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2 - Unravelling the genetics of autism spectrum disorders

Published online by Cambridge University Press:  04 February 2011

By
Inês De Sousa ,
Richard Holt ,
Alistair Pagnamenta  and
Anthony Monaco
Edited by
Ilona Roth  and
Payam Rezaie
Ilona Roth
Affiliation:
The Open University, Milton Keynes
Payam Rezaie
Affiliation:
The Open University, Milton Keynes
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Summary

Since autism was first described in 1943, it has become evident that the condition is one of the most heritable of all the childhood onset neurodevelopmental disorders. In this chapter we chart the progress of researchers' attempts to understand the genetic components of autism spectrum disorders and how these studies have tracked the advances in technology and knowledge in the field of genetics in general. We start by describing the evidence that autism spectrum disorders have such a strong genetic component. We then consider approaches to identify susceptibility genes such as linkage, candidate gene studies and association analysis. Various epigenetic mechanisms of potential relevance to autism as well as the expanding area of copy number variations are also highlighted. Some of the theoretical background to each of these approaches is given and findings from each approach are summarized and discussed. In addition, several specific examples are given for each method to demonstrate in detail the way in which they have been employed to yield key successes within the field of autism genetics. Finally, we look towards the future and suggest possible further avenues of investigation, as well as newly arising challenges, in this difficult, yet exciting field of study.

Evidence for genetic liability and the multifactorial model for autism

In 1943, Leo Kanner, an Austrian psychiatrist, was the first to describe a condition observed in a group of eleven children with developmental abnormalities, a disorder that today is known as autism (Kanner, 1943).

Type
Chapter
Information
Researching the Autism Spectrum
Contemporary Perspectives
 , pp. 53 - 111
Publisher: Cambridge University Press
Print publication year: 2011

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References

Adams, M., Lucock, M., Stuart, J., et al. (2007). Preliminary evidence for involvement of the folate gene polymorphism 19bp deletion-DHFR in occurrence of autism. Neuroscience Letters, 422: 24–29.CrossRefGoogle ScholarPubMed
Alarcón, M., Cantor, R.M., Liu, J., Gilliam, T.C., Geschwind, D.H. and the Autism Genetic Research Exchange Consortium. (2002). Evidence for a language quantitative trait locus on chromosome 7q in multiplex autism families. American Journal of Human Genetics, 70: 60–71.CrossRefGoogle ScholarPubMed
Alarcón, M., Yonan, A.L., Gilliam, T.C., Cantor, R.M., Geschwind, D.H. (2005). Quantitative genome scan and Ordered-Subsets Analysis of autism endophenotypes support language QTLs. Molecular Psychiatry, 10: 747–757.CrossRefGoogle ScholarPubMed
Alarcón, M., Abrahams, B.S., Stone, J.L., et al. (2008). Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. American Journal of Human Genetics, 82: 150–159.CrossRefGoogle ScholarPubMed
Alvarez Retuerto, A.I., Cantor, R.M., Gleeson, J.G., et al. (2008). Association of common variants in the Joubert syndrome gene (AHI1) with autism. Human Molecular Genetics, 17: 3887–3896.CrossRefGoogle ScholarPubMed
Anderson, B.M., Schnetz-Boutaud, N.C., Bartlett, J., et al. (2009). Examination of association of genes in the serotonin system to autism. Neurogenetics, 10: 209–216.CrossRefGoogle ScholarPubMed
Anderson, G.M., Freedman, D.X., Cohen, D.J., et al. (1987). Whole blood serotonin in autistic and normal subjects. Journal of Child Psychology and Psychiatry, 28: 885–900.CrossRefGoogle ScholarPubMed
Anitha, A., Nakamura, K., Yamada, K., et al. (2008). Genetic analyses of roundabout (ROBO) axon guidance receptors in autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B: 1019–1027.CrossRefGoogle ScholarPubMed
Arking, D.E., Cutler, D.J., Brune, C.W., et al. (2008). A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. American Journal of Human Genetics, 82: 160–164.CrossRefGoogle ScholarPubMed
Ashley-Koch, A., Wolpert, C.M., Menold, M.M., et al. (1999). Genetic studies of autistic disorder and chromosome 7. Genomics, 61: 227–236.CrossRefGoogle ScholarPubMed
Ashley-Koch, A.E., Mei, H., Jaworski, J., et al. (2006). An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder. Annals of Human Genetics, 70: 281–292.CrossRefGoogle ScholarPubMed
Ashley-Koch, A.E., Jaworski, J., Ma, Q., et al. (2007). Investigation of potential gene-gene interactions between APOE and RELN contributing to autism risk. Psychiatric Genetics, 17: 221–226.CrossRefGoogle ScholarPubMed
Auranen, M., Vanhala, R., Varilo, T., et al. (2002). A genomewide screen for autism-spectrum disorders: evidence for a major susceptibility locus on chromosome 3q25–27. American Journal of Human Genetics, 71: 777–790.CrossRefGoogle Scholar
Bacchelli, E., Maestrini, E. (2006). Autism spectrum disorders: molecular genetic advances. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 142: 13–23.CrossRefGoogle Scholar
Badner, J.A., Gershon, E.S. (2002). Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7. Molecular Psychiatry, 7: 56–66.CrossRefGoogle ScholarPubMed
Baker, P., Piven, J., Schwartz, S., Patil, S. (1994). Brief report: duplication of chromosome 15q11–13 in two individuals with autistic disorder. Journal of Autism and Developmental Disorders, 24: 529–535.CrossRefGoogle ScholarPubMed
Bailey, A., Couteur, A., Gottesman, I., et al. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25: 63–77.CrossRefGoogle ScholarPubMed
Bailey, A., Phillips, W., Rutter, M. (1996). Autism: towards an integration of clinical, genetic, neuropsychological and neurobiological perspectives. Journal of Child Psychology and Psychiatry, 37: 89–126.CrossRefGoogle ScholarPubMed
Bailey, A., Palferman, S., Heavey, L., Couteur, A. (1998). Autism: the phenotype in relatives. Journal of Autism and Developmental Disorders, 28: 369–392.CrossRefGoogle ScholarPubMed
Bakkaloglu, B., O'Roak, B.J., Louvi, A., et al. (2008). Cytogenetic analysis and resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum Disorders. American Journal of Human Genetics, 82: 165–173.CrossRefGoogle ScholarPubMed
Ballif, B.C., Hornor, S.A., Jenkins, E., et al. (2007). Discovery of a previously unrecognized microdeletion syndrome of 16p11.2–p12.2. Nature Genetics, 39: 1071–1073.CrossRefGoogle ScholarPubMed
Barnby, G., Abbott, A., Sykes, N., et al. (2005). Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. American Journal of Human Genetics, 76: 950–966.CrossRefGoogle ScholarPubMed
Barrett, S., Beck, J.C., Bernier, R., et al. (1999). An autosomal genomic screen for autism. Collaborative linkage study of autism. American Journal of Medical Genetics, 88: 609–615.Google ScholarPubMed
