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Epigenetics at the Interface of Genetics and Environmental Factors in Autism

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Environmental Epigenomics in Health and Disease

Part of the book series: Epigenetics and Human Health ((EHH))

Abstract

Autism spectrum disorders have a complex etiology, suggesting that multiple genetic and environmental factors play a role in their etiology. The apparent rise in the prevalence of autism spectrum disorders in recent decades is currently an unresolved problem. Epigenetic mechanisms, such as DNA methylation, act at the interface of genes and environment and are of critical importance for human brain development. This chapter reviews the known epigenetic pathways with known genetic bases in autism spectrum disorders and some recent studies showing epigenetic changes in human autism samples. In addition, environmental factors are discussed for their roles in impacting DNA methylation, with a focus on the persistent organic pollutants because of their bioaccumulation in brain. Dietary factors are also discussed, particularly folic acid supplementation during pregnancy because of the known contributions to DNA methylation and the protection for neural tube defects and, more recently, autism. Further investigation into epigenetic factors at the gene/environment interface will likely be important for making progress in preventing and treating autism in the future.

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Abbreviations

CNV:

Copy-number variation

DNMT:

DNA methyltransferase

ICF:

Immunodeficiency, centromeric region instability, and facial anomalies

MECP2:

Methyl-CpG-binding protein 2

RTT:

Rett syndrome

IAP:

Intracisternal A particle

POP:

Persistent organic pollutants

PBDE:

Polybrominated diphenyl ether

PCB:

Polychlorinated biphenyl

CHARGE:

Childhood Autism Risks from Genetics and theEnvironment

SAM:

S-adenosylmethionine

SNP:

Single-nucleotide polymorphism

References

  • Alaee M (2003) Recommendations for monitoring of polybrominated diphenyl ethers in the Canadian environment. Environ Monit Assess 88:327–341

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Sykes N, Pagnamenta AT, Almeida J, Bacchelli E, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Carson AR, Casallo G, Casey J, Chu SH, Cochrane L, Corsello C, Crawford EL, Crossett A, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Melhem NM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Piven J, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Wing K, Wittemeyer K, Wood S, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Betancur C, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Gallagher L, Geschwind DH, Gill M, Haines JL, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Scherer SW, Sutcliffe JS, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Devlin B, Ennis S, Hallmayer J (2010) A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19:4072–4082

    Article  PubMed  CAS  Google Scholar 

  • Baccarelli A, Bollati V (2009) Epigenetics and environmental chemicals. Curr Opin Pediatr 21:243–251

    Article  PubMed  Google Scholar 

  • Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J (2009) Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 179:572–578

    Article  PubMed  CAS  Google Scholar 

  • Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21

    Article  PubMed  CAS  Google Scholar 

  • Bird A, Taggart M, Frommer M, Miller OJ, Macleod D (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40:91–99

    Article  PubMed  CAS  Google Scholar 

  • Bollati V, Baccarelli A, Hou L, Bonzini M, Fustinoni S, Cavallo D, Byun HM, Jiang J, Marinelli B, Pesatori AC, Bertazzi PA, Yang AS (2007) Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res 67:876–880

    Article  PubMed  CAS  Google Scholar 

  • Bruc I, Philippart M, Giraldi D, Antoniuk S (1991) Difference in early development of presumed monozygotic twins with Rett syndrome. Am J Med Genet 39:415–417

    Article  Google Scholar 

  • Cheslack-Postava K, Liu K, Bearman PS (2011) Closely spaced pregnancies are associated with increased odds of autism in California sibling births. Pediatrics 127:246–253

    Article  PubMed  Google Scholar 

  • Christian SL, Fantes JA, Mewborn SK, Huang B, Ledbetter DH (1999) Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11-q13). Hum Mol Genet 8:1025–1037

    Article  PubMed  CAS  Google Scholar 

  • Cook EH Jr, Scherer SW (2008) Copy-number variations associated with neuropsychiatric conditions. Nature 455:919–923

    Article  PubMed  CAS  Google Scholar 

  • Cook EH Jr, Lindgren V, Leventhal BL, Courchesne R, Lincoln A, Shulman C, Lord C, Courchesne E (1997) Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 60:928–934

    PubMed  CAS  Google Scholar 

  • Currenti SA (2009) Understanding and determining the etiology of autism. Cell Mol Neurobiol 30:161–171

