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New Genetic Approaches for Early Diagnosis and Treatment of Autism Spectrum Disorders

  • Meryem AlagozEmail author
  • Nasim Kherad
  • Meral Gavaz
  • Adnan Yuksel
Review Paper
  • 7 Downloads

Abstract

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders, characterized by disruptions in social interactions, communication, and limitations in behavior. Early diagnosis is an important step to prevent progression of ASD. Recent developments in genetic technology provide useful tools to investigate the molecular mechanisms involved in autism. Despite a number of noteworthy studies, there is not yet enough understanding of the genetic etiology of ASD. Research should focus on multidisciplinary approaches to improve early diagnosis and intervention of autism. It is important to study the combinatorial effects of genetic, epigenetic, and environmental factors. This review focuses on current research in ASD, highlighting the importance of identifying new approaches, such as next generation sequencing (NGS) and microRNA (miRNA) technologies, to introduce possible ways for developing new biomarkers and drugs.

Keywords

Autism spectrum disorders Next generation sequencing Early diagnosis and treatment New genetic approaches 

Notes

References

  1. Abdallah, M. W., Larsen, N., Grove, J., Norgaard-Pedersen, B., Thorsen, P., Mortensen, E. L., & Hougaard, D. M. (2013). Amniotic fluid inflammatory cytokines: potential markers of immunologic dysfunction in autism spectrum disorders. The World Journal of Biological Psychiatry, 14(7), 528–553.Google Scholar
  2. Abidi, F. E., Holloway, L., Moore, C. A., Weaver, D. D., Simensen, R. J., Stevenson, R. E., Rogers, R. C., & Schwartz, C. E. (2008). Mutations in JARID1C are associated with X-linked mental retardation, short stature and hyperreflexia. Journal of Medical Genetics.  https://doi.org/10.1136/jmg.2008.058990.
  3. Abrahams, B. S., & Geschwind, D. H. (2008). Advances in autism genetics: on the threshold of a new neurobiology. Nature Reviews Genetics, 9(5), 341–355.Google Scholar
  4. Adegbola, A., Gao, H., Sommer, S., & Browning, M. (2008). A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). American Journal of Medical Genetics. Part A.  https://doi.org/10.1002/ajmg.a.32142.
  5. Ahn, J. W., Bint, S., Bergbaum, A., Mann, K., Hall, R. P., & Ogilvie, C. M. (2013). Array CGH as a first line diagnostic test in place of karyotyping for postnatal referrals-results from four years’ clinical application for over 8,700 patients. Molecular Cytogenetics, 6(1), 16.Google Scholar
  6. Almad, A. A., & Maragakis, N. J. (2012). Glia: an emerging target for neurological disease therapy. Stem Cell Research & Therapy, 3, 37.Google Scholar
  7. Alter, M. D., Kharkar, R., Ramsey, K. E., Craig, D. W., Melmed, R. D., Grebe, T. A., Bay, R. C., Ober-Reynolds, S., Kirwan, J., Jones, J. J., Turner, J. B., Hen, R., & Stephan, D. A. (2011). Autism and increased paternal age related changes in global levels of gene expression regulation. PLoS One, 6, e16715.Google Scholar
  8. Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpGbinding protein 2. Nature Genetics, 23, 185–188.Google Scholar
  9. Anney, R., Klei, L., Pinto, D., et al. (2010). A genome-wide scan for common alleles affecting risk for autism. Human Molecular Genetics, 19(20), 4072–4082.Google Scholar
  10. Ansel, A., Rosenzweig, J. P., Zisman, P. D., Melamed, M., & Gesundheit, B. (2017). Variation in gene expression in autism spectrum disorders: an extensive review of transcriptomics studies. Frontiers in Neuroscience, 10, 601.Google Scholar
  11. Aronica, E., Fluiter, K., Iyer, A., Zurolo, E., Vreijling, J., van Vliet, E. A., Baayen, J. C., & Gorter, J. A. (2010). Expression pattern of miR-146a, aninflammation-associated microRNA, in experimental and human temporallobe epilepsy. The European Journal of Neuroscience, 31, 1100–1107.Google Scholar
  12. Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995). Autism as a strongly genetic disorder: evidence from a British twin study. Psychological Medicine, 25(1), 63–77.Google Scholar
  13. Beckmann, J. S., & Antonarakis, S. E. (2010). Lessons from the genome-wide association studies for complex multifactorial disorders and traits. In M. R. Speicher, A. G. Motulsky, & S. E. Antonarakis (Eds), Vogel and Motulsky’s human genetics. Berlin, Heidelberg: Springer. Vogel and Motulsky’s Human Genetics, 287–297.  https://doi.org/10.1007/978-3-540-37654-5_10.
