Long-term alterations to DNA methylation as a biomarker of prenatal alcohol exposure: From mouse models to human children with fetal alcohol spectrum disorders

Alcohol

Volumn 60, Issue , 2017, Pages 67-75

  Laufer, Benjamin I ^a   Chater Diehl, Eric J ^a   Kapalanga, Joachim ^a   Singh, Shiva M ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

Clustered protocadherins; DNA methylation; Epigenetics; Epigenomics; Fetal alcohol spectrum disorders (FASD); Genomic imprinting; Neurodevelopment; Neuroepigenomics; Personalized medicine; Prenatal alcohol exposure; Translational research

Indexed keywords

ALCOHOL; BIOLOGICAL MARKER; DNA; TRANSCRIPTOME;

CPG ISLAND; DNA METHYLATION; EPIGENETICS; FETAL ALCOHOL SYNDROME; FETUS; GENE EXPRESSION; GENE SEQUENCE; GENETIC HETEROGENEITY; GENOME IMPRINTING; HUMAN; NERVE CELL DIFFERENTIATION; NEXT GENERATION SEQUENCING; NONHUMAN; PRENATAL EXPOSURE; PROMOTER REGION; REVIEW; ANIMAL; DISEASE MODEL; DRINKING BEHAVIOR; DRUG EFFECTS; FEMALE; GENE EXPRESSION PROFILING; GENETIC EPIGENESIS; GENETIC MARKER; GENETICS; GENOTYPE ENVIRONMENT INTERACTION; GESTATIONAL AGE; MATERNAL EXPOSURE; MOUSE; PREGNANCY; RISK FACTOR; TIME FACTOR;

ALCOHOL DRINKING; ANIMALS; DISEASE MODELS, ANIMAL; DNA METHYLATION; EPIGENESIS, GENETIC; ETHANOL; FEMALE; FETAL ALCOHOL SPECTRUM DISORDERS; GENE EXPRESSION PROFILING; GENE-ENVIRONMENT INTERACTION; GENETIC MARKERS; GESTATIONAL AGE; HUMANS; MATERNAL EXPOSURE; MICE; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RISK FACTORS; TIME FACTORS; TRANSCRIPTOME;

EID: 85011547166     PISSN: 07418329     EISSN: 18736823     Source Type: Journal    
DOI: 10.1016/j.alcohol.2016.11.009     Document Type: Review

References (131)

1. American Psychiatric Association, Diagnostic and statistical manual of mental disorders: DSM-V. 2013, American Psychiatric Association.
2. Anitha, A., Thanseem, I., Nakamura, K., Yamada, K., Iwayama, Y., Toyota, T., et al. Protocadherin α (PCDHA) as a novel susceptibility gene for autism. Journal of Psychiatry & Neuroscience: JPN 38:3 (2013), 192–198.
3. Basavarajappa, B., Subbanna, S., Epigenetic mechanisms in developmental alcohol-induced neurobehavioral deficits. Brain Sciences, 6(2), 2016, 12.
4. Bekdash, R.A., Zhang, C., Sarkar, D.K., Gestational choline supplementation normalized fetal alcohol-induced alterations in histone modifications, DNA methylation, and proopiomelanocortin (POMC) gene expression in b-endorphin-producing POMC neurons of the hypothalamus. Alcoholism: Clinical and Experimental Research 37:7 (2013), 1133–1142.
5. Bernstein, B.E., Mikkelsen, T.S., Xie, X., Kamal, M., Huebert, D.J., Cuff, J., et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:2 (2006), 315–326.
6. Bird, A., Perceptions of epigenetics. Nature 447:7143 (2007), 396–398.
7. Brenet, F., Moh, M., Funk, P., Feierstein, E., Viale, A.J., Socci, N.D., et al. DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS One, 6(1), 2011, e14524.
8. Chater-Diehl, E.J., Laufer, B.I., Castellani, C.A., Alberry, B.L., Singh, S.M., Alteration of gene expression, DNA methylation, and histone methylation in free radical scavenging networks in adult mouse Hippocampus following fetal alcohol exposure. PloS One, 11(5), 2016, e0154836.
9. Chen, W.V., Maniatis, T., Clustered protocadherins. Development 140:16 (2013), 3297–3302.
10. Chen, Y., Ozturk, N.C., Zhou, F.C., DNA methylation program in developing Hippocampus and its alteration by alcohol. PLoS One, 8(3), 2013, e60503.
