Skip to main content
SpringerLink
Log in

Genetics of Autism Spectrum Disorder: Experience in Developing Countries

  • Reference work entry
Comprehensive Guide to Autism

  • 815 Accesses

Abstract

Autism is a group of neurodevelopmental disorders. The knowledge about the etiology of autism is still in a nascent stage. This chapter will focus on the role of genetics in the development of autism. Genetics plays an important role in autism and 12 genes have been linked strongly in the development of autism. To identify genes involved in autism, experimental techniques such as linkage analysis, cytogenetics, resequencing, genome-wide association studies, and array comparative genome hybridization have been used. The California Autism Twins Study has showed that as compared to genetic factors, environmental factors play an equally important role in the pathogenesis of autism. Further research is being carried out to find other factors such as environment or gene-environment interactions and neurological, infectious, immunological, and metabolic factors that may be involved in the onset of autism. This can aid in the early diagnosis and treatment of autism.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,199.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr JM. The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol. 2009;2009:1–7.

    Google Scholar 

  • Akefeldt A, Gillberg C. Behavior and personality characteristics of children and young adults with Prader-Willi syndrome: a controlled study. J Am Acad Child Adolesc Psychiatry. 1999;38(6):761–9.

    Article  PubMed  Google Scholar 

  • Al-Farsi YM, Al-Sharbati MM, Al-Farsi OA, Al-Shafaee MS, Brooks DR, Waly MI. Brief report: prevalence of autistic spectrum disorders in the Sultanate of Oman. J Autism Dev Disord. 2011;41(6):821–5.

    Article  PubMed  Google Scholar 

  • Baird G, Charman T, Baron-Cohen S, et al. A screening instrument for autism at 18 months of age: a 6-year follow-up study. J Am Acad Child Adolesc Psychiatry. 2000;39:694–702.

    Article  PubMed  Google Scholar 

  • Barrett S, Beck JC, Bernier R, et al. An autosomal genomic screen for autism. Collaborative linkage study of autism. Am J Med Genet. 1999;88:609–15.

    Article  PubMed  Google Scholar 

  • Berkel S, Tang W, Trevino M, Vogt M, Obenhaus HA, et al. Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology. Hum Mol Genet. 2011;21(2):344–57.

    Article  PubMed  Google Scholar 

  • Beyer KS, Klauck SM, Wiemann S, Poustka A. Construction of a physical map of an autism susceptibility region in 7q32.3-q33. Gene. 2001;272(1–2):85–91.

    Article  PubMed  Google Scholar 

  • Boyar FZ, Whitney MM, Lossie AC, Gray BA, Keller KL, Stalker HJ, Zori RT, Geffken G, Mutch J, Edge PJ, et al. A family with a grand-maternally derived interstitial duplication of proximal 15q. Clin Genet. 2001;60(6):421–30.

    Article  PubMed  Google Scholar 

  • Cantor RM, Kono N, Duvall JA, Alvarez-Retuerto A, Stone JL, Alarcón M, Nelson SF, Geschwind DH. Replication of autism linkage: fine-mapping peak at 17q21. Am J Hum Genet. 2005;76(6):1050–6.

    Article  PubMed  Google Scholar 

  • Celestino-Soper PB, Shaw CA, Sanders SJ, Li J, Murtha MT, Ercan-Sencicek AG, Davis L, Thomson S, Gambin T, Chinault AC, et al. Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE. Hum Mol Genet. 2011;20(22):4360–70.

    Article  PubMed  Google Scholar 

  • Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, et al. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry. 2008;63:1111–1117.

    Article  PubMed  Google Scholar 

  • Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, Karamohamed S, Badner JA, Matsui S, Conroy J, McQuaid D, Gergel J, Hatchwell E, Gilliam TC, Gershon ES, Nowak NJ, Dobyns WB, Cook Jr EH. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry. 2011;63:1111–7.

    Article  Google Scholar 

  • Christina HM, Par S, Sven C. Perinatal risk factors for infantile autism. Epidemiology. 2002;13(4):417–23.

    Article  Google Scholar 

  • Chugani DC. Role of altered brain serotonin mechanisms in autism. Mol Psychiatry. 2002;7 (Suppl 2):S16–7.