Benayed, R., Gharani, N., Rossman, I., et al. (2005). Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus. American Journal of Human Genetics, 77: 851–868.CrossRefGoogle ScholarPubMed
Benayed, R., Choi, J., Matteson, P.G., et al. (2009). Autism-associated haplotype affects the regulation of the homeobox gene, ENGRAILED 2. Biological Psychiatry, 66: 911–917.CrossRefGoogle ScholarPubMed
Betancur, C., Corbex, M., Spielewoy, C., et al. (2002). Serotonin transporter gene polymorphisms and hyperserotonemia in autistic disorder. Molecular Psychiatry, 7: 67–71.CrossRefGoogle ScholarPubMed
Blasi, F., Bacchelli, E., Pesaresi, G., et al. (2006). Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 141: 220–221.CrossRefGoogle Scholar
Bolton, P., Macdonald, H., Pickles, A., et al. (1994). A case-control family history study of autism. Journal of Child Psychology and Psychiatry, 35: 877–900.CrossRefGoogle ScholarPubMed
Bonora, E., Bayer, K.S., Lamb, J.A., et al. (2003). Analysis of reelin as a candidate gene for autism. Molecular Psychiatry, 8: 885–892.CrossRefGoogle ScholarPubMed
Bonora, E., Lamb, J.A., Barnby, G., et al. (2005). Mutation screening and association analysis of six candidate genes for autism on chromosome 7q. European Journal of Human Genetics, 13: 198–207.CrossRefGoogle ScholarPubMed
Bradford, Y., Haines, J., Hutcheson, H., et al. (2001). Incorporating language phenotypes strengthens evidence of linkage to autism. American Journal of Medical Genetics, 105: 539–547.CrossRefGoogle ScholarPubMed
Bucan, M., Abrahams, B.S., Wang, K., et al. (2009). Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genetics, 5: e1000536.CrossRefGoogle Scholar
Burns, J.C., Shimizu, C., Gonzalez, E., et al. (2005). Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. Journal of Infectious Diseases, 192: 344–349.CrossRefGoogle ScholarPubMed
Butler, M.G., Dasouki, M.J., Zhou, X.P., et al. (2005). Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. Journal of Medical Genetics, 42: 318–321.CrossRefGoogle ScholarPubMed
Buxbaum, J.D., Silverman, J.M., Smith, C.J., et al. (2001). Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. American Journal of Human Genetics, 68: 1514–1520.CrossRefGoogle ScholarPubMed
Buxbaum, J.D., Silverman, J.M., Smith, C.J., et al. (2002). Association between a GABRB3 polymorphism and autism. Molecular Psychiatry, 7: 311–316.CrossRefGoogle ScholarPubMed
Buxbaum, J.D., Silverman, J., Keddache, M., et al. (2004). Linkage analysis for autism in a subset of families with obsessive-compulsive behaviors: evidence for an autism susceptibility gene on chromosome 1 and further support for susceptibility genes on chromosomes 6 and 19. Molecular Psychiatry, 9: 144–150.CrossRefGoogle Scholar
Buyske, S., Williams, T.A., Mars, A.E., et al. (2006). Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genetics, 7: 8.CrossRefGoogle Scholar
Campbell, D.B., Sutcliffe, J.S., Ebert, P.J.et al. (2006). A genetic variant that disrupts MET transcription is associated with autism. Proceedings of the National Academy of Sciences USA, 103: 16834–16839.CrossRefGoogle ScholarPubMed
Campbell, D.B., Li, C., Sutcliffe, J.S., Persico, A.M., Levitt, P. (2008). Genetic evidence implicating multiple genes in the MET receptor tyrosine kinase pathway in autism spectrum disorder. Autism Research, 1: 159–168.CrossRefGoogle ScholarPubMed
Campbell, D.B., Buie, T.M., Winter, H., et al. (2009). Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics, 123: 1018–1024.CrossRefGoogle ScholarPubMed
Cantor, R.M., Kono, N., Duvall, J.A., et al. (2005). Replication of autism linkage: fine-mapping peak at 17q21. American Journal of Human Genetics, 76: 1050–1056.CrossRefGoogle Scholar
Cheng, L., Ge, Q., Xiao, P., et al. (2009). Association study between BDNF gene polymorphisms and autism by three-dimensional gel-based microarray. International Journal of Molecular Science, 10: 2487–2500.CrossRefGoogle ScholarPubMed
Chinnery, P.F. (2007). Mutations in SUCLA2: a tandem ride back to the Krebs cycle. Brain, 130: 606–609.CrossRefGoogle ScholarPubMed
Cho, I.H., Yoo, H.J., Park, M., Lee, Y.S., Kim, S.A. (2007). Family-based association study of 5-HTTLPR and the 5-HT2A receptor gene polymorphisms with autism spectrum disorder in Korean trios. Brain Research,1139: 34–41.CrossRefGoogle ScholarPubMed
Christian, S.L., Brune, C.W., Sudi, J., et al. (2008). Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biological Psychiatry, 63: 1111–1117.CrossRefGoogle ScholarPubMed
Chung, S., Hong, J.P., Yoo, H.K. (2007). Association of the DAO and DAOA gene polymorphisms with autism spectrum disorders in boys in Korea: a preliminary study. Psychiatry Research, 153: 179–182.CrossRefGoogle Scholar
Colella, S., Yau, C., Taylor, J.M., et al. (2007). QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Research, 35: 2013–2025.CrossRefGoogle ScholarPubMed
Collins, A.L., Ma, D., Whitehead, P.L., et al. (2006). Investigation of autism and GABA receptor subunit genes in multiple ethnic groups. Neurogenetics, 7: 167–174.CrossRefGoogle ScholarPubMed
Conciatori, M., Stodgell, C.J., Hyman, S.L., et al. (2004). Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Biological Psychiatry, 55: 413–419.CrossRefGoogle ScholarPubMed
Connors, S.L., Crowell, D.E., Eberhart, C.G., et al. (2005). Beta2-adrenergic receptor activation and genetic polymorphisms in autism: data from dizygotic twins. Journal of Child Neurology, 20: 876–884.CrossRefGoogle ScholarPubMed
Conrad, D.F., Andrews, T.D., Carter, N.P., Hurles, M.E., Pritchard, J.K. (2006). A high-resolution survey of deletion polymorphism in the human genome. Nature Genetics, 38: 75–81.CrossRefGoogle ScholarPubMed
Conroy, J., Meally, E., Kearney, G., et al. (2004). Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Molecular Psychiatry, 9: 587–593.CrossRefGoogle Scholar
Conroy, J., Cochrane, L., Anney, R.J., et al. (2009). Fine mapping and association studies in a candidate region for autism on chromosome 2q31–q32. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B: 535–544.CrossRefGoogle Scholar
Cook, E.H., Lindgren, V., Leventhal, B.L., et al. (1997a). Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. American Journal of Human Genetics, 60: 928–934.Google Scholar
Cook, E.H., Courchesne, R., Lord, C., et al. (1997b). Evidence of linkage between the serotonin transporter and autistic disorder. Molecular Psychiatry, 2: 247–250.Google ScholarPubMed
Cook, E.H., Courchesne, R.Y., Cox, N.J., et al. (1998). Linkage-disequilibrium mapping of autistic disorder, with 15q11–13 markers. American Journal of Human Genetics, 62: 1077–1083.CrossRefGoogle ScholarPubMed
Coon, H., Dunn, D., Lainhart, J., et al. (2005). Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 135: 42–46.CrossRefGoogle Scholar
Correia, C., Coutinho, A.M., Almeida, J., et al. (2009). Association of the alpha4 integrin subunit gene (ITGA4) with autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B: 1147–1151.CrossRefGoogle ScholarPubMed