  14. Brookes, E., Laurent, B., Õunap, K., Carroll, R., Moeschler, J. B., Field, M., Schwartz, C. E., Gecz, J., & Shi, Y. (2015). Mutations in the intellectual disability gene KDM5C reduce protein stability and demethylase activity. Human Molecular Genetics.  https://doi.org/10.1093/hmg/ddv046.
  15. Brown, A. S., Sourander, A., Hinkka-Yli-Salomaki, S., McKeague, I. W., Sundvall, J., & Surcel, H. M. (2014). Elevated maternal C-reactive protein and autism in a national birth cohort. Molecular Psychiatry, 19, 259–264.Google Scholar
  16. Burstyn, I., Wang, X., Yasui, Y., Sithole, F., & Zwaigenbaum, L. (2011). Autism spectrum disorders and fetal hypoxia in a population-based cohort: accounting for missing exposures via estimation-maximization algorithm. BMC Medical Research Methodology, 11, 2.Google Scholar
  17. Bustos, M., Venkataramanan, R., & Caritis, S. (2017). Nausea and vomiting of pregnancy—what’s new? Autonomic Neuroscience, 202, 62–72.Google Scholar
  18. Caglayan, A. O. (2010). Genetic causes of syndromic and non-syndromic autism. Developmental Medicine and Child Neurology, 52(2), 130–138.Google Scholar
  19. Chahrour, M. H., Yu, T. W., Lim, E. T., Ataman, B., Coulter, M. E., Hill, R. S., Stevens, C. R., Schubert, C. R., ARRA Autism Sequencing Collaboration, Greenberg, M. E., Gabriel, S. B., & Walsh, C. A. (2012). Whole exome sequencing and homozygosity analysis implicate depolarization regulated neuronal genes in autism. PLoS Genetics, 8, e1002635.Google Scholar
  20. Chen, Y. L., & Shen, C. K. (2013). Modulation of mGluR-dependent MAP1B translationand AMPA receptor endocytosis by microRNA miR-146a-5p. The Journal of Neuroscience, 33, 9013–9020.Google Scholar
  21. Cheng, T. L., & Qiu, Z. (2014). MeCP2: multifaceted roles in gene regulation and neuraldevelopment. Neuroscience Bulletin.  https://doi.org/10.1007/s12264-014-1452-6.
  22. Cho, S. C., Yim, S. H., Yoo, H. K., Kim, M. Y., Jung, G. Y., Shin, G. W., Kim, B. N., Hwang, J. W., Kang, J. J., Kim, T. M., & Chung, Y. J. (2009). Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridiza-tion. Psychiatric Genetics, 19(4), 177–185.Google Scholar
  23. Chung, B. H., Tao, V. Q., & Tso, W. W. (2014). Copy number variation and autism: new insights and clinical implications. Journal of the Formosan Medical Association, 113, 400–408.Google Scholar
  24. Connolly, J. J., & Hakonarson, H. (2012). The impact of genomics on pediatric research and medicine. Pediatrics, 129, 1150–1160.Google Scholar
  25. Cuscó, I., Medrano, A., Gener, B., Vilardell, M., Gallastegui, F., Villa, O., González, E., Rodríguez-Santiago, B., Vilella, E., Del Campo, M., & Pérez-Jurado, L. A. (2009). Autism-specific copy number variants further implicate the phosphatidylinositol signalling pathway and the glutamatergic synapse in the etiology of the disorder. Human Molecular Genetics, 18(10), 1795–1804.Google Scholar
  26. Daniels, J. L., Forssen, U., Hultman, C. M., Cnattingius, S., Savitz, D. A., Feychting, M., & Sparen, P. (2008). Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics, 121, e1357–e1356.Google Scholar
  27. De Rubeis, S., He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Cicek, A. E., Kou, Y., Liu, L., Fromer, M., Walker, S., et al. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515, 209–215.Google Scholar
  28. Deckelbaum, R. J., Worgall, T. S., & Seo, T. (2006). n-3 fatty acids and gene expression. The American Journal of Clinical Nutrition, 83(6 Suppl), 1520S–1525S.Google Scholar
  29. Dong, S., Walker, M. F., Carriero, N. J., DiCola, M., Willsey, A. J., Ye, A. Y., Waqar, Z., Gonzale, L. E., Overton, J. D., Frahm, S., et al. (2014). De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder. Cell Reports, 9, 16–23.Google Scholar
  30. E.C.T.S. Consortium. (1993). Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell.  https://doi.org/10.1016/0092-8674(93)90618-Z.