11. Chudley, A.E., Conry, J., Cook, J.L., Loock, C., Rosales, T., LeBlanc, N., Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ 172:5 SUPPL. (2005), S1–S21.
12. Clarren, S.K., Smith, D.W., The fetal alcohol syndrome. The New England Journal of Medicine 298:19 (1978), 1063–1067.
13. Dallosso, A.R., Hancock, A.L., Szemes, M., Moorwood, K., Chilukamarri, L., Tsai, H.-H., et al. Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumor. PLoS Genetics, 5(11), 2009, e1000745.
14. Davies, W., Isles, A.R., Humby, T., Wilkinson, L.S., What are imprinted genes doing in the brain?. Advances in Experimental Medicine and Biology 626:4 (2008), 62–70.
15. Day, J.J., New approaches to manipulate the epigenome. Dialogues in Clinical Neuroscience 16:3 (2014), 345–357.
16. Dietz, W.H., Masterson, K., Sittig, L.J., Redei, E.E., Herzing, L.B.K., Imprinting and expression of Dio3os mirrors Dio3 in rat. Frontiers in Genetics, 3, 2012, 279.
17. Doi, A., Park, I.-H., Wen, B., Murakami, P., Aryee, M.J., Irizarry, R., et al., Feinberg, A.P., Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nature Genetics 41:12 (2009), 1350–1353.
18. Downing, C., Johnson, T.E., Larson, C., Leakey, T.I., Siegfried, R.N., Rafferty, T.M., et al. Subtle decreases in DNA methylation and gene expression at the mouse Igf2 locus following prenatal alcohol exposure: Effects of a methyl-supplemented diet. Alcohol 45:1 (2011), 65–71.
19. Doyle, L.R., Mattson, S.N., Neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE): Review of evidence and guidelines for assessment. Current Developmental Disorders Reports 2:3 (2015), 175–186.
20. Fatemi, M., Pao, M.M., Jeong, S., Gal-Yam, E.N., Egger, G., Weisenberger, D.J., et al. Footprinting of mammalian promoters: Use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule level. Nucleic Acids Research, 33(20), 2005, e176.
21. Filippova, G.N., Genetics and epigenetics of the multifunctional protein CTCF. Current Topics in Developmental Biology 80 (2007), 337–360.
22. Gangisetty, O., Bekdash, R., Maglakelidze, G., Sarkar, D.K., Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus e113228. PLoS One, 9(11), 2014, e113228.
23. Gardiner-Garden, M., Frommer, M., CpG Islands in vertebrate genomes. Journal of Molecular Biology 196:2 (1987), 261–282.
24. Garro, a J., McBeth, D.L., Lima, V., Lieber, C.S., Ethanol consumption inhibits fetal DNA methylation in mice: Implications for the fetal alcohol syndrome. Alcoholism: Clinical and Experimental Research 15:3 (1991), 395–398.
25. Gil-Mohapel, J., Boehme, F., Kainer, L., Christie, B.R., Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models. Brain Research Reviews 64:2 (2010), 283–303.
26. Golan-Mashiach, M., Grunspan, M., Emmanuel, R., Gibbs-Bar, L., Dikstein, R., Shapiro, E., Identification of CTCF as a master regulator of the clustered protocadherin genes. Nucleic Acids Research 40:8 (2012), 3378–3391.
27. Gottesman, I.I., Gould, T.D., The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry 160:4 (2003), 636–645.
28. Govorko, D., Bekdash, R.A., Zhang, C., Sarkar, D.K., Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biological Psychiatry 72:5 (2012), 378–388.
29. Greenbaum, R.L., Stevens, S.A., Nash, K., Koren, G., Rovet, J., Social cognitive and emotion processing abilities of children with fetal alcohol spectrum disorders: A comparison with attention deficit hyperactivity disorder. Alcoholism: Clinical and Experimental Research 33:10 (2009), 1656–1670.
30. Green, C.R., Roane, J., Hewitt, A., Muhajarine, N., Mushquash, C., Sourander, A., et al. Frequent behavioural challenges in children with fetal alcohol spectrum disorder: A needs-based assessment reported by caregivers and clinicians. Journal of Population Therapeutics and Clinical Pharmacology 21:3 (2014), e405–e420.
