English Українська
  • Main
  • Useful links
  • Information for Contributors
  • About
  • Editorial board

    •
    Article
    World of Medicine and Biology / №1(59), 2017 / GENETICS OF AUTISM SPECTRUM DISORDERS
    Pomohaibo V.M., Berezan O.I., Petrushov A.V.

    GENETICS OF AUTISM SPECTRUM DISORDERS

    About the author: Pomohaibo V.M., Berezan O.I., Petrushov A.V.
    Heading LITERATURE REVIEWS
    Type of article Review article
    Annotation The review of research results of genetic mechanisms of autism spectrum disorders is carried out. According to current ideas there are two extreme forms of autism: a form of direct genetic definiteness of disorder and a form of hereditary tendency to pathology between which there are various intermediate illness forms. In case of tendency to a disease the significant role in its development is played by provocative factors of environment, the variety and the number of which is constantly increasing in the modern techno genetic world. Genetic component takes an important role in autism etiology, because the coefficient of its heritability can reach up to 90%. The mutations of certain genes are the reason of nearly 15% of cases of autism, typical for particular families. The other cases are polygenic. Over 100 genes connected with autism have been determined so far. About 60% of them are dominant and about 40% are recessive. These genes are found practically in all chromosomes, except the 13th, 18th, 21st and Y-chromosome. Their greatest number is in the X-chromosome (45) and the 17th chromosome (7); in other autosomes – on average there are about 3 genes.
    Tags autism spectrum disorders, genetic definiteness, hereditary tendency, coefficient of heritability, genes, mutations
    Bibliography
    • Amir R.E. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 / R.E. Amir, I.B. Van den Veyver [et al.] // Nat. Genet. – 1999. – Vol. 23. – No. 2. – P. 185-188.
    • Abrahams B.S. Advances in autism genetics: on the threshold of a new neurobiology / B.S. Abrahamsand, D.H. Geschwind // Nat. Rev. Genet. – 2008. – Vol. 9. – No. 5. – P. 341-355.
    • Anney R. A genome-wide scan for common alleles affecting risk for autism / R. Anney, L. Klei, D. Pinto [et al.] // Hum. Mol. Genet. – 2010. – Vol. 19. – No. 20. – P. 4072-4082.
    • Auyeung B. Foetal testosterone and autistic traits in 18 to 24-month-old children / B. Auyeung, K. Taylor, G. Hackett [et al.] // Mol. Autism. – 2010. – Vol. 1. – Art. 11. – 8 p.
    • Anney R. Meta-analysis of European ancestry individuals with Autism Spectrum Disorder reveals genome-wide significant association at the astrotactin 2 (ASTN2) gene locus on chromosome 9 / R. Anney // Ulster Med. J.– 2013. – Vol. 82. – No. 3. – P. 197-204.
    • Bourgeron T. A synaptic trek to autism / T. Bourgeron // Curr. Opin. Neurobiol. – 2009. – Vol. 19. – No. 2. – P. 231-234.
    • Berger B.E. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination – United States, 2001-2010 / B.E. Berger, A.M. Navar-Boggan, S.B. Omer // BMC Public Health. – 2011. – Vol. 11. – Art. 340. – 5 p.
    • Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting / C. Betancur // Brain Res. – 2011. – Vol. 1380. – P. 42-77.
    • Berg, J.M. Autism genetics: searching for specificity and convergence / J.M. Berg, D.H. Geschwind // Genome biology. – 2012. – Vol. 13. – P. 247-262.
    • Baron-Cohen S. Elevated fetal steroidogenic activity in autism / S. Baron-Cohen, B. Auyeung, B. Norgaard-Pedersen [et al.] // Mol. Psychiatry. – 2015. – Vol. 20. – No. 3. – P. 369–376.
    • CDGPG Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis / Cross-Disorder Group of the Psychiatric Genomics Consortium // Lancet. – 2013. – Vol. 381. – No. 9875. – P. 1371-1379.
    • Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. – Washington, DC: American Psychiatric Association, -2013. – 992 p.
    • Glasson E.J. Perinatal factors and the development of autism: a population study / E.J. Glasson, C. Bower, B. Petterson [et al.] // Arch. Gen. Psychiatry. – 2004. – Vol. 61. – No. 6. – P. 618-627.
    • Girirajan S. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay / S. Girirajan,J.A. Rosenfeld, G.M. Cooper et al. // Nat. Genet. – 2010. – Vol. 42. – No. 3. – P. 203-209.
    • Geier D.A. An evaluation of the role and treatment of elevated male hormones in autism spectrum disorders / D.A. Geier, J.K. Kern, P.G. King [et al.] // Acta Neurobiol. Exp. – 2012. – Vol. 72. – No. 1. – P. 1-17.
    • Gaugler T. Most genetic risk for autism resides with common variation / T. Gaugler, L. Klei, S.J. Sanderset [et al.] // Nat. Genet. – 2014. – Vol. 46. – No. 8. – P. 881-885.