  31. Ellis, S. E., Gupta, S., Moes, A., West, A. B., & Arking, D. E. (2017). Exaggerated CpH methylation in the autism-affected brain. Molecular Autism.  https://doi.org/10.1186/s13229-017-0119-y.
  32. Endersby, R., & Baker, S. J. (2008). PTEN signaling in brain: neuropathology and tumorigenesis. Oncogene, 27, 5416–5430.Google Scholar
  33. Fischbach, G. D., & Lord, C. (2010). The Simons simplex collection: a resource for identification of autism genetic risk factors. Neuron, 68, 192–195.Google Scholar
  34. Foley, D. L., Craig, J. M., Morley, R., Olsson, C. A., Dwyer, T., Smith, K., & Saffery, R. (2009). Prospects for epigenetic epidemiology. American Journal of Epidemiology, 169, 389–400.Google Scholar
  35. Folstein, S. E., & Rosen-Sheidley, B. (2001). Genetics of autism: complex aetiology for a heterogeneous disorder. Nature Reviews. Genetics, 2, 943–955.Google Scholar
  36. Fregeac, J., Colleaux, L., & Nguyen, L. M. (2016). The emerging roles of MicroRNAs in autism spectrum disorders. Neuroscience and Biobehavioral Reviews, 71, 729–738.Google Scholar
  37. Freitag, C. M., Staal, W., & Klauck, S. M. (2010). Genetics of autis¬tic disorders: review and clinical implications. European Child & Adolescent Psychiatry, 19, 169–178.Google Scholar
  38. Gallagher, D., Voronova, A., Zander, M. A., Cancino, G. I., Bramall, A., Krause, M. P., Abad, C., Tekin, M., Neilsen, P. M., Callen, D. F., Scherer, S. W., Keller, G. M., Kaplan, D. R., Walz, K., & Miller, F. D. (2015). Ankrd11 is a chromatin regulator involved in autism that is essential for neural development. Developmental Cell, 32, 31–42.Google Scholar
  39. Gardener, H., Spiegelman, D., & Buka, S. L. (2009). Prenatal risk factors for autism: comprehensive meta-analysis. The British Journal of Psychiatry, 195, 7–14.Google Scholar
  40. Girirajan, S., Dennis, M. Y., Baker, C., Malig, M., Coe, B. P., & Campbell, C. D. (2013). Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. American Journal of Human Genetics, 92, 221–237.Google Scholar
  41. Goines, P. E., Croen, L. A., Braunschweig, D., Yoshida, C. K., Grether, J., Hansen, R., et al. (2011). Increased mid-gestational IFN-gamma IFN I gamma-4 and IL-5 in women giving birth to a child with autism: a case-control study. Molecular Autism, 2(1), 13.Google Scholar
  42. Gray, S. J., Matagne, V., Bachaboina, L., Yadav, S., Ojeda, S. R., & Samulski, R. J. (2011). Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. Molecular Therapy, 19, 1058–1069.Google Scholar
  43. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B., Torigoe, T., et al. (2011). Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry, 68, 1095–1102.Google Scholar
  44. Holtmann M, Bölte S, Poustka F. (2007). Autism spectrum disorders: sex differences in autistic behaviour domains and coexisting psychopathology. Developmental Medicine and Child Neurology 49(5):361–6.Google Scholar
  45. Hsiao, E. Y., McBride, S. W., Chow, J., Mazmanian, S. K., & Patterson, P. H. (2012). Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proceedings of the National Academy of Sciences of the United States of America, 109(31), 12776–12781.Google Scholar
  46. Hultman, C. M., Sandin, S., Levine, S. Z., Lichtenstein, P., & ReichenbergA. (2011). Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular Psychiatry, 16, 1203–1212.Google Scholar
