Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders.

BACKGROUND: Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth. METHODS: We performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryonic placental tissue, we selected 27 newborns whose mothers had consumed alcohol up to gestational week 7 at maximum to the separate analyses. Furthermore, to explore the effects of early alcohol exposure on embryonic cells, human embryonic stem cells (hESCs) as well as hESCs during differentiation into endodermal, mesodermal, and ectodermal cells were exposed to alcohol in vitro. RESULTS: DPPA4, FOXP2, and TACR3 with significantly decreased DNAm were discovered-particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When hESCs were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNAm similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNAm changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways in the enrichment analysis, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development. CONCLUSIONS: Our study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.

Next generation sequencing analysis of lung cancer datasets: A functional genomics perspective.

Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epithelial cells lining the respiratory tracts. Several researchers in the recent past have theorized that the next generation sequencing (NGS), especially transcriptome sequencing has enhanced understanding lung cancers and other epithelial epidemics. Conversely, pathogenesis specific to lung cancer with respect to molecular fraction of genomic ribonucleic acid has some mutant effect in various populations like smokers with lung cancer, healthy never smokers and vice versa. We review the impending impact of NGS data while providing insights into the biology of lung cancer affecting various populations, which we believe would be an add-on service for predictive biology approaches. Furthermore, we conclude what would be the outcome of such analysis for Indian population. Bioinformatics analysis was performed using various tools. We identified five genes namely epidermal growth factor receptor, Kirsten rat sarcoma, adenomatosis polyposis down regulated-1, N-ethylmaleimide-sensitive factor attachment protein, gamma and Piezo type mechanosensitive ion channel component 2 whose role was implicated in lung cancer and further analysis has to be performed to check whether or not the genes are indeed completely involved in causing lung cancer.