The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2015
Epigenetic markers for newborn congenital heart defect (CHD).
СтатьяНазвание и аннотация: Перевод в очереди
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Bahado-Singh Ray O, Zaffra Rita, Albayarak Samet, Chelliah Anushka, Bolinjkar Rashmi, Turkoglu Onur, Radhakrishna Uppala
Аннотация
OBJECTIVE: Our objective was to determine whether there were significant differences in genome-wide DNA methylation in newborns with major congenital heart defect (CHD) compared to controls. We also evaluated methylation of cytosines in CpG motifs for the detection of these CHDs.
METHODS: Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls.
RESULTS: Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, p < 0.00001).
CONCLUSION: Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.
METHODS: Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls.
RESULTS: Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, p < 0.00001).
CONCLUSION: Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.