Involvement of gene-diet/drug interaction in DNA methylation and its contribution to complex diseases: From cancer to schizophrenia

Clinical Genetics

Volumn 64, Issue 6, 2003, Pages 451-460

  Singh, S M ^a   Murphy, B ^a   O'Reilly, R L ^a  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

Aging; DNA methylation; Epigenetics; Ethnic; Mutations; Nutrition; Polymorphism

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ARYLBUTYRIC ACID DERIVATIVE; AZACITIDINE; BUDESONIDE; CARBOXYPEPTIDASE; CHEMICAL AGENT; CHOLINE; CISPLATIN; CLOZAPINE; CYANOCOBALAMIN; CYTOSINE; DIETHYLNITROSAMINE; DNA; FOLIC ACID; FR 901228; GLUCOSE; HALOPERIDOL; HISTONE; METAL; METHIONINE; METHYL GROUP; N (2 FLUORENYL)ACETAMIDE; PYRIDOXINE; RIBOFLAVIN; TRANSCRIPTION FACTOR; UNINDEXED DRUG; VITAMIN B GROUP; VORINOSTAT; ZINC;

BINDING SITE; CANCER; CHROMATIN; CHROMOSOME; CLINICAL TRIAL; COMPLEX FORMATION; DEACETYLATION; DIETARY INTAKE; DNA METHYLATION; ENVIRONMENTAL FACTOR; GENE EXPRESSION; GENE INTERACTION; GENE SILENCING; GENETIC REGULATION; GENETIC STABILITY; GENOME ANALYSIS; HEREDITY; HUMAN; MATERNAL NUTRITION; MULTIFACTORIAL GENETIC DISORDER; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; SCHIZOPHRENIA; SHORT SURVEY;

DIET; DNA METHYLATION; FEMALE; FOOD-DRUG INTERACTIONS; GENE EXPRESSION REGULATION; HUMANS; MATERNAL NUTRITION PHYSIOLOGY; NEOPLASMS; PREGNANCY; S-ADENOSYLHOMOCYSTEINE; S-ADENOSYLMETHIONINE; SCHIZOPHRENIA;

EID: 0345602849     PISSN: 00099163     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1399-0004.2003.00190.x     Document Type: Short Survey

References (124)

