1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genomics and Human Genetics
  4. Volume 5, 2004
  5. Article

Annual Review of Genomics and Human Genetics

Volume 5, 2004

EPIGENETICS AND HUMAN DISEASE

Abstract

▪ Abstract 

Epigenetics is comprised of the stable and heritable (or potentially heritable) changes in gene expression that do not entail a change in DNA sequence. The role of epigenetics in the etiology of human disease is increasingly recognized with the most obvious evidence found for genes subject to genomic imprinting. Mutations and epimutations in imprinted genes can give rise to genetic and epigenetic phenotypes, respectively; uniparental disomy and imprinting defects represent epigenetic disease phenotypes. There are also genetic disorders that affect chromatin structure and remodeling. These disorders can affect chromatin in or in , as well as expression of both imprinted and nonimprinted genes. Data from Angelman and Beckwith-Wiedemann syndromes and other disorders indicate that a monogenic or oligogenic phenotype can be caused by a mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model. The MEGDI model may apply to some complex disease traits and could explain negative results in genome-wide genetic scans.

Keyword(s): chromatin remodeling, complex traits, DNA methylation, genomic imprinting
Loading

Article metrics loading...

/content/journals/10.1146/annurev.genom.5.061903.180014
2004-09-22
2024-05-18
Loading full text...

Full text loading...

/deliver/fulltext/gg/5/1/annurev.genom.5.061903.180014.html?itemId=/content/journals/10.1146/annurev.genom.5.061903.180014&mimeType=html&fmt=ahah