Coutinho, A.M., Oliveira, G., Morgadinho, T., et al. (2004). Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Molecular Psychiatry, 9: 264–271.CrossRefGoogle ScholarPubMed
Coutinho, A.M., Sousa, I., Martins, M., et al. (2007). Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Human Genetics, 121: 243–256.CrossRefGoogle ScholarPubMed
Curran, S., Powell, J., Neale, B.M., et al. (2006). An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder. Molecular Psychiatry, 11: 709–713.CrossRefGoogle ScholarPubMed
D'Amelio, M., Ricci, I., Sacco, R., et al. (2005). Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions. Molecular Psychiatry, 10: 1006–1016.CrossRefGoogle Scholar
Darden, L. (2005). Relations among fields: Mendelian, cytological and molecular mechanisms. Studies in History and Philosophy of Biological and Biomedical Sciences, 36: 349–371.CrossRefGoogle ScholarPubMed
Krom, M., Staal, W.G., Ophoff, R.A., et al. (2009). A common variant in DRD3 receptor is associated with autism spectrum disorder. Biological Psychiatry, 65: 625–630.CrossRefGoogle ScholarPubMed
Ravel, T.J., Devriendt, K., Fryns, J.P., Vermeesch, J.R. (2007). What's new in karyotyping? The move towards array comparative genomic hybridisation (CGH). European Journal of Pediatrics, 166: 637–643.CrossRefGoogle Scholar
Devlin, B., Bennett, P., Dawson, G., et al. (2004). Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 126: 46–40.CrossRefGoogle Scholar
Devlin, B., Cook, E.H., Coon, H., et al. (2005). Autism and the serotonin transporter: the long and short of it. Molecular Psychiatry, 10: 1110–1116.CrossRefGoogle Scholar
Durand, C.M., Betancur, C., Boeckers, T.M., et al. (2007). Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics, 39: 25–27.CrossRefGoogle ScholarPubMed
Dutta, S., Guhathakurta, S., Sinha, S., et al. (2007). Reelin gene polymorphisms in the Indian population: a possible paternal 5'UTR-CGG-repeat-allele effect on autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144: 106–112.CrossRefGoogle Scholar
Dutta, S., Sinha, S., Ghosh, S., et al. (2008). Genetic analysis of reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population. Neuroscience Letters, 441: 56–60.CrossRefGoogle ScholarPubMed
Elston, R.C., Thompson, E.A. (2000). A century of biometrical genetics. Biometrics, 56: 659–666.CrossRefGoogle ScholarPubMed
Feng, J.et al. (2006). High frequency of neurexin-1beta signal peptide structural variants in patients with autism. Neuroscience Letters, 409: 10–13.CrossRefGoogle ScholarPubMed
Folstein, S.E., Rosen-Sheidley, B. (2001). Genetics of autism: complex aetiology for a heterogeneous disorder. Nature Reviews Genetics, 21: 943–955.CrossRefGoogle Scholar
Folstein, S., Rutter, M. (1977). Infantile autism: a genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry, 18: 297–321.CrossRefGoogle ScholarPubMed
Fombonne, E. (2005). Epidemiology of autistic disorder and other pervasive developmental disorders. Journal of Clinical Psychiatry, 66 (Suppl. 10): 3–8.Google ScholarPubMed
Frazer, K.A., Ballinger, D.G., Cox, D.R. and the International HapMap Consortium. (2007). A second generation human haplotype map of over 3.1 million SNPs. Nature, 449: 851–861.CrossRefGoogle ScholarPubMed
Freitag, C.M., Agelopoulos, K., Huy, E., et al. (2010). Adenosine A(2A) receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder. European Child and Adolescent Psychiatry, 19: 67–74.CrossRefGoogle ScholarPubMed
Gauthier, J., Bonnel, A., St-Onge, J., et al. (2005). NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 132: 74–75.CrossRefGoogle Scholar
Gauthier, J., Spiegelman, D., Piton, A., et al. (2009). Novel de novo SHANK3 mutation in autistic patients. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B: 421–424.CrossRefGoogle ScholarPubMed
Ghebranious, N., Giampietro, P.F., Wesbrook, F.P., Reazkalla, S.H. (2007). A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation. American Journal of Medical Genetics, 143: 1462–1471.CrossRefGoogle Scholar
Gillberg, C., Steffenburg, S., Wahlstrom, J., et al. (1991). Autism associated with marker chromosome. Journal of the American Academy of Child and Adolescent Psychiatry, 30: 489–494.CrossRefGoogle ScholarPubMed
Glessner, J., Wang, K., Cai, G., et al. (2009). Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature, 459: 569–573.CrossRefGoogle ScholarPubMed
Gonzalez, E., Kulkarni, H., Bolivar, H., et al. (2005). The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science, 307: 1434–1440.CrossRefGoogle ScholarPubMed
Grigorenko, E.L., Han, S.S., Yrigollen, C.M., et al. (2008): Macrophage migration inhibitory factor and autism spectrum disorders. Pediatrics, 122: e438–445.CrossRefGoogle ScholarPubMed
Guhathakurta, S., Ghosh, S., Sinha, S., et al. (2006). Serotonin transporter promoter variants: Analysis in Indian autistic and control population. Brain Research, 1092: 28–35.CrossRefGoogle ScholarPubMed
Guhathakurta, S., Sinha, S., Ghosh, S., et al. (2008). Population-based association study and contrasting linkage disequilibrium pattern reveal genetic association of SLC6A4 with autism in the Indian population from West Bengal. Brain Research, 1240: 12–21.CrossRefGoogle ScholarPubMed
Hallmayer, J., Herbert, J.M., Spiker, D., et al. (1996a). Autism and the X chromosome. Multipoint sib-pair analysis. Archives of General Psychiatry, 53: 985–989.CrossRefGoogle ScholarPubMed
Hallmayer, J., Spiker, D., Lotspeich, L., et al. (1996b). Male-to-male transmission in extended pedigrees with multiple cases of autism. American Journal of Medical Genetics, 67: 13–18.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
Hauser, E.R., Watanabe, R.M., Duren, W.L., et al. (2004). Ordered subset analysis in genetic linkage mapping of complex traits. Genetic Epidemiology, 27: 53–63.CrossRefGoogle ScholarPubMed
Henningsson, S., Jonsson, L., Ljunggren, E., et al. (2009). Possible association between the androgen receptor gene and autism spectrum disorder. Psychoneuroendocrinology, 34: 752–761.CrossRefGoogle ScholarPubMed
Herault, J., Petit, E., Martineau, J., et al. (1995). Autism and genetics: clinical approach and association study with two markers of HRAS gene. American Journal of Medical Genetics, 60: 276–281.CrossRefGoogle ScholarPubMed
Hettinger, J.A., Liu, X., Schwartz, C.E., Michaelis, R.C., Holden, J.J. (2008a). A DRD1 haplotype is associated with risk for autism spectrum disorders in male-only affected sib-pair families. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B: 628–636.CrossRefGoogle ScholarPubMed
Hettinger, J.A., Liu, X., Holden, J.J. (2008b). The G22A polymorphism of the ADA gene and susceptibility to autism spectrum disorders. Journal of Autism and Developmental Disorders, 38: 14–19.CrossRefGoogle ScholarPubMed
Hinds, D.A., Kloek, A.P., Jen, M., Chen, X., Frazer, K.A. (2006). Common deletions and SNPs are in linkage disequilibrium in the human genome. Nature Genetics, 38: 82–85.CrossRefGoogle ScholarPubMed
