Abstract
We have learned more about the molecular genetics of autism in the last 3 years than in the previous 30. This includes both a new appreciation for the role of rare genetic variation and the identification of the first contributory common variants by genome-wide association. These data show that although the population attributable risk of common variation may be moderate to large, the genotype risk of common variants at the individual level are small. In contrast, a large number of diverse rare mutations of large effect have been identified, but none appear specific to autism. All of these findings point to extreme genetic heterogeneity suggesting complex gene-gene or gene-environment interactions in autism etiology. Available knowledge, reviewed below, also suggests that phenotypic presentation is the result of complex interactions, and that implicated genetic risk factors in many cases cross the boundaries of established clinical diagnostic categories. Acceptance of this complexity and efforts to understand genetic variation in terms of intermediate phenotypes represent important directions for future research.
Keywords
- Autism Spectrum Disorder
- Autism Spectrum Disorder
- Tourette Syndrome
- Rett Syndrome
- Acad Child Adolesc Psychiatry
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Abrahams BS, Geschwind DH (2009) Connecting genes to brain in the autisms. Arch Neurol (in press)
Abrahams BS, Tentler D, Perederiy JV, Oldham MC, Coppola G, Geschwind DH (2007) Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc Natl Acad Sci USA 104(45):17849–17854
Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9(5):341–355
Alarcon M, Abrahams BS, Stone JL et al (2008) Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82(1):150–159
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(2):185–188
Weiss, Arking DE on behalf of the Gene Discovery Project of John Hopkins and the Autism Consortium (2009) A genome-wide linkage and association scan reveals novel loci for autism. Nature (in press)
Arking DE, Cutler DJ, Brune CW et al (2008) A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 82(1):160–164
Artigiani S, Conrotto P, Fazzari P et al (2004) Plexin-B3 is a functional receptor for semaphorin 5A. EMBO Rep 5(7):710–714
Badner JA, Gershon ES (2002) Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7. Mol Psychiatry 7(1):56–66
Baker P, Piven J, Sato Y (1998) Autism and tuberous sclerosis complex: prevalence and clinical features. J Autism Dev Disord 28(4):279–285
Bailey A, Le Couteur A, Gottesman I et al (1995) Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25(1):63–77
Baird G, Charman T, Pickles A et al (2008) Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study. J Autism Dev Disord 38(10):1827–1836
Bakkaloglu B, O'Roak BJ, Louvi A et al (2008) Molecular cytogenetic analysis and resequencing of contactin associated Protein-Like 2 in autism spectrum disorders. Am J Hum Genet 82(1):165–173
Belloso JM, Bache I, Guitart M et al (2007) Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome. Eur J Hum Genet 15(6):711–713
Ben-Shachar S, Lanpher B, German JR (2009) Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet 46(6):382–388
Biederer T, Sudhof TC (2000) Mints as adaptors. Direct binding to neurexins and recruitment of munc18. J Biol Chem 275(51):39803–39806
Bijlsma EK, Gijsbers AC, Schuurs-Hoeijmakers JH (2009) Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals. Eur J Med Genet 52:77–87
Bishop DV, Maybery M, Maley A, Wong D, Hill W, Hallmayer J (2004) Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the autism-spectrum quotient. J Child Psychol Psychiatry 45(8):1431–1436
Bittel DC, Kibiryeva N, Butler MG (2006) Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader—Willi syndrome. Pediatrics 118(4):e1276–e1283
Bodmer W, Bonilla C (2008) Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 40(6):695–701
Bolton P, Macdonald H, Pickles A et al (1994) A case-control family history study of autism. J Child Psychol Psychiatry 35(5):877–900
Bonati MT, Russo S, Finelli P et al (2007) Evaluation of autism traits in Angelman syndrome: a resource to unfold autism genes. Neurogenetics 8(3):169–178
Bonora E, Beyer KS, Lamb JA et al (2003) Analysis of reelin as a candidate gene for autism. Mol Psychiatry 8(10):885–892