  47. Ivanov, H. Y., Stoyanova, V. K., Popov, N. T., & Vachev, T. I. (2015). Autism spectrum disorder - A complex genetic disorder. Folia Medica, 57(1), 19–28.Google Scholar
  48. Iyer, A., Zurolo, E., Prabowo, A., Fluiter, K., Spliet, W. G., van Rijen, P. C., Gorter, J. A., & Aronica, E. (2012). MicroRNA-146a: a key regulator of astrocyte-mediatedinflammatory response. PLoS One, 7, e44789.Google Scholar
  49. Jacquemont, M. L., Sanlaville, D., Redon, R., Raoul, O., Cormier-Daire, V., Lyonnet, S., Amiel, J., Le Merrer, M., Heron, D., de Blois, M. C., Prieur, M., Vekemans, M., Carter, N. P., Munnich, A., Colleaux, L., & Philippe, A. (2006). Array-based comparative genomic hybridisationidentifies high frequency of cryptic chromosomal rearrangements in patientswith syndromic autism spectrum disorders. Journal of Medical Genetics, 43, 843–849.Google Scholar
  50. Jin, P., Zarnescu, D. C., Ceman, S., Nakamoto, M., Mowrey, J., Jongens, T. A., Nelson, D. L., Moses, K., & Warren, S. T. (2004). Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nature Neuroscience, 7, 113–117.Google Scholar
  51. Jovičić, A., Roshan, R., Moisoi, N., Pradervand, S., Moser, R., Pillai, B., & Luthi-Carter, R. (2013). Comprehensive expression analyses of neuralcell-type-specific miRNAs identify new determinants of the specification andmaintenance of neuronal phenotypes. The Journal of Neuroscience, 33, 5127–5137.Google Scholar
  52. Kichukova, T. M., Popov, N. T., Ivanov, I. S., & Vachev, T. I. (2017). Profiling of circulating serum MicroRNAs in children with autism Spectrum disorder using stem-loop qRT-PCR assay. Folia Med (Plovdiv).  https://doi.org/10.1515/folmed-2017-0009.
  53. Koks, N., Ghassabian, A., Greaves-Lord, K., Hofman, A., Jaddoe, V. W., Verhulst, F. C., & Tiemeier, H. (2016). Maternal C-reactive protein concentration in early pregnancy and child autistic traits in the general population. Paediatric and Perinatal Epidemiology, 30(2), 181–189.Google Scholar
  54. Kolevzon, A., Gross, R., & Reichenberg, A. (2007). Prenatal and perinatal risk factors for autism: a review and integration of findings. Archives of Pediatrics & Adolescent Medicine, 161, 326–333.Google Scholar
  55. Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., et al. (2012). Rate of de novo mutations and the importance of father’s age to disease risk. Nature, 488, 471–475.Google Scholar
  56. Kumar, R. A., & Christian, S. L. (2009). Genetics of autism spec¬trum disorders. Current Neurology and Neuroscience Reports, 9, 188–197.Google Scholar
  57. Kumsta, R., Hummel, E., Chen, F. S., & Heinrichs, M. (2013). Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience. Frontiers in Neuroscience, 7, 83.Google Scholar
  58. Kyle, S. M., Saha, P. K., Brown, H. M., Chan, L. C., & Justice, M. J. (2016). MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex. Human Molecular Genetics, 25(14), 3029–3041.Google Scholar
  59. Lee, B. K., & McGrath, J. J. (2015). Advancing parental age and autism: multifactorial pathways. Trends in Molecular Medicine, 21, 118–125.Google Scholar
  60. Lee, B., Lee, K., Panda, S., Gonzales-Rojas, R., Chong, A., Bugay, V., Park, H. M., Brenner, R., Murthy, N., & Lee, H. Y. (2018). Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nature Biomedical Engineering.  https://doi.org/10.1038/s41551-018-0252-8.