    Article  PubMed  Google Scholar 

  • Deans E. Autism and Vitamin D: the sun is not the enemy. Evol Psychiatry. 2011. Available from: http://www.psychologytoday.com/blog/evolutionary-psychiatry/201104/autism-and-vitamin-d.

  • Filipek PA, Juranek J, Smith M, Mays LZ, Ramos ER, Bocian M, Masser-Frye D, Laulhere TM, Modahl C, Spence MA, et al. Mitochondrial dysfunction in autistic patients with 15q inverted duplication. Ann Neurol. 2003;53(6):801–4.

    Article  PubMed  Google Scholar 

  • Folstein SE, Mankoski RE. Chromosome 7q: where autism meets language disorder? Am J Hum Genet. 2000;67(2):278–81.

    Article  PubMed  Google Scholar 

  • Fombonne E. The epidemiology of child and adolescent psychiatric disorders: recent developments and issues. Epidemiol Psichiatr Soc. 1998;7(3):161–6.

    Article  PubMed  Google Scholar 

  • Gillberg C, Billstedt E. Autism and asperger syndrome: coexistence with other clinical disorders. Acta Psychiatr Scand. 2000;102(5):321–30.

    Article  PubMed  Google Scholar 

  • Gillberg C, Coleman M. The biology of the autistic syndromes. 3rd ed. London: Mac Keith Press; 2000. Distributed by Cambridge University Press.

    Google Scholar 

  • Guo H, Hu Z, Zhao J, Xia K. Genetics of autism spectrum disorders. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36(8):703–11.

    PubMed  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. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011;68(11):1095–102.

    Article  PubMed  Google Scholar 

  • Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet. 2000;26(1):93–6.

    Article  PubMed  Google Scholar 

  • IMGSAC. A full genome screen for autism with evidence for linkage to a region of chromosome 7q. Hum Mol Genet. 1998;7:571–8.

    Article  Google Scholar 

  • IMGSAC. A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p. Am J Hum Genet. 2001;69:570–81.

    Article  Google Scholar 

  • Ingram JL, Stodgell CJ, Hyman SL, Figlewicz DA, Weitkamp LR, Rodier PM. Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology. 2000;62:393–405.

    Article  PubMed  Google Scholar 

  • Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T, Paris Autism Research International Sibpair (PARIS) Study. Linkage and association of glutamate receptor 6 gene with Autism. Mol Psychiatry. 2002;7(3):302–10.

    Article  PubMed  Google Scholar 

  • Jamain S, Quach H, Betancur C, RÃ¥stam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T, Paris Autism Research International Sibpair Study. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with Autism. Nat Genet. 2003;34(1):27–9.

    Article  PubMed  Google Scholar 

  • Kanner L. Early infantile autism revisited. Psychiatry Dig. 1968;29(2):17–28.

    PubMed  Google Scholar 

  • Kelemenova S, Schmidtova E, Ficek A, Celec P, Kubranska A, Ostatnikova D. Polymorphisms of candidate genes in Slovak autistic patients. Psychiatr Genet. 2010;20(4):137–9.

    Article  PubMed  Google Scholar 

  • Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress and risk for autism. Neurosci Biobehav Rev. 2008;32(8):1519–32.

    Article  PubMed  Google Scholar 

  • Lander E, Krygkyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995;11(3):241–7.

    Article  PubMed  Google Scholar 

  • Le Couteur A, Bailey A, Goode S, Pickles A, Robertson S, Gottesman I, et al. A broader phenotype of autism: the clinical spectrum in twins. J Child Psychol Psychiatry. 1996;37(7):785–801.

    Article  PubMed  Google Scholar 

  • Leblond CS, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G, et al. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 2012;8:e1002521.

    Article  PubMed  Google Scholar 

  • Magnusson A, Stordal E, Brodtkorb E, Steinlein O. Schizophrenia, psychotic illness and other psychiatric symptoms in families with autosomal dominant nocturnal frontal lobe epilepsy caused by different mutations. Psychiatr Genet. 2003;13(2):91–5.

    PubMed  Google Scholar 

  • Malzac P, Webber H, Moncla A, Graham JM, Kukolich M, Williams C, Pagon RA, Ramsdell LA, Kishino T, Wagstaff J. Mutation analysis of UBE3A in Angelman syndrome patients. Am J Hum Genet. 1998;62(6):1353–60.

