Associative DNA methylation changes in children with prenatal alcohol exposure

被引:66
作者
Laufer, Benjamin I. [1 ]
Kapalanga, Joachim [2 ]
Castellani, Christina A. [1 ]
Diehl, Eric J. [1 ]
Yan, Liying [3 ]
Singh, Shiva M. [1 ,2 ,4 ]
机构
[1] Univ Western Ontario, Dept Biol, Mol Genet Unit, London, ON N6A 5B7, Canada
[2] Univ Western Ontario, Dept Pediat, London, ON N6A 5B7, Canada
[3] EpigenDx Inc, Hopkinton, MA 01748 USA
[4] Univ Western Ontario, Program Neurosci, London, ON N6A 5B7, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
cohesin; CTCF; fetal alcohol spectrum disorders; glutamatergic synapse; hippo signaling; neurodevelopment; protocadherin; synapse; ETHANOL EXPOSURE; GAMMA-PROTOCADHERINS; GENE-EXPRESSION; MOUSE MODEL; SPECTRUM DISORDERS; BRAIN; DIVERSITY; CADHERINS; SURVIVAL; ALTERS;
D O I
10.2217/epi.15.60
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Aim: Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD). Previously, we assessed PAE in brain tissue from mouse models, however whether these changes are present in humans remains unknown. Materials & methods: In this report, we show some identical changes in DNA methylation in the buccal swabs of six children with FASD using the 450K array. Results: The changes occur in genes related to protocadherins, glutamatergic synapses, and hippo signaling. The results were found to be similar in another heterogeneous replication group of six FASD children. Conclusion: The replicated results suggest that children born with FASD have unique DNA methylation defects that can be influenced by sex and medication exposure. Ultimately, with future clinical development, assessment of DNA methylation from buccal swabs can provide a novel strategy for the diagnosis of FASD.
引用
收藏
页码:1259 / 1274
页数:16
相关论文
共 62 条
[21]   Postsynaptic and differential localization to neuronal subtypes of protocadherin β16 in the mammalian central nervous system [J].
Junghans, Dirk ;
Heidenreich, Matthias ;
Hack, Iris ;
Taylor, Verdon ;
Frotscher, Michael ;
Kemler, Rolf .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2008, 27 (03) :559-571
[22]   Fate Analysis of Adult Hippocampal Progenitors in a Murine Model of Fetal Alcohol Spectrum Disorder (FASD) [J].
Kajimoto, Kenta ;
Allan, Andrea ;
Cunningham, Lee Anna .
PLOS ONE, 2013, 8 (09)
[23]   Changes in subcellular distribution of protocadherin gamma proteins accompany maturation of spinal neurons [J].
Kallenbach, S ;
Khantane, S ;
Carroll, P ;
Gayet, O ;
Alonso, S ;
Henderson, CE ;
Dudley, K .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 72 (05) :549-556
[24]   Evidence for positive selection on Protocadherin Y gene in Homo sapiens: Implications for schizophrenia [J].
Kalmady, Sunil V. ;
Venkatasubramanian, Ganesan .
SCHIZOPHRENIA RESEARCH, 2009, 108 (1-3) :299-300
[25]   Maternal Ethanol Consumption Alters the Epigenotype and the Phenotype of Offspring in a Mouse Model [J].
Kaminen-Ahola, Nina ;
Ahola, Arttu ;
Maga, Murat ;
Mallitt, Kylie-Ann ;
Fahey, Paul ;
Cox, Timothy C. ;
Whitelaw, Emma ;
Chong, Suyinn .
PLOS GENETICS, 2010, 6 (01)
[26]   Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome [J].
Kim, Tae Hoon ;
Abdullaev, Ziedulla K. ;
Smith, Andrew D. ;
Ching, Keith A. ;
Loukinov, Dmitri I. ;
Green, Roland D. ;
Zhang, Michael Q. ;
Lobanenkov, Victor V. ;
Ren, Bing .
CELL, 2007, 128 (06) :1231-1245
[27]   Third Trimester-Equivalent Ethanol Exposure Is Characterized by an Acute Cellular Stress Response and an Ontogenetic Disruption of Genes Critical for Synaptic Establishment and Function in Mice [J].
Kleiber, Morgan L. ;
Laufer, Benjamin I. ;
Stringer, Randa L. ;
Singh, Shiva M. .
DEVELOPMENTAL NEUROSCIENCE, 2014, 36 (06) :499-519
[28]   Long-term genonnic and epigenonnic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders [J].
Kleiber, Morgan L. ;
Diehl, Eric J. ;
Laufer, Benjamin I. ;
Mantha, Katarzyna ;
Chokroborty-Hoque, Aniruddho ;
Alberry, Bonnie ;
Singh, Shiva M. .
FRONTIERS IN GENETICS, 2014, 5
[29]   Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure [J].
Kleiber, Morgan L. ;
Mantha, Katarzyna ;
Stringer, Randa L. ;
Singh, Shiva M. .
JOURNAL OF NEURODEVELOPMENTAL DISORDERS, 2013, 5 :1-19
[30]   Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders [J].
Kleiber, Morgan L. ;
Laufer, Benjamin I. ;
Wright, Elise ;
Diehl, Eric J. ;
Singh, Shiva M. .
BRAIN RESEARCH, 2012, 1458 :18-33