1. Bird AP. CpG-rich islands and the function of DNA methylation. Nature 1986: 321: 209-213.
2. Jones PA, Rideout WM 3rd, Shen JC, Spruck CH, Tsai YC. Methylation, mutation and cancer. Bioessays 1992: 14 (1): 53-57.
3. Larsen F, Gundersen G, Lopez R, Prydz H. CpG islands as gene markers in the human genome. Genomics 1992: 13 (4): 1095-1107.
4. Chen T, Ueda Y, Dodge JE, Wang J, Li E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol Cell Biol 2003: 23 (16): 5594 5605.
5. Rampersaud GC, Kauwell GP, Hutson AD et al. Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am J Clin Nutr 2000: 72: 998-1003.
6. Ono T, Uehara Y, Kurishita A et al. Biological significance of DNA methylation in the aging process. Age Ageing 1993: 22: S34-S43.
7. Rath PC, Kanungo MS. Methylation of repetitive DNA sequences in the brain during aging of the rat. FEBS Lett 1989: 244: 193-198.
8. Ono T, Shinya K, Uehara Y et al. Endogenous virus genomes become hypomethylated tissue-specifically during aging process of C57BL mice. Mech Ageing Dev 1989: 50: 27-36.
9. Singhal RP, Mays-Hoopes LL, Eichhorn GL. DNA methylation in aging of mice. Mech Ageing Dev 1987: 41: 199-210.
10. Issa JP, Ottaviano YL, Celano P et al. Methylation of the oestrogen receptor CpG island links aging and neoplasia in human colon. Nat Genet 1994: 7: 536-540.
11. Toyota M, Ahuja N, Ohe-Toyota M et al. CpG island methylator phenotype in colorectal cancer. PNAS 1999: 96: 8681-8686.
12. Issa JP. CpG-island methylation in aging and cancer. Curr Top Microbiol Immunol 2000: 249: 101-118.
13. Weindruch R, Kayo T, Lee CK, Prolla TA. Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J Nutr 2001: 131: 918S-923S.
14. Richardson BC. Role of DNA methylation in the regulation of cell function: autoimmunity, aging and cancer. J Nutr 2002: 132: 2401S-2405S.
15. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001: 410: 227-230.
16. Johnston JM, Kredich MN. Inhibition of methylation by adenosine in adenosine deaminase-inhibited, phytohemagglutinin-stimulated human lymphocytes. J Immunol 1979: 123: 97-103.
17. Varela-Moreiras G, Perez-Olleros L, Garcia-Cuevas M, Ruiz-Poso B. Effects of aging on folate metabolism in rats fed a long-term folate deficient diet. Int J Vitam Nutr Res 1994: 64: 294-299.
18. Brown R, Strathdee G. Epigenomics and epigenetic therapy of cancer. Trends Mol Med 2002: 8 (4): S43-S48.
19. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 1992: 69: 915-926.
20. Bestor TH. The host defense function of genomic methylation patterns. Novartis Found Symp 1998: 214: 187-195.
21. Whitelaw F, Martin DI. Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nat Genet 2001: 27: 361-365.
22. Sado T, Fenner MH, Tan SS et al. X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random) X inactivation. Dev Biol 2000: 225: 294-303.
23. Davis TL, Tremblay KD, Bartolomei MS. Imprinted expression and methylation of the mouse H19 gene are conserved in extraembryonic lineages. Dev Genet 1998: 23: 111-118.
24. Pogribny IP, Basnakian AG, Miller BJ et al. Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl-deficient rats. Cancer Res 1995: 55: 1894-1901.
25. Litz CE, Etzell J. Aberrant DNA methylation of genomic regions translocated in myeloid malignancies. Leuk Lymphoma 1998: 30: 1-9.
26. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969: 56: 111-128.
27. Kang SS, Wong PW, Susmano A et al. Thermolabile methylenetretrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 1991: 48: 536-545.
28. Nishimura M, Yoshimo K, Tomita Y et al. Central and peripheral nervous system pathology of homocystinuria due to 5,10 methylenetetrahydrofolate reductase deficiency. Pediatr Neurol 1985: 1: 375-378.
29. Amir RE, Van den Veyver IB, Wan M et al. Rett syndrome is caused by mutations in X-linked MeCP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999: 23: 185-188.
30. Hansen RS, Wijmenga C, Luo P et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. PNAS 1999: 96: 14412-14417.
31. Albrecht U, Sutcliffe JS, Cattanach BM et al. Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat Genet 1997: 17: 75-78.
32. Van den Veyver IB. Genetic effects of methylation diets. Annu Rev Nutr 2002: 22: 255-282.
33. Institute of Medicine, National Academy of Sciences USA. Dietary reference intakes for folate, thiamin, riboflavin, niacin, vitamin B12, panthothenic acid, biotin, and choline, Vol. 1. Washington, DC: National Academy Press, 1998.
