Epigenetic epidemiology of autism and other neurodevelopmental disorders

Epigenetic Epidemiology

Volumn , Issue , 2014, Pages 321-342

  Woods, Rima ^a   Lasalle, Janine M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84931466855     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-94-007-2495-2_17     Document Type: Chapter

References (149)

1. Yen RW, Vertino PM, Nelkin BD, Yu JJ, el-Deiry W, Cumaraswamy A et al (1992) Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Res 20:2287-2291
2. Goto K, Numata M, Komura JI, Ono T, Bestor TH, Kondo H (1994) Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation 56:39-44
3. Feng J, Chang H, Li E, Fan G (2005) Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res 79:734-746
4. Argentaro A, Yang JC, Chapman L, Kowalczyk MS, Gibbons RJ, Higgs DR et al (2007) Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX. Proc Natl Acad Sci USA 104:11939-11944
5. Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857-869
6. LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL et al (2010) Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13:1137-1143
7. Wilkinson LS, Davies W, Isles AR (2007) Genomic imprinting effects on brain development and function. Nat Rev Neurosci 8:832-843
8. Thatcher K, LaSalle JM (2006) Dynamic changes in histone H3 lysine 9 acetylation localization patterns during neuronal maturation require MeCP2. Epigenetics 1:24-31
9. Chateauvieux S, Morceau F, Dicato M, Diederich M (2010) Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol 2010:1-19
10. Keverne EB, Fundele R, Narasimha M, Barton SC, Surani MA (1996) Genomic imprinting and the differential roles of parental genomes in brain development. Brain Res Dev Brain Res 92:91-100
11. Schanen NC (2006) Epigenetics of autism spectrum disorders. Hum Mol Genet 15(Spec No 2):R138-R150
12. Lalande M, Calciano MA (2007) Molecular epigenetics of angelman syndrome. Cell Mol Life Sci 64:947-960
13. Hogart A, Leung KN, Wang NJ, Wu DJ, Driscoll J, Vallero RO et al (2009) Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 46:86-93
14. Yashiro K, Riday TT, Condon KH, Roberts AC, Bernardo DR, Prakash R et al (2009) Ube3a is required for experience-dependent maturation of the neocortex. Nat Neurosci 12:777-783
15. Sato M, Stryker MP (2010) Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proc Natl Acad Sci USA 107:5611-5616
16. Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW et al (2010) The angelman syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 140:704-716
17. Robinson WP, Bottani A, Xie YG, Balakrishman J, Binkert F, Machler M et al (1991) Molecular, cytogenetic, and clinical investigations of prader-willi syndrome patients. Am J Hum Genet 49:1219-1234
18. Robinson WP, Dutly F, Nicholls RD, Bernasconi F, Penaherrera M, Michaelis RC et al (1998) The mechanisms involved in formation of deletions and duplications of 15q11-q13. J Med Genet 35:130-136
19. Buiting K, Saitoh S, Gross S, Dittrich B, Schwartz S, Nicholls RD et al (1995) Inherited microdeletions in the angelman and prader-willi syndromes define an imprinting centre on human chromosome. Nat Genet 9:395-400
20. Sutcliffe JS, Nakao M, Christian S, Orstavik KH, Tommerup N, Ledbetter DH 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
21. Dittrich B, Buiting K, Korn B, Rickard S, Buxton J, Saitoh S et al (1996) Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene. Nat Genet 14:163-170
22. Glenn CC, Nicholls RD, Robinson WP, Saitoh S, Niikawa N, Schinzel A et al (1993) Modification of 15q11-q13 DNA methylation imprints in unique angelman and prader-willi patients. Hum Mol Genet 2:1377-1382
23. Runte M, Huttenhofer A, Gross S, Kiefmann M, Horsthemke B, Buiting K (2001) The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum Mol Genet 10:2687-2700
24. Leung KN, Vallero RO, DuBose AJ, Resnick JL, LaSalle JM (2009) Imprinting regulates mammalian snoRNA-encoding chromatin decondensation and neuronal nucleolar size. Hum Mol Genet 18:4227-4238
25. Hogart A et al (2010) The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13. Neurobiol Dis 38(2):181-191
26. Robinson WP, Kuchinka BD, Bernasconi F, Petersen MB, Schulze A, Brondum-Nielsen K et al (1998) Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Hum Mol Genet 7:1011-1019
27. Cook EH Jr, Lindgren V, Leventhal BL, Courchesne R, Lincoln A, Shulman C et al (1997) Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 60:928-934
28. Veltman MW, Thompson RJ, Craig EE, Dennis NR, Roberts SE, Moore V et al (2005) A paternally inherited duplication in the prader-willi/angelman syndrome critical region: a case and family study. J Autism Dev Disord 35:117-127