31. Guo, Y., Monahan, K., Wu, H., Gertz, J., Varley, K.E., Li, W., et al. CTCF/cohesin-mediated DNA looping is required for protocadherin α promoter choice. Proceedings of the National Academy of Sciences of the United States of America 109:51 (2012), 21081–21086.
32. Guo, Y., Xu, Q., Canzio, D., Shou, J., Li, J., Gorkin, D.U., et al. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell 162:4 (2015), 900–910.
33. Gurard-Levin, Z.A., Almouzni, G., Histone modifications and a choice of variant: A language that helps the genome express itself. F1000Prime Reports, 6(76), 2014, 76.
34. Hajj, N., El Dittrich, M., Böck, J., Kraus, T.F.J., Nanda, I., Müller, T., et al. Epigenetic dysregulation in the developing Down syndrome cortex. Epigenetics 11:8 (2016), 563–578.
35. Hayashi, S., Takeichi, M., Emerging roles of protocadherins: From self-avoidance to enhancement of motility. Journal of Cell Science 128:8 (2015), 1455–1464.
36. Haycock, P.C., Fetal alcohol spectrum disorders: The epigenetic perspective. Biology of Reproduction 81:4 (2009), 607–617.
37. Haycock, P.C., Ramsay, M., Exposure of mouse embryos to ethanol during preimplantation development: Effect on DNA methylation in the h19 imprinting control region. Biology of Reproduction 81:4 (2009), 618–627.
38. Hemberger, M., Dean, W., Reik, W., Epigenetic dynamics of stem cells and cell lineage commitment: Digging Waddington's canal. Nature Reviews Molecular Cell Biology 10:8 (2009), 526–537.
39. Hirano, S., Takeichi, M., Cadherins in brain morphogenesis and wiring. Physiological Reviews 92:2 (2012), 597–634.
40. Hutson, J.R., Stade, B., Lehotay, D.C., Collier, C.P., Kapur, B.M., Folic acid transport to the human fetus is decreased in pregnancies with chronic alcohol exposure. PLoS One, 7(5), 2012, e38057.
41. Irizarry, R.A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nature Genetics 41:2 (2009), 178–186.
42. Isbel, L., Prokopuk, L., Wu, H., Daxinger, L., Oey, H., Spurling, A., et al. Wiz binds active promoters and CTCF-binding sites and is required for normal behaviour in the mouse. eLife, 5, 2016.
43. Jirikowic, T., Olson, H.C., Kartin, D., Sensory processing, school performance, and adaptive behavior of young school-age children with fetal alcohol spectrum disorders. Physical & Occupational Therapy in Pediatrics 28:2 (2008), 117–136.
44. Jones, K.L., Smith, D.W., Ulleland, C.N., Streissguth, P., Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 1:7815 (1973), 1267–1271.
45. Joubert, B.R., Felix, J.F., Yousefi, P., Bakulski, K.M., Just, A.C., Breton, C., et al. DNA methylation in newborns and maternal smoking in pregnancy: Genome-wide consortium meta-analysis. American Journal of Human Genetics 98:4 (2016), 680–696.
46. Joubert, B.R., Haberg, S.E., Nilsen, R.M., Wang, X., Vollset, S.E., Murphy, S.K., et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environmental Health Perspectives 120:10 (2012), 1425–1431.
47. Kaminen-Ahola, N., Ahola, A., Maga, M., Mallitt, K.A., Fahey, P., Cox, T.C., et al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genetics, 6(1), 2010, e1000811.
48. Katori, S., Hamada, S., Noguchi, Y., Fukuda, E., Yamamoto, T., Yamamoto, H., et al. Protocadherin-alpha family is required for serotonergic projections to appropriately innervate target brain areas. Journal of Neuroscience 29:29 (2009), 9137–9147.
49. Kernohan, K.D., Bérubé, N.G., Genetic and epigenetic dysregulation of imprinted genes in the brain. Epigenomics 2:6 (2010), 743–763.
50. Kiecker, C., The chick embryo as a model for the effects of prenatal exposure to alcohol on craniofacial development. Developmental Biology 415:2 (2016), 314–325.
51. Kleiber, M.L., Diehl, E.J., Laufer, B.I., Mantha, K., Chokroborty-Hoque, A., Alberry, B., et al. Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: A model for fetal alcohol spectrum disorders. Frontiers in Genetics, 5, 2014, 161.