Hirschhorn, J.N., Daly, M.J. (2005). Genome-wide association studies for common diseases and complex traits. Nature Reviews Genetics, 6: 95–108.CrossRefGoogle ScholarPubMed
Hutcheson, H.B., Olson, L.M., Bradford, Y., et al. (2004). Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Medical Genetics, 5: 12.CrossRefGoogle ScholarPubMed
Iafrate, A.J., Feuk, L., Rivera, M.N., et al. (2004). Detection of large-scale variation in the human genome. Nature Genetics, 36: 949–951.CrossRefGoogle ScholarPubMed
,IMGSAC – International Molecular Genetic Study of Autism Consortium. (1998). A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Human Molecular Genetics, 7: 571–578.CrossRefGoogle Scholar
,IMGSAC – International Molecular Genetic Study of Autism Consortium. (2001). A genomewide screen for autism: Strong evidence for linkage to chromosomes 2q, 7q, and 16p. American Journal of Human Genetics, 69: 570–581.CrossRefGoogle Scholar
Ingram, J.L., Stodgell, C.J., Hyman, S.L., et al. (2000). Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology, 62: 393–405.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Jackson, P.B., Boccuto, L., Skinner, C., et al. (2009). Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder. Autism Research, 2: 232–236.CrossRefGoogle ScholarPubMed
Jacob, S., Brune, C.W., Carter, C.S., et al. (2007). Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neuroscience Letters, 417: 6–9.CrossRefGoogle ScholarPubMed
Jacquemont, M.L., 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. Journal of Medical Genetics, 43: 843–849.CrossRefGoogle ScholarPubMed
Jamain, S., Betancur, C., Quach, H., et al. (2002). Linkage and association of the glutamate receptor 6 gene with autism. Molecular Psychiatry, 7: 302–310.CrossRefGoogle ScholarPubMed
Jamain, S., Quach, H., Betancur, C., et al. (2003). Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature Genetics, 34: 27–29.CrossRefGoogle ScholarPubMed
Jiang, Y.H., Sahoo, T., Michaelis, R.C., et al. (2004). A mixed epigenetic/genetic model for oligogenic inheritance of autism with a limited role for UBE3A. American Journal of Medical Genetics, 131: 1–10.CrossRefGoogle ScholarPubMed
Johnson, W.G., Buyske, S., Mars, A.E., et al. (2009). HLA-DR4 as a risk allele for autism acting in mothers of probands possibly during pregnancy. Archives of Pediatrics and Adolescent Medicine, 163: 542–546.CrossRefGoogle ScholarPubMed
Junaid, M.A., Kowal, D., Barua, M., et al. (2004). Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor. American Journal of Medical Genetics, 131: 11–17.CrossRefGoogle ScholarPubMed
Kanner, L. (1943). Autistic disturbances of affective contact. Nervous Child, 2: 217–250.Google Scholar
Kato, C., Tochigi, M., Ohashi, J., et al. (2008). Association study of the 15q11–q13 maternal expression domain in Japanese autistic patients. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B: 1008–1012.CrossRefGoogle ScholarPubMed
Kilpinen, H., Ylisaukko-oja, T., Hennah, W., et al. (2008). Association of DISC1 with autism and Asperger syndrome. Molecular Psychiatry, 13: 187–196.CrossRefGoogle ScholarPubMed
Kim, H.G., Kishikawa, S., Higgins, A.W., et al. (2008b). Disruption of neurexin 1 associated with autism spectrum disorder. American Journal of Human Genetics, 82: 199–207.CrossRefGoogle ScholarPubMed
Kim, H.W., Cho, S.C., Kim, J.W., et al. (2009). Family-based association study between NOS-I and -IIA polymorphisms and autism spectrum disorders in Korean trios. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B: 300–306.CrossRefGoogle ScholarPubMed
Kim, S.A., Kim, J.H., Park, M., Cho, I.H., Yoo, H.J. (2006). Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios. Neuropsychobiology, 54: 160–165.CrossRefGoogle ScholarPubMed
Kim, S.A., Kim, J.H., Park, M., Cho, I.H., Yoo, H.J. (2007). Family-based association study between GRIK2 polymorphisms and autism spectrum disorders in the Korean trios. Neuroscience Research, 58: 332–335.CrossRefGoogle ScholarPubMed
Kim, S.J., Young, L.J., Gonen, D., et al. (2002). Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Molecular Psychiatry, 7: 503–507.CrossRefGoogle ScholarPubMed
Kim, S.J., Brune, C.W., Kistner, E.O., et al. (2008a). Transmission disequilibrium testing of the chromosome 15q11–q13 region in autism. American Journal of Medical Genetics Part B:Neuropsychiatric Genetics, 147B: 1116–1125.CrossRefGoogle ScholarPubMed
Klauck, S.M. (2006). Genetics of autism spectrum disorder. European Journal of Human Genetics, 14: 714–720.CrossRefGoogle ScholarPubMed
Klauck, S.M., Poustka, F., Benner, A., Lesch, K.P., Poustka, A. (1997). Serotonin transporter (5-HTT) gene variants associated with autism? Human Molecular Genetics, 6: 2233–2238.CrossRefGoogle ScholarPubMed
Knickmeyer, R.C., Baron-Cohen, S. (2006). Fetal testosterone and sex differences in typical social development and in autism. Journal of Child Neurology, 21: 825–845.CrossRefGoogle ScholarPubMed
Koishi, S., Yamamoto, K., Matsumoto, H., et al. (2006). Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population. Brain and Development, 28: 257–260.CrossRefGoogle ScholarPubMed
Krebs, M.O., Betancur, C., Leroy, S., et al. (2002). Absence of association between a polymorphic GGC repeat in the 5' untranslated region of the reelin gene and autism. Molecular Psychiatry, 7: 801–804.CrossRefGoogle ScholarPubMed
Kumar, R.A., KaraMohamed, S., Sudi, J., et al. (2007). Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics, 17: 628–638.CrossRefGoogle ScholarPubMed
Lam, C.W., Yeung, W.L., Ko, C.H., et al. (2000). Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome. Journal of Medical Genetics, 37: e41.CrossRefGoogle ScholarPubMed
Lamb, J.A., Barnby, G., Bonora, E., et al. (2005). Analysis of IMGSAC autism susceptibility loci: evidence for sex limited and parent of origin specific effects. Journal of Medical Genetics, 42: 132–137.CrossRefGoogle ScholarPubMed
Lander, E., Kruglyak, L. (1995). Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genetics, 11: 241–247.CrossRefGoogle ScholarPubMed
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. American Journal of Human Genetics, 74: 552–557.CrossRefGoogle ScholarPubMed
Lauritsen, M.B., Als, T.D., Dahl, H.A., et al. (2006). A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands. Molecular Psychiatry, 11: 37–46.CrossRefGoogle ScholarPubMed
Lerer, E., Levi, S., Salomon, S., et al. (2008). Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Molecular Psychiatry, 13: 980–988.CrossRefGoogle ScholarPubMed
Lewis, R. (2007). Human Genetics – Concepts and Applications, 7th edn. New York: McGraw-Hill.Google Scholar
Li, H., Yamagata, T., Mori, M., Momoi, M.Y. (2005). Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients. Brain and Development, 27: 207–210.CrossRefGoogle ScholarPubMed
Li, J., Nguyen, L., Gleason, C., et al. (2004). Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 126: 51–57.CrossRefGoogle Scholar