29. Mohandas TK, Park JP, Spellman RA, Filiano JJ, Mamourian AC, Hawk AB et al (1999) Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay. Am J Med Genet 82:294-300
30. Kao DI, Aldridge GM, Weiler IJ, Greenough WT (2010) Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci USA 107:15601-15606
31. Brown V, Small K, Lakkis L, Feng Y, Gunter C, Wilkinson KD et al (1998) Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein. J Biol Chem 273:15521-15527
32. Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A et al (2009) Advances in the treatment of fragile X syndrome. Pediatrics 123:378-390
33. Chonchaiya W, Schneider A, Hagerman RJ (2009) Fragile X: a family of disorders. Adv Pediatr 56:165-186
34. Hagerman PJ (2008) The fragile X prevalence paradox. J Med Genet 45:498-499
35. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905-914
36. Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S et al (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047-1058
37. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT et al (1991) Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 66:817-822
38. Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D et al (1992) DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet 1:397-400
39. Malter HE, Iber JC, Willemsen R, de Graaff E, Tarleton JC, Leisti J et al (1997) Characterization of the full fragile X syndrome mutation in fetal gametes. Nat Genet 15:165-169
40. Kumari D, Usdin K (2010) The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome. Hum Mol Genet 19:4634-4642
41. Hagerman RJ, Leehey M, Heinrichs W, Tassone F, Wilson R, Hills J et al (2001) Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology 57:127-130
42. Jacquemont S, Hagerman RJ, Leehey MA, Hall DA, Levine RA, Brunberg JA et al (2004) Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 291:460-469
43. Snow K, Doud LK, Hagerman R, Pergolizzi RG, Erster SH, Thibodeau SN (1993) Analysis of a CGG sequence at the FMR-1 locus in fragile X families and in the general population. Am J Hum Genet 53:1217-1228
44. Berry-Kravis E, Potanos K, Weinberg D, Zhou L, Goetz CG (2005) Fragile X-associated tremor/ataxia syndrome in sisters related to X-inactivation. Ann Neurol 57:144-147
45. Tassone F, Hagerman RJ, Taylor AK, Gane LW, Godfrey TE, Hagerman PJ (2000) Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 66:6-15
46. Greco CM, Hagerman RJ, Tassone F, Chudley AE, Del Bigio MR, Jacquemont S et al (2002) Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain 125:1760-1771
47. Arocena DG, Iwahashi CK, Won N, Beilina A, Ludwig AL, Tassone F et al (2005) Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. Hum Mol Genet 14:3661-3671
48. Tassone F, Adams J, Berry-Kravis EM, Cohen SS, Brusco A, Leehey MA et al (2007) CGG repeat length correlates with age of onset of motor signs of the fragile X-associated tremor/ ataxia syndrome (FXTAS). Am J Med Genet B Neuropsychiatr Genet 144B:566-569
49. Willemsen R, Hoogeveen-Westerveld M, Reis S, Holstege J, Severijnen LA, Nieuwenhuizen IM et al (2003) The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. Hum Mol Genet 12:949-959
50. Hagleitner MM, Lankester A, Maraschio P, Hulten M, Fryns JP, Schuetz C et al (2008) Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). J Med Genet 45:93-99
51. Ehrlich M, Sanchez C, Shao C, Nishiyama R, Kehrl J, Kuick R et al (2008) ICF, an immunodefi ciency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation. Autoimmunity 41:253-271
52. Sumner AT, Mitchell AR, Ellis PM (1998) A FISH study of chromosome fusion in the ICF syndrome: involvement of paracentric heterochromatin but not of the centromeres themselves. J Med Genet 35:833-835
53. Brown DC, Grace E, Sumner AT, Edmunds AT, Ellis PM (1995) ICF syndrome (immunodeficiency, centromeric instability and facial anomalies): investigation of heterochromatin abnormalities and review of clinical outcome. Hum Genet 96:411-416
54. Jefferson A, Colella S, Moralli D, Wilson N, Yusuf M, Gimelli G et al (2010) Altered intranuclear organisation of heterochromatin and genes in ICF syndrome. PLoS One 5:e11364
55. Jin B, Tao Q, Peng J, Soo HM, Wu W, Ying J et al (2008) DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis and immune function. Hum Mol Genet 17:690-709
56. Yehezkel S, Segev Y, Viegas-Pequignot E, Skorecki K, Selig S (2008) Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17:2776-2789
57. Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10:228-236