34. Mato JM, Alvarez L, Ortiz P, Pajares MA. S-adenosyl-methionine synthesis: molecular mechanisms and clinical implications. Pharmacol Ther 1997: 73: 265-280.
35. Cai J, Mao Z, Hwang JJ, Lu SC. Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells. Cancer Res 1998: 58: 1444-1450.
36. Wainfan E, Dizik M, Stender M, Christman J. Rapid appearance of hypomethylated DNA in livers of rats fed cancer promoting, methyl-deficient diets. Cancer Res 1989: 49: 4094-4097.
37. Vachtenheim J, Horakova I, Novotna H. Hypomethylation of CCGG sites in the 3′ region of H-ras protooncogene is frequent and is associated with H-ras allele loss in non-small cell lung cancer. Cancer Res 1994: 54: 1145-1148.
38. Lu SC, Huang ZZ, Yang H et al. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am J Physiol Gastrointest Liver Physiol 2000: 279: G178-G185.
39. Richardson B, Scheinbart L, Strahler J et al. Evidence for impaired T cell DNA methylation in systemic lupus erthematosus and rheumatoid arthritis. Arthritis Rheum 1990: 33: 1665-1673.
40. Deng C, Kaplan MJ, Yang J et al. Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum 2001: 44: 397-407.
41. Friso S, Choi SW. Gene-nutrient interactions and DNA methylation. J Nutr 2002: 132: 2382S-2387S.
42. Furumai R, Matsuyama A, Kobashi N et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002: 62 (17): 4916-4921.
43. Tsujiuchi T, Tsutsumi M, Sasaki Y et al. Hypomethylation of CpG sites and c-myc gene overexpression in hepatocellular carcinomas, but not hyperplastic nodules, induced by a choline-deficient 1-amino acid-defined diet in rats. Jpn J Cancer Res 1999: 90: 909-1295.
44. Jhaveri MS, Wagner C, Trepel JB. Impact of extracellular folate levels on global gene expression. Mol Pharmacol 2001: 60: 1288-1295.
45. Van der Put NM, Gabreels F, Stevens EM et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998: 62: 1044-1051.
46. Christensen B, Arbour L, Tran P et al. Genetic polymorphism in methylenetetrahydrofolate reductase and methionine synthetase, folate levels in red blood cells and risk of neural tube defects. Am J Med Genet 1999: 84: 151-157.
47. Yamada K, Chen ZM, Rozen R, Matthews RG. Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase. Pros Natl Acad Sci USA 2001: 98 (26): 14853-14858.
48. Stover PJ, Garza C. Bringing individuality to public health recommendations. J Nutr 2002: 132: 2476S-2480S.
49. Ma J, Stampfer MJ, Giovannucci E et al. Methylenetetrahydrofolate reductase polymorphism, dietary interaction, risk of colorectal cancer. Cancer Res 1997: 57: 1098-1102.
50. James SJ, Pogribna M, Pogribny IP et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 1999: 70: 495-501.
51. Lievers KJA, Kluijtman LAJ, Boers GHJ et al. Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561X→T) on plasma homocysteine, folate and vitamin B12 levels and its relationship to cardiovascular disease risk. Atherosclerosis 2002: 164: 269-273.
52. Devlin AM, Ling EH, Peerson JM et al. Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Hum Mol Genet 2000: 9: 2837-2844.
53. Bailey LB, Gregory JF. Polymorphisms of methylemetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirements. J Nutr 1999: 129: 919-922.
54. Waterland RA, Garza C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr 1999: 69: 179-197.
55. Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 1996: 295: 349-353.
56. Leon DA, Ben-Shlomo Y. A life-course approach to chronic disease epidemiology. Oxford, United Kingdom: Oxford University Press, 1997: 45-77.
57. Curhan GC, Chertow GM, Willett WC et al. Birth weight and adult hypertension and obesity in women. Circulation 1996: 94: 1310-1315.
58. McKeigue PM. Diabetes and insulin action. In: A Life-Course Approach to Chronic Disease Epidemiology (Kuh D, Ben-Shlomo Y, eds). Oxford, United Kingdom: Oxford University Press, 1997:78-100.
59. Lucas A. Programming by early nutrition in man. Ciba Found Symp 1981: 156: 38-50.
60. Cooney CA, Dave AA, Wolff GL. Maternal methyl supplements in mice affect epigenetic variation and DNA methylation of offspring. J Nutr 2002: 132: 2393S-2400S.
61. Waterland RA, Jirtle RL. Transposable Elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 2003: 23 (15): 5293-5300.
62. Nyce JW. Drug-induced DNA hypermethylation: a potential mediator of acquired drug resistance during cancer chemotherapy. Mutat Res 1997: 386: 153-161.