    Article  PubMed  Google Scholar 

  • Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008;82(2):477–88.

    Article  PubMed  Google Scholar 

  • Martin ER, Menold MM, Wolpert CM, Bass MP, Donnelly SL, Ravan SA, Zimmerman A, Gilbert JR, Vance JM, Maddox LO, et al. Analysis of linkage disequilibrium in gamma-aminobutyric acid receptor subunit genes in autistic disorder. Am J Med Genet. 2000;96(1):43–8.

    Article  PubMed  Google Scholar 

  • Matuszek G, Talebizadeh Z. Autism Genetic Database (AGD): a comprehensive database including autism susceptibility Gene-CNVs integrated with known noncoding RNAs and fragile sites. BMC Med Genet. 2009;10:102.

    Article  PubMed  Google Scholar 

  • Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER, Ravan SA, Abramson RK, Wright HH, Delong GR, et al. Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet. 2001;15(3–4):245–59.

    Article  PubMed  Google Scholar 

  • Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics. 2004;113(5):e472–86.

    Article  PubMed  Google Scholar 

  • Nurmi EL, Dowd M, Tadevosyan-Leyfer O, Haines JL, Folstein SE, Sutcliffe JS. Exploratory subsetting of autism families based on savant skills improves evidence of genetic linkage to 15q11-q13. J Am Acad Child Adolesc Psychiatry. 2003;42(7):856–63.

    Article  PubMed  Google Scholar 

  • Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci. 2002;3(9):715–27.

    Article  PubMed  Google Scholar 

  • Persico AM, D’Agruma L, Maiorano N, Totaro A, Militerni R, Bravaccio C, Wassink TH, Schneider C, Melmed R, Trillo S, et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry. 2001;6(2):150–9.

    Article  PubMed  Google Scholar 

  • Petek E, Windpassinger C, Vincent JB, Cheung J, Boright AP, Scherer SW, Kroisel PM, Wagner K. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am J Hum Genet. 2001;68(4):848–58.

    Article  PubMed  Google Scholar 

  • Potts P, Bellows B. Autism and diet. J Epidemiol Community Health. 2006;60(5):375.

    Article  PubMed  Google Scholar 

  • Rineer S, Finucane B, Simon EW. Autistic symptoms among children and young adults with isodicentric chromosome 15. Am J Med Genet. 1998;81(5):428–33.

    Article  PubMed  Google Scholar 

  • Robinson PD, Schutz CK, Macciardi F, White BN, Holden JJ. Genetically determined low maternal serum dopamine beta-hydroxylase levels and the etiology of autism spectrum disorders. Am J Med Genet. 2001;100:30–6.

    Article  PubMed  Google Scholar 

  • Rogers SJ, Wehner DE, Hagerman R. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr. 2001;22(6):409–17.

    Article  PubMed  Google Scholar 

  • Roman GC. Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents. J Neurol Sci. 2007;262(1–2):15–26.

    Article  PubMed  Google Scholar 

  • Sato D, Lionel AC, Leblond CS, Prasad A, Pinto D, Walker S, O’Conner I, Russell C, Drmic IE, Hamdan FF, et al. SHANK1 deletions in males with autism spectrum disorder. Am J Hum Genet. 2012;90:1–9.

    Article  Google Scholar 

  • Schain RJ, Freedman DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatr. 1961;58:315–20.

    Article  PubMed  Google Scholar 

  • Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, et al. Human chromosome 7: DNA sequence and biology. Science. 2003;300(5620):767–72.

    Article  PubMed  Google Scholar 

  • Serajee FJ, Zhong H, Nabi R, Huq AH. The metabotropic glutamate receptor 8 gene at 7q31: partial duplication and possible association with autism. J Med Genet. 2003;40(4):e42.

    Article  PubMed  Google Scholar 

  • Siegel B. Early screening and diagnosis in autistic spectrum disorders: the Pervasive Developmental Disorders Screening Test (PDDST). Presented at NIH State of the Science in Autism, Screening and Diagnosis Working Conference; Bethesda; 1998.

    Google Scholar 

  • Smalley SL, Tanguay PE, Smith M, Gutierrez G. Autism and tuberous sclerosis. J Autism Dev Disord. 1992;22(3):339–55.