58. Deng Z, Campbell AE, Lieberman PM (2010) TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells. Cell Cycle 9:69-74
59. Deng Z, Norseen J, Wiedmer A, Riethman H, Lieberman PM (2009) TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35:403-413
60. Perrini B, Piacentini L, Fanti L, Altieri F, Chichiarelli S, Berloco M et al (2004) HP1 Controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila. Mol Cell 15:467-476
61. Gecz J, Shoubridge C, Corbett M (2009) The genetic landscape of intellectual disability arising from chromosome X. Trends Genet 25:308-316
62. El-Hattab AW et al (2011) Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. Clin Genet 79(6):531-538
63. Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C et al (2009) A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet 41:535-543
64. Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP et al (2008) Mutations in the chromatin-associated protein ATRX. Hum Mutat 29:796-802
65. Gibbons RJ, Picketts DJ, Villard L, Higgs DR (1995) Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell 80:837-845
66. Cohn DM, Pagon RA, Hudgins L, Schwartz CE, Stevenson RE, Friez MJ (2009) Partial ATRX gene duplication causes ATR-X syndrome. Am J Med Genet A 149A:2317-2320
67. Gibbons R (2006) Alpha thalassaemia-mental retardation, X linked. Orphanet J Rare Dis 1:15
68. Berube NG, Mangelsdorf M, Jagla M, Vanderluit J, Garrick D, Gibbons RJ et al (2005) The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. J Clin Invest 115:258-267
69. McDowell TL, Gibbons RJ, Sutherland H, O'Rourke DM, Bickmore WA, Pombo A et al (1999) Localization of a putative transcriptional regulator (ATRX) at pericentromeric heterochromatin and the short arms of acrocentric chromosomes. Proc Natl Acad Sci USA 96:13983-13988
70. Nan X, Hou J, Maclean A, Nasir J, Lafuente MJ, Shu X et al (2007) Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proc Natl Acad Sci USA 104:2709-2714
71. Baumann C, De La Fuente R (2009) ATRX marks the inactive X chromosome (Xi) in somatic cells and during imprinted X chromosome inactivation in trophoblast stem cells. Chromosoma 118:209-222
72. Gibbons RJ, McDowell TL, Raman S, O'Rourke DM, Garrick D, Ayyub H et al (2000) Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation. Nat Genet 24:368-371
73. Kernohan KD, Jiang Y, Tremblay DC, Bonvissuto AC, Eubanks JH, Mann MR et al (2010) ATRX partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain. Dev Cell 18:191-202
74. Gonzales ML, LaSalle JM (2010) The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep 12:127-134
75. Ng HH, Bird A (1999) DNA methylation and chromatin modification. Curr Opin Genet Dev 9:158-163
76. Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY (2002) Insight into Rett syndrome: MeCP2 levels display tissue-and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 11:115-124
77. Balmer D, Goldstine J, Rao YM, LaSalle JM (2003) Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation. J Mol Med 81:61-68
78. Braunschweig D, Simcox T, Samaco RC, LaSalle JM (2004) X-Chromosome inactivation ratios affect wild-type MeCP2 expression within mosaic Rett syndrome and Mecp2-/+ mouse brain. Hum Mol Genet 13:1275-1286
79. Nan X, Tate P, Li E, Bird A (1996) DNA methylation specifies chromosomal localization of MeCP2. Mol Cell Biol 16:414-421
80. Skene PJ, Illingworth RS, Webb S, Kerr AR, James KD, Turner DJ et al (2010) Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 37:457-468
81. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N et al (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187-191
82. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN et al (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386-389
83. Georgel PT, Horowitz-Scherer RA, Adkins N, Woodcock CL, Wade PA, Hansen JC (2003) Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation. J Biol Chem 278:32181-32188
84. Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T (2005) Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 37:31-40
85. Kumar A, Kamboj S, Malone BM, Kudo S, Twiss JL, Czymmek KJ et al (2008) Analysis of protein domains and Rett syndrome mutations indicate that multiple regions influence chromatin-binding dynamics of the chromatin-associated protein MECP2 in vivo. J Cell Sci 121:1128-1137
86. Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF et al (2005) Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc Natl Acad Sci USA 102:17551-17558
87. Yasui DH, Peddada S, Bieda MC, Vallero RO, Hogart A, Nagarajan RP et al (2007) Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci USA 104:19416-19421
88. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J et al (2008) MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224-1229
89. Chao HT, Zoghbi HY, Rosenmund C (2007) MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56:58-65
90. Maezawa I, Swanberg S, Harvey D, LaSalle JM, Jin LW (2009) Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 29:5051-5061
91. Ballas N, Lioy DT, Grunseich C, Mandel G (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 12:311-317
92. Traynor J, Agarwal P, Lazzeroni L, Francke U (2002) Gene expression patterns vary in clonal cell cultures from Rett syndrome females with eight different MECP2 mutations. BMC Med Genet 3:12
93. Tudor M, Akbarian S, Chen RZ, Jaenisch R (2002) Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. Proc Natl Acad Sci USA 99:15536-15541
94. Peddada S, Yasui DH, LaSalle JM (2006) Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome. Hum Mol Genet 15:2003-2014
95. Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S et al (2007) FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice. Hum Mol Genet 16:640-650
96. Urdinguio RG, Lopez-Serra L, Lopez-Nieva P, Alaminos M, Diaz-Uriarte R, Fernandez AF et al (2008) Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS One 3:e3669
97. 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 23:185-188
98. Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO et al (2008) Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 70:1313-1321
99. Lin C, Franco B, Rosner MR (2005) CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet 14:3775-3786
100. Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R et al (2005) CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome. Hum Mol Genet 14:1935-1946
101. Schanen C (2001) Rethinking the fate of males with mutations in the gene that causes Rett syndrome. Brain Dev 23(Suppl 1):S144-S146
102. Clayton-Smith J, Watson P, Ramsden S, Black GC (2000) Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males. Lancet 356:830-832
103. Hoffbuhr K, Devaney JM, LaFleur B, Sirianni N, Scacheri C, Giron J et al (2001) MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurology 56:1486-1495
104. 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
105. Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K et al (2005) Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 77:442-453
106. Lugtenberg D, Kleefstra T, Oudakker AR, Nillesen WM, Yntema HG, Tzschach A et al (2009) Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum Genet 17:444-453
107. Campos M Jr, Churchman SM, Santos-Reboucas CB, Ponchel F, Pimentel MM (2010) High frequency of nonrecurrent MECP2 duplications among Brazilian males with mental retardation. J Mol Neurosci 41:105-109
108. Ramocki MB, Peters SU, Tavyev YJ, Zhang F, Carvalho CM, Schaaf CP et al (2009) Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome. Ann Neurol 66:771-782
109. Nagarajan RP, Hogart AR, Gwye Y, Martin MR, Lasalle JM (2006) Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 1:172-182
110. Nagarajan RP, Patzel KA, Martin M, Yasui DH, Swanberg SE, Hertz-Picciotto I et al (2008) Mecp2 Promoter methylation and X chromosome inactivation in autism. Autism Res 1:169-178
111. Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM (2004) Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet 13:629-639
112. Patterson SY, Smith V, Jelen M (2010) Behavioural intervention practices for stereotypic and repetitive behaviour in individuals with autism spectrum disorder: a systematic review. Dev Med Child Neurol 52:318-327
113. Jones JR, Skinner C, Friez MJ, Schwartz CE, Stevenson RE (2008) Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. Am J Med Genet A 146A:2213-2220
114. Bill BR, Geschwind DH (2009) Genetic advances in autism: heterogeneity and convergence on shared pathways. Curr Opin Genet Dev 19:271-278
115. Holt R, Barnby G, Maestrini E, Bacchelli E, Brocklebank D, Sousa I et al (2010) Linkage and candidate gene studies of autism spectrum disorders in European populations. Eur J Hum Genet 18:1013-1019
116. Yirmiya N, Charman T (2010) The prodrome of autism: early behavioral and biological signs, regression, peri-and post-natal development and genetics. J Child Psychol Psychiatry 51:432-458
117. Lasalle JM, Yasui DH (2009) Evolving role of MeCP2 in Rett syndrome and autism. Epigenomics 1:119-130
118. Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, Fauchereau F et al (2010) Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends Genet 26:363-372
119. Landrigan PJ (2010) What causes autism? Exploring the environmental contribution. Curr Opin Pediatr 22:219-225
