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Understanding Autism Through Genetics

Michael J. Dougherty

articlehighlights

Over the last decade the genomics revolution has profoundly changed our understanding of autism and autism spectrum disorders (ASD). In the process, ASD has become a model for the challenges of complex traits because:

  • There are no definitive “biomarkers” for autism or ASD;
  • Scientists are still uncovering valuable information about the relative influences of new, or de novo genetic mutations on the heritability of ASD cases;
  • Recent findings indicate that ASD causation involves neurobiology, that is, the development and/or function of cells in the brain (neurons).

June 2013

Introduction

Have you ever been driving when suddenly your car’s “check engine” warning light comes on? You take the car to the mechanic, who tells you “more than a hundred different malfunctions can trigger that light.” Autism, we now know, is a bit like that, with potentially hundreds of genetic variations leading to the warning signs of the disorder.1 Unfortunately, determining exactly which of those many possibilities is the real culprit is not as simple as hooking your car’s central computer to a diagnostic tester. Rather, in autism many culprits may be acting at once, each contributing something different to the problems that characterize the disorder.

Autism is a group of disorders that are characterized by a wide range of symptoms, impairments, and disabilities.

Autism: Not one disease

Autism spectrum disorders (ASDs) are a class of varied disorders typified by impairments in language development, social development, and narrow or restricted interests and/or repetitive behaviors. Most children with an ASD have normal intelligence.

  • A minority (about 35 percent) have intellectual disability, which is defined as an IQ below 70.2

  • A small minority of so-called autistic savants may be capable of remarkable memory feats or other capabilities.3

  • The prevalence of ASDs has increased 78 percent since 2002 according to the most recent estimates by the Centers for Disease Control and now stands at 1 in 88 children.4

  • ASDs are nearly five times more common in boys (1 in 54) than girls, and although all racial and ethnic groups are affected, ASDs are most often diagnosed in Caucasians.5

Most children with an autism spectrum disorder (ASD) have normal intelligence.

Michael J. Dougherty, Ph.D. is Director of Education for the American Society of Human Genetics (ASHG) and Associate Professor Adjoint of Pediatrics at the University of Colorado School of Medicine. He focuses on improving genetics education from high school through post-graduate training and leads research efforts to better understand the teaching and learning of genetics. Prior to joining ASHG, he spent nine years on the biology faculty at Hampden-Sydney College in Virginia, where he taught genetics, molecular biology, biochemistry, and introductory biology and conducted research on prion genetics. Dougherty has 20 years of formal genetics education experience, which began when he joined the Biological Sciences Curriculum Study (BSCS) as a curriculum developer in 1993 and eventually served as associate director of BSCS. He has co-authored several textbooks and genetics curriculum modules. He earned his B.A. degree from the University of Colorado, Boulder, and a Ph.D. from the University of Massachusetts, Amherst, in molecular biology and biochemistry. He has been Burroughs Wellcome Fellow in Alzheimer’s disease, Visiting Senior Lecturer at the University of Kent, UK, and the McGavacks of Loudoun Chair in Biochemistry at Hampden-Sydney College.

Understanding Autism Through Genetics

What is Autism?

Autism Speaks has a comprehensive list of resources about autism and ASD, including a 100 Day Kit for families to use in the first 100 days following a child’s diagnosis with autism or ASD, and special sections on Asperger Syndrome, PDD-NOS, and your child’s rights.
http://www.autismspeaks.org/what-autism

Diagnosis of Autism

This scholarly paper, published in the British Medical Journal (BMJ), includes a table of features most often used in the diagnosis of autism (also called “the autistic continuum”).
Baird, G., Cass, H., & Slonims, V. (2003). Diagnosis of autism. BMJ: British Medical Journal, 327(7413), 488.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC188387/

Autism Fact Sheet

The National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) has a wealth of information about the signs, diagnosis, and treatment of autism spectrum disorder (ASD), as well as current research and sources for more information.
http://www.ninds.nih.gov/disorders/autism/detail_autism.htm

Diagnosis and Evaluation

The Autism Society provides multiple pages of information about how autism and ASD are diagnosed through school evaluation, medical diagnosis, and differential diagnosis. Related conditions and diagnostic classifications are also discussed in detail.
http://www.autism-society.org/about-autism/diagnosis/

Genetics of Autism Spectrum Disorders

The National Autistic Society (UK) has published detailed information on the heritability of ASD, strategies used to study the genetics of ASD, and genetic research that has been conducted to date. The main website also contains information for health professionals, parents of toddlers with autism, eye care and dental professionals, and educators.
http://www.autism.org.uk/working-with/health/screening-and-diagnosis/the-genetics-of-autism-spectrum-disorders.aspx