    • Hogart A. The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13 / A. Hogart, D. Wu, J.M. LaSalle [et al.] // Neurobiol. Dis. – 2010. – Vol. 38. – No. 2. – P. 181-191.
    • Hultman C.M. Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies / C.M. Hultman, S. Sandin, S.Z. Levine [et al.] // Mol. Psychiatry. – 2011. – Vol. 16. – No. 12. – P. 1203-1212.
    • Iossifov I. The contribution of de novo coding mutations to autism spectrum disorder / I. Iossifov, B.J. O'Roak, S.J. [et al.] // Nature. – 2014. – Vol. 515. – No. 7526. – P. 216-221.
    • Jamain S. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism / S. Jamain, H. Quach, C. Betancur [et al.] // Nat. Genet. – 2003. – Vol. 34. – No. 1. – P. 27-29.
    • Kishino T. UBE3A/E6-AP mutations cause Angelman syndrome / T. Kishino, M. Lalande, J. Wagstaff // Nat. Genet. – 1997. – Vol. 15. – No. 1. – P. 70-73.
    • Knickmeyer R. Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia / R. Knickmeyer, S. Baron-Cohen,B.A. Fane [et al.] // Horm. Behav. – 2006. – Vol. 50. – No. 1. – P. 148-153.
    • Klei L.Common genetic variants, acting additively, are a major source of risk for autism / L. Klei, S.J. Sanders, M.T. Murtha [et al.] // Mol. Autism. – 2012. – Vol. 3. – Art. 9. – 13 p.
    • Levy D. Rare de novo and transmitted copy-number variation in autistic spectrum disorders / D. Levy, M. Ronemus, B. Yamrom [et al.] // Neuron. – 2011. – Vol. 70. – No. 5. – P. 886-897.
    • Marshall C.R. Structural variation of chromosomes in autism spectrum disorder / C.R. Marshall, A. Noor, J.B. Vincent [et al.] // Am. J. Hum. Genet. – 2008. – Vol. 82. – No. 2. – P. 477-488.
    • Pinto D. Functional impact of global rare copy number variation in autism spectrum disorders / D. Pinto, A.T. Pagnamenta, L. Klei [et al.] // Nature. – 2010. – Vol. 466. – No. 7304. – P. 368-372.
    • Pinto D. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders / D. Pinto, E. Delaby, D. Merico [et al.] // Am J Hum Genet. – 2014. – Vol. 94. – No. 5. – P. 677-694.
    • Perrone-McGovern K. Prenatal and perinatal factors related to autism, IQ, and adaptive functioning / K. Perrone-McGovern, S. Simon-Dack, L. Niccolai // J. Genet. Psychol. – 2015. – Vol. 176. – No. 1. – P. 1-10.
    • Ronald A. Autism spectrum disorders and autistic traits: a decade of new twin studies / A. Ronald, R.A. Hoekstra // Am. J. Med. Genet. Part B. – 2011. – Vol. 156. – No. 3. – P. 255-274.
    • Saitoh Sh. Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation / Sh. Saitoh, K. Buiting, S.B. Cassidy [et al.] // Am. J. Med. Genet. – 1997. – Vol. 68.-No. 2.-P. 195-206.
    • Splawski I. CaV1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism / I. Splawski, K.W. Timothy, L.M. Sharpe [et al.] // Cell. – 2004. – Vol. 119. – No. 1. – P. 19-31.
    • Strauss K.A. Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2 / K.A. Strauss, E.G. Puffenberger, M.J. Huentelman [et al.] // N. Engl. J. Med. – 2006. – Vol. 354. – No. 13. – P. 1370-1377.
    • Sebat J. Strong association of de novo copy number mutations with autism / J. Sebat, B. Lakshmi, D. Malhotra [et al.] // Science. – 2007. – Vol. 316. – No. 5823. – P. 445-449.
    • Stankiewicz P. Structural variation in the human genome and its role in disease / P. Stankiewicz, J.R. Lupski // Annu. Rev. Med. – 2010. – Vol. 61. – P. 437-455.
    • Stefansson H. CNVs conferring risk of autism or schizophrenia affect cognition in controls / H. Stefansson, A. Meyer-Lindenberg, S. Steinberg [et al.] // Nature. – 2014. – Vol. 505. – No. 7483. – P. 361-366.
    • St Pourcain B. Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence / B. St Pourcain, D.H. Skuse, W.P. Mandy [et al.] // Mol. Autism. – 2014. – Vol. 5.-Art. 18.-12 p.
    • TECh16TS Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16 / The European Chromosome 16 Tuberous Sclerosis Consortium // Cell. – 1993. – Vol. 75. – No. 7. – P. 1305-1315.
    • The National Center for Biotechnology Information: Gene. – URL: http://www.ncbi.nlm.nih.gov/gene.
    • Verkerk A.J. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome / A.J. Verkerk, M. Pieretti, J.S. Sutcliffe [et al.] // Cell. – 1991. – Vol. 65. – No. 5. – P. 905-914.
    • Wang K. Common genetic variants on 5p14.1 associate with autism spectrum disorders / K. Wang, H. Zhang, D. Ma [et al.] // Nature. – 2009. – Vol. 459. – No. 7246. – P. 528-533.
    • Whitehouse A. J. CNTNAP2 variants affect early language development in the general population / A.J. Whitehouse, D.V. Bishop, Q.W. Ang [et al.] // Genes Brain Behav. – 2011. – Vol. 10. – No. 4. – P. 451-456.
    Publication of the article «World of Medicine and Biology» №1(59), 2017 year, 208-212 pages, index UDK 616.896