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. Molecular Psychiatry, 14: 705–718.CrossRefGoogle ScholarPubMed
Liu, X., Novosedlik, N., Wang, A., et al. (2009). The DLX1 and DLX2 genes and susceptibility to autism spectrum disorders. European Journal of Human Genetics, 17: 228–235.CrossRefGoogle ScholarPubMed
Loat, C.S., Curran, S., Lewis, C.M., et al. (2008). Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism. Genes Brain and Behavior, 7: 754–760.CrossRefGoogle ScholarPubMed
Locke, D.P., Sharp, A.J., McCarroll, S.A., et al. (2006). Linkage disequilibrium and heritability of copy-number polymorphisms within duplicated regions of the human genome. American Journal of Human Genetics, 79: 275–290.CrossRefGoogle ScholarPubMed
Longo, D., Schuler-Faccini, L., Brandalize, A.P., dos Santos Riesgo, R., Bau, C.H. (2009). Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Research, 1267: 9–17.CrossRefGoogle Scholar
Lord, C., Cook, E.H., Leventhal, B.L., Amaral, D.G. (2000). Autism spectrum disorders. Neuron, 28: 355–363.CrossRefGoogle ScholarPubMed
Ma, D.Q., Whitehead, P.L., Menold, M.M., et al. (2005). Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism. American Journal of Human Genetics, 77: 377–388.CrossRefGoogle ScholarPubMed
Ma, D., Salyakina, D., Jaworski, J.M., et al. (2009). A genome-wide association study of autism reveals a common novel risk locus at 5p14.1. Annals of Human Genetics, 73: 263–273.CrossRefGoogle ScholarPubMed
Ma, D.Q., Rabionet, R., Konidari, I., et al. (2010). Association and gene-gene interaction of SLC6A4 and ITGB3 in autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B: 477–483.CrossRefGoogle ScholarPubMed
MacGregor, A.J., Snieder, H., Schork, N.J., Spector, T.D. (2000). Twins. Novel uses to study complex traits and genetic diseases. Trends in Genetics, 16: 131–134.CrossRefGoogle ScholarPubMed
Maestrini, E., Marlow, A.J., Weeks, D.E., Monaco, A.P. (1998). Molecular genetic investigations of autism. Journal of Autism and Developmental Disorders, 28: 427–437.CrossRefGoogle ScholarPubMed
Maestrini, E., Lai, C., Marlow, A., et al. (1999). Serotonin transporter (5-HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium. American Journal of Medical Genetics, 88: 492–496.3.0.CO;2-X>CrossRefGoogle Scholar
Maestrini, E., Paul, A., Monaco, A.P., Bailey, A. (2000). Identifying autism susceptibility genes. Neuron, 28: 19–24.CrossRefGoogle ScholarPubMed
Maestrini, E., Pagnamenta, A.T., Lamb, J.A., 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. Molecular Psychiatry, Epub ahead of print doi: 10.1038/mp.2009.34Google Scholar
Mamtani, M., Rovin, B., Brey, R., et al. (2007). CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythematosus. Annals of the Rheumatic Diseases, 67: 1076–1083.CrossRefGoogle Scholar
Marshall, C.R., Noor, A., Vincent, J.B., et al. (2008). Structural variation of chromosomes in autism spectrum disorder. American Journal of Human Genetics, 82: 477–488.CrossRefGoogle ScholarPubMed
Martin, C.L., Duvall, J.A., Ilkin, Y., et al. (2007). Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144: 869–876.CrossRefGoogle Scholar
Martin, E.R., Menold, M.M., Wolpert, C.M., et al. (2000). Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. American Journal of Medical Genetics, 96: 43–48.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
Marui, T., Hashimoto, O., Nanba, E., et al. (2004). Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 131: 43–47.CrossRefGoogle Scholar
Marui, T., Funatogawa, I., Koishi, S., et al. (2009a). Association between autism and variants in the wingless-type MMTV integration site family member 2 (WNT2) gene. International Journal of Neuropsychopharmacology, Epub ahead of print doi: 10.1017/S1461145709990903.Google Scholar
Marui, T., Funatogawa, I., Koishi, S., et al. (2009b). Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism. International Journal of Neuropsychopharmacology, 12: 1–10.CrossRefGoogle ScholarPubMed
Maussion, G., Carayol, J., Lepagnol-Bestel, A.M., et al. (2008). Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism. Human Molecular Genetics, 17: 2541–2551.CrossRefGoogle ScholarPubMed
McCarroll, S.A., Hadnott, T.N., Perry, G.H., et al. (2006). Common deletion polymorphisms in the human genome. Nature Genetics, 38: 86–92.CrossRefGoogle ScholarPubMed
McCarthy, S.E., Makarov, V., Kirov, G., et al. (2009). Microduplications of 16p11.2 are associated with schizophrenia. Nature Genetics, 41: 1223–1227.CrossRefGoogle ScholarPubMed
McCauley, J.L., Olson, L.M., Dowd, M., et al. (2004a). Linkage and association analysis at the serotonin transporter (SLC6A4) locus in a rigid-compulsive subset of autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 127: 104–112.CrossRefGoogle Scholar
McCauley, J.L., Olson, L.M., Delahanty, R., et al. (2004b). A linkage disequilibrium map of the 1-Mb 15q12 GABA(A) receptor subunit cluster and association to autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 131: 51–59.CrossRefGoogle Scholar
McCauley, J.L., Li, C., Jiang, L., et al. (2005). Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Medical Genetics, 6: 1.CrossRefGoogle ScholarPubMed
McKinney, C., Merriman, M.E., Chapman, P.T., et al. (2008). Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Annals of the Rheumatic Diseases, 67: 409–413.CrossRefGoogle ScholarPubMed
Menold, M.M., Shao, Y., Wolpert, C.M., et al. (2001). Association analysis of chromosome 15 GABAA receptor subunit genes in autistic disorder. Journal of Neurogenetics, 15: 245–259.CrossRefGoogle ScholarPubMed
Miller, D.T., Shen, Y., Weiss, L.A., et al. (2008). Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. Journal of Medical Genetics, 46: 242–248.CrossRefGoogle ScholarPubMed
Ming, X., Johnson, W.G., Stenroos, E.S., et al. (2010). Genetic variant of glutathione peroxidase 1 in autism. Brain and Development, 32: 105–109.CrossRefGoogle ScholarPubMed
Moessner, R., Marshall, C.R., Sutcliffe, J.S., et al. (2007). Contribution of SHANK3 mutations to autism spectrum disorder. American Journal of Human Genetics, 81: 1289–1297.CrossRefGoogle ScholarPubMed
Moffatt, M.F., Kabesch, M., Liang, L., et al. (2007). Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature, 448: 470–473.CrossRefGoogle ScholarPubMed
Molloy, C.A., Keddache, M., Martin, L.J. (2005). Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Molecular Psychiatry, 10: 741–746.CrossRefGoogle Scholar
Muhle, R., Trentacoste, S.V., Rapin, I. (2004). The genetics of autism. Pediatrics, 113: 472–486.CrossRefGoogle ScholarPubMed
Mulder, E.J., Anderson, G.M., Kema, I.P., et al. (2005). Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 133: 93–96.CrossRefGoogle Scholar
Nabi, R., Serajee, F.J., Chugani, D.C., Zhong, H., Huq, A.H. (2004). Association of tryptophan 2,3 dioxygenase gene polymorphism with autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 125: 63–68.CrossRefGoogle Scholar