Autism NOW

The National Autism Resource & Information Center offers resources for individuals diagnosed with autism or ASD, including guidance on transitioning from high school to college, tips for planning and seeking employment options, and ways to build positive relationships with friends and family.
http://autismnow.org/

Autism Speaks

Get involved with state or federal initiatives, sign up to get action alerts on your mobile phone, or learn how to lobby for insurance reform. You can also find ways to contact your legislators or donate to support the ongoing efforts of Autism Speaks.
http://www.autismspeaks.org/advocacy

Autism Society

The Autism Society offers members and supporters a variety of ways to become active in autism advocacy issues. Sign up for a free bimonthly e-newsletter or action alerts, take a free online course, or even find a local AMC Theater that offers “Sensory Friendly Films” for families affected by autism and other disabilities.
http://www.autism-society.org/get-involved/

Autistic Self Advocacy Network (ASAN)

ASAN is a unique organization run both by and for autistic individuals. Members include family members and friends of autistic people who want to learn how to become stronger allies, as well as autistic individuals who are dedicated to self-advocacy. Find out how you can volunteer with local chapters or as a part of online planning/research communities, or make a contribution to support ASAN’s efforts to better serve the broader autistic community.
http://autisticadvocacy.org/get-involved/

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Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Advanced Bioinformatics: Genetic Research
This curriculum unit explores how bioinformatics is used to perform genetic research. Students examine DNA sequences from different animal species, investigate the relationship between protein structure and function, and explore evolutionary relationships among eukaryotic organisms. Throughout the unit, students are presented with a number of career options in which the tools of bioinformatics are developed or used.
http://www.nwabr.org/curriculum/advanced-bioinformatics-genetic-research

Kids Health: Autism

An informational page about autism written just for kids to help them understand what autism is, what causes autism, and how they can either get help or support friends who have been diagnosed with autism or ASD.
http://kidshealth.org/kid/health_problems/brain/autism.html#

Teaching Resources for World Autism Day

Do you have a child with ASD in your class? Would you like to learn more about how to create a learning environment that is suitable for all students, including those with autism and ASD? The Guardian Teacher Network has compiled a list of resources, including guides for teachers, strategies for supporting students with ASD, and resources for promoting understanding in schools. You can also sign up to receive these articles direct to your inbox and access hundreds of other free resources.
http://www.guardian.co.uk/teacher-network/teacher-blog/2013/apr/02/teaching-resources-world-autism-day

Autism Acceptance Month: 10 Things I Wish Your Kids Knew About Autism

April is Autism Awareness Month, but this list applies to every month of the year. Help educate kids (and adults) about autism acceptance and awareness by sharing these 10 facts.
http://www.babble.com/mom/autism-acceptance-month-10-things-i-wish-your-kids-knew-about-autism/

Autism Teaching Tools

A practical source of information and teaching tips for working with autistic students and those with PDDs (pervasive developmental disorders). Browse a variety of resources, including information on teaching specific skills, using art, dealing with behavior issues, as well as curriculum guides and other educational materials.
http://www.autismteachingtools.com/