    Article  PubMed  Google Scholar 

  • Czeizel AE, Dudas I (1992) Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 327:1832–1835

    Article  PubMed  CAS  Google Scholar 

  • Darnerud PO, Aune M, Larsson L, Hallgren S (2007) Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47. Chemosphere 67:S386–S392

    Article  PubMed  CAS  Google Scholar 

  • Depienne C, Moreno-De-Luca D, Heron D, Bouteiller D, Gennetier A, Delorme R, Chaste P, Siffroi JP, Chantot-Bastaraud S, Benyahia B, Trouillard O, Nygren G, Kopp S, Johansson M, Rastam M, Burglen L, Leguern E, Verloes A, Leboyer M, Brice A, Gillberg C, Betancur C (2009) Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders. Biol Psychiatry 66:349–359

    Article  PubMed  CAS  Google Scholar 

  • Dolinoy DC, WeidmanJR WRA, Jirtle RL (2006) Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 114:567–572

    Article  PubMed  CAS  Google Scholar 

  • Dolinoy DC, Huang D, Jirtle RL (2007) Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA 104:13056–13061

    Article  PubMed  CAS  Google Scholar 

  • Dufault C, Poles G, Driscoll LL (2005) Brief postnatal PBDE exposure alters learning and the cholinergic modulation of attention in rats. Toxicol Sci 88:172–180

    Article  PubMed  CAS  Google Scholar 

  • Ellis-Hutchings RG, Cherr GN, Hanna LA, Keen CL (2006) Polybrominated diphenyl ether (PBDE)-induced alterations in vitamin A and thyroid hormone concentrations in the rat during lactation and early postnatal development. Toxicol Appl Pharmacol 215:135–145

    Article  PubMed  CAS  Google Scholar 

  • Fan G, Beard C, Chen RZ, Csankovszki G, Sun Y, Siniaia M, Biniszkiewicz D, Bates B, Lee PP, Kuhn R, Trumpp A, Poon C, Wilson CB, Jaenisch R (2001) DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals. J Neurosci 21:788–797

    PubMed  CAS  Google Scholar 

  • Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430

    Article  PubMed  CAS  Google Scholar 

  • Fernie KJ, Shutt JL, Mayne G, Hoffman D, Letcher RJ, Drouillard KG, Ritchie IJ (2005) Exposure to polybrominated diphenyl ethers (PBDEs): changes in thyroid, vitamin A, glutathione homeostasis, and oxidative stress in American kestrels (Falco sparverius). Toxicol Sci 88:375–383

    Article  PubMed  CAS  Google Scholar 

  • Feuk L, Carson AR, Scherer SW (2006) Structural variation in the human genome. Nat Rev Genet 7:85–97

    Article  PubMed  CAS  Google Scholar 

  • Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609

    Article  PubMed  CAS  Google Scholar 

  • Frederiksen M, Vorkamp K, Mathiesen L, Mose T, Knudsen LE (2010) Placental transfer of the polybrominated diphenyl ethers BDE-47, BDE-99 and BDE-209 in a human placenta perfusion system: an experimental study. Environ Health 9:32

    Google Scholar 

  • Geschwind DH (2008) Autism: many genes, common pathways? Cell 135:391–395

    Article  PubMed  CAS  Google Scholar 

  • Gonzalgo ML, Jones PA (1997) Mutagenic and epigenetic effects of DNA methylation. Mutat Res 386:107–118

    Article  PubMed  CAS  Google Scholar 

  • Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, Costa E (2005) Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA 102:9341–9346

    Article  PubMed  CAS  Google Scholar 

  • Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA (2009) Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 7:62

    Article  PubMed  Google Scholar 

  • Hallgren S, Darnerud PO (2002) Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects. Toxicology 177:227–243

    Article  PubMed  CAS  Google Scholar 

  • Hallgren S, Sinjari T, Hakansson H, Darnerud PO (2001) Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. Arch Toxicol 75:200–208

    Article  PubMed  CAS  Google Scholar 

  • Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N (2011) Genetic heritability and shared environmental factors among twin pairs with autism. Archives of general psychiatry 68(11):1095–1102.

