Skip to main content Accessibility help
×
Hostname: page-component-77c89778f8-m8s7h Total loading time: 0 Render date: 2024-07-17T15:43:05.070Z Has data issue: false hasContentIssue false

Chapter 5 - The Genetics of Autism Spectrum Disorders

Published online by Cambridge University Press:  18 January 2019

Fred R. Volkmar
Affiliation:
Yale University, Connecticut
Get access

Summary

Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, DC.Google Scholar
American Psychiatric Association. (1952). Diagnostic and statistical manual of mental disorders (First Edition) Washington, DC: American Psychiatric Association.Google Scholar
American Psychiatric Association. (1968). Diagnostic and statistical manual of mental disorders (Second Edition). Washington, DC: American Psychiatric Association.Google Scholar
American Psychiatric Association. (1980). Diagnostic and statistical manual of mental disorders (Third Edition). Arlington, VA: American Psychiatric Association.Google Scholar
Anney, R., Klei, L., Pinto, D., et al. (2012). Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum Mol Genet, 21(21): 47814792.Google Scholar
Anney, R., Ripke, S., Arking, D., et al. (2013). Meta-analysis of European Ancestry Individuals with Autism Spectrum Disorder reveals Strong Association 3' of the Astrotactin 2 (ASTN2) Gene Locus on Chromosome 9. World Congress of Psychiatric Genetics, Boston, MA.Google Scholar
Autism Spectrum Disorders Working Group of the Psychiatric Genomics. (2017). Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol Autism, 8: 21.Google Scholar
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): 6377.Google Scholar
Berg, J. M. and Geschwind, D. H. (2012). Autism genetics: searching for specificity and convergence. Genome Biol, 13(7): 247.Google Scholar
Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res, 1380: 4277.Google Scholar
Bi, C., Wu, J., Jiang, T., et al. (2012). Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Hum Mutat, 33(12): 16351638.Google Scholar
Bleuler, E. (1950). Dementia Praecox or the Group of Schizophrenias (translated by Zinkin, J.). New York: International Universities Press.Google Scholar
Bourgeron, T. (2015). From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci, 16(9): 551563.Google Scholar
Buxbaum, J. D. (2009). Multiple rare variants in the etiology of autism spectrum disorders. Dialogues Clin Neurosci, 11(1): 3543.Google Scholar
Buxbaum, J. D., Daly, M. J., Devlin, B., et al. (2012). The autism sequencing consortium: large-scale, high-throughput sequencing in autism spectrum disorders. Neuron, 76(6): 10521056.Google Scholar
Chahrour, M. H., Yu, T. W., Lim, E. T., et al. (2012). Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet, 8(4): e1002635.Google Scholar
Clifford, S., Dissanayake, C., Bui, Q. M., et al. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and premutation. J Autism Dev Disord, 37(4): 738747.Google Scholar
Colvert, E., Tick, B., McEwen, F., et al. (2015). Heritability of autism spectrum disorder in a UK population-based twin sample. JAMA Psychiatry, 72(5): 415423.Google Scholar
Committee on Bioethics. and Committee on Genetics, and the American College of Medical Genetics, Genomics Social, Ethical and Legal Issues committee (2013). Ethical and policy issues in genetic testing and screening of children. Pediatrics, 131(3): 620622.Google Scholar
Constantino, J. N. (2011). The quantitative nature of autistic social impairment. Pediatr Res, 69(5 Pt 2): 55R62R.Google Scholar
Crowe, R. R. (1993). Candidate genes in psychiatry: an epidemiological perspective. Am J Med Genet, 48(2): 7477.Google Scholar
De Rubeis, S., He, X., Goldberg, A. P., et al. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515(7526): 209215.Google Scholar
Devlin, B. and Scherer, S. W. (2012). Genetic architecture in autism spectrum disorder. Curr Opin Genet Dev, 22(3): 229237.Google Scholar
Dunham, I., Kundaje, A., Aldred, S. F., et al. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489(7414): 5774.Google Scholar
Fernandez, B. A., Roberts, W., Chung, B., et al. (2010). Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet, 47(3): 195203.Google Scholar
Folstein, S. and Rutter, M. (1977). Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry, 18(4): 297321.Google Scholar
Freed, D. and Pevsner, J. (2016). The contribution of mosaic variants to autism spectrum disorder. PLoS Genet, 12(9): e1006245.CrossRefGoogle ScholarPubMed