  1. Banerjee-Basu, S. and Packer, A. 2010. SFARI Gene: an evolving database for the autism research community. Dis. Model Mech. 3: 133-135.
  2. Centers for Disease Control (CDC). 2012. Prevalence of autism spectrum disorders- Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveillance Summaries. 61: 1-19. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm?s_cid=ss6103a1_w
  3. Dougherty, M. 2000. The Genetics of Autism. http://www.actionbioscience.org/genomic/dougherty.html
  4. Centers for Diseases Control. 2008. http://www.cdc.gov/ncbddd/autism/addm.html
  5. Centers for Diseases Control. 2012. Autism and Developmental Disabilities Monitoring (ADDM) Network Fact Sheet. http://www.cdc.gov/NCBDDD/autism/states/ADDM_fact_sheet_2012.pdf
  6. Keyes, K.M., Susser, E., Cheslack-Postava, K., Fountain, C., Liu, K. et al. 2012. Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California. Int. J. Epidemiol. 41: 495-503.
  7. Baird, G., Cass, H., and Slonims, V. 2003. Diagnosis of autism. BMJ. 327: 488-493.
  8. Diagnostic and Statistical Manual of Mental Disorders, http://www.psychiatry.org/practice/dsm
  9. Potocki, L., Bi., W., Treadwell-Deering, D., Carvalho, C.M.B., Eifert, A., et al. 2007. Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey and autism phenotype. Am. J. Hum. Genet. 80: 633-649.
  10. Casey, J.P., Magalhaes, T., Conroy, J.M., Regan, R., Shah, N. et al. 2012. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum. Genet. 131: 565-579.
  11. Hallmayer, J., Cleveland, S., Torres, A., Phillips, J., Cohen, B. et al. 2011. Genetic heritability and shared environmental factors among twin pairs with autism. Arch. Gen. Psychiatry. 68: 1095-1102.
  12. McGowan, P.O., Sasaki, A., D’Alessio, A.C., Dymov, S., Labonte, B. et al., 2009. Epigenetic regulation of the glucocorticoid receptor in human grain associates with childhood abuse. Nat. Neurosci. 12: 342-348.
  13. Al-Murrani, A., Ashton, F., Aftimos, S., George, A.M., and Love, D. 2012. Amino-terminal microdeletion within the CNTNAP2 gene associated with variable expressivity of speech delay. Case Reports in Gen. Article ID 172408, 4 pages, doi:10.1155/2012/172408
  14. Gregor, A., Albrecht, B., Bader, I., Bijlsma, E.K., Ekici, A.B., et al. 2011. Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1. BMC Med Genet. 12: 106.
  15. Abrahams, B.S. and Geschwind, D.H. (2008). Advances in autism genetics: On the threshold of a new neurobiology. Nat. Rev. Gen. 9(5): 341-355.
  16. King, B.H. and Lord, C. 2011. Is schizophrenia on the autism spectrum? Brain Res. 1380: 34-41.
  17. Cross-Disorder Group of the Psychiatric Genomics Consortium et al. 2013. Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet. 381(9875): 1371-9.
  18. Devlin, B. and Scherer, S.W. 2012. Genetic architecture in autism spectrum disorder. Curr. Opin Genet. Dev. 22: 229-237.
  19. Durkin, M.S., Maenner, M.J., Newschaffer, C.J., Lee, L.C., Cunniff, C.M. et al. 2008. Advanced paternal age and the risk of autism spectrum disorder. Am. J. Epidemiol. 168: 1268-1276.
  20. Sandin, S., Hultman, C.M., Koleyzon, A., Gross, R., MacCabe, J.H. et al. 2012. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J. Am. Acad. Child Adolesc. Psychiatry. 51: 477-486.
  21. Kong, A., Frigge, M.L., Masson, G., Besenbacher, S., Sulem, P. et al. 2012. Rate of de novo mutation and the importance of father’s age to disease risk. Nature. 488: 471-475.
  22. Weiss, L.A., Shen, Y., Korn, J.M., Arking, D.E., Miller, D.T. et al.. 2008. Association between microdeletion and microduplication at 16p11.2 and autism. N. Engl. J. Med. 358: 667-675.
  23. Kumar, R.A., Mohamed, S.K., Sudil, J., Conrad, D.F., Brune, C. et al. 2008. Recurrent 16p11.2 microdeletions in autism. Hum. Mol. Genet. 17: 628-638.
  24. O’Roak, B.J., Deriziotis, P., Lee, C., Vives, L., Girirajan, S. et al. 2011. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Gen. 43: 585-589.
  25. Girirajan, S., Brkanac, Z., Coe, B.P., Baker, C., Vives, L. et al., 2011. Relative burden of large CNVs on a range of neurodevelopmental phenotypes. PLoS Genet. 7(11):e1002334. doi: 10.1371/journal.pgen.1002334. Epub 2011 Nov 10.
  26. Casey, J.P, Magalhaes, T., Conroy, J.M., Regan, R., Shah, N. et al. 2012. A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum. Genet. 131(4): 565-579.
  27. Falivelli, G., De Jaco, A., Favaloro, F.L., Kim, H., Wilson, J. et al. 2012. Inherited genetic variants in autism-related CNTNAP2 show perturbed trafficking and ATF6 activation. Hum Mol Genet. 21(21): 4761-4773.
  28. Penagarikano, O., Abrahams, B.S., Herman, E.I., Winden, K.D., Gdalyahu, A. et al., 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. 147(1): 235-46.
  29. Kang, H.J., Kawasawa, Y.I., Cheng, F., Zhu, Y., Xu, X. et al. 2011. Spatio-temporal transcriptome of the human brain. Nature 478(7370): 483-489.
  30. Novarino, G., El-Fishawy, P., Kayserili, H., Meguid, N.A., Scott, E.M. et al. 2012. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science 338: 294-297.
  31. Celestino-Soper, P.B., Violante, S., Crawford, E.L., Luo, R., Lionel, A.C. et al. 2012. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Proc. Nat. Acad. Sci. 109: 7974-7981.
  32. Beaudet, A.L. 2012. Preventable forms of autism? Science 388: 342-343.

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