Boteva K, Lieberman J (2003) Reconsidering the classification of schizophrenia and manic depressive illness—a critical analysis and new conceptual model. World J Biol Psychiatry 4(2):81–92
Boucard AA, Chubykin AA, Comoletti D, Taylor P, Sudhof TC (2005) A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neur-exins. Neuron 48(2):229–236
Bucan M, Abrahams BS, Wang K (2009) Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PloS Genetics 5:e1000536
Butler MG, Dasouki MJ, Zhou XP et al (2005) Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 42(4):318–321
Buxbaum JD, Silverman J, Keddache M et al (2004) Linkage analysis for autism in a subset families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosome 6 and 19. Mol Psychiatry 9(2):144–150
Cai G, Edelmann L, Goldsmith JE et al (2008) Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT. BMC Med Genomics 1:50
Campbell DB, Sutcliffe JS, Ebert PJ et al (2006) A genetic variant that disrupts MET transcription is associated with autism. Proc Natl Acad Sci USA 103(45):16834–16839
Campbell DB, D'Oronzio R, Garbett K et al (2007) Disruption of cerebral cortex MET signaling in autism spectrum disorder. Ann Neurol 62(3):243–250
Campbell DB, Buie TM, Winter H et al (2009) Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics 123(3):1018–1024
Cantor RM, Kono N, Duvall JA et al (2005) Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet 76(6):1050–1056
Cantor RM, Yoon JL, Furr J, Lajonchere CM (2007) Paternal age and autism are associated in a family-based sample. Mol Psychiatry 12(5):419–421
Catalucci D, Zhang DH, DeSantiago J et al (2009) Akt regulates L-type Ca2+ channel activity by modulating Cavalpha1 protein stability. J Cell Biol 184(6):923–933
CDC (2007) Prevalence of autism spectrum disorders -Autism and developmental disabilities monitoring network. MMWR Surveill Summ 56:1–28
Chang Q, Khare G, Dani V, Nelson S, Jaenisch R (2006) The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49(3):341–348
Chen GK, Kono N, Geschwind DH, Cantor RM (2006) Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder. Mol Psychiatry 11(2):214–220
Chen WG, Chang Q, Lin Y et al (2003) Derepression of BDNF transcription involves calcium-dependent phospho-rylation of MeCP2. Science 302(5646):885–889
Conrotto P, Corso S, Gamberini S, Comoglio PM, Giordano S (2004) Interplay between scatter factor receptors and B plex-ins controls invasive growth. Oncogene 23(30):5131–5137
Cook EH Jr, Lindgren V, Leventhal BL et al (1997) Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 60(4):928–934
Craddock N, O'Donovan MC, Owen MJ (2006) Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology, Schizophr. Bull 32(1):9–16
Delorme R, Gousse V, Roy I et al (2007) Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder. Eur Psychiatry 22(1):32–38
Dempster EL, Toulopoulou T, McDonald C et al (2006) Episodic memory performance predicted by the 2bp deletion in exon 6 of the “alpha 7-like” nicotinic receptor subunit gene. Am J Psychiatry 163(10):1832–1834
Descheemaeker MJ, Govers V, Vermeulen P, Fryns JP (2006) Pervasive developmental disorders in Prader—Willi syndrome: the Leuven experience in 59 subjects and controls. Am J Med Genet 140(11):1136–1142
Deykin EY, MacMahon B (1979) Viral exposure and autism. Am J Epidemiol 109(6):628–638
Doornbos M, Sikkema-Raddatz B, Ruijvenkamp CA (2009) Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader—Willi critical region, possibly associated with behavioural disturbances. Eur J Med Genet 52(2-3):108–115
Durand CM, Betancur C, Boeckers TM et al (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39(1):25–27
Duvall JA, Lu A, Cantor RM, Todd RD, Constantino JN, Geschwind DH (2007) A quantitative trait locus analysis of social responsiveness in multiplex autism families. Am J Psychiatry 164(4):656–662
Feng J, Schroer R, Yan J et al (2006) High frequency of neurexin 1beta signal peptide structural variants in patients with autism. Neurosci Lett 409(1):10–13
Fernandez T, Morgan T, Davis N et al (2004) Disruption of contactin 4 (CNTN4) results in developmental delay and other features of 3p deletion syndrome. Am J Hum Genet 74(6):1286–1293
Fine SE, Weissman A, Gerdes M et al (2005) Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. J Autism Dev Disord 35(4):461–470
Folstein SE, Rutter ML (1988) Autism: familial aggregation and genetic implications. J Autism Dev Disord 18(1): 3–30