52. Kleiber, M.L., Laufer, B.I., Wright, E., Diehl, E.J., Singh, S.M., Long-term alterations to the brain transcriptome in a maternal voluntary consumption model of fetal alcohol spectrum disorders. Brain Research 1458 (2012), 18–33.
53. Kleiber, M.L., Wright, E., Singh, S.M., Maternal voluntary drinking in C57BL/6J mice: Advancing a model for fetal alcohol spectrum disorders. Behavioural Brain Research 223:2 (2011), 376–387.
54. Knezovich, J.G., Ramsay, M., The effect of preconception paternal alcohol exposure on epigenetic remodeling of the H19 and Rasgrf1 imprinting control regions in mouse offspring. Frontiers in Genetics, 3, 2012, 10.
55. Kobor, M.S., Weinberg, J., Focus on: Epigenetics and fetal alcohol spectrum disorders. Alcohol Res Health 34:1 (2011), 29–37.
56. Kolarova, J., Tangen, I., Bens, S., Gillessen-Kaesbach, G., Gutwein, J., Kautza, M., et al. Array-based DNA methylation analysis in individuals with developmental delay/intellectual disability and normal molecular karyotype. European Journal of Medical Genetics 58:8 (2015), 419–425.
57. Kong, L., Tan, L., Lv, R., Shi, Z., Xiong, L., Wu, F., et al. A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands. Nucleic Acids Research 44:18 (2016), 8682–8692.
58. Ladd-Acosta, C., Shu, C., Lee, B.K., Gidaya, N., Singer, A., Schieve, L.A., et al. Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood. Environmental Research 144:Pt A (2016), 139–148.
59. LaSalle, J.M., Epigenomic strategies at the interface of genetic and environmental risk factors for autism. Journal of Human Genetics 58:7 (2013), 396–401.
60. LaSalle, J.M., Powell, W.T., Yasui, D.H., Epigenetic layers and players underlying neurodevelopment. Trends in Neurosciences 36:8 (2013), 460–470.
61. Laufer, B.I., A long-term neuroepigenomic profile of prenatal alcohol exposure. Electronic thesis and dissertation repository., 2016, University of Western Ontario.
62. Laufer, B.I., Kapalanga, J., Castellani, C.A., Diehl, E.J., Yan, L., Singh, S.M., Associative DNA methylation changes in children with prenatal alcohol exposure. Epigenomics 7:8 (2015), 1259–1274 (Journal Article).
63. Laufer, B.I., Mantha, K., Kleiber, M.L., Diehl, E.J., Addison, S.M.F., Singh, S.M., Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice. Disease Models & Mechanisms 6:4 (2013), 977–992.
64. Laufer, B.I., Singh, S.M., A macro role for imprinted clusters of MicroRNAs in the brain. MicroRNA 1:1 (2012), 59–64.
65. Laufer, B.I., Singh, S.M., Strategies for precision modulation of gene expression by epigenome editing: An overview. Epigenetics & Chromatin, 8(1), 2015, 34.
66. Lee, B.Y., Park, S.Y., Ryu, H.M., Shin, C.Y., Ko, K.N., Han, J.Y., et al. Changes in the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families exposed to alcohol during the periconceptional period. Alcoholism: Clinical and Experimental Research 39:2 (2015), 239–250.
67. Lefebvre, J.L., Kostadinov, D., Chen, W.V., Maniatis, T., Sanes, J.R., Protocadherins mediate dendritic self-avoidance in the mammalian nervous system. Nature 488:7412 (2012), 517–521.
68. Lemoine, P., Harousseau, H., Borteyru, J.P., Menuet, J.C., Les enfants de parents alcooliques: Anomalies observees a propos de 127 cas. Ouest Méd 21 (1968), 476–482.
69. Lesch, B.J., Dokshin, G.A., Young, R.A., McCarrey, J.R., Page, D.C., A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis. Proceedings of the National Academy of Sciences of the United States of America 110:40 (2013), 16061–16066.
70. Ling, J.Q., Li, T., Hu, J.F., Vu, T.H., Chen, H.L., Qiu, X.W., et al. CTCF mediates interchromosomal colocalization between Igf2/H19 and wsb1/nf1. Science 312:571 (2006), 269–272.
71. Lister, R., Pelizzola, M., Dowen, R.H., Hawkins, R.D., Hon, G., Tonti-Filippini, J., et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:7271 (2009), 315–322.