  61. Li, X., Zou, H., & Brown, W. T. (2012). Genes associated with autism spectrum disorder. Brain Research Bulletin, 88, 543–552.Google Scholar
  62. Li, Y., Yiming, W., & Bai-Lin, W. (2015). Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of autism. Science China. Life Sciences.  https://doi.org/10.1007/s11427-015-4941-1.
  63. Liu, X., & Takumi, T. (2014). Genomic and genetic aspects of autism spectrum disorder. Biochemical and Biophysical Research Communications, 452, 244–253.Google Scholar
  64. Liu, L., Gao, J., He, X., Cai, Y., Wang, L., & Fan, X. (2017). Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Scientific Reports.  https://doi.org/10.1038/srep46207.
  65. Loke, Y. J., Hannan, A. J., & Craig, J. M. (2015). The role of epigenetic change in autism spectrum disorders. Frontiers in Neurology.  https://doi.org/10.3389/fneur.2015.00107.
  66. Lokody, I. (2014). Epigenetics: mechanisms underlying fragile X syndrome. Nature Reviews Genetics.  https://doi.org/10.1038/nrg3714.
  67. Lyall, K., Munger, K. L., O’Reilly, É. J., Santangelo, S. L., & Ascherio, A. (2013). Maternal dietary fat intake in association with autism spectrum disorders. American Journal of Epidemiology, 178, 209–220.Google Scholar
  68. Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012). Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain, Behavior, and Immunity, 26(4), 607–616.Google Scholar
  69. Matagne, V., Ehinger, Y., Saidi, L., Borges-Correia, A., Barkats, M., Bartoli, M., Villard, L., & Roux, J. C. (2017). A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome. Neurobiology of Disease, 99, 1–11.Google Scholar
  70. Matson, J. L., & Neal, D. (2010). Differentiating communication disorders and autism in children. Research in Autism Spectrum Disorders, 4(4), 626–632.Google Scholar
  71. Mayo, J., Chlebowski, C., Fein, D. A., & Eigsti, I.-M. (2013). Age of first words predicts cognitive ability and adaptive skills in children with ASD. Journal of Autism and Developmental Disorders, 43(2), 253–264.Google Scholar
  72. Mei, J., et al. (2011). MicroRNA-146a inhibits glioma development by targetingNotch1. Molecular and Cellular Biology, 31, 3584–3592.Google Scholar
  73. Melnyk, S., Fuchs, G. J., Schulz, E., Lopez, M., Kahler, S. G., Fussell, J. J., Bellando, J., Pavliv, O., Rose, S., Seidel, L., Gaylor, D. W., & James, S. J. (2012). Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. Journal of Autism and Developmental Disorders.  https://doi.org/10.1007/s10803-011-1260-7.
  74. Nguyen, A., Rauch, T. A., Pfeifer, G. P., & Hu, V. W. (2010). Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. The FASEB Journal, 24, 3036–3051.Google Scholar
  75. Nguyen, L. S., Lepleux, M., Makhlouf, M., Martin, C., Fregeac, J., Siquier-Pernet, K., Philippe, A., Feron, F., Gepner, B., Rougeulle, C., Humeau, Y., & Colleaux, L. (2016). Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology. Molecular Autism, 7, 1.Google Scholar
  76. Niemeijer, M. N., Grooten, I. J., Vos, N., Bais, J. M., van der Post, J. A., Mol, B. W., Roseboom, T. J., Leeflang, M. M., & Painter, R. C. (2014). Diagnostic markers for hyperemesis gravidarum: a systematic review and metaanalysis. American Journal of Obstetrics and Gynecology.  https://doi.org/10.1016/j.ajog.2014.02.012.
  77. 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, 246–250.Google Scholar
  78. Ounap, K., Puusepp-Benazzouz, H., Peters, M., Vaher, U., Rein, R., Proos, A., Field, M., & Reimand, T. (2012). A novel c.2T > C mutation of the KDM5C/JARID1C gene in one large family with X-linked intellectual disability. European Journal of Medical Genetics, 55(3), 178–184.Google Scholar
  79. Ozonoff, S., Young, G. S., Carter, A., Messinger, D., Yirmiya, N., Zwaigenbaum, L., Bryson, S., Carver, L. J., Constantino, J. N., Dobkins, K., et al. (2011). Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics., 128(3), e488–e495.Google Scholar
  80. Parletta, N., Niyonsenga, T., & Duff, J. (2016). Omega-3 and omega-6 polyunsaturated fatty acid levels and correlations with symptoms in children with attention deficit hyperactivity disorder, autistic Spectrum disorder and typically developing controls. PLoS One.  https://doi.org/10.1371/journal.pone.0156432.