63. Tao L, Li Y, Wang W et al. Effect of budesonide on the methylation and mRNA expression of the insulin-like growth factor 2 and c-myc genes in mouse lung tumors. Mol Carcinog 2002: 35: 93-102.
64. Cameron EE et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999: 21: 103-107.
65. Poirier LA. The effects of diet, genetics and chemicals on toxicity and aberrant DNA methylation: an introduction. J Nutr 2002: 132: 2336S-2339S.
66. Hillman RS, Steinberg SE. The effects of alcohol on folate metabolism. Annu Rev Med 1982: 33: 345-354.
67. Li S, Washburn KA, Moore R et al. Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus. Cancer Res 1997: 57 (19): 4356-4359.
68. Cornacchia E, Golbus J, Maybaum J et al. Hydralazind and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol 1988: 140: 2197-2200.
69. Khaled MA, Watkins CL, Krumdieck CL. Inactivation of B-12 and folate coenzymes by butyl nitrite as observed by NMR. implications on one-carbon transfer mechanism. Biochem Biophys Res Commun 1986: 135: 201-207.
70. Trans HHS. Workshop: diet, DNA methylation processes and health. J Nutr 2001: 132: 8S: 2329S-2484S.
71. Costello JF, Plass C. Methylation matters. J Med Genet 2001: 38: 285-303.
72. Hedenfalk I, Duggan D, Chen Y et al. Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001: 344 (8): 539-548.
73. Kim YI. Folate and cancer prevention. a new medical application of folate beyond hyperhomocysteinemia and neural tube defects. Nutr Rev 1999: 57 (10): 314-321.
74. Marks P, Rifkind RA, Richon VM et al. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 2001: 1 (3): 194-202.
75. Torrey EF, Miller J, Rawlings R, Yolken RH. Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr Res 1997: 28: 1-38.
76. Mednick SA, Machon RA, Huttunen MO, Bonett D. Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychol 1988: 45 (2): 189-192.
77. Karlsson H, Bachmann S, Schroder J, McArthur J, Torrey EF, Yolken RH. Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. PNAS 2001: 98 (8): 4634-4639.
78. Jablensky A. Epidemiology of schizophrenia: the global burden of disease and disability. Eur Arch Psychiatry Clin Neurosci 2000: 250: 274-285.
79. Hallmayer J. The epidemiology of the genetic liability of schizophrenia. Aust N Z J Psychiatry 2000: 34 (Suppl.): S47-S55.
80. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ et al. Heritability estimates for psychotic disorders: The Maudsley twin psychosis series. Arch Gen Psychiatry 1999: 56: 162-168.
81. Tienari PJ, Wynne LC. Adoption studies of schizophrenia. Ann Med 1994: 26 (4): 233-237.
82. Fischer M. Genetic and environmental factors in schizophrenia: a study of schizophrenic twins and their families. Acta Psychiatr Scand 1973: 238 (Suppl.): 1-158.
83. Franzek E, Beckmann H. Different genetic background of schizophrenia spectrum psychosis: a twin study. Am J Psychol 1998: 155: 76-83.
84. Kringlen E, Cramer G. Offspring of monozygotic twins discordant for schizophrenia. Arch Gen Psychiatry 1989: 46: 873-877.
85. Sherman SL, DeFries JC et al. Recent developments in human behavioural genetics: past accomplishments and future directions. Am J Hum Genet 1997: 60: 1265-1275.
86. Albright CD, Tsai AY, Friedrich CB et al. Choline availability alters embryonic development of the hippocampus and septum in the rat. Brain Res Dev Brain Res 1999: 113: 13-20.
87. Albright CD, Friedrich CB, Brown EC et al. Maternal dietary choline availability alters mitosis, apoptosis and the localization of TOAD-64 protein in the developing fetal rat septum. Brain Res Dev Brain Res 1999: 115: 123-129.
88. Moyers S, Bailey LB. Fetal malformations and folate metabolism: review of recent evidence. Nutr Rev 2001: 59: 215-224.
89. Coy JF, Sedlacek Z, Bachne D et al. A complex pattern of evolutionary conservation and alternative polyadenylation within the long-3′ untranslated region of the methyl-CpG-binding protein 2 gene (MeCP2) suggests a regulatory role in gene expression. Hum Mol Genet 1999: 8 (7): 1253-1262.
90. Shahbazian MD, Antalffy B, Armstrong DL et al. Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 2002: 15: 115-124.
91. Lam CW, Yeung WL, Ko CH et al. Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. J Med Genet 2000: 37: E41.
92. Couvert P, Bienvenu T, Aquaviva C et al. MECP2 is highly mutated in X-linked mental retardation. Hum Mol Genet 2001: 10 (9): 941-946.
93. Hendrich B, Guy J, Ramsahoye B et al. Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev 2001: 15: 710-723.