Literature Cited

  1. Albrecht U, Sutcliffe JS, Cattanach BM, Beechey CV, Armstrong D. et al. 1997. Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat. Genet. 17:75–78 [Google Scholar]
  2. Allshire R. 2002. Molecular biology. RNAi and heterochromatin–a hushed-up affair Science 297:1818–19 [Google Scholar]
  3. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. 1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23:185–88 [Google Scholar]
  4. Ausio J, Levin DB, De Amorim GV, Bakker S, MacLeod PM. 2003. Syndromes of disordered chromatin remodeling. Clin. Genet. 64:83–95 [Google Scholar]
  5. Bandyopadhyay D, Medrano EE. 2003. The emerging role of epigenetics in cellular and organismal aging. Exp. Gerontol. 38:1299–307 [Google Scholar]
  6. Bartolomei MS, Webber AL, Brunkow ME, Tilghman SM. 1993. Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 7:1663–73 [Google Scholar]
  7. Beaudet AL. 2002. Is medical genetics neglecting epigenetics. Genet. Med. 4:399–402 [Google Scholar]
  8. Beaudet AL, Jiang J. 2002. A rheostat model for a rapid and reversible form of imprinting-dependent evolution. Am. J. Hum. Genet. 70:1389–97 [Google Scholar]
  9. Becker PB, Horz W. 2002. ATP-dependent nucleosome remodeling. Annu. Rev. Biochem. 71:247–73 [Google Scholar]
  10. Bell AC, West AG, Felsenfeld G. 1999. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98:387–96 [Google Scholar]
  11. Bestor TH, Tycko B. 1996. Creation of genomic methylation patterns. Nat. Genet. 12:363–67 [Google Scholar]
  12. Bickmore WA, van der Maarel SM. 2003. Perturbations of chromatin structure in human genetic disease: recent advances. Hum. Mol. Genet. 12:R207–13 [Google Scholar]
  13. Bird A. 2001. Molecular biology. Methylation talk between histones and DNA Science 294:2113–15 [Google Scholar]
  14. Boumil RM, Lee JT. 2001. Forty years of decoding the silence in X-chromosome inactivation. Hum. Mol. Genet. 10:2225–32 [Google Scholar]
  15. Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH. 2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–39 [Google Scholar]
  16. Bray NJ, Buckland PR, Owen MJ, O'Donovan MC. 2003. Cis-acting variation in the expression of a high proportion of genes in human brain. Hum. Genet. 113:149–53 [Google Scholar]
  17. Brehm A, Tufteland KR, Aasland R, Becker PB. 2004. The many colours of chromodomains. Bioessays 26:133–40 [Google Scholar]
  18. Buiting K, Gross S, Lich C, Gillessen-Kaesbach G, El Maarri O, Horsthemke B. 2003. Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am. J. Hum. Genet. 72:571–77 [Google Scholar]
  19. Cassidy S, Dykens E, Williams C. 2000. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am. J. Med. Genet. 97:136–46 [Google Scholar]
  20. Cattanach BM, Beechey CV. 1990. Autosomal and X-chromosome imprinting. Development (Suppl.)63–72 [Google Scholar]
  21. Cattanach BM, Kirk M. 1985. Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315:496–98 [Google Scholar]
  22. Chao W, Huynh KD, Spencer RJ, Davidow LS, Lee JT. 2002. CTCF, a candidate trans-acting factor for X-inactivation choice. Science 295:345–47 [Google Scholar]
  23. Chen CZ, Li L, Lodish HF, Bartel DP. 2004. MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86 [Google Scholar]
  24. Chen WG, Chang Q, Lin Y, Meissner A, West AE. et al. 2003. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302:885–89 [Google Scholar]
  25. Chen Z, Karaplis AC, Ackerman SL, Pogribny IP, Melnyk S. et al. 2001. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum. Mol. Genet. 10:433–43 [Google Scholar]
  26. Chess A. 1998. Expansion of the allelic exclusion principle. Science 279:2067–68 [Google Scholar]
  27. Clayton-Smith J. 2003. Genomic imprinting as a cause of disease. Br. Med. J. 327:1121–22 [Google Scholar]
  28. Coffee B, Zhang F, Ceman S, Warren ST, Reines D. 2002. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am. J. Hum. Genet. 71:923–32 [Google Scholar]
  29. Coffee B, Zhang F, Warren ST, Reines D. 1999. Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nat. Genet. 22:98–101 [Google Scholar]
  30. Constancia M, Pickard B, Kelsey G, Reik W. 1998. Imprinting mechanisms. Genome Res. 8:881–900 [Google Scholar]
  31. Cox GF, Burger J, Lip V, Mau UA, Sperling K. et al. 2002. Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am. J. Hum. Genet. 71:162–64 [Google Scholar]
  32. Cui H, Cruz-Correa M, Giardiello FM, Hutcheon DF, Kafonek DR. et al. 2003. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science 299:1753–55 [Google Scholar]