72. Liu, Y., Balaraman, Y., Wang, G., Nephew, K.P., Zhou, F.C., Alcohol exposure alters DNA methylation profiles in mouse embryos at early neurulation. Epigenetics 4:7 (2009), 500–511.
73. Lussier, A.A., Stepien, K.A., Neumann, S.M., Pavlidis, P., Kobor, M.S., Weinberg, J., Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain. Alcoholism: Clinical and Experimental Research 39:2 (2015), 251–261.
74. Maier, S.E., Cramer, J.A., West, J.R., Sohrabji, F., Alcohol exposure during the first two trimesters equivalent alters granule cell number and neurotrophin expression in the developing rat olfactory bulb. Journal of Neurobiology 41:3 (1999), 414–423.
75. Marjonen, H., Sierra, A., Nyman, A., Rogojin, V., Grohn, O., Linden, A.M., et al., Kaminen-Ahola, N., Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model. PLoS One, 10(5), 2015, e0124931.
76. Masemola, M.L., van der Merwe, L., Lombard, Z., Viljoen, D., Ramsay, M., Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero: a South african fetal alcohol syndrome cohort study. Frontiers in Genetics, 6, 2015, 85.
77. Mattson, S.N., Riley, E.P., A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcoholism: Clinical and Experimental Research 22:2 (1998), 279–294.
78. Maunakea, A.K., Nagarajan, R.P., Bilenky, M., Ballinger, T.J., D'Souza, C., Fouse, S.D., et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466:7303 (2010), 253–257.
79. McGowan, P.O., Suderman, M., Sasaki, A., Huang, T.C.T., Hallett, M., Meaney, M.J., et al. Broad epigenetic signature of maternal care in the brain of adult rats. PLoS One, 6(2), 2011, e14739.
80. Morison, I.M., Ramsay, J.P., Spencer, H.G., A census of mammalian imprinting. Trends in Genetics 21:8 (2005), 457–465.
81. Mould, A.W., Pang, Z., Pakusch, M., Tonks, I.D., Stark, M., Carrie, D., et al. Smchd1 regulates a subset of autosomal genes subject to monoallelic expression in addition to being critical for X inactivation. Epigenetics & Chromatin, 6(1), 2013, 19.
82. Nardone, S., Sams, D.S., Reuveni, E., Getselter, D., Oron, O., Karpuj, M., et al. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Translational Psychiatry, 4, 2014, e433.
83. O'Malley, K.D., Nanson, J., Clinical implications of a link between fetal alcohol spectrum disorder and attention-deficit hyperactivity disorder. Canadian Journal of Psychiatry 47:4 (2002), 349–354.
84. Paolozza, A., Munn, R., Munoz, D.P., Reynolds, J.N., Eye movements reveal sexually dimorphic deficits in children with fetal alcohol spectrum disorder. Frontiers in Neuroscience, 9, 2015, 76.
85. Paolozza, A., Rasmussen, C., Pei, J., Hanlon-Dearman, A., Nikkel, S.M., Andrew, G., et al. Deficits in response inhibition correlate with oculomotor control in children with fetal alcohol spectrum disorder and prenatal alcohol exposure. Behavioural Brain Research 259 (2014), 97–105.
86. Paolozza, A., Rasmussen, C., Pei, J., Hanlon-Dearman, A., Nikkel, S.M., Andrew, G., et al. Working memory and visuospatial deficits correlate with oculomotor control in children with fetal alcohol spectrum disorder. Behavioural Brain Research 263 (2014), 70–79.
87. Paolozza, A., Treit, S., Beaulieu, C., Reynolds, J.N., Response inhibition deficits in children with Fetal Alcohol Spectrum Disorder: Relationship between diffusion tensor imaging of the corpus callosum and eye movement control. NeuroImage: Clinical 5 (2014), 53–61.
88. Pauli, A., Rinn, J.L., Schier, A.F., Non-coding RNAs as regulators of embryogenesis. Nature Reviews Genetics 12:2 (2011), 136–149.
89. Peadon, E., Elliott, E.J., Distinguishing between attention-deficit hyperactivity and fetal alcohol spectrum disorders in children: Clinical guidelines. Neuropsychiatric Disease and Treatment 6 (2010), 509–515.