  81. Parner, E. T., Baron-Cohen, S., Lauritsen, M. B., Jørgensen, M., Schieve, L. A., Yeargin-Allsopp, M., et al. (2012). Parental age and autism spectrum disorders. Annals of Epidemiology.  https://doi.org/10.1016/j.annepidem.2011.12.006.
  82. Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends in Molecular Medicine, 17, 389–394.Google Scholar
  83. Pepper, G. V., & Craig Roberts, S. (2006). Rates of nausea and vomiting in pregnancy and dietary characteristics across populations. Proceedings of the Biological Sciences, 273, 2675–2679.Google Scholar
  84. Perera, F., & Herbstman, J. (2011). Prenatal environmental exposures, epigenetics, and disease. Reproductive Toxicology.  https://doi.org/10.1016/j.reprotox.2010.12.055.
  85. Persico, A. M., & Napolioni, V. (2013). Autism genetics. Behavioural Brain Research.  https://doi.org/10.1016/j.bbr.2013.06.012.
  86. Pignataro, D., Sucunza, D., Vanrell, L., Lopez-Franco, E., Dopeso-Reyes, I. G., Vales, A., Hommel, M., Rico, A. J., Lanciego, J. L., & Gonzalez-Aseguinolaza, G. (2017). Adeno-associated viral vectors serotype 8 for cell-specific delivery of therapeutic genes in the central nervous system. Frontiers in Neuroanatomy.  https://doi.org/10.3389/fnana.2017.00002.
  87. Puffenberger, E. G., Jinks, R. N., Wang, H., et al. (2012). A homo¬zygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Human Mutation, 33, 1639–1646.Google Scholar
  88. Qiao, Y., Riendeau, N., Koochek, M., Liu, X., Harvard, C., Hildebrand, M. J., Holden, J. J., Rajcan-Separovic, E., & Lewis, M. E. (2009). Phenomic determinants of genomic variation in autism spectrum disorders. Journal of Medical Genetics, 46(10), 680–688.Google Scholar
  89. Ronald, A., & Hoekstra, R. A. (2011). Autism spectrum disorders and autistic traits: a decade of new twin studies. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 156B, 255–274.Google Scholar
  90. Roth, C., Magnus, P., Schjølberg, S., Stoltenberg, C., Surén, P., McKeague, I. W., et al. (2011). Folic acid supplements in pregnancy and severe language delay in children. JAMA, 306, 1566–1573.Google Scholar
  91. Salehi, M., Kamali, E., Karahmadi, M., & Mousavi, S. M. (2017). RORA and autism in the Isfahan population: is there an epigenetic relationship. Cell Journal, 18(4), 540–546.Google Scholar
  92. Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. Journal of the American Academy of Child & Adolescent Psychiatry.  https://doi.org/10.1016/j.jaac.2012.02.018.
  93. Santos-Rebouças, C. B., Fintelman-Rodrigues, N., Jensen, L. R., Kuss, A. W., Ribeiro, M. G., Campos, M., Jr., Santos, J. M., & Pimentel, M. M. (2011). A novel nonsense mutation in KDM5C/JARID1C gene causing intellectual disability, short stature and speech delay. Neuroscience Letters.  https://doi.org/10.1016/j.neulet.2011.04.065.
  94. Sarachana, T., & Hu, V. W. (2013). Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder. Molecular Autism, 4, 14.Google Scholar
  95. Schellenberg, G. D., et al. (2006). Evidence for multiple loci from a genome scan of autism kindreds. Molecular Psychiatry, 11, 1049–1060.Google Scholar
  96. Schmidt, R. J., Tancredi, D. J., Ozonoff, S., Hansen, R. L., Hartiala, J., Allayee, H., et al. (2012). Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood autism risks from genetics and environment) case-control study. The American Journal of Clinical Nutrition, 96, 80–89.Google Scholar
  97. Schreibman L. (2000). Intensive behavioral/psychoeducational treatments for autism: research needs and future directions. Journal of Autism and Developmental Disorders, (5):373–8.Google Scholar
  98. Schroeder, D. I., Blair, J. D., Lott, P., Yu, H. O., Hong, D., Crary, F., Ashwood, P., Walker, C., Korf, I., Robinson, W. P., et al. (2013). The human placenta methylome. Proceedings of the National Academy of Sciences of the United States of America.  https://doi.org/10.1073/pnas.1215145110.