Nakamura, K., Anitha, A., Yamada, K., et al. (2008). Genetic and expression analyses reveal elevated expression of syntaxin 1A (STX1A) in high functioning autism. International Journal of Neuropsychopharmacology, 11: 1073–1084.CrossRefGoogle Scholar
Nicholas, B., Rudrasingham, V., Nash, S., et al. (2007). Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Molecular Psychiatry, 12: 581–592.CrossRefGoogle ScholarPubMed
Nishimura, K., Nakamura, K., , Anitha, A., et al. (2007). Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism. Biochemical and Biophysical Research Communications, 356: 200–206.CrossRefGoogle ScholarPubMed
Nurmi, E.L., Bradford, Y., Chen, Y., et al. (2001). Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families. Genomics, 77: 105–113.CrossRefGoogle ScholarPubMed
Nurmi, E.L., Amin, T., Olson, L.M., et al. (2003). Dense linkage disequilibrium mapping in the 15q11–q13 maternal expression domain yields evidence for association in autism. Molecular Psychiatry, 8: 624–634.CrossRefGoogle ScholarPubMed
Ober, C., Hoffjan, S. (2006). Asthma genetics 2006: the long and winding road to gene discovery. Genes and Immunity, 7: 95–100.CrossRefGoogle Scholar
Odell, D., Maciulis, A., Cutler, A., et al. (2005). Confirmation of the association of the C4B null allelle in autism. Human Immunology, 66: 140–145.CrossRefGoogle ScholarPubMed
Orabona, G.M., Griesi-Oliveira, K., Vadasz, E., et al. (2009). HTR1B and HTR2C in autism spectrum disorders in Brazilian families. Brain Research, 1250: 14–19.CrossRefGoogle ScholarPubMed
O'Roak, BJ, State, M.W. (2008). Autism genetics: strategies, challenges and opportunities. Autism Research, 1: 4–17.CrossRefGoogle ScholarPubMed
Pagnamenta, A.T., Wing, K., Akha, E.S., et al. (2008). A 15q13.3 microdeletion segregating with autism. European Journal of Human Genetics, 17: 687–692.CrossRefGoogle ScholarPubMed
Peiffer, D.A., Le, J.M., Steemers, F.J., et al. (2006). High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. Genome Research, 16: 1136–1148.CrossRefGoogle ScholarPubMed
Perry, G.H., Ben-Dor, A., Tsalenko, A., et al. (2008). The fine-scale and complex architecture of human copy-number variation. American Journal of Human Genetics, 82: 685–695.CrossRefGoogle ScholarPubMed
Persico, A.M., Bourgeron, T. (2006). Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends in Neurosciences, 29: 349–358.CrossRefGoogle ScholarPubMed
Persico, A.M., D'Agruma, L., Maiorano, N., et al. (2001). Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Molecular Psychiatry, 6: 150–159.CrossRefGoogle ScholarPubMed
Persico, A.M., Pascucci, T., Puglisi-Allegra, S., et al. (2002). Serotonin transporter gene promoter variants do not explain the hyperserotoninemia in autistic children. Molecular Psychiatry, 7: 795–800.CrossRefGoogle Scholar
Persico, A.M., D'Agruma, L., Zelante, L., et al. (2004). Enhanced APOE2 transmission rates in families with autistic probands. Psychiatric Genetics, 14: 73–82.CrossRefGoogle ScholarPubMed
Philippe, A., Martinez, M., Guilloud-Bataille, M., et al. (1999). Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Human Molecular Genetics, 8: 805–812.CrossRefGoogle ScholarPubMed
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. Molecular Psychiatry, 10: 950–960.CrossRefGoogle ScholarPubMed
Philippi, A., Tores, F., Carayol, J., et al. (2007). Association of autism with polymorphisms in the paired-like homeodomain transcription factor 1 (PITX1) on chromosome 5q31: a candidate gene analysis. BMC Medical Genetics, 8: 74.CrossRefGoogle ScholarPubMed
Piven, J., Tsai, G.C., Nehme, E., et al. (1991). Platelet serotonin, a possible marker for familial autism. Journal of Autism and Developmental Disorders, 21: 51–59.CrossRefGoogle ScholarPubMed
Ramoz, N., Reichert, J.G., Corwin, T.E., et al. (2006). Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism. Biological Psychiatry, 60: 186–191.CrossRefGoogle ScholarPubMed
Ramoz, N., Cai, G., Reichert, J.G., Silverman, J.M., Buxbaum, J.D. (2008). An analysis of candidate autism loci on chromosome 2q24-q33: evidence for association to the STK39 gene. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B: 1152–1158.CrossRefGoogle ScholarPubMed
Redon, R., Ishikawa, S., Fitch, K.R., et al. (2006). Global variation in copy number in the human genome. Nature, 444: 444–454.CrossRefGoogle ScholarPubMed
Rehnstrom, K., Ylisaukko-oja, T., Nummela, I., et al. (2009). Allelic variants in HTR3C show association with autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B: 741–746.CrossRefGoogle ScholarPubMed
Risch, N. (1990). Linkage strategies for genetically complex traits. I. Multilocus models. American Journal of Human Genetics, 46: 222–228.Google ScholarPubMed
Risch, N. (2001). Implications of multilocus inheritance for gene-disease association studies. Theoretical Population Biology, 60: 215–220.CrossRefGoogle ScholarPubMed
Risch, N., Merikangas, K. (1996). The future of genetic studies of complex human diseases. Science, 273: 1516–1517.CrossRefGoogle ScholarPubMed
Risch, N., Spiker, D., Lotspeich, L., et al. (1999). A genomic screen of autism: evidence for a multilocus etiology. American Journal of Human Genetics, 65: 493–507.CrossRefGoogle ScholarPubMed
Ritvo, E.R., Jorde, L.B., Mason-Brothers, A., et al. (1989). The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. American Journal of Psychiatry, 146: 1032–1036.Google ScholarPubMed
Robinson, P.D., Schutz, C.K., Macciardi, F., White, B.N., Holden, J.J. (2001). Genetically determined low maternal serum dopamine beta-hydroxylase levels and the etiology of autism spectrum disorders. American Journal of Medical Genetics, 100: 30–36.CrossRefGoogle ScholarPubMed
Rutter, M. (2000). Genetic studies of autism: from the 1970s into the millennium. Journal of Abnormal Child Psychology, 28: 3–14.CrossRefGoogle ScholarPubMed
Rutter, M. (2005). Aetiology of autism: findings and questions. Journal of Intellectual Disability Research, 49: 231–238.CrossRefGoogle ScholarPubMed
Salmon, B., Hallmayer, J., Rogers, T. (1999). Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism. American Journal of Medical Genetics, 88: 551–556.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Samaco, R.C., Nagarajan, R.P., Braunschweig, D., LaSalle, J.M. (2004). Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Human Molecular Genetics, 13: 629–639.CrossRefGoogle ScholarPubMed
Samaco, R.C., Hogart, A., LaSalle, J.M. (2005). Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Human Molecular Genetics, 14: 483–492.CrossRefGoogle ScholarPubMed
Santangelo, S.L., Tsatsanis, K. (2005) What is known about autism: genes, brain and behavior. American Journal of Pharmacogenetics, 5: 71–92.CrossRefGoogle ScholarPubMed
Schanen, N.C. (2006). Epigenetics of autism spectrum disorders. Human Molecular Genetics, 15: 138–150 (Special Issue).CrossRefGoogle ScholarPubMed
Sebat, J., Lakshmi, B., Troge, J., et al. (2004). Large-scale copy number polymorphism in the human genome. Science, 305: 525–528.CrossRefGoogle ScholarPubMed
