学术讲座- Array-based Analysis of DNA Methylation Alterations in Alcoholics and
Validation Using A Mouse Model
主讲人：Huiping Zhang, Ph.D., Assistant Professor
Department of Psychiatry, Yale University School of Medicine, USA
时间：2011年12月1日 星期四，上午9:00-
地点：8797威尼斯老品牌二楼会议室
Background: Epigenetic regulation through DNA methylation may influence vulnerability to numerous disorders, including alcohol dependence (AD).
Methods: Peripheral blood DNA methylation levels of 384 CpGs in promoter regions of 82 candidate genes were examined in 285 African Americans (AAs; 141 AD cases and 144 controls) and 249 European Americans (EAs; 144 AD cases and 105 controls) using Illumina GoldenGate Methylation Array assays. Effects of AD on DNA methylation were analyzed using multivariate analyses of covariance with consideration of sex, age and ancestry. A five-day Drinking-in-the Dark paradigm was applied to 28 male outbred CD-1 mice (15 ethanol-exposed and 13 water-drinking) to examine ethanol-induced DNA methylation changes (quantified by the Sequenom method) in mouse blood and brain reward regions.
Results: In AAs, 21 CpGs (19 genes) were more highly methylated in AD cases than in controls (0.001£P£0.050). In EAs, 43 CpGs (34 genes) were more highly methylated in AD cases than in controls (0.00001£P£0.048); CpG cg08989585 in HTR3A promoter region showed a significantly higher methylation level in EA cases than in EA controls after correction for multiplicity (P=0.00001). Ethanol-induced methylation changes in Htr3a promoter CpGs (eight CpGs around the transcription start site were examined) were observed in mouse blood and nine brain regions. The mean methylation level of these eight CpGs was significantly higher in the blood (P=0.029) but trended to be lower in the dorsomedial prefrontal cortex (P=0.074) in ethanol-exposed mice than in water-drinking mice.
Conclusions: Alcohol consumption may induce tissue-specific methylation changes in both human and mouse genes.
Biography of Dr. Huiping Zhang
Dr. Huiping Zhang is Assistant Professor in Division of Human Genetics, Department of Psychiatry at Yale University School of Medicine. He received his Bachelor’s Degree of Science from Huazhong Normal University in 1990, Master’s Degree of Medicine from Wuhan Institute of Biological Products/Tongji Medical University in 1993, and Doctor’s Degree of Philosophy from Queen’s University at Kingston, Canada in 2004. His current research goal is to understand the genetic and epigenetic mechanisms of alcohol dependence and other psychiatric disorders. Dr. Zhang is using a number of approaches (such as candidate gene and genome-wide association, genome-wide DNA methylation, genome-wide expression, next-generation sequencing and functional genomic studies) to identify genetic variants and epigenetic events that influence the vulnerability to the disorders. He has published about 30 research papers in peer reviewed journals. Dr. Zhang is the reviewer of more than 10 academic journals such as Human Molecular Genetics, PLoS One, Pharmacogenetics and Genomics, Brain Research, and Biological Psychiatry. He is also the Editor of the Special Issue “Alcoholism” of the Journal of Addiction Research & Therapy.