    Article  PubMed  Google Scholar 

  • Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM (1999) The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci USA 96:14412–14417

    Article  PubMed  CAS  Google Scholar 

  • Hertz-Picciotto I, Delwiche L (2009) The rise in autism and the role of age at diagnosis. Epidemiology 20:84–90

    Article  PubMed  Google Scholar 

  • Hites RA, Foran JA, Schwager SJ, Knuth BA, Hamilton MC, Carpenter DO (2004) Global assessment of polybrominated diphenyl ethers in farmed and wild salmon. Environ Sci Technol 38:4945–4949

    Article  PubMed  CAS  Google Scholar 

  • Hogart A, Wu D, Lasalle JM, Schanen NC (2010) The comorbidity of autism with the genomic disorders of chromosome 15q112-q13. Neurobiol Dis 38:181–191

    Article  PubMed  CAS  Google Scholar 

  • Hopf NB, Ruder AM, Succop P (2009) Background levels of polychlorinated biphenyls in the US population. Sci Total Environ 407:6109–6119

    Article  PubMed  CAS  Google Scholar 

  • Hultman CM, Sandin S, Levine SZ, Lichtenstein P, Reichenberg A (2011) Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Mol Psychiatry 16:1203–1212

    Article  PubMed  CAS  Google Scholar 

  • Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW, Lee C (2004) Detection of large-scale variation in the human genome. Nat Genet 36:949–951

    Article  PubMed  CAS  Google Scholar 

  • Inano K, Suetake I, Ueda T, Miyake Y, Nakamura M, Okada M, Tajima S (2000) Maintenance-type DNA methyltransferase is highly expressed in post-mitotic neurons and localized in the cytoplasmic compartment. J Biochem 128:315–321

    Article  PubMed  CAS  Google Scholar 

  • International Schizophrenia Consortium (2008) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237–241

    Article  Google Scholar 

  • Jeanpierre M, Turleau C, Aurias A, Prieur M, Ledeist F, Fischer A, Viegas-Pequignot E (1993) An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome. Hum Mol Genet 2:731–735

    Article  PubMed  CAS  Google Scholar 

  • Ladd-Acosta C, Pevsner J, Sabunciyan S, Yolken RH, Webster MJ, Dinkins T, Callinan PA, Fan JB, Potash JB, Feinberg AP (2007) DNA methylation signatures within the human brain. Am J Hum Genet 81:1304–1315

    Article  PubMed  CAS  Google Scholar 

  • Leeming RJ, Lucock M (2009) Autism: is there a folate connection? J Inherit Metab Dis 32:400–402

    Article  PubMed  CAS  Google Scholar 

  • Lind Y, Darnerud PO, Atuma S, Aune M, Becker W, Bjerselius R, Cnattingius S, Glynn A (2003) Polybrominated diphenyl ethers in breast milk from Uppsala County, Sweden. Environ Res 93:186–194

    Article  PubMed  CAS  Google Scholar 

  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322

    Article  PubMed  CAS  Google Scholar 

  • Lyall K, Pauls DL, Santangelo S, Spiegelman D, Ascherio A (2011) A maternal early life factors associated with hormone levels and the risk of having a child with an autism spectrum disorder in the nurses health study II. J Autism Dev Disord 41:618–627

    Article  PubMed  Google Scholar 

  • Mao R, Jalal SM, Snow K, Michels VV, Szabo SM, Babovic-Vuksanovic D (2000) Characteristics of two cases with dup(15)(q112-q12): one of maternal and one of paternal origin. Genet Med 2:131–135

    Article  PubMed  CAS  Google Scholar 

  • Meerts IA, van Zanden JJ, Luijks EA, van Leeuwen-Bol I, Marsh G, Jakobsson E, Bergman A, Brouwer A (2000) Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol Sci 56:95–104

    Article  PubMed  CAS  Google Scholar 

  • Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454:766–770

    PubMed  CAS  Google Scholar 

  • Migeon BR, Dunn MA, Thomas G, Schmeckpeper BJ, Naidu S (1995) Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosome is not involved in Rett syndrome. Am J Hum Genet 56:647–653

    PubMed  CAS  Google Scholar 

  • Millar SE, Miller MW, Stevens ME, Barsh GS (1995) Expression and transgenic studies of the mouse agouti gene provide insight into the mechanisms by which mammalian coat color patterns are generated. Development 121:3223–3232