90. Pedrosa, E., Stefanescu, R., Margolis, B., Petruolo, O., Lo, Y., Nolan, K., et al. Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia. Schizophrenia Research 102:1–3 (2008), 210–219.
91. Popova, S., Lange, S., Shield, K., Mihic, A., Chudley, A.E., Mukherjee, R.A.S., et al. Comorbidity of fetal alcohol spectrum disorder: A systematic review and meta-analysis. The Lancet 387:10022 (2016), 978–987.
92. Portales-Casamar, E., Lussier, A.A., Jones, M.J., MacIsaac, J.L., Edgar, R.D., Mah, S.M., et al. DNA methylation signature of human fetal alcohol spectrum disorder. Epigenetics & Chromatin 9:25 (2016), 81–101.
93. Portales-Casamar, E., Mah, S.M., MacIsaac, J.L., Barhdadi, A., Provost, S., Dubé, M.-P., et al. DNA methylation changes in fetal alcohol spectrum disorder. International Journal of Developmental Neuroscience, 47(Pt A), 2015, 126.
94. Ramsay, M., Epigenetic epidemiology: Is there cause for optimism?. Epigenomics 7:5 (2015), 683–685.
95. Reik, W., Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447:7143 (2007), 425–432.
96. Resendiz, M., Mason, S., Lo, C.L., Zhou, F.C., Epigenetic regulation of the neural transcriptome and alcohol interference during development. Frontiers in Genetics, 5, 2014, 285.
97. Reynolds, J.N., Weinberg, J., Clarren, S., Beaulieu, C., Rasmussen, C., Kobor, M., et al. Fetal alcohol spectrum disorders: Gene-environment interactions, predictive biomarkers, and the relationship between structural alterations in the brain and functional outcomes. Seminars in Pediatric Neurology 18:1 (2011), 49–55.
98. Rienecker, K.D.A., Hill, M.J., Isles, A.R., Methods of epigenome editing for probing the function of genomic imprinting. Epigenomics 8:10 (2016), 1389–1398.
99. Rinn, J.L., LncRNAs: Linking RNA to chromatin. Cold Spring Harbor Perspectives in Biology, 6(8), 2014.
100. Rooryck, C., Diaz-Font, A., Osborn, D.P.S., Chabchoub, E., Hernandez-Hernandez, V., Shamseldin, H., et al. Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nature Genetics 43:3 (2011), 197–203.
101. Sandoval, J., Heyn, H.A., Moran, S., Serra-Musach, J., Pujana, M.A., Bibikova, M., et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics 6:6 (2011), 692–702.
102. Sarkar, D.K., Male germline transmits fetal alcohol epigenetic marks for multiple generations: A review. Addiction Biology 21:1 (2016), 23–34.
103. Saxonov, S., Berg, P., Brutlag, D.L., A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proceedings of the National Academy of Sciences of the United States of America 103:5 (2006), 1412–1417.
104. Seisenberger, S., Peat, J.R., Hore, T.A., Santos, F., Dean, W., Reik, W., Reprogramming DNA methylation in the mammalian life cycle: Building and breaking epigenetic barriers. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 368(1609), 2013, 20110330.
105. Shen, Y., Yue, F., McCleary, D.F., Ye, Z., Edsall, L., Kuan, S., et al. A map of the cis-regulatory sequences in the mouse genome. Nature 488:7409 (2012), 116–120.
106. Shukla, P.K., Sittig, L.J., Ullmann, T.M., Redei, E.E., Candidate placental biomarkers for intrauterine alcohol exposure. Alcoholism: Clinical and Experimental Research 35:3 (2011), 559–565.
107. Singh, S.M., Laufer, B.I., Kapalanga, J., Fetal alcohol and the right to be born healthy. Frontiers in Genetics, 5, 2014, 356 (SEP).
108. Sittig, L.J., Shukla, P.K., Herzing, L.B.K., Redei, E.E., Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III. The FASEB Journal 25:7 (2011), 2313–2324.
109. Smith, Z.D., Meissner, A., DNA methylation: Roles in mammalian development. Nature Reviews Genetics 14:3 (2013), 204–220.
110. Spalding, K.L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H.B., et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 153:6 (2013), 1219–1227.
111. Stratton, K., Howe, C., Battaglia, F.C., Fetal alcohol syndrome: Diagnosis, epidemiology, prevention, and treatment. 1996, National Academies Press.
