharam newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT naziamsaiyed newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT nitishkmishra newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT chittibabuguda newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof AT raybahadosingh newbornblooddnaepigeneticvariationsandsignalingpathwaygenesassociatedwithtetralogyoffallottof |