    PubMed  CAS  Google Scholar 

  • Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869

    Article  PubMed  CAS  Google Scholar 

  • Miller DT, Shen Y, Weiss LA, Korn J, Anselm I, Bridgemohan C, Cox GF, Dickinson H, Gentile J, Harris DJ, Hegde V, Hundley R, Khwaja O, Kothare S, Luedke C, Nasir R, Poduri A, Prasad K, Raffalli P, Reinhard A, Smith SE, Sobeih MM, Soul JS, Stoler J, Takeoka M, Tan WH, Thakuria J, Wolff R, Yusupov R, Gusella JF, Daly MJ, Wu BL (2008) Microdeletion/duplication at 15q132q133 among individuals with features of autism and other neuropsychiatric disorders. J Med Genet 46:242–248

    Article  PubMed  Google Scholar 

  • Milner KM, Craig EE, Thompson RJ, Veltman MW, Thomas NS, Roberts S, Bellamy M, Curran SR, Sporikou CM, Bolton PF (2005) Prader-Willi syndrome: intellectual abilities and behavioural features by genetic subtype. J Child Psychol Psychiatry 46:1089–1096

    Article  PubMed  Google Scholar 

  • Miniou P, Jeanpierre M, Blanquet V, Sibella V, Bonneau D, Herbelin C, Fischer A, Niveleau A, Viegas-Pequignot E (1994) Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients. Hum Mol Genet 3:2093–2102

    Article  PubMed  CAS  Google Scholar 

  • Mitchell MM, Woods R, Chi LH, Schmidt RJ, Pessah IN, Kostyniak PJ, Lasalle JM (2012) Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11–q13 duplication autism spectrum disorder. Environmental and Molecular Mutagenesis. doi:10.1002/em.21722.

    PubMed  Google Scholar 

  • Mohandas TK, Park JP, Spellman RA, Filiano JJ, Mamourian AC, Hawk AB, Belloni DR, Noll WW, Moeschler JB (1999) Paternally derived de novo interstitial duplication of proximal 15q in a patient with developmental delay. Am J Med Genet 82:294–300

    Article  PubMed  CAS  Google Scholar 

  • Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218–223

    Article  PubMed  CAS  Google Scholar 

  • MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338:131–137

    Article  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Google Scholar 

  • North KD (2004) Tracking polybrominated diphenyl ether releases in a wastewater treatment plant effluent, Palo Alto, California. Environ Sci Technol 38:4484–4488

    Article  PubMed  CAS  Google Scholar 

  • Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257

    Article  PubMed  CAS  Google Scholar 

  • Onishchenko N, Karpova N, Sabri F, Castren E, Ceccatelli S (2008) Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J Neurochem 106:1378–1387

    Article  PubMed  CAS  Google Scholar 

  • Pacyniak E, Roth M, Hagenbuch B, Guo GL (2010) Mechanism of polybrominated diphenyl ether uptake into the liver: PBDE congeners are substrates of human hepatic OATP transporters. Toxicol Sci 115:344–353

    Article  PubMed  CAS  Google Scholar 

  • Panning B, Jaenisch R (1996) DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes Dev 10:1991–2002

    Article  PubMed  CAS  Google Scholar 

  • Penner MR, McFadyen MP, Carrey N, Brown RE (2001) Effects of chronic and acute methylphenidate hydrochloride (Ritalin) administration on locomotor activity, ultrasonic vocalizations, and neuromotor development in 3–11-day-old CD-1 mouse pups. Dev Psychobiol 39:216–228

    Article  PubMed  CAS  Google Scholar 

  • Petreas M, She J, Brown FR, Winkler J, Windham G, Rogers E, Zhao G, Bhatia R, Charles MJ (2003) High body burdens of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in California women. Environ Health Perspect 111:1175–1179

    Article  PubMed  CAS  Google Scholar 

  • Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368–372

    Article  PubMed  CAS  Google Scholar 

  • Ramocki MB, Zoghbi HY (2008) Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature 455:912–918

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Rose M, Bennett DH, Bergman A, Fangstrom B, Pessah IN, Hertz-Picciotto I (2010) PBDEs in 2–5 year-old children from California and associations with diet and indoor environment. Environ Sci Technol 44:2648–2653

    Google Scholar 

  • Rosenberg RE, Law JK, Yenokyan G, McGready J, Kaufmann WE, Law PA (2009) Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med 163:907–914

    Article  PubMed  Google Scholar 

  • Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC (2008) Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect 116:1547–1552