  99. Schroeder, D. I., Schmidt, R. J., Crary-Dooley, F. K., Walker, C. K., Ozonoff, S., Tancredi, D. J., Hertz-Picciotto, I., & LaSalle, J. M. (2016). Placental methylome analysis from a prospective autism study. Molecular Autism.  https://doi.org/10.1186/s13229-016-0114-8.
  100. Schumann, C. M., Sharp, F. R., Ander, B. P., & Stamova, B. (2017). Possible sexually dimorphic role of miRNA and other sncRNA in ASD brain. Molecular Autism.  https://doi.org/10.1186/s13229-017-0117-0.
  101. Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316, 445–449.Google Scholar
  102. Shimojo, H., Isomura, A., Ohtsuka, T., Kori, H., Miyachi, H., & Kageyama, R. (2016). Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis. Genes & Development, 30(1), 102–116.Google Scholar
  103. Silverman, J. L., et al. (2012). Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social defcits in mouse models of autism. Science Translational Medicine.  https://doi.org/10.1126/scitranslmed.3003501.
  104. Siniscalco, D., Cirillo, A., Bradstreet, J. J., et al. (2013). Epigenetic findings in autism: new perspectives for therapy. International Journal of Environmental Research and Public Health, 10, 4261–4273.Google Scholar
  105. Siu, M. T., & Weksberg, R. (2017). Epigenetics of autism spectrum disorder. Advances in Experimental Medicine and Biology, 978, 63–90.Google Scholar
  106. Sivanesan, S., Tan, A., Jeyaraj, R., Lam, J., Gole, M., Hardan, A., Ashkan, K., & Rajadas, J. (2017). Pharmaceuticals and stem cells in autism spectrum disorders: wishful thinking? World Neurosurgery, 98, 659–672.Google Scholar
  107. Staahl, B. T., Benekareddy, M., Coulon-Bainier, C., Banfal, A. A., Floor, S. N., Sabo, J. K., Urnes, C., Munares, G. A., Ghosh, A., & Doudna, J. A. (2017). Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes. Nature Biotechnology, 35(5), 431–434.Google Scholar
  108. Steffenburg, S., Gillberg, C., Hellgren, L., Andersson, L., Gillberg, I. C., Jakobsson, G., & Bohman, M. (1989). A twin study of autism in Denmark: Finland, Iceland, Norway and Sweden. Journal of Child Psychology and Psychiatry and Allied Disciplines, 30(3), 405–416.Google Scholar
  109. Surén, P., Roth, C., Bresnahan, M., Haugen, M., Hornig, M., Hirtz, D., Lie, K. K., Lipkin, W. I., Magnus, P., Reichborn-Kjennerud, T., Schjølberg, S., Davey Smith, G., Øyen, A. S., Susser, E., & Stoltenberg, C. (2013). Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA.  https://doi.org/10.1001/jama.2012.155925.
  110. Sztainberg, Y., & Zoghbi, H. Y. (2016). Lessons learned from studying syndromic autism spectrum disorders. Nature Neuroscience, 19(11), 1408–1417.Google Scholar
  111. Tao, J., et al. (2016). Negative allosteric modulation of mGluR5 partially corrects pathophysiology in a mouse model of Rett syndrome. The Journal of Neuroscience, 36, 11946–11958.Google Scholar
  112. Vallianatos, C. N., Farrehi, C., Friez, M. J., Burmeister, M., Keegan, C. E., & Iwase, S. (2018). Altered gene-regulatory function of KDM5C by a novel mutation associated with autism and intellectual disability. Frontiers in Molecular Neuroscience.  https://doi.org/10.3389/fnmol.2018.00104.