Fombonne E (2009) Epidemiology of pervasive developmental disorders. Pediatr Res 65(6):591–598
Geschwind DH (2008) Autism: many genes, common pathways? Cell 135(3):391–395
Geschwind DH (2009) Advances in autism. Annu Rev Med 60:367–380
Geschwind DH, Sowinski J, Lord C et al (2001) The autism genetic resource exchange: a resource for the study of autism and related neuropsychiatric conditions. Am J Hum Genet 69(2):463–466
Gharani N, Benayed R, Mancuso V, Brzustowicz LM, Millonig JH (2004) Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder. Mol Psychiatry 9(5):474–484
Gillberg C, Billstedt E (2000) Autism and Asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand 102(5):321–330
Glasson EJ, Bower C, Petterson B, de Klerk N, Chaney G, Hallmayer JF (2004) Perinatal factors and the development of autism: a population study. Arch Gen Psychiatry 61(6):618–627
Glessner JT, Wang K, Cai G et al (2009) Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459(7246):569–573
Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4):636–645
Hansen RL, Ozonoff S, Krakowiak P et al (2008) Regression in autism: prevalence and associated factors in the CHARGE Study. Ambul Pediatr 8(1):25–31
Hatton DD, Sideris J, Skinner M et al (2006) Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet 140(17):1804–1813
Hemara-Wahanui A, Berjukow S, Hope CI (2005) A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation. Proc Natl Acad Sci USA 102(21):7553–7558
Hertz-Picciotto I, Delwiche L (2009) The rise in autism and the role of age at diagnosis. Epidemiology 20(1):84–90
International Schizophrenia Consortium (2008) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455(7210):237–241
Jackman C, Horn ND, Molleston JP, Sokol DK (2009) Gene associated with seizures, autism, and hepatomegaly in an amish girl. Pediatr Neurol 40(4):310–313
Jacquemont ML, Sanlaville D, Redon R et al (2006) Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet 43(11):843–849
Jamain S, Quach H, Betancur C et al (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34(1):27–29
Jansiewicz EM, Goldberg MC, Newschaffer CJ, Denckla MB, Landa R, Mostofsky SH (2006) Motor signs distinguish children with high functioning autism and Asperger's syndrome from controls. J Autism Dev Disord 36(5):613–621
Jorde LB, Hasstedt SJ, Ritvo ER et al (1991) Complex segregation analysis of autism. Am J Hum Genet 49(5):932–938
Kent L, Bowdin S, Kirby GA, Cooper WN, Maher ER (2008) Beckwith Weidemann syndrome: a behavioral phe-notype-genotype study. Am J Med Genet B Neuropsychiatr Genet 147B(7):1295–1297
Kim HG, Kishikawa S, Higgins AW et al (2008) Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet 82(1):199–207
Kirov G, Gumus D, Chen W et al (2008) Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 17(3):458–465
Kozlov SV, Bogenpohl JW, Howell MP et al (2007) The imprinted gene Magel2 regulates normal circadian output. Nat Genet 39(10):1266–1272
Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, Croen LA, Hansen RL (2008) Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. J Sleep Res 17(2):197–206
Kumar RA, KaraMohamed S, Sudi J (2008) Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet 17(4):628–638
Kumar RA, Marshall CR, Badner JA, 2 (2009) Association and mutation analyses of 16p11.2 autism candidate genes. PLoS One 4:e4582
Laumonnier F, Bonnet-Brilhault F, Gomot M et al (2004) X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 74(3):552–557
Lawson-Yuen A, Saldivar JS, Sommer S, Picker J (2008) Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet 16(5):614–618
Levitt P, Campbell DB (2009) The genetic and neurobio-logic compass points toward common signaling dysfunctions in autism spectrum disorders. J Clin Invest 119(4):747–754
Landa R, Piven J, Wzorek MM, Gayle JO, Chase GA, Folstein SE (1992) Social language use in parents of autistic individuals. Psychol Med 22(1):245–254
Leekam SR, Nieto C, Libby SJ, Wing L, Gould J (2007) Describing the sensory abnormalities of children and adults with autism. J Autism Dev Disord 37(5):894–910
Lintas C, Sacco R, Garbett K et al (2009) Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression. Mol Psychiatry 14:705–718
Lowenthal R, Paula CS, Schwartzman JS, Brunoni D, Mercadante MT (2007) Prevalence of pervasive developmental disorder in Down's syndrome. J Autism Dev Disord 37(7):1394–1395