    Article  PubMed  CAS  Google Scholar 

  • Sato K, Fukata H, Kogo Y, Ohgane J, Shiota K, Mori C (2009) Neonatal exposure to diethylstilbestrol alters expression of DNA methyltransferases and methylation of genomic DNA in the mouse uterus. Endocr J 56:131–139

    Article  PubMed  CAS  Google Scholar 

  • Schecter A, Papke O, Harris TR, Tung KC, Musumba A, Olson J, Birnbaum L (2006) Polybrominated diphenyl ether (PBDE) levels in an expanded market basket survey of US food and estimated PBDE dietary intake by age and sex. Environ Health Perspect 114:1515–1520

    Article  PubMed  CAS  Google Scholar 

  • Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I (2011) Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 22(4):476–485

    Article  PubMed  Google Scholar 

  • Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, MÃ¥nér S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M (2004) Large-scale copy number polymorphism in the human genome. Science 305:525–528

    Article  PubMed  CAS  Google Scholar 

  • Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M (2007) Strong association of de novo copy number mutations with autism. Science 316:445–449

    Article  PubMed  CAS  Google Scholar 

  • Shelton JF, Tancredi DJ, Hertz-Picciotto I (2010) Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Res 3:30–39

    Article  PubMed  Google Scholar 

  • Shemer R, Birger Y, Dean WL, Reik W, Riggs AD, Razin A (1996) Dynamic methylation adjustment and counting as part of imprinting mechanisms. Proc Natl Acad Sci USA 93:6371–6376

    Article  PubMed  CAS  Google Scholar 

  • Smeets DF, Moog U, Weemaes CM, Vaes-Peeters G, Merkx GF, Niehof JP, Hamers G (1994) ICF syndrome: a new case and review of the literature. Hum Genet 94:240–246

    Article  PubMed  CAS  Google Scholar 

  • Steenland K, Hein MJ, Cassinelli RT 2nd, Prince MM, Nilsen NB, Whelan EA, Waters MA, Ruder AM, Schnorr TM (2006) Polychlorinated biphenyls and neurodegenerative disease mortality in an occupational cohort. Epidemiology 17:8–13

    Article  PubMed  Google Scholar 

  • Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S, Fossdal R, Sigurdsson E, Sigmundsson T, Buizer-Voskamp JE, Hansen T, Jakobsen KD, Muglia P, Francks C, Matthews PM, Gylfason A, Halldorsson BV, Gudbjartsson D, Thorgeirsson TE, Sigurdsson A, Jonasdottir A, Jonasdottir A, Bjornsson A, Mattiasdottir S, Blondal T, Haraldsson M, Magnusdottir BB, Giegling I, Möller HJ, Hartmann A, Shianna KV, Ge D, Need AC, Crombie C, Fraser G, Walker N, Lonnqvist J, Suvisaari J, Tuulio-Henriksson A, Paunio T, Toulopoulou T, Bramon E, Di Forti M, Murray R, Ruggeri M, Vassos E, Tosato S, Walshe M, Li T, Vasilescu C, Mühleisen TW, Wang AG, Ullum H, Djurovic S, Melle I, Olesen J, Kiemeney LA, Franke B, Sabatti C, Freimer NB, Gulcher JR, Thorsteinsdottir U, Kong A, Andreassen OA, Ophoff RA, Georgi A, Rietschel M, Werge T, Petursson H, Goldstein DB, Nöthen MM, Peltonen L, Collier DA, St Clair D, Stefansson K, GROUP (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455:232–236

    Article  PubMed  CAS  Google Scholar 

  • Stoker TE, Cooper RL, Lambright CS, Wilson VS, Furr J, Gray LE (2005) In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture. Toxicol Appl Pharmacol 207:78–88

    Article  PubMed  CAS  Google Scholar 

  • Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N, Simon I, Yakhini Z, Cedar H (2009) Developmental programming of CpG island methylation profiles in the human genome. Nat Struct Mol Biol 16:564–571

    Article  PubMed  CAS  Google Scholar 

  • Tagliaferri S, Caglieri A, Goldoni M, Pinelli S, Alinovi R, Poli D, Pellacani C, Giordano G, Mutti A, Costa LG (2010) Low concentrations of the brominated flame retardants BDE-47 and BDE-99 induce synergistic oxidative stress-mediated neurotoxicity in human neuroblastoma cells. Toxicol In Vitro 24:116–122