Sebat, J., Lakshmi, B, Malhotra, D., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316: 445–449.CrossRefGoogle ScholarPubMed
Segurado, R., Conroy, J., Meally, E., et al. (2005). Confirmation of association between autism and the mitochondrial aspartate/glutamate carrier SLC25A12 gene on chromosome 2q31. American Journal of Psychiatry, 162: 2182–2184.CrossRefGoogle ScholarPubMed
Seng, K.C., Seng, C.K. (2008). The success of the genome-wide association approach: a brief story of a long struggle. European Journal of Human Genetics, 16: 554–564.CrossRefGoogle ScholarPubMed
Serajee, F.J.Zhong, H., Nabi, R., Huq, A.H. (2003a). The metabotropic glutamate receptor 8 gene at 7q31: partial duplication and possible association with autism. Journal of Medical Genetics, 40: e42.CrossRefGoogle ScholarPubMed
Serajee, F.J., Nabi, R., Zhong, H., Mahbubul Huq, A.H. (2003b). Association of INPP1, PIK3CG, and TSC2 gene variants with autistic disorder: implications for phosphatidylinositol signalling in autism. Journal of Medical Genetics, 40: e119.CrossRefGoogle ScholarPubMed
Serajee, F.J., Nabi, R., Zhong, H., , Huq, M. (2004). Polymorphisms in xenobiotic metabolism genes and autism. Journal of Child Neurology, 19: 413–417.CrossRefGoogle ScholarPubMed
Serajee, F.J., Zhong, H., Mahbubul Huq, A.H. (2006). Association of Reelin gene polymorphisms with autism. Genomics, 87: 75–83.CrossRefGoogle ScholarPubMed
Shao, Y., Wolpert, C.M., Raiford, K.L. (2002a). Genomic screen and follow-up analysis for autistic disorder. American Journal of Medical Genetics, 114: 99–105.CrossRefGoogle ScholarPubMed
Shao, Y., Raiford, K.L., Wolpert, C.M., et al. (2002b). Phenotypic homogeneity provides increased support for linkage on chromosome 2 in autistic disorder. American Journal of Human Genetics, 70: 1058–1061.CrossRefGoogle ScholarPubMed
Shao, Y., Cuccaro, M.L., Hauser, E.R. (2003). Fine mapping of autistic disorder to chromosome 15q11–q13 by use of phenotypic subtypes. American Journal of Human Genetics, 72: 539–548.CrossRefGoogle ScholarPubMed
Sharp, A.J., Locke, D.P., McGrath, S.D., et al. (2005). Segmental duplications and copy-number variation in the human genome. American Journal of Human Genetics, 77: 78–88.CrossRefGoogle ScholarPubMed
Sharp, A.J., Hansen, S., Selzer, R.R., et al. (2006). Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nature Genetics, 38: 1038–1042.CrossRefGoogle ScholarPubMed
Shibayama, A., Cook, E.H., Feng, J., et al. (2004). MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 128: 50–53.CrossRefGoogle Scholar
Shinawi, M., Schaaf, C.P., Bhatt, S.S., et al. (2009). A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nature Genetics, 41: 1269–1271.CrossRefGoogle ScholarPubMed
Shuang, M., Liu, J., Jia, M.X., et al. (2004). Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 131: 48–50.CrossRefGoogle Scholar
Skaar, D.A., Shao, Y., Haines, J.L., et al. (2005). Analysis of the RELN gene as a genetic risk factor for autism. Molecular Psychiatry, 10: 563–571.CrossRefGoogle ScholarPubMed
Slater, H.R., Bruno, D.L., Ren, H., et al. (2003). Rapid, high throughput prenatal detection of aneuploidy using a novel quantitative method (MLPA). Journal of Medical Genetics, 40: 907–912.CrossRefGoogle Scholar
Sousa, I., Clark, T.G., Toma, C., et al. (2009). MET and autism susceptibility: family and case-control studies. European Journal of Human Genetics, 17: 749–759.CrossRefGoogle ScholarPubMed
Spielman, R.S., McGinnis, R.E., Ewens, W.J. (1993). Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). American Journal of Human Genetics, 52: 506–516.Google Scholar
Splawski, I., Yoo, D.S., Stotz, S.C., et al. (2006). CACNA1H mutations in autism spectrum disorders. Journal of Biological Chemistry, 281: 22085–22091.CrossRefGoogle ScholarPubMed
Stefansson, H., Rujescu, D., Cichon, S., et al. (2008). Large recurrent microdeletions associated with schizophrenia. Nature, 455: 232–236.CrossRefGoogle ScholarPubMed
Steffenburg, S., Gillberg, C., Hellgren, L., et al. (1989). A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry, 30: 405–416.CrossRefGoogle ScholarPubMed
Stoltenberg, S.F., Burmeister, M. (2000). Recent progress in psychiatric genetics – some hope but no hype. Human Molecular Genetics, 9: 927–935.CrossRefGoogle ScholarPubMed
Stone, J.L., Merriman, B., Cantor, R.M., et al. (2004). Evidence for sex-specific risk alleles in autism spectrum disorder. American Journal of Human Genetics, 75: 1117–1123.CrossRefGoogle ScholarPubMed
Stone, J.L., Merriman, B., Cantor, R.M., Gerschwind, D.H., Nelson, S.F. (2007). High density SNP association study of a major autism linkage region on chromosome 17. Human Molecular Genetics, 16: 704–715.CrossRefGoogle Scholar
Strachan, T., Read, A. (1996). Human Molecular Genetics. Oxford, UK: BIOS Scientific Publishers Ltd.Google Scholar
Strom, S.P., Stone, J.L., Ten Bosch, J.R., et al. (2009). High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene. Molecular Psychiatry, Epub ahead of print doi: 10.1038/mp.2009.41Google Scholar
Sutcliffe, J.S., Delahanty, R.J., Prasad, H.C., et al. (2005). Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors. American Journal of Human Genetics, 77: 265–279.CrossRefGoogle ScholarPubMed
Sykes, N.H., Toma, C., Wilson, N., et al. (2009). Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection. European Journal of Human Genetics, 17: 1347–1353.CrossRefGoogle ScholarPubMed
Szatmari, P., Jones, M.B., Zwaigenbaum, L., MacLean, J.E. (1998). Genetics of autism: overview and new directions. Journal of Autism and Developmental Disorders, 28: 351–368.CrossRefGoogle ScholarPubMed
Szatmari, P., Paterson, A.D., Zwaigenbaum, L., et al. (Autism Genome Project Consortium) (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genetics, 39: 319–328.Google ScholarPubMed
Talebizadeh, Z., Lam, D.Y., Theodoro, M.F., et al. (2006). Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. Journal of Medical Genetics, 43: e21.Google ScholarPubMed
,The International HapMap Project. (2003). International HapMap Consortium. Nature, 426: 789–796.CrossRefGoogle Scholar
Tischfield, M.A., Bosley, T.M., Salih, M.A., et al. (2005). Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nature Genetics, 37: 1035–1037.CrossRefGoogle ScholarPubMed
Tochigi, M., Kato, C., Koishi, S., et al. (2007). No evidence for significant association between GABA receptor genes in chromosome 15q11–q13 and autism in a Japanese population. Journal of Human Genetics, 52: 985–989.CrossRefGoogle Scholar
Tordjman, S., Gutknecht, L., Carlier, M., et al. (2001). Role of the serotonin transporter gene in the behavioral expression of autism. Molecular Psychiatry, 6: 434–439.CrossRefGoogle ScholarPubMed
Torres, A.R., Sweeten, T.L., Cutler, A., et al. (2006). The association and linkage of the HLA-A2 class I allele with autism. Human Immunology, 67: 346–351.CrossRefGoogle Scholar