120. Rubenstein JL (2010) Three hypotheses for developmental defects that may underlie some forms of autism spectrum disorder. Curr Opin Neurol 23:118-123
121. Delahanty RJ, Kang JQ, Brune CW, Kistner EO, Courchesne E, Cox NJ et al (2009) Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Mol Psychiatry
122. Castermans D, Volders K, Crepel A, Backx L, De Vos R, Freson K et al (2010) SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large densecore vesicles. Hum Mol Genet 19:1368-1378
123. Freitag CM, Staal W, Klauck SM, Duketis E, Waltes R (2010) Genetics of autistic disorders: review and clinical implications. Eur Child Adolesc Psychiatry 19:169-178
124. Abrahams BS, Geschwind DH (2010) Connecting genes to brain in the autism spectrum disorders. Arch Neurol 67:395-399
125. Gong X, Bacchelli E, Blasi F, Toma C, Betancur C, Chaste P et al (2008) Analysis of X chromosome inactivation in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 147B:830-835
126. Samaco RC, Hogart A, LaSalle JM (2005) Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet 14:483-492
127. Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM (2007) 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 16:691-703
128. Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA et al (2009) Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7:62
129. Nguyen A, Rauch TA, Pfeifer GP, Hu VW (2010) Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J 24:3036-3051
130. Rush D (1994) Periconceptional folate and neural tube defect. Am J Clin Nutr 59:511S-515S, discussion 515S-516S
131. Adams M, Lucock M, Stuart J, Fardell S, Baker K, Ng X (2007) Preliminary evidence for involvement of the folate gene polymorphism 19 bp deletion-DHFR in occurrence of autism. Neurosci Lett 422:24-29
132. Pasca SP, Dronca E, Kaucsar T, Craciun EC, Endreffy E, Ferencz BK et al (2009) One carbon metabolism disturbances and the C677T MTHFR gene polymorphism in children with autism spectrum disorders. J Cell Mol Med 13:4229-4238
133. Mohammad NS, Jain JM, Chintakindi KP, Singh RP, Naik U, Akella RR (2009) Aberrations in folate metabolic pathway and altered susceptibility to autism. Psychiatr Genet 19:171-176
134. Goin-Kochel RP, Porter AE, Peters SU, Shinawi M, Sahoo T, Beaudet AL (2009) The MTHFR 677 C- T polymorphism and behaviors in children with autism: exploratory genotype-phenotype correlations. Autism Res 2:98-108
135. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10:111-113
136. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW et al (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 80:1611-1617
137. James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW (2008) Abnormal transmethylation/ transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord 38:1966-1975
138. James SJ, Melnyk S, Jernigan S, Pavliv O, Trusty T, Lehman S et al (2010) A functional polymorphism in the reduced folate carrier gene and DNA hypomethylation in mothers of children with autism. Am J Med Genet B Neuropsychiatr Genet 153B:1209-1220
139. Rogers EJ (2008) Has enhanced folate status during pregnancy altered natural selection and possibly autism prevalence? A closer look at a possible link. Med Hypotheses. doi: 10.1016/j. mehy.2008.04.013
140. Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ et al (2011) Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 22:476-485
141. Herbert MR (2010) Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 23:103-110
142. Kinney DK, Barch DH, Chayka B, Napoleon S, Munir KM (2010) Environmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? Med Hypotheses 74:102-106
143. Roberts EM, English PB, Grether JK, Windham GC, Somberg L, Wolff C (2007) Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect 115:1482-1489
144. Windham GC, Zhang L, Gunier R, Croen LA, Grether JK (2006) Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area. Environ Health Perspect 114:1438-1444
145. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH et al (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179:572-578
146. Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B et al (2009) Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 117:217-222
147. Lee DH, Jacobs DR Jr, Porta M (2009) Hypothesis: a unifying mechanism for nutrition and chemicals as lifelong modulators of DNA hypomethylation. Environ Health Perspect 117:1799-1802
148. de Greef JC et al (2011) Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am J Hum Genet 88(6):796-804
149. Hallmayer J et al (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, Accepted Article