    Article  PubMed  CAS  Google Scholar 

  • Tarantini L, Bonzini M, Apostoli P, Pegoraro V, Bollati V, Marinelli B, Cantone L, Rizzo G, Hou L, Schwartz J, Bertazzi PA, Baccarelli A (2009) Effects of particulate matter on genomic DNA methylation content and iNOS promoter methylation. Environ Health Perspect 117:217–222

    PubMed  CAS  Google Scholar 

  • Vairapandi M, Duker NJ (1994) Excision of ultraviolet-induced photoproducts of 5-methylcytosine from DNA. Mutat Res 315:85–94

    Article  PubMed  CAS  Google Scholar 

  • Veenstra-Vanderweele J, Cook E Jr, Lombroso PJ (2003) Genetics of childhood disorders: XLVI Autism, part 5: genetics of autism. J Am Acad Child Adolesc Psychiatry 42:116–118

    Article  PubMed  Google Scholar 

  • Volkmar FR, Pauls D (2003) Autism. Lancet 362:1133–1141

    Google Scholar 

  • Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, Owley T, Sweeney JA, Brune CW, Cantor RM, Bernier R, Gilbert JR, Cuccaro ML, McMahon WM, Miller J, State MW, Wassink TH, Coon H, Levy SE, Schultz RT, Nurnberger JI, Haines JL, Sutcliffe JS, Cook EH, Minshew NJ, Buxbaum JD, Dawson G, Grant SF, Geschwind DH, Pericak-Vance MA, Schellenberg GD, Hakonarson H (2009) Common genetic variants on 5p141 associate with autism spectrum disorders. Nature 459:528–533

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, LaSalle JM (2012) Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Human Molecular Genetics 21(11):2399–2411.

    Article  PubMed  CAS  Google Scholar 

  • Wright RO, Schwartz J, Wright RJ, Bollati, V, Tarantini L, Park SK, Hu H, Sparrow D, Vokonas P, Baccarelli A (2010) Biomarkers of lead exposure and DNA methylation within retrotransposons. Environ Health Perspect 118:790–795

    Google Scholar 

  • Xie H, Wang M, Bonaldo Mde F, Smith C, Rajaram V, Goldman S, Tomita T, Soares MB (2009) High-throughput sequence-based epigenomic analysis of Alu repeats in human cerebellum. Nucleic Acids Res 37:4331–4340

    Article  PubMed  CAS  Google Scholar 

  • Xu GL, Bestor TH, Bourc’his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Pequignot E (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402:187–191

    Article  PubMed  CAS  Google Scholar 

  • Yoder JA, Walsh CP, Bestor TH (1997) Cytosine methylation and the ecology of intragenomic parasites. Trends Genet 13:335–340

    Article  PubMed  CAS  Google Scholar 

  • Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP (1997) Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci USA 94:10907–10912

    Article  PubMed  CAS  Google Scholar 

  • Zoghbi HY (2003) Postnatal neurodevelopmental disorders: meeting at the synapse? Science 302:826–830

    Article  PubMed  CAS  Google Scholar 

  • Zota AR, Rudel RA, Morello-Frosch RA, Brody JG (2008) Elevated house dust and serum concentrations of PBDEs in California: unintended consequences of furniture flammability standards? Environ Sci Technol 42:8158–8164

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Medical Microbiology and Immunology, School of Medicine, Genome Center, and M.I.N.D. Institute, University of California, One Shields Ave, Davis, CA, 95616, USA

    Janine M. LaSalle, Roxanne O. Vallero & Michelle M. Mitchell

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  1. Janine M. LaSalle
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  2. Roxanne O. Vallero
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  3. Michelle M. Mitchell
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Correspondence to Janine M. LaSalle .

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  1. , Department of Oncology, University of Wisconsin-Madison, University Avenue 1400, Madison, 53706, Wisconsin, USA

    Randy L. Jirtle

  2. National Institute of Environmental Hea, NIEHS, National Institutes of Health, Research Triangle Park, 27709, North Carolina, USA

    Frederick L. Tyson

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LaSalle, J.M., Vallero, R.O., Mitchell, M.M. (2013). Epigenetics at the Interface of Genetics and Environmental Factors in Autism. In: Jirtle, R., Tyson, F. (eds) Environmental Epigenomics in Health and Disease. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36827-1_6

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