Toyoda, T., Nakamura, K., Yamada, K., et al. (2007). SNP analyses of growth factor genes EGF, TGFbeta-1, and HGF reveal haplotypic association of EGF with autism. Biochemical and Biophysical Research Communications, 360: 715–720.CrossRefGoogle ScholarPubMed
Trikalinos, T.A., Karvouni, A., Zintzaras, E., et al. (2006). A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Molecular Psychiatry, 11: 29–36.CrossRefGoogle ScholarPubMed
Turunen, J.A., Rehnstrom, K., Kilpinen, H., et al. (2008). Mitochondrial aspartate/glutamate carrier SLC25A12 gene is associated with autism. Autism Research, 1: 189–192.CrossRefGoogle ScholarPubMed
Tuzun, E., Sharp, A.J., Bailey, J.A., et al. (2005). Fine-scale structural variation of the human genome. Nature Genetics, 37: 727–732.CrossRefGoogle ScholarPubMed
Vliet, J., Oates, N.A., Whitelaw, E. (2007). Epigenetic mechanisms in the context of complex diseases. Cellular and Molecular Life Sciences, 64: 1531–1538.CrossRefGoogle ScholarPubMed
Veenstra-VanderWeele, J., Cook, E.H. (2004). Molecular genetics of autism spectrum disorder. Molecular Psychiatry, 9: 819–832.CrossRefGoogle ScholarPubMed
Vincent, J.B., Konecki, D.S., Munstermann, E., et al. (1996). Point mutation analysis of the FMR-1 gene in autism. Molecular Psychiatry, 1: 227–231.Google ScholarPubMed
Vincent, J.B., Kolozsvari, D., Roberts, W.S., et al. (2004). Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 129: 82–84.CrossRefGoogle Scholar
Mering, C., Jensen, L.K., Kuhn, M.et al. (2007). STRING 7 – recent developments in the integration and prediction of protein interactions. Nucleic Acids Research, 35 (Database Issue): D358–362.CrossRefGoogle Scholar
Vourc'h, P., Martin, I., Bonnet-Brilhault, F., et al. (2003). Mutation screening and association study of the UBE2H gene on chromosome 7q32 in autistic disorder. Psychiatric Genetics, 13: 221–225.CrossRefGoogle ScholarPubMed
Walsh, T., McClellan, J.M., McCarthy, S.E., et al. (2008). Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science, 320: 539–543.CrossRefGoogle Scholar
Wang, K., Zhang, H., Ma, D., et al. (2009). Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature, 459: 528–533.CrossRefGoogle ScholarPubMed
Wang, L., Jia, M., Yue, W., et al. (2008). Association of the ENGRAILED 2 (EN2) gene with autism in Chinese Han population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B: 434–438.CrossRefGoogle ScholarPubMed
Warren, R.P., Odell, J.D., Warren, W.L., et al. (1996). Strong association of the third hypervariable region of HLA-DR beta 1 with autism. Journal of Neuroimmunology, 67: 97–102.CrossRefGoogle ScholarPubMed
Wassink, T.H., Piven, J., Vieland, V.J., et al. (2001). Evidence supporting WNT2 as an autism susceptibility gene. American Journal of Medical Genetics, 105: 406–413.CrossRefGoogle ScholarPubMed
Wassink, T.H., Piven, J., Vieland, V.J., et al. (2004). Examination of AVPR1a as an autism susceptibility gene. Molecular Psychiatry, 9: 968–972.CrossRefGoogle ScholarPubMed
Weiss, L.A., Shen, Y., Korn, J.M., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. New England Journal of Medicine, 358: 667–675.CrossRefGoogle ScholarPubMed
Weiss, L.A., Arking, D.E., Daly, M.J., Chakravarti, A. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461: 802–808.CrossRefGoogle ScholarPubMed
Wermter, A., Kamp-Becker, I., Strauch, K., Schulte-Korne, G., Remschmidt, H. (2008). No evidence for involvement of genetic variants in the X-linked neuroligins genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high functioning level. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147: 535–537.CrossRefGoogle Scholar
Wu, S., Guo, Y., Jia, M., et al. (2005a). Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios. Neuroscience Letters, 381: 1–5.CrossRefGoogle ScholarPubMed
Wu, S., Jia, M., Ruan, Y., et al. (2005b). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological Psychiatry, 58: 74–77.CrossRefGoogle ScholarPubMed
Wu, S., Yue, W., Jia, M., et al. (2007). Association of the neuropilin-2 (NRP2) gene polymorphisms with autism in Chinese Han population. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144: 492–495.CrossRefGoogle Scholar
Yan, J., Oliveira, G., Coutinho, A., et al. (2005). Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Molecular Psychiatry, 10: 329–332.CrossRefGoogle ScholarPubMed
Yashin, A.I., Iachine, I.A. (1995). Genetic analysis of durations: correlated frailty model applied to survival of Danish twins. Genetic Epidemiology, 12: 529–538.CrossRefGoogle ScholarPubMed
Yirmiya, N., Pilowsky, T., Nemanov, L., et al. (2001). Evidence for an association with the serotonin transporter promoter region polymorphism and autism. American Journal of Medical Genetics, 105: 381–386.CrossRefGoogle ScholarPubMed
Yirmiya, N., Rosenberg, C., Levi, S., et al. (2006). Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Molecular Psychiatry, 11: 488–494.CrossRefGoogle Scholar
Ylisaukko-oja, T., Rehnstrom, K., Auranen, M., et al. (2005). Analysis of four neuroligin genes as candidates for autism. European Journal of Human Genetics, 13: 1285–1292.CrossRefGoogle ScholarPubMed
Yonan, A.L., Alarcon, M., Cheng, R., et al. (2003). A genomewide screen of 345 families for autism-susceptibility loci. American Journal of Human Genetics, 73: 886–897.CrossRefGoogle ScholarPubMed
Yoo, H.J., Cho, I.H., Park, M., et al. (2008): Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios. Neuroscience Research, 62: 66–69.CrossRefGoogle ScholarPubMed
Yoo, H.J., Lee, S.K., Park, M., et al. (2009a): Family- and population-based association studies of monoamine oxidase A and autism spectrum disorders in Korean. Neuroscience Research, 63: 172–176.CrossRefGoogle ScholarPubMed
Yoo, H.K., Chung, S., Hong, J.P., Kim, B.N., Cho, S.C. (2009b). Microsatellite marker in gamma-aminobutyric acid-a receptor beta 3 subunit gene and autism spectrum disorders in Korean trios. Yonsei Medical Journal, 50: 304–306.CrossRefGoogle ScholarPubMed
Yrigollen, C.M., Han, S.S., Kochetkova, A., et al. (2008). Controlling affiliative behavior as candidate genes for autism. Biological Psychiatry, 63: 911–916.CrossRefGoogle ScholarPubMed
Zhang, H., Liu, X., Zhang, C., et al. (2002). Reelin gene alleles and susceptibility to autism spectrum disorders. Molecular Psychiatry, 7: 1012–1017.CrossRefGoogle ScholarPubMed
Zhao, X., Leotta, A., Kustanovich, V., et al. (2007). A unified genetic theory for sporadic and inherited autism. Proceedings of the National Academy of Sciences USA, 104: 12831–12836.CrossRefGoogle ScholarPubMed
Zhong, N., Ye, L., Ju, W., et al. (1999). 5-HTTLPR variants not associated with autistic spectrum disorders. Neurogenetics, 2: 129–131.CrossRefGoogle Scholar
Zhou, X.L., Giacobini, M., Anderlid, B.M., et al. (2007). Association of adenomatous polyposis coli (APC) gene polymorphisms with autism spectrum disorder (ASD). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 144: 351–354.CrossRefGoogle Scholar

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