  33. D'Esposito M, Ciccodicola A, Gianfrancesco F, Esposito T, Flagiello L. et al. 1996. A synaptobrevin-like gene in the Xq28 pseudoautosomal region undergoes X inactivation. Nat. Genet. 13:227–29 [Google Scholar]
  34. DeBaun MR, Niemitz EL, Feinberg AP. 2003. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet. 72:156–60 [Google Scholar]
  35. DeChiara TM, Robertson EJ, Efstratiadis A. 1991. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–59 [Google Scholar]
  36. Dennis C. 2003. Epigenetics and disease: altered states. Nature 421:686–88 [Google Scholar]
  37. Eddy SR. 2001. Non-coding RNA genes and the modern RNA world. Nat. Rev. Genet. 2:919–29 [Google Scholar]
  38. Engel E, Antonarakis SE. 2002. Genomic Imprinting and Uniparental Disomy in Medicine: Clinical and Molecular Aspects New York: Wiley-Liss
  39. Ensminger AW, Chess A. 2004. Coordinated replication timing of monoallelically expressed genes along human autosomes. Hum. Mol. Genet. 13:651–58 [Google Scholar]
  40. Feil R, Walter J, Allen ND, Reik W. 1994. Developmental control of allelic methylation in the imprinted mouse Igf2 and H19 genes. Development 120:2933–43 [Google Scholar]
  41. Felsenfeld G, Groudine M. 2003. Controlling the double helix. Nature 421:448–53 [Google Scholar]
  42. Ferguson-Smith AC, Sasaki H, Cattanach BM, Surani MA. 1993. Parental-origin-specific epigenetic modification of the mouse H19 gene. Nature 362:751–55 [Google Scholar]
  43. Fernandez-Funez P, Nino-Rosales ML, de Gouyon B, She WC, Luchak JM. et al. 2000. Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408:101–6 [Google Scholar]
  44. Ferrante RJ, Kubilus JK, Lee J, Ryu H, Beesen A. et al. 2003. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J. Neurosci. 23:9418–27 [Google Scholar]
  45. Fournier C, Goto Y, Ballestar E, Delaval K, Hever AM. et al. 2002. Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes. EMBO J. 21:6560–70 [Google Scholar]
  46. Friso S, Choi SW, Girelli D, Mason JB, Dolnikowski GG. et al. 2002. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc. Natl. Acad. Sci. USA 99:5606–11 [Google Scholar]
  47. Gibbons RJ, McDowell TL, Raman S, O'Rourke DM, Garrick D. et al. 2000. Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat. Genet. 24:368–71 [Google Scholar]
  48. Gibbons RJ, Pellagatti A, Garrick D, Wood WG, Malik N. et al. 2003. Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat. Genet. 34:446–49 [Google Scholar]
  49. Grosveld F. 1999. Activation by locus control regions. Curr. Opin. Genet. Dev. 9:152–57 [Google Scholar]
  50. Gruenbaum Y, Cedar H, Razin A. 1982. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature 295:620–22 [Google Scholar]
  51. Hajkova P, Erhardt S, Lane N, Haaf T, El Maarri O. et al. 2002. Epigenetic reprogramming in mouse primordial germ cells. Mech. Dev. 117:15–23 [Google Scholar]
  52. Hall JG. 1990. How imprinting is relevant to human disease. Development (Suppl.)141–48 [Google Scholar]
  53. Hall JG. 1997. Genomic imprinting: nature and clinical relevance. Annu. Rev. Med. 48:35–44 [Google Scholar]
  54. Hammer S, Dorrani N, Dragich J, Kudo S, Schanen C. 2002. The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome. Ment. Retard. Dev. Disabil. Res. Rev. 8:94–98 [Google Scholar]
  55. Hampsey M, Reinberg D. 2003. Tails of intrigue: phosphorylation of RNA polymerase II mediates histone methylation. Cell 113:429–32 [Google Scholar]
  56. Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK. et al. 1999. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc. Natl. Acad. Sci. USA 96:14412–17 [Google Scholar]
  57. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. 2000. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–89 [Google Scholar]
  58. Hata K, Okano M, Lei H, Li E. 2002. Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice. Development 129:1983–93 [Google Scholar]
  59. Hekimi S, Guarente L. 2003. Genetics and the specificity of the aging process. Science 299:1351–54 [Google Scholar]
  60. Hendrich B, Bickmore W. 2001. Human diseases with underlying defects in chromatin structure and modification. Hum. Mol. Genet. 10:2233–42 [Google Scholar]
  61. Hendrich B, Bird A. 1998. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol. Cell Biol. 18:6538–47 [Google Scholar]
  62. Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A. 2001. Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev. 15:710–23 [Google Scholar]