Maestrini E, Pagnamenta AT, Lamb JA et al (2009) High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. Mol Psychiatry (in press)
Malow BA, Marzec ML, McGrew SG, Wang L, Henderson LM, Stone WL (2006) Characterizing sleep in children with autism spectrum disorders: a multidimensional approach. Sleep 29(12):1563–1571
Manning MA, Cassidy SB, Clericuzio C et al (2004) Terminal 22q deletion syndrome: a newly recognized cause of speech and language disability in the autism spectrum. Pediatrics 114(2):451–457
Marshall CR, Noor A, Vincent JB et al (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82(2):477–488
Mefford HC, Sharp AJ, Baker C (2008) Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 359(16):1685–1699
Melke J, Goubran Botros H, Chaste P et al (2008) Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 13(1):90–98
Milani D, Pantaleoni C, D'Arrigo S, Selicorni A, Riva D (2005) Another patient with MECP2 mutation without classic Rett syndrome phenotype. Pediatr Neurol 32(5):355–357
Ming X, Brimacombe M, Wagner GC (2007) Prevalence of motor impairment in autism spectrum disorders. Brain Dev 29(9):565–570
Moessner R, Marshall CR, Sutcliffe JS et al (2007) Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 81(6):1289–1297
Molloy CA, Keddache M, Martin LJ (2005) Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Mol Psychiatry 10(8):741–746
Morrow EM, Yoo SY, Flavell SW et al (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321(5886):218–223
Napoli I, Mercaldo V, Boyl PP et al (2008) The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134(6):1042–1054
Need AC, Ge D, Weale ME et al (2009) A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genet 5(2):e1000373
Nishimura Y, Martin CL, Vazquez-Lopez A et al (2007) Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum Mol Genet 16(14):1682–1698
Orrico A, Galli L, Buoni S, Orsi A, Vonella G, Sorrentino V (2009) Novel PTEN mutations in neurodevelopmental disorders and macrocephaly. Clin Genet 75(2):195–198
Peters SU, Beaudet AL, Madduri N, Bacino CA (2004) Autism in Angelman syndrome: implications for autism research. Clin Genet 66(6):530–536
Philippi A, Roschmann E, Tores F et al (2005) Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism. Mol Psychiatry 10(10):950–960
Piven J, Palmer P (1997) Cognitive deficits in parents from multiple-incidence autism families. J Child Psychol Psychiatry 38(8):1011–1021
Poliak S, Gollan L, Martinez R (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxta-paranodes of myelinated axons and associates with K + channels. Neuron 24(4):1037–1047
Potocki L, Bi W, Treadwell-Deering D (2007) Characterization of Potocki-Lupski syndrome (dup(17) (p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet 80(4):633–649
Reichenberg A, Gross R, Weiser M et al (2006) Advancing paternal age and autism. Arch Gen Psychiatry 63(9):1026–1032
Ritvo ER, Jorde LB, Mason-Brothers A et al (1989) The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. Am J Psychiatry 146(8):1032–1036
Ronald A, Happe F, Bolton P et al (2006) Genetic heterogeneity between the three components of the autism spectrum: a twin study. J Am Acad Child Adolesc Psychiatry 45(6):691–699
Roohi J, Montagna C, Tegay DH et al (2009) Disruption of contactin 4 in three subjects with autism spectrum disorder. J Med Genet 46(3):176–182
Rujescu D, Ingason A, Cichon S et al (2009) Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet 18(5):988–996
Rujescu D, Meisenzahl EM, Krejcova S (2007) Plexin B3 is genetically associated with verbal performance and white matter volume in human brain. Mol Psychiatry 12(2):190– 194 115
Rzhetsky A, Wajngurt D, Park N, Zheng T (2007) Probing genetic overlap among complex human phenotypes. Proc Natl Acad Sci USA 104(28):11694–11699
Sadakata T, Washida M, Iwayama Y et al (2007) Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients. J Clin Invest. 117(4):931–943
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(4):483–492
Sebat J, Lakshmi B, Malhotra D et al (2007) Strong association of de novo copy number mutations with autism. Science 316(5823):445–449
Schellenberg GD, Dawson G, Sung YJ et al (2006) Evidence for multiple loci from a genome scan of autism kindreds. Mol Psychiatry 11(11):1049–1060
Sharp AJ, Mefford HC, Li K (2008) A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat Genet 40(3):322–328
Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G (2008) Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 47(8):921–929
Splawski I, Timothy KW, Sharpe LM (2004) Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119(1):19–31
Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT (2006) CACNA1H mutations in autism spectrum disorders. J Biol Chem 281(31):22085–22091
Stefansson H, Rujescu D, Cichon S et al (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455(7210):232–236
Steffenburg S, Gillberg C, Hellgren L et al (1989) A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 30(3):405–416
Stone JL, Merriman B, Cantor RM et al (2004) Evidence for sex-specific risk alleles in autism spectrum disorder. Am J Hum Genet 75(6):1117–1123
Strauss KA, Puffenberger EG, Huentelman MJ et al (2006) Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N Engl J Med 354(13):1370–1377
Strom SP, Stone JL, ten Bosch JR et al (2009) High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene. Mol Psychiatry (in press)
Sutcliffe JS, Delahanty RJ, Prasad HC et al (2005) Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet 77(2):265–279
Szatmari P, Paterson AD, Zwaigenbaum L et al (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39(3):319–328
Tierney E, Nwokoro NA, Porter FD, Freund LS, Ghuman JK, Kelley RI (2001) Behavior phenotype in the RSH/ Smith-Lemli-Opitz syndrome. Am J Med Genet 98(2):191–200
Trikalinos TA, Karvouni A, Zintzaras E et al (2006) A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry 11(1):29–36
Tuchman R, Rapin I (2002) Epilepsy in autism. Lancet Neurol 1(6):352–358
Ueda S, Fujimoto S, Hiramoto K, Negishi M, Katoh H (2008) Dock4 regulates dendritic development in hip-pocampal neurons. J Neurosci Res 86(14):3052–3061
van Bon BW, Mefford HC, Menten B et al (2009) Further delineation of the 15q13 microdeletion and duplication syndromes: A clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet 46(8):511–23
Van Esch H, Bauters M, Ignatius J 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(3):442–453
Varga EA, Pastore M, Prior T, Herman GE, McBride KL (2009) The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly. Genet Med 11(2): 111–117
Verkerk AJ, Mathews CA, Joosse M, Eussen BH, Heutink P, Oostra BA (2003) CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 82(1):1–9
Vernes SC, Newbury DF, Abrahams BS et al (2008) A functional genetic link between distinct developmental language disorders. N Engl J Med 359(22): 2337–2345
Volkmar FR, Nelson DS (1990) Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry 29(1):127–129
Vorstman JA, Morcus ME, Duijff SN (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45(9):1104–1113
Vorstman JA, Staal WG, van Daalen E, van Engeland H, Hochstenbach PF, Franke L (2006) Identification of novel autism candidate regions through analysis of reported cyto-genetic abnormalities associated with autism. Mol Psychiatry 11(1):18–28 1
Wang K, Zhang H, Ma D (2009) Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 459(7246):528–533
Weiss LA, Escayg A, Kearney JA et al (2003) Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol Psychiatry 8(2):186–194
Weiss LA, Kosova G, Delahanty RJ et al (2006) Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility. Eur J Hum Genet 14(8): 923–931
Weiss LA, Shen Y, Korn JM (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358(7):667–675
Wong D, Maybery M, Bishop DV, Maley A, Hallmayer J (2006) Profiles of executive function in parents and siblings of individuals with autism spectrum disorders. Genes Brain Behav 5(8):561–576
Xue M, Brimacombe M, Chaaban J, Zimmerman-Bier B, Wagner GC (2008) Autism spectrum disorders: concurrent clinical disorders. J Child Neurol 23(1):6–13
Yan J, Oliveira G, Coutinho A et al (2005) Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychi-atric patients. Mol Psychiatry 10(4):329–332
Zafeiriou DI, Ververi A, Vargiami E (2007) Childhood autism and associated comorbidities. Brain Dev 29(5): 257–272
Zoghbi HY (2003) Postnatal neurodevelopmental disorders: meeting at the synapse? Science 302(5646):826–830
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Abrahams, B.S., Geschwind, D.H. (2010). Genetics of Autism. In: Speicher, M.R., Motulsky, A.G., Antonarakis, S.E. (eds) Vogel and Motulsky's Human Genetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-37654-5_29
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