    Article  PubMed  Google Scholar 

  • Steffenburg S, Gillberg CL, Steffenburg U, Kyllerman M. Autism in Angelman syndrome: a population-based study. Pediatr Neurol. 1996;14(2):131–6.

    Article  PubMed  Google Scholar 

  • Steinlein O, Smigrodzki R, Lindstrom J, Anand R, Köhler M, Tocharoentanaphol C, Vogel F. Refinement of the localization of the gene for neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) to human chromosome 20q13.2-q13.3. Genomics. 1994;22(2):493–5.

    Article  PubMed  Google Scholar 

  • Stodgell, et al. Association of HOXD1 and GBX2 allelic variants with Autism Spectrum Disorders. Presented at the CPEA/STAART Annual Scientific Meeting; 2004.

    Google Scholar 

  • Stromland K, Nordin V, Miller M, Akerstrom B, Gillberg C. Autism in thalidomide embryopathy: a population study. Dev Med Child Neurol. 1994;36(4):351–6.

    Article  PubMed  Google Scholar 

  • Sutcliffe JS, Nurmi EL, Lombroso PJ. Genetics of childhood disorders: XLVII. Autism, part 6: duplication and inherited susceptibility of chromosome 15q11-q13 genes in autism. J Am Acad Child Adolesc Psychiatry; 2003;42(2):253–6.

    Article  PubMed  Google Scholar 

  • Tanne JH. Maternal obesity and diabetes are linked to children’s autism and similar disorders. BMJ. 2012;344:e2768.

    Article  PubMed  Google Scholar 

  • Vervoort VS, Beachem MA, Edwards PS, Ladd S, Miller KE, de Mollerat X, Clarkson K, DuPont B, Schwartz CE, Stevenson RE, et al. AGTR2 mutations in X-linked mental retardation. Science. 2002;296(5577):2401–3.

    PubMed  Google Scholar 

  • Vincent JB, Herbrick JA, Gurling HM, Bolton PF, Roberts W, Scherer SW. Identification of a novel gene on chromosome 7q31 that is interrupted by a translocation breakpoint in an autistic individual. Am J Hum Genet. 2000;67(2):510–4.

    Article  PubMed  Google Scholar 

  • Volkmar F, Cook E. Autism and genes. National Institute of Child Health and Human Development (NICHD); 2005.

    Google Scholar 

  • Walsh CA, Morrow EM, Rubenstein JL. Autism and brain development. Cell. 2008;135(3):396–400.

    Article  PubMed  Google Scholar 

  • Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH. Fetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol. 2001;43(3):202–6.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, Sultan Qaboos University, College of Medicine and Health Sciences, 35, Al-Khoudh, Sultanate of Oman

    Allal Ouhtit

  2. College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, Oman

    Yahya M. Al-Farsi

  3. Department of Genetics, Sultan Qaboos University, College of Medicine and Health Sciences, Al-Khoudh, Sultanate of Oman

    Ishita Gupta

  4. Sultan Qaboos University, Muscat, Sultanate of Oman

    Mostafa I. Waly

  5. Department of Behavioral Medicine, Sultan Qaboos University, College of Medicine and Health Sciences, 35, Al-Khoudh, Sultanate of Oman

    Marwan M. Al-Sharbati

Authors
  1. Allal Ouhtit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yahya M. Al-Farsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ishita Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mostafa I. Waly
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marwan M. Al-Sharbati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allal Ouhtit .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, Faculty of Science & Technology, London, United Kingdom

    Vinood B. Patel

  2. Nutritional Sciences Division and Genomics Centre, King's College London, London, United Kingdom

    Victor R. Preedy

  3. Faculty of Society and Health, Buckinghamshire New University, Middlesex, United Kingdom

    Colin R. Martin

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this entry

Cite this entry

Ouhtit, A., Al-Farsi, Y.M., Gupta, I., Waly, M.I., Al-Sharbati, M.M. (2014). Genetics of Autism Spectrum Disorder: Experience in Developing Countries. In: Patel, V., Preedy, V., Martin, C. (eds) Comprehensive Guide to Autism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4788-7_149

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-4788-7_149

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-4787-0

  • Online ISBN: 978-1-4614-4788-7

  • eBook Packages: Behavioral Science

Publish with us

Policies and ethics

Search

Navigation