  63. Herbert A. 2004. The four Rs of RNA-directed evolution. Nat. Genet. 36:19–25 [Google Scholar]
  64. Hermann A, Schmitt S, Jeltsch A. 2003. The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J. Biol. Chem. 278:31717–21 [Google Scholar]
  65. Hodges MD, Rees HC, Seckl MJ, Newlands ES, Fisher RA. 2003. Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J. Med. Genet. 40:e95 [Google Scholar]
  66. Holliday R. 1994. Epigenetics: an overview. Dev. Genet. 15:453–57 [Google Scholar]
  67. Holliday R. 2002. Epigenetic mechanisms of gene regulation. ed. V Russo, RA Martienssen, AD Riggs pp.5–27 Cold Spring Harbor, NY: Cold Spring Harbor Press [Google Scholar]
  68. Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C. et al. 2001. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell 104:829–38 [Google Scholar]
  69. Huang C, Sloan EA, Boerkoel CF. 2003. Chromatin remodeling and human disease. Curr. Opin. Genet. Dev. 13:246–52 [Google Scholar]
  70. Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG. et al. 2003. Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 361:1693–99 [Google Scholar]
  71. Ishizuka A, Siomi MC, Siomi H. 2002. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 16:2497–508 [Google Scholar]
  72. Issa JP, Baylin SB. 1996. Epigenetics and human disease. Nat. Med. 2:281–82 [Google Scholar]
  73. Jaenisch R, Bird A. 2003. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33:(Suppl.)245–54 [Google Scholar]
  74. Jenuwein T, Allis CD. 2001. Translating the histone code. Science 293:1074–80 [Google Scholar]
  75. Jin P, Zarnescu DC, Ceman S, Nakamoto M, Mowrey J. et al. 2004. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat. Neurosci. 7:113–17 [Google Scholar]
  76. Jirtle RL, Sander M, Barrett JC. 2000. Genomic imprinting and environmental disease susceptibility. Environ. Health Perspect. 108:271–78 [Google Scholar]
  77. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU. et al. 1998. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat. Genet. 19:187–91 [Google Scholar]
  78. Judson H, Hayward BE, Sheridan E, Bonthron DT. 2002. A global disorder of imprinting in the human female germ line. Nature 416:539–42 [Google Scholar]
  79. Kaati G, Bygren LO, Edvinsson S. 2002. Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur. J. Hum. Genet. 10:682–88 [Google Scholar]
  80. Kan PX, Popendikyte V, Kaminsky ZA, Yolken RH, Petronis A. 2004. Epigenetic studies of genomic retroelements in major psychosis. Schizophr. Res. 67:95–106 [Google Scholar]
  81. Kearns M, Preis J, McDonald M, Morris C, Whitelaw E. 2000. Complex patterns of inheritance of an imprinted murine transgene suggest incomplete germline erasure. Nucleic Acids Res. 28:3301–9 [Google Scholar]
  82. Kleinjan DA, van Heyningen V. 2003. Turned off by RNA. Nat. Genet. 34:125–26 [Google Scholar]
  83. Kleinjan DJ, van Heyningen V. 1998. Position effect in human genetic disease. Hum. Mol. Genet. 7:1611–18 [Google Scholar]
  84. Lachner M, Jenuwein T. 2002. The many faces of histone lysine methylation. Curr. Opin. Cell Biol. 14:286–98 [Google Scholar]
  85. Lachner M, O'Sullivan RJ, Jenuwein T. 2003. An epigenetic road map for histone lysine methylation. J. Cell Sci. 116:2117–24 [Google Scholar]
  86. Lane N, Dean W, Erhardt S, Hajkova P, Surani A. et al. 2003. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88–93 [Google Scholar]
  87. Lauritsen M, Ewald H. 2001. The genetics of autism. Acta Psychiatr. Scand. 103:411–27 [Google Scholar]
  88. Lawler SD. 1984. Genetic studies on hydatidiform moles. Adv. Exp. Med. Biol. 176:147–61 [Google Scholar]
  89. Lee J, Inoue K, Ono R, Ogonuki N, Kohda T. et al. 2002. Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129:1807–17 [Google Scholar]
  90. Levine MA, Germain-Lee E, Jan dB. 2003. Genetic basis for resistance to parathyroid hormone. Horm. Res. 60:(Suppl.) 387–95 [Google Scholar]
  91. Li E, Beard C, Jaenisch R. 1993. Role for DNA methylation in genomic imprinting. Nature 366:362–65 [Google Scholar]
  92. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–26 [Google Scholar]
  93. Li E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3:662–73 [Google Scholar]
  94. Lin SP, Youngson N, Takada S, Seitz H, Reik W. et al. 2003. Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat. Genet. 35:97–102 [Google Scholar]
