This web page was produced as an assignment for an undergraduate course at Davidson College.

Garrett Smith's Genomics Web Assignment 1

Genomics of Autism

Prevalence

According to statistics obtained from the Centers for Disease Control and Prevention (CDC), about 1 in 88 children in the United States have some form of ASD. The condition is about five times more common in males. A ten-fold increase in the number of autism diagnoses has occurred over the last 40 years, a trend only partially explained by the improved awareness and diagnosis techniques for the condition. This makes autism the fastest growing developmental disability in the United States. No known cure for autism exists [2], but some pharmaceuticals and behavioral interventions have shown promise in reducing the severity of behavioral symptoms of the disease [8].

Causes

Genetic

There are many forms of autism and likewise, there appear to be no singular causes of the disorder. Among neuropsychiatric disorders, however, autism is among the most influenced by genetics. In fact, heritability of the condition (the extent of differences in a trait that is due to genetic differences) has been reported to be as high as 90% [3]. Siblings of autistic children are 25 times more likely than the general population to be autistic, and while 20-30% of dizygotic twins both have autism, about 60% f monozygotic twins both have autism, suggesting a substantial influence of genetic on the etiology of the disease [4]. The inheritance patterns of autism and families varies substantially [7].

                  Certain specific genes and other genetic loci have been implicated in the etiology of autism through genome-wide linkage analyses, of genome wide association (GWA) studies [5]. GWA studies analyze the differential genetic profile between healthy persons and individuals with a certain condition such as autism, typically looking for differences at the level of single nucleotides between the two groups. No more than 1% of autism cases can be explained by a single mutation in any of these candidate genes, suggesting a great variety in nature of the mutations of these genes [6], indeed about 200 genes have been identified that are disproportionately associated with autism [7]. A technique called chromosome microarray analysis which can analyzes the composition of many genes at once, can utilize this information acquired in the lab to help physicians diagnose autism [7]

Environmental

                  Myriad possible contributors to autism pathology outside of genetics have also been identified, toxins in the atmosphere, factors in the prenatal environment, complications at birth and parental age. The exact contributions of environmental toxins have been difficult to study, but the contributions of prenatal environment are better understood [9, 10]. One interesting discovery made in the past few years is that parental age at the time of conception also appears to play role in the etiology of autism. Mothers over 40, for example are about 51% more likely to give birth to an autistic child than a mother 25-29 years old, and men over 40 were 78% more likely to father an autistic child than a father under 25 years old [10]. This contribution by the father may be due to an increased accumulation of mutations in gametes occurring over life, or modification of DNA at the epigenetic level.  Epigenetic changes can include methylation of nucleotides or deacetylation of histones, both processes of which may inhibit gene transcription [10]. There is no well-supported evidence that modern vaccines have contributed to the prevalence of autism [11].

    For additional information regarding autism visit the Autism Society, and advocacy group or the awareness and treatment of autism.

References

 [1] Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators, Centers for Disease Control and Prevention (CDC) (2009) Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ 58: 1–20.

[2] http://www.cdc.gov/media/releases/2012/p0329_autism_disorder.html

[3] Klauck, S. M., (2006). Genetics of autism spectrum disorder. European Journal of Human Genetics, 14, 714–720.

[4] Geschwind, D. H. (2009). Advances in autism. Annual Reviews of Medicine, 60, 367-80.

[5] Weiss, L. A., Arking, D. E., Gene Discovery Project of Johns Hopkins & the Autism Consortium, Daly, M. J. & Chakravarti, A. (2009). A genome-wide linkage and association scan reveals novel loci for autism. Nature, 461 (7265), 802-808.

[6] Betancur, C. (2011). Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Research, 1380, 42–77.

[7] Heil, K. M. & Schaaf, C. P. (2013). The genetics of autism spectrum disorders - a guide for clinicians. Current Psychiatry Reports, 15(1), 334.

[8] Blue, L. (2013). New gene variant slinked to autism. TIME, Health & Family. <http://healthland.time.com/2013/01/15/new-gene-variants-linked-to-autism/>

[9] Gardener, H., Spiegelman, D. & Buka, S. L. (2009). Prenatal risk factors for autism: comprehensive meta-analysis.  British Journal of Psychiatry, 195(1):7-14.

[10] Shelton, J. F., Tancredi, D. J. & Hertz-Picciotto, I. (2010). Independent and dependent contributions of advanced maternal and paternal ages to autism risk. Autism Research, 3(1):30-39.

[11] Muhle, R., Trentacoste, S. V. & Rapin, I. (2004). The genetics of autism. Pediatrics, 113(5), e472-86.


Return to Garrett's Home Page

Genomics Page    Biology Home Page

Email Questions or Comments to gasmith@davidson.edu.



© Copyright 2013 Department of Biology, Davidson College, Davidson, NC 28035