94. Chen Z, Karaplis AC, Ackerman SL et al. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 2001: 10: 433-443.
95. Botez MI, Young SN, Bachevalier J et al. Folate deficiency and decreased brain 5-hydroxtryptamine synthesis in man and rat. Nature 1979: 278: 182-183.
96. Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984: 2: 196-198.
97. Bottiglieri T, Laundy M, Crellin R et al. Homocysteine, folate, methylation and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000: 69: 228-232.
98. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademethionine (S-adenosylmethionine) in neurological disorders. Drugs 1994: 48: 137-152.
99. Gomes-Trolin C, Yassin M, Gottfries CG et al. Erythrocyte and brain methionine adenosyltransferase activities in patients with schizophrenia. J Neural Transm 1998: 105 (10-12): 1293-1305.
100. Regland B, Germgard T, Gottfries CG et al. Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis. J Neural Transm 1997: 104 (8 and 9): 931-941.
101. Regland B, Johansson BV, Gottfries CG. Homocysteinemia and schizophrenia as a case of methylation deficiency. J Neural Transm General Sect 1994: 98 (2): 143-152.
102. Regland B, Johansson BV, Grenfeldt B et al. Homocysteinemia is a common feature of schizophrenia. J Neural Transm Gen Sect 1995: 100 (2): 165-169.
103. Clarke S, Banfield K. S-adenosylmethionine-dependent methyltransferases. In: Homocysteine in Health and Disease (Carmel R, Jacobson DW, eds). Oxford, UK: Cambridge Press, 2001: 63-78.
104. Zeisel SH, Blusztajn JK. Choline and human nutrition. Annu Rev Nutr 1994: 14: 269-296.
105. Meck WH, Smith RA, Williams CL. Pre- and postnatal choline supplementation produces long-term facilitation of special memory. Dev Psychobiol 1998: 21: 339-353.
106. Mirnics K, Middleton FA, Marquez A et al. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000: 28 (1): 53-67.
107. Hakak Y, Walker J R, Li C et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. PNAS 2001: 98 (8): 4746-4751.
108. Bahn S, Augood SJ, Ryan M et al. Gene expression profiling in the post-mortem human brain-no cause for dismay. J Chem Neuroanat 2001: 22 (1 and 2): 79-94.
109. Mirnics K, Middleton FA, Lewis DA, Levitt P. Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse. Trends Neurosci 2001: 24 (8): 479-486.
110. Vawter MP, Crook JM, Hyde TM et al. Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Schizophr Res 2002: 58 (1): 11-20.
111. Pongrac J, Middleton FA, Lewis DA et al. Gene expression profiling with DNA microarrays: advancing our understanding of psychiatric disorders. Neurochem Res 2002: 27 (10): 1049-1063.
112. Tsujita T, Niikawa N, Yamashita H. Genomic discordance between monozygotic twins discordant for schizophrenia. Am J Psychol 1998: 155: 422-424.
113. McDonald P, Lewis M, Murphy B, O'Reilly R, Singh SM. Appraisal of genetic and epigenetic congruity of a monozygotic twin pair discordant for schizophrenia. J Med Genet 2003: 40 (2): E16.
114. Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 2000: 26: 219-225.
115. O'Connor DL. Interaction of iron and folate during reproduction. Prog Food Nutr Sci 1991: 15: 231-254.
116. Issa JP, Vertino PM, Boehm CD et al. Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. PNAS 1996: 93 (21): 11757-11762.
117. Stancheva I, Meehan RR. Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. Genes Dev 2000: 14: 313-327.
118. Hobbs CA, Sherman SL, Yi P et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet 2000: 67: 623-630.
119. Baylin SB, Herman JG, Graff JR et al. Alterations in DNA methylation: a fundamental aspect of neoplasm. Adv Cancer Res 1998: 72: 141-196.
120. Christman JK, Sheikhnejad G, Dizik M et al. Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency. Carcinogenesis 1993: 14 (4): 551-557.
121. Sohn K, Stempak JM, Reid S et al. The effect of dietary folate on genomic and p53-specific DNA methyaltion in rat colon. Carcinogenesis 2003: 24 (1): 81-90.
122. Petronis A, Paterson AD, Kennedy JL. Schizophrenia: an epigenetic puzzle? Schizophr Bull 1999: 25 (4): 639-655.
123. Singh SM, Murphy B, O'Reilly R. Epigenetic contributors to the discordance of monozygotic twins. Clin Genet 2002: 62: 97-103.
124. Singh SM, Murphy B, O'Reilly R. Monozygotic twins with chromosome 22q11 deletion and discordant phenotypes: updates with an epitgenetic hypothesis. J Med Genet 2002: 39: e71.