  95. Lo HS, Wang Z, Hu Y, Yang HH, Gere S. et al. 2003. Allelic variation in gene expression is common in the human genome. Genome Res. 13:1855–62 [Google Scholar]
  96. Lusser A, Kadonaga JT. 2003. Chromatin remodeling by ATP-dependent molecular machines. Bioessays 25:1192–200 [Google Scholar]
  97. Maher ER, Afnan M, Barratt CL. 2003. Epigenetic risks related to assisted reproductive technologies: epigenetics, imprinting, ART and icebergs. Hum. Reprod. 18:2508–11 [Google Scholar]
  98. Martinowich K, Hattori D, Wu H, Fouse S, He F. et al. 2003. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302:890–93 [Google Scholar]
  99. Matarazzo MR, De Bonis ML, Gregory RI, Vacca M, Hansen RS. et al. 2002. Allelic inactivation of the pseudoautosomal gene SYBL1 is controlled by epigenetic mechanisms common to the X and Y chromosomes. Hum. Mol. Genet. 11:3191–98 [Google Scholar]
  100. Mattick JS. 2003. Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25:930–39 [Google Scholar]
  101. Matzke MA, Matzke AJ, Pruss GJ, Vance VB. 2001. RNA-based silencing strategies in plants. Curr. Opin. Genet. Dev. 11:221–27 [Google Scholar]
  102. McCampbell A, Taye AA, Whitty L, Penney E, Steffan JS, Fischbeck KH. 2001. Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc. Natl. Acad. Sci. USA 98:15179–84 [Google Scholar]
  103. McGrath J, Solter D. 1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37:179–83 [Google Scholar]
  104. McKittrick E, Gafken PR, Ahmad K, Henikoff S. 2004. Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc. Natl. Acad. Sci. USA 101:1525–30 [Google Scholar]
  105. Michaud EJ, van Vugt MJ, Bultman SJ, Sweet HO, Davisson MT, Woychik RP. 1994. Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev. 8:1463–72 [Google Scholar]
  106. Migeon BR, Luo S, Jani M, Jeppesen P. 1994. The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation. Am. J. Hum. Genet. 55:497–504 [Google Scholar]
  107. Morison IM, Reeve AE. 1998. A catalogue of imprinted genes and parent-of-origin effects in humans and animals. Hum. Mol. Genet. 7:1599–609 [Google Scholar]
  108. Mostoslavsky R, Singh N, Tenzen T, Goldmit M, Gabay C. et al. 2001. Asynchronous replication and allelic exclusion in the immune system. Nature 414:221–25 [Google Scholar]
  109. Nakao M. 2001. Epigenetics: interaction of DNA methylation and chromatin. Gene 278:25–31 [Google Scholar]
  110. Nan X, Meehan RR, Bird A. 1993. Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res. 21:4886–92 [Google Scholar]
  111. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM. et al. 1998. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–89 [Google Scholar]
  112. Neves G, Zucker J, Daly M, Chess A. 2004. Stochastic yet biased expression of multiple Dscam splice variants by individual cells. Nat. Genet. 36:240–46 [Google Scholar]
  113. Ng HH, Bird A. 1999. DNA methylation and chromatin modification. Curr. Opin. Genet. Dev. 9:158–63 [Google Scholar]
  114. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM. et al. 1999. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat. Genet. 23:58–61 [Google Scholar]
  115. Okano M, Bell DW, Haber DA, Li E. 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–57 [Google Scholar]
  116. Okano M, Xie S, Li E. 1998. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet. 19:219–20 [Google Scholar]
  117. Okano M, Xie S, Li E. 1998. Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res. 26:2536–40 [Google Scholar]
  118. Pal-Bhadra M, Leibovitch BA, Gandhi SG, Rao M, Bhadra U. et al. 2004. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303:669–72 [Google Scholar]
  119. Pastinen T, Sladek R, Gurd S, Sammak A, Ge B. et al. 2004. A survey of genetic and epigenetic variation affecting human gene expression. Physiol. Genomics 16:184–93 [Google Scholar]
  120. Pembrey M. 1996. Imprinting and transgenerational modulation of gene expression; human growth as a model. Acta Genet. Med. Gemellol. (Roma.) 45:111–25 [Google Scholar]
  121. Pembrey ME. 2002. Time to take epigenetic inheritance seriously. Eur. J. Hum. Genet. 10:669–71 [Google Scholar]
  122. Petronis A. 2000. The genes for major psychosis: aberrant sequence or regulation. Neuropsychopharmacology 23:1–12 [Google Scholar]
  123. Petronis A. 2001. Human morbid genetics revisited: relevance of epigenetics. Trends Genet. 17:142–46 [Google Scholar]
  124. Petronis A. 2003. Epigenetics and bipolar disorder: new opportunities and challenges. Am. J. Med. Genet. 123C:65–75 [Google Scholar]
