Browsing by Subject "Fetal alcohol syndrome"

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    Environmental Alterations of Epigenetics Prior to the Birth
    (Elsevier, 2014) Lo, Chiao-Ling; Zhou, Feng C.; Anatomy, Cell Biology and Physiology, School of Medicine
    The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, noncoding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late-onset neuropsychiatric diseases, or idiosyncratic mental disorders.
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    Implications of genomic signatures in the differential vulnerability to fetal alcohol exposure in C57BL/6 and DBA/2 mice
    (Frontiers Media, 2014-06-11) Lossie, Amy C.; Muir, William M.; Lo, Chiao-Ling; Timm, Floyd; Liu, Yunlong; Gray, Whitney; Zhou, Feng C.; Medicine, School of Medicine
    Maternal alcohol consumption inflicts a multitude of phenotypic consequences that range from undetectable changes to severe dysmorphology. Using tightly controlled murine studies that deliver precise amounts of alcohol at discrete developmental stages, our group and other labs demonstrated in prior studies that the C57BL/6 and DBA/2 inbred mouse strains display differential susceptibility to the teratogenic effects of alcohol. Since the phenotypic diversity extends beyond the amount, dosage and timing of alcohol exposure, it is likely that an individual's genetic background contributes to the phenotypic spectrum. To identify the genomic signatures associated with these observed differences in alcohol-induced dysmorphology, we conducted a microarray-based transcriptome study that also interrogated the genomic signatures between these two lines based on genetic background and alcohol exposure. This approach is called a gene x environment (GxE) analysis; one example of a GxE interaction would be a gene whose expression level increases in C57BL/6, but decreases in DBA/2 embryos, following alcohol exposure. We identified 35 candidate genes exhibiting GxE interactions. To identify cis-acting factors that mediated these interactions, we interrogated the proximal promoters of these 35 candidates and found 241 single nucleotide variants (SNVs) in 16 promoters. Further investigation indicated that 186 SNVs (15 promoters) are predicted to alter transcription factor binding. In addition, 62 SNVs created, removed or altered the placement of a CpG dinucleotide in 13 of the proximal promoters, 53 of which overlapped putative transcription factor binding sites. These 53 SNVs are also our top candidates for future studies aimed at examining the effects of alcohol on epigenetic gene regulation.