Fryns, J. P., Jacobs, J., Kleczkowska, A., and van den Berghe, H. (1984). The psychological profile of the fragile X syndrome. Clin Genet, 25(2): 131134.Google Scholar
Gaugler, T., Klei, L., Sanders, S. J., et al. (2014). Most genetic risk for autism resides with common variation. Nat Genet, 46(8): 881885.Google Scholar
Gillberg, C. and Forsell, C. (1984). Childhood psychosis and neurofibromatosis – more than a coincidence? J Autism Dev Disord, 14(1): 18.Google Scholar
Gilman, S. R., Iossifov, I., Levy, D., et al. (2011). Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron, 70(5): 898907.Google Scholar
Girirajan, S., Rosenfeld, J. A., Coe, B. P., et al. (2012). Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N Engl J Med, 367(14): 13211331.Google Scholar
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., et al. (2010). A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet, 42(3): 203209.Google Scholar
Goodwin, S., McPherson, J. D., and McCombie, W. R. (2016). Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet, 17(6): 333351.CrossRefGoogle ScholarPubMed
Hallmayer, J., Cleveland, S., Torres, A., et al. (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 68(11): 10951102.Google Scholar
Hanson, D. R. and Gottesman, II (1976). The genetics, if any, of infantile autism and childhood schizophrenia. J Autism Child Schizophr, 6(3): 209234.Google Scholar
Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., et al. (2014). A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP. Nat Genet, 46(4): 380384.Google Scholar
Hodge, S. E. (1995). An oliogenic disease displaying weak marker associations: a summary of contributions to problem 1 of GAW9. Genet Epidemiol, 12(6): 545554.Google Scholar
Iafrate, A. J., Feuk, L., Rivera, M. N., et al. (2004). Detection of large-scale variation in the human genome. Nat Genet, 36(9): 949951.Google Scholar
Iossifov, I., O'Roak, B. J., Sanders, S. J., et al. (2014). The contribution of de novo coding mutations to autism spectrum disorder. Nature, 515(7526): 216221.Google Scholar
Iossifov, I., Ronemus, M., Levy, D., et al. (2012). De novo gene disruptions in children on the autistic spectrum. Neuron, 74(2): 285299.Google Scholar
Jacobs, P. A., Browne, C., Gregson, N., Joyce, C., and White, H. (1992). Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet, 29(2): 103108.Google Scholar
Jiang, Y. H., Yuen, R. K., Jin, X., et al. (2013). Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Am J Hum Genet, 93(2): 249263.Google Scholar
Kanner, L. (1968). Autistic disturbances of affective contact. Acta Paedopsychiatr., 35(4): 100136.Google ScholarPubMed
Klei, L., Sanders, S. J., Murtha, M. T., et al. (2012). Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism, 3(1): 9.Google Scholar
Kolvin, I. (1972a). Infantile autism or infantile psychoses. Br Med J, 3(5829): 753755.Google Scholar
Kolvin, I. (1972b). Late onset psychosis. Br Med J, 3(5830): 816817.CrossRefGoogle ScholarPubMed
Krupp, D. R., Barnard, R. A., Duffourd, Y., et al. (2017). Exonic mosaic mutations contribute risk for autism spectrum disorder. Am J Hum Genet, 101(3): 369390.Google Scholar
Lai, M. C., Lombardo, M. V., Auyeung, B., Chakrabarti, B., and Baron-Cohen, S. (2015). Sex/gender differences and autism: setting the scene for future research. J Am Acad Child Adolesc Psychiatry, 54(1): 1124.Google Scholar
Leblond, C. S., Heinrich, J., Delorme, R., et al. (2012). Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet, 8(2): e1002521.CrossRefGoogle ScholarPubMed
Lim, E. T., Raychaudhuri, S., Sanders, S. J., et al. (2013). Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. Neuron, 77(2): 235242.Google Scholar
Lim, E. T., Uddin, M., De Rubeis, S., et al. (2017). Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nat Neurosci, 20(9): 12171224.Google Scholar
Liu, L., Sabo, A., Neale, B. M., et al. (2013). Analysis of rare, exonic variation amongst subjects with autism spectrum disorders and population controls. PLoS Genet, 9(4): e1003443.Google Scholar
Macdonald, J. R., Ziman, R., Yuen, R. K., Feuk, L., and Scherer, S. W. (2013). The database of genomic variants: a curated collection of structural variation in the human genome. Nucleic Acids Res, 2014 Jan; 42(Database issue): D986–92.Google Scholar
Manning, M., Hudgins, L., Professional, P., and Guidelines, C. (2010). Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med, 12(11): 742745.Google Scholar