  125. Petronis A, Gottesman II, Kan P, Kennedy JL, Basile VS. et al. 2003. Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance. Schizophr. Bull. 29:169–78 [Google Scholar]
  126. Plath K, Mlynarczyk-Evans S, Nusinow DA, Panning B. 2002. Xist RNA and the mechanism of X chromosome inactivation. Annu. Rev. Genet. 36:233–78 [Google Scholar]
  127. Plenge RM, Hendrich BD, Schwartz C, Arena JF, Naumova A. et al. 1997. A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Nat. Genet. 17:353–56 [Google Scholar]
  128. Powell SM, Petersen GM, Krush AJ, Booker S, Jen J. et al. 1993. Molecular diagnosis of familial adenomatous polyposis. N. Engl. J. Med. 329:1982–87 [Google Scholar]
  129. Prioleau MN, Nony P, Simpson M, Felsenfeld G. 1999. An insulator element and condensed chromatin region separate the chicken beta-globin locus from an independently regulated erythroid-specific folate receptor gene. EMBO J. 18:4035–48 [Google Scholar]
  130. Rakyan V, Whitelaw E. 2003. Transgenerational epigenetic inheritance. Curr. Biol. 13:R6 [Google Scholar]
  131. Rampersaud GC, Kauwell GP, Hutson AD, Cerda JJ, Bailey LB. 2000. Genomic DNA methylation decreases in response to moderate folate depletion in elderly women. Am. J. Clin. Nutr. 72:998–1003 [Google Scholar]
  132. Reik W. 1989. Genomic imprinting and genetic disorders in man. Trends Genet. 5:331–36 [Google Scholar]
  133. Reik W, Dean W, Walter J. 2001. Epigenetic reprogramming in mammalian development. Science 293:1089–93 [Google Scholar]
  134. Risch N, Spiker D, Lotspeich L, Nouri N, Hinds D. et al. 1999. A genomic screen of autism: evidence for a multilocus etiology. Am. J. Hum. Genet. 65:493–507 [Google Scholar]
  135. Rougeulle C, Glatt H, Lalande M. 1997. The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain. Nat. Genet. 17:14–15 [Google Scholar]
  136. Rozen R. 1996. Molecular genetics of methylenetetrahydrofolate reductase deficiency. J. Inherit. Metab. Dis. 19:589–94 [Google Scholar]
  137. Saitoh N, Bell AC, Recillas-Targa F, West AG, Simpson M. et al. 2000. Structural and functional conservation at the boundaries of the chicken beta-globin domain. EMBO J. 19:2315–22 [Google Scholar]
  138. Sapienza C, Hall JG. 2004. Genomic imprinting in human disease. In The Metabolic and Molecular Bases of Inherited Disease ed. Scriver, AL Beaudet, D Valle, WS Sly pp.417–31 New York: McGraw Hill [Google Scholar]
  139. Schwahn B, Rozen R. 2001. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am. J. Pharmacogenomics. 1:189–201 [Google Scholar]
  140. Shaffer LG, Ledbeter DH, Lupski JR. 2001. Molecular cytogenetics of contiguous gene syndromes: mechanisms and consequences of gene dosage imbalance. In The Molecular and Metabolic Bases of Inherited Disease ed. CR Scriver, AL Beaudet, D Valle, WS Sly pp.1291–324 New York: McGraw-Hill [Google Scholar]
  141. Shemer R, Birger Y, Riggs AD, Razin A. 1997. Structure of the imprinted mouse Snrpn gene and establishment of its parental-specific methylation pattern. Proc. Natl. Acad. Sci. USA 94:10267–72 [Google Scholar]
  142. Singh N, Ebrahimi FA, Gimelbrant AA, Ensminger AW, Tackett MR. et al. 2003. Coordination of the random asynchronous replication of autosomal loci. Nat. Genet. 33:339–41 [Google Scholar]
  143. Spence JE, Perciaccante RG, Greig GM, Willard HF, Ledbetter DH. et al. 1988. Uniparental disomy as a mechanism for human genetic disease. Am. J. Hum. Genet. 42:217–26 [Google Scholar]
  144. Strohman R. 2002. Maneuvering in the complex path from genotype to phenotype. Science 296:701–3 [Google Scholar]
  145. Strohman RC. 1995. Linear genetics, non-linear epigenetics: complementary approaches to understanding complex diseases. Integr. Physiol. Behav. Sci. 30:273–82 [Google Scholar]
  146. Surti U, Hoffner L, Chakravarti A, Ferrell RE. 1990. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin Am. J. Hum. Genet. 47:635–43 [Google Scholar]
  147. Sutcliffe JS, Nakao M, Christian S, Orstavik KH, Tommerup N. et al. 1994. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region. Nat. Genet. 8:52–58 [Google Scholar]
  148. Tada T, Tada M, Hilton K, Barton SC, Sado T. et al. 1998. Epigenotype switching of imprintable loci in embryonic germ cells. Dev. Genes Evol. 207:551–61 [Google Scholar]
  149. Tamaru H, Selker EU. 2001. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414:277–83 [Google Scholar]
  150. Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H. et al. 2003. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat. Genet. 34:157–65 [Google Scholar]