112. Strong, E., Butcher, D.T., Singhania, R., Mervis, C.B., Morris, C.A., De Carvalho, D., et al. Symmetrical dose-dependent DNA-methylation profiles in children with deletion or duplication of 7q11.23. American Journal of Human Genetics 97:2 (2015), 216–227.
113. Suderman, M., McGowan, P.O., Sasaki, A., Huang, T.C.T., Hallett, M.T., Meaney, M.J., et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proceedings of the National Academy of Sciences 109:Suppl 2 (2012), 17266–17272.
114. Suo, L., Lu, H., Ying, G., Capecchi, M.R., Wu, Q., Protocadherin clusters and cell adhesion kinase regulate dendrite complexity through Rho GTPase. Journal of Molecular Cell Biology 4:6 (2012), 362–376.
115. Sweatt, D.J., Meaney, M.J., Nestler, E.J., Akbarian, S., Epigenetic regulation in the nervous System: Basic mechanisms and clinical impact. 2012, Academic Press.
116. Toyoda, S., Kawaguchi, M., Kobayashi, T., Tarusawa, E., Toyama, T., Okano, M., et al. Developmental epigenetic modification regulates stochastic expression of clustered Protocadherin genes, generating single neuron diversity. Neuron 82:1 (2014), 94–108.
117. Vastenhouw, N.L., Schier, A.F., Bivalent histone modifications in early embryogenesis. Current Opinion in Cell Biology 24:3 (2012), 374–386.
118. Veazey, K.J., Parnell, S.E., Miranda, R.C., Golding, M.C., Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects. Epigenetics & Chromatin, 8(1), 2015, 39.
119. Waddington, C.H., Canalization of development and the inheritance of acquired characters. Nature 150:3811 (1942), 563–565.
120. Waddington, C.H., The epigenotype. 1942. International Journal of Epidemiology 41:1 (2012), 10–13.
121. Wallis, R., Mitchell, D.A., Schmid, R., Schwaeble, W.J., Keeble, A.H., Paths reunited: Initiation of the classical and lectin pathways of complement activation. Immunobiology 215:1 (2010), 1–11.
122. Wang, K.-H., Lin, C.-J., Liu, C.-J., Liu, D.-W., Huang, R.-L., Ding, D.-C., et al. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: Serving as diagnostic markers comparable to HPV. Cancer Medicine 4:1 (2015), 43–55.
123. Wang, L.L., Zhang, Z., Li, Q., Yang, R., Pei, X., Xu, Y., et al. Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Human Reproduction 24:3 (2009), 562–579.
124. Williams, A., Flavell, R.A., The role of CTCF in regulating nuclear organization. The Journal of Experimental Medicine 205:4 (2008), 747–750.
125. Williams, L., Jackson, C.P.T., Choe, N., Pelland, L., Scott, S.H., Reynolds, J.N., Sensory-motor deficits in children with fetal alcohol spectrum disorder assessed using a robotic virtual reality platform. Alcoholism: Clinical and Experimental Research 38:1 (2014), 116–125.
126. Williams, J.F., Smith, V.C., Fetal alcohol spectrum disorders. American Academy of Pediatrics 136:5 (2015), e1395–1406.
127. Yasui, D.H., Peddada, S., Bieda, M.C., Vallero, R.O., Hogart, A., Nagarajan, R.P., et al. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proceedings of the National Academy of Sciences of the United States of America 104:49 (2007), 19416–19421.
128. Zeisel, S.H., What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders. Molecular Neurobiology 44:3 (2011), 185–191.
129. Zhang, C.R., Ho, M.-F., Vega, M.C.S., Burne, T.H.J., Chong, S., Prenatal ethanol exposure alters adult hippocampal VGLUT2 expression with concomitant changes in promoter DNA methylation, H3K4 trimethylation and miR-467b-5p levels. Epigenetics & Chromatin, 8(1), 2015, 40.
130. Zhou, F.C., Balaraman, Y., Teng, M., Liu, Y., Singh, R.P., Nephew, K.P., Alcohol alters DNA methylation patterns and inhibits neural stem cell differentiation. Alcoholism: Clinical and Experimental Research 35:4 (2011), 735–746.
131. Zizzo, N., Di Pietro, N., Green, C., Reynolds, J., Bell, E., Racine, E., Comments and reflections on ethics in screening for biomarkers of prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 37:9 (2013), 1451–1455.