Marshall, C. R., Noor, A., Vincent, J. B., et al. (2008). Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet, 82(2): 477488.Google Scholar
Marshall, C. R. and Scherer, S. W. (2012). Detection and characterization of copy number variation in autism spectrum disorder. Methods Mol Biol, 838: 115135.Google Scholar
McDonald-McGinn, D., Sullivan, E. V., Marino, B., et al. (2015). 22q11.2 deletion syndrome. Nature Reviews Disease Primers, 1.Google Scholar
McGlashan, T. H. (2011). Eugen Bleuler: centennial anniversary of his 1911 publication of Dementia Praecox or the group of schizophrenias. Schizophr Bull, 37(6): 11011103.Google Scholar
Meienberg, J., Bruggmann, R., Oexle, K., and Matyas, G. (2016). Clinical sequencing: is WGS the better WES? Hum Genet, 135(3): 359362.Google Scholar
Miles, J. H., McCathren, R. B., Stichter, J., and Shinawi, M. (1993). Autism spectrum disorders. GeneReviews®. R. A. Pagon, M. P. Adam, T. D. Bird et al. Seattle, WA.Google Scholar
Miller, D. T., Adam, M. P., Aradhya, S., et al. (2010). Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet, 86(5): 749764.Google Scholar
Mitchel, M. W., Moreno-De-Luca, D., Myers, S. M., et al. (1993). 17q12 recurrent deletion syndrome. GeneReviews®. M. P. Adam, H. H. Ardinger, R. A. Pagon et al. Seattle, WA.Google Scholar
Neale, B. M., Kou, Y., Liu, L., et al. (2012). Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 485(7397): 242245.Google Scholar
Noll, A. C., Miller, N. A., Smith, L. D., et al. (2016). Clinical detection of deletion structural variants in whole-genome sequences. NPJ Genom Med, 1: 16026.Google Scholar
Noor, A., Whibley, A., Marshall, C. R., et al. (2010). Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability. Sci Transl Med, 2(49): 49ra68.Google Scholar
O'Roak, B. J., Vives, L., Fu, W., et al. (2012). Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science, 338(6114): 16191622.Google Scholar
O'Roak, B. J., Vives, L., Girirajan, S., et al. (2012). Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485(7397): 246250.Google Scholar
Ozonoff, S., Young, G. S., Carter, A., et al. (2011). Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics, 128(3): e488–495.Google Scholar
Pagnamenta, A. T., Khan, H., Walker, S., et al. (2011). Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability. J Med Genet, 48(1): 4854.Google Scholar
Pang, A. W., MacDonald, J. R., Pinto, D., et al. (2010). Towards a comprehensive structural variation map of an individual human genome. Genome Biol, 11(5): R52.Google Scholar
Pang, A. W., Macdonald, J. R., Yuen, R. K., Hayes, V. M., and Scherer, S. W. (2013). Performance of high-throughput sequencing for the discovery of genetic variation across the complete size spectrum. G3 (Bethesda), 4(1): 6365.CrossRefGoogle Scholar
Pinto, D., Pagnamenta, A. T., Klei, L., et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 466(7304): 368372.Google Scholar
Prasad, A., Merico, D., Thiruvahindrapuram, B., et al. (2012). A discovery resource of rare copy number variations in individuals with autism spectrum disorder. G3 (Bethesda), 2(12): 16651685.Google Scholar
Reiff, M., Giarelli, E., Bernhardt, B. A., et al. (2015). Parents' perceptions of the usefulness of chromosomal microarray analysis for children with autism spectrum disorders. J Autism Dev Disord, 45(10): 32623275.Google Scholar
Richards, C., Jones, C., Groves, L., Moss, J., and Oliver, C. (2015). Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry, 2(10): 909916.Google Scholar
Ritvo, E. R., Freeman, B. J., Mason-Brothers, A., Mo, A., and Ritvo, A. M. (1985). Concordance for the syndrome of autism in 40 pairs of afflicted twins. Am J Psychiatry, 142(1): 7477.Google Scholar
Ronemus, M., Iossifov, I., Levy, D., and Wigler, M. (2014). The role of de novo mutations in the genetics of autism spectrum disorders. Nat Rev Genet, 15(2): 133141.Google Scholar
Rutter, M. (1968). Concepts of autism: a review of research. J Child Psychol Psychiatry, 9(1): 125.Google Scholar
Rutter, M. (1972). Childhood schizophrenia reconsidered. J Autism Child Schizophr, 2(4): 315337.Google Scholar
Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., et al. (2011). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70(5): 863885.Google Scholar
Sanders, S. J., He, X., Willsey, A. J., et al. (2015). Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron, 87(6): 12151233.CrossRefGoogle ScholarPubMed