  151. Tycko B, Morison IM. 2002. Physiological functions of imprinted genes. J. Cell Physiol 192:245–58 [Google Scholar]
  152. Ueland PM, Refsum H. 1989. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy. J. Lab. Clin. Med. 114:473 [Google Scholar]
  153. van der Put NM, Eskes TK, Blom HJ. 1997. Is the common 677C→T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects. A meta-analysis QJM 90:111–15 [Google Scholar]
  154. Vu TH, Hoffman AR. 1994. Promoter-specific imprinting of the human insulin-like growth factor-II gene. Nature 371:714–17 [Google Scholar]
  155. Vu TH, Hoffman AR. 1997. Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain. Nat. Genet. 17:12–13 [Google Scholar]
  156. Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP. 1999. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat. Genet. 23:62–66 [Google Scholar]
  157. Walter J, Paulsen M. 2003. Imprinting and disease. Semin. Cell Dev. Biol. 14:101–10 [Google Scholar]
  158. Warren ST, Sherman SL. 2001. The fragile X syndrome. In The Metabolic and Molecular Bases of Inherited Disease ed. CR Scriver, AL Beaudet, D Valle, WS Sly pp.1257–89 New York: McGraw Hill [Google Scholar]
  159. Waterland RA, Jirtle RL. 2003. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol. Cell Biol. 23:5293–300 [Google Scholar]
  160. Weksberg R, Smith AC, Squire J, Sadowski P. 2003. Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal development. Hum. Mol. Genet. 121:R61–68 [Google Scholar]
  161. Wijmenga C, van Deutekom JC, Hewitt JE, Padberg GW, van Ommen GJ. et al. 1994. Pulsed-field gel electrophoresis of the D4F104S1 locus reveals the size and the parental origin of the facioscapulohumeral muscular dystrophy (FSHD)-associated deletions. Genomics 19:21–26 [Google Scholar]
  162. Wilkins JF, Haig D. 2003. What good is genomic imprinting: the function of parent-specific gene expression. Nat. Rev. Genet. 4:359–68 [Google Scholar]
  163. Williams CA, Zori RT, Hendrickson J, Stalker H, Marum T. et al. 1995. Angelman syndrome. Curr. Probl. Pediatr. 25:216–31 [Google Scholar]
  164. Wolff GL, Kodell RL, Moore SR, Cooney CA. 1998. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J. 12:949–57 [Google Scholar]
  165. Wutz A. 2003. RNAs templating chromatin structure for dosage compensation in animals. Bioessays 25:434–42 [Google Scholar]
  166. Xin Z, Allis CD, Wagstaff J. 2001. Parent-specific complementary patterns of histone H3 lysine 9 and H3 lysine 4 methylation at the Prader-Willi syndrome imprinting center. Am. J. Hum. Genet. 69:1389–94 [Google Scholar]
  167. Xin Z, Tachibana M, Guggiari M, Heard E, Shinkai Y, Wagstaff J. 2003. Role of histone methyltransferase G9a in CpG methylation of the Prader-Willi syndrome imprinting center. J. Biol. Chem. 278:14996–5000 [Google Scholar]
  168. Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N. et al. 1999. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402:187–91 [Google Scholar]
  169. Yamasaki K, Joh K, Ohta T, Masuzaki H, Ishimaru T. et al. 2003. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum. Mol. Genet. 12:837–47 [Google Scholar]
  170. Yamazaki Y, Mann MR, Lee SS, Marh J, McCarrey JR. et al. 2003. Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc. Natl. Acad. Sci. USA 100:12207–12 [Google Scholar]
  171. Yntema HG, Poppelaars FA, Derksen E, Oudakker AR, van Roosmalen T. et al. 2002. Expanding phenotype of XNP mutations: mild to moderate mental retardation. Am. J. Med. Genet. 110:243–47 [Google Scholar]
  172. Yoder JA, Walsh CP, Bestor TH. 1997. Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 13:335–40 [Google Scholar]
  173. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D. 1999. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 13:1924–35 [Google Scholar]
  174. Jiang Y, Sahoo T, Michaelis R, Bercovich D, Bressler J. et al. 2004. A mixed epigenetic/genetic model for oligogenic inheritance of austism with a limited role for UBE3A. Am. J. Med. Genet. In press [Google Scholar]
/content/journals/10.1146/annurev.genom.5.061903.180014
Loading
EPIGENETICS AND HUMAN DISEASE
Annual Review of Genomics and Human Genetics 5, 479 (2004); https://doi.org/10.1146/annurev.genom.5.061903.180014
/content/journals/10.1146/annurev.genom.5.061903.180014
/content/journals/10.1146/annurev.genom.5.061903.180014
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error