  113. Van Balkom, I. D., Bresnahan, M., Vuijk, P. J., Hubert, J., Susser, E., & Hoek, H. W. (2012). Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: Aruba. PLoS One, 7, e45090.Google Scholar
  114. Van Slegtenhorst, M., De Hoogt, R., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Van den Ouweland, A., Halley, D., & Young, J. (1997). Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science, 277, 805–808.Google Scholar
  115. Volkmar, F. R., State, M., & Klin, A. (2009). Autism and autism spectrum disorders: diagnostic issues for the coming decade. Journal of Child Psychology and Psychiatry, 50, 108–115.  https://doi.org/10.1111/j.1469-7610.2008.Google Scholar
  116. Wang, K., Zhang, H., Ma, D., et al. (2009). Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature, 459, 528–533.Google Scholar
  117. Wang, M., Li, K., Zhao, D., & Li, L. (2017). The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis. Molecular Autism, 8, 51.Google Scholar
  118. Weinstock, M. (2008). The long-term behavioural consequences of prenatal stress. Neuroscience and Biobehavioral Reviews, 32, 1073–1086.Google Scholar
  119. Weiss, L. A., Arking, D. E., Daly, M. J., et al. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461, 802–808.Google Scholar
  120. Wiles, E. T., & Selker, E. U. (2017). H3K27 methylation: a promiscuous repressive chromatin mark. Current Opinion in Genetics & Development, 43, 31–37.Google Scholar
  121. Windham, G. C., Lyall, K., Anderson, M., & Kharrazi, M. (2016). Autism spectrum disorder risk in relation to maternal mid-pregnancy serum hormone and protein markers from prenatal screening in California. Journal of Autism and Developmental Disorders, 46, 478–488.Google Scholar
  122. Wu, Y. E., Parikshak, N. N., Belgard, T. G., & Geschwind, D. H. (2016). Genome-wide, integrative analysis implicates microRNA dysregulation in autism spectrum disorder. Nature Neuroscience, 19(11), 1463–1476.Google Scholar
  123. Xu, J., Zwaigenbaum, L., Szatmari, P., & Scherer, S. W. (2004). Molecular cytogenetics of autism. Current Genomics.  https://doi.org/10.2174/1389202043349246.
  124. Xu, G., Jing, J., Bowers, K., Liu, B., & Bao, W. (2014). Maternal diabetes and the risk of autism spectrum disorders in the offspring: a systematic review and meta-analysis. Journal of Autism and Developmental Disorders, 44(4), 766–775.Google Scholar
  125. Yang, S., Chang, R., Yang, H., Zhao, T., Hong, Y., Kong, H. E., Sun, X., Qin, Z., Jin, P., Li, S., & Li, X. J. (2017). CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington’s disease. The Journal of Clinical Investigation.  https://doi.org/10.1172/JCI92087.
  126. Yeh, E., & Weiss, L. A. (2016). If genetic variation could talk: what genomic data may teach us about the importance of gene expression regulation in the genetics of autism. Molecular and Cellular Probes, 30, 346–356.Google Scholar
  127. Yin, J., & Schaaf, C. P. (2017). Autism genetics- an overview. Prenatal Diagnosis, 37(14), 30.Google Scholar
  128. Yonan, A. L., Alarcon, M., Cheng, R., Magnusson, P. K. E., Spence, S. J., Palmer, A. A., et al. (2003). A genomewide screen of 345 families for autismsusceptibility loci. American Journal of Human Genetics, 73, 886–897.Google Scholar
  129. Zahir, F., & Friedman, J. M. (2007). The impact of array genomic hybridization on mental retardation research: a review of current technologies and their clinical utility. Clinical Genetics, 72, 271–287.Google Scholar
  130. Zerbo, O., Qian, Y., Yoshida, C., Grether, J. K., Van de Water, J., & Croen, L. A. (2015). Maternal infection during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 45(12), 4015–4025.Google Scholar
  131. Zerbo, O., Traglia, M., Yoshida, C., Heuer, L. S., Ashwood, P., Delorenze, G. N., Hansen, R. L., Kharrazi, M., Van de Water, J., Yolken, R. H., Weiss, L. A., & Croen, L. A. (2016). Maternal mid-pregnancy C-reactive protein and risk of autism spectrum disorders: the early markers for autism study. Translational Psychiatry, 6(4), e783.Google Scholar

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Authors and Affiliations

  1. 1.Department of Molecular Biology and Genetics, Genome CentreBiruni UniversitesiIstanbulTurkey

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