Sanders, S. J., Murtha, M. T., Gupta, A. R., et al. (2012). De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 485(7397): 237241.Google Scholar
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., et al. (2014). The familial risk of autism. JAMA, 311(17): 17701777.Google Scholar
Sandin, S. P. Lichtenstein, R. Kuja-Halkola et al. (2017). The Heritability of Autism Spectrum Disorder. JAMA. 318: 11821184.Google Scholar
Sebat, J., Lakshmi, B., Troge, J., et al. (2004). Large-scale copy number polymorphism in the human genome. Science, 305(5683): 525528.Google Scholar
Shi, L., Zhang, X., Golhar, R., et al. (2013). Whole-genome sequencing in an autism multiplex family. Mol Autism, 4(1): 8.Google Scholar
Smalley, S. L., Asarnow, R. F., and Spence, M. A. (1988). Autism and genetics. A decade of research. Arch Gen Psychiatry, 45(10): 953961.Google Scholar
Smalley, S. L., Tanguay, P. E., Smith, M., and Gutierrez, G. (1992). Autism and tuberous sclerosis. J Autism Dev Disord, 22(3): 339355.Google Scholar
Speicher, M. R. and Carter, N. P. (2005). The new cytogenetics: blurring the boundaries with molecular biology. Nat Rev Genet, 6(10): 782792.Google Scholar
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): 405416.Google Scholar
Sumi, S., Taniai, H., Miyachi, T., and Tanemura, M. (2006). Sibling risk of pervasive developmental disorder estimated by means of an epidemiologic survey in Nagoya, Japan. J Hum Genet, 51(6): 518522.Google Scholar
Szatmari, P., Paterson, A. D., Zwaigenbaum, L., et al. (2007). Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet, 39(3): 319328.Google Scholar
Talkowski, M. E., Rosenfeld, J. A., Blumenthal, I., et al. (2012). Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell, 149(3): 525537.Google Scholar
Tammimies, K., Marshall, C. R., Walker, S., et al. (2015). Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children with Autism Spectrum Disorder. JAMA, 314(9): 895903.Google Scholar
Taniai, H., Nishiyama, T., Miyachi, T., Imaeda, M., and Sumi, S. (2008). Genetic influences on the broad spectrum of autism: study of proband-ascertained twins. Am J Med Genet B Neuropsychiatr Genet, 147B(6): 844849.Google Scholar
Teo, S. M., Pawitan, Y., Ku, C. S., Chia, K. S., and Salim, A. (2012). Statistical challenges associated with detecting copy number variations with next-generation sequencing. Bioinformatics, 28(21): 27112718.Google Scholar
Volkmar, F., Siegel, M., Woodbury-Smith, M., et al. (2014). Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry, 53(2): 237257.Google Scholar
Vorstman, J. A. and Ophoff, R. A. (2013). Genetic causes of developmental disorders. Curr Opin Neurol, 26(2): 128136.Google Scholar
Vorstman, J. A., Parr, J. R., Moreno-De-Luca, D., et al. (2017). Autism genetics: opportunities and challenges for clinical translation. Nat Rev Genet. 18: 362376.Google Scholar
Vorstman, J. A., Staal, W. G., van Daalen, E., et al. (2006). Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry, 11(1): 1, 1828.Google Scholar
Walker, S. and Scherer, S. W. (2013). Identification of candidate intergenic risk loci in autism spectrum disorder. BMC Genomics, 14(1): 499.Google Scholar
Weiss, L. A., Arking, D. E., Daly, M. J., and Chakravarti, A. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461(7265): 802808.Google Scholar
Werling, D. M. and Geschwind, D. H. (2015). Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins. Mol Autism, 6: 27.Google Scholar
Wisniowiecka-Kowalnik, B., Nesteruk, M., Peters, S. U., et al. (2010). Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay. Am J Med Genet B Neuropsychiatr Genet, 153B(5): 983993.Google Scholar
Wood, C. L., Warnell, F., Johnson, M., et al. (2015). Evidence for ASD recurrence rates and reproductive stoppage from large UK ASD research family databases. Autism Res, 8(1): 7381.Google Scholar
Yu, T. W., Chahrour, M. H., Coulter, M. E., et al. (2013). Using whole-exome sequencing to identify inherited causes of autism. Neuron, 77(2): 259273.Google Scholar
Yuen, R. K., Merico, D., Cao, H., et al. (2016). Genome-wide characteristics of de novo mutations in autism. NPJ Genom Med, 1: 1602711602710.Google Scholar
Yuen, R. K., Merico, D., Bookman, M., et al. (2017). Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci, 20(4): 602611.Google Scholar
Yuen, R. K., Thiruvahindrapuram, B., Merico, D., et al. (2015). Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med, 21(2): 185191.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×