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Autism Genome Project



The Autism Genome Project (AGP) was officially launched in 2004 to study and identify genes associated with the development of autism spectrum disorder (ASD). The project is the world’s largest collaboration dedicated to the study of genetics and autism. Scientists have been longing to study how genetics play a role in autism since the 1977 study conducted by Flostein and Rutter on the prevalence of autism in identical and fraternal twins.1 To date, the Autism Genome Project has been conducted in two phases:


  • Phase 1- Scans of DNA are conducted on 1,200 multiplex (two or more individuals affected by autism spectrum disorder) families.2 The researchers used a DNA microarray, or gene chip, to scan large stretches of sequence for commonalities in deletions within the study families.3 This phase of research was conducted from 2004 to 2007 by 120 scientists representing 19 different countries and 50 different institutions.2

  • Phase 2- Members of the Autism Genome Project analyzed the data gathered in Phase 1 to discover several genes that influence the incidence of autism spectrum disorders. Ideally, the discovery of these genes will help science to better understand approaches for the diagnosis, prevention, and treatment of autism spectrum disorder.2

Phase 1
So far, research has discovered more than 100 genes and gene mutations linked with ASD and other developmental disabilities.4 The Autism Genome Project was able utilize new technology, like the DNA microarray, which allows researchers to efficiently scan the human genome for the genetic sources of autism spectrum disorder (ASD).3 The study investigated all 23 chromosome pairs including specific regions of interests found within these chromosomes. One strategy scientists employed to specify what regions to investigate within the genome is known as linkage analysis. The use of linkage analysis “involves searching for areas on chromosomes that show systematic variations in autistic subjects and in autistic subjects alone.”5 According to Autism Speaks, linkage analysis “is a technique that helps identify where genes are located in the human genome. It refers to the tendency of genetic markers, which are segments of DNA inherited from a person’ parents, including those that may be associated with diseases, to be located together on a chromosome.”6


The project also examined copy number variants (CNVS) to address the massive scope of how genetics affect autism spectrum disorder. In layman’s terms, CNVs are small additions and deletions to the DNA sequence.7 The study concluded that those with autism carried a higher number of rare copy number variants. These “sub-microscopic anomalies…are relatively common in the human genome and aren’t necessarily harmful. However, recent evidence suggests that these anomalies may contribute to risk for – or rarely even cause – autism if they affect certain sites associated with the disorder.”8 The CNVs found in children with autism can either be inherited or “de novo”, meaning they are present only in affected offspring and not in the parents.9

In 2007, the conclusion of the first phase of the Autism Genome Project yielded some promising results. A gene that has already been associated with developmental disabilities such as fragile X syndrome and tuberous sclerosis was implicated as playing a critical role in the development of autism spectrum disorder. The gene, known as neurexin 1 (NRXN1), is located on chromosome 2.3 Neurexin 1 “is associated with glutamate, the neurotransmitter known to elevate neuronal activity and play a role in wiring the brain during early development.” 3 NRXN1 interacts with neuroligins, a class of cell adhesion molecules, or proteins which control how brain cells connect with each other. 6 This discovery is promising because “the neurexin-neuroligin link is important for the functioning of the synapses which control the release of a neurotransmitter called glutamate. Many scientists theorize aberrant glutamate function is involved in ASD.” 6

Another area of interest discovered, during phase 1 of the Autism Genome Project is a small area on chromosome 11, known as 11p12-p1310. The detection of chromosome 11 is important because “the region identified by the AGP on chromosome 11 is the one most likely to be involved in all forms of autism… but other regions could play a role in certain forms or particular cases of autistic syndromes.” 5 The first phase of the AGP made it possible to seek out the malfunctioning of certain genes involved in the brain’s development, which plays a role in the appearance of autism disorders. The goal of the second phase of the AGP project is to investigate these susceptible genes further.


Phase 2
The second phase of the Autism Genome Project began in 2007 and was completed in 2010, with the initial results first published in the journal Nature and Human Molecular Genetics. 11 Phase 2 was made possible with $16 million worth of funding from international, private, and public partners. The project was headed by Professor Anthony Monaco of Oxford University. 12 The project resulted in identifying “three new genes and the chromosomal locations (loci) of two other genes the researchers believe make individuals more susceptible to autism. These genes –Shank213, SYNGAP1, DLGAP2, and the DDX53-PTCHD1 loci– belong to synaptic pathways that allow neurons to conduct electrical and chemical signals and are involved in cellular proliferation and intracellular signaling.” 7 The discovery of these autism susceptibility genes may “lead to the development of new treatment approaches.” 14



The results of this project coincide with “an emerging consensus within the scientific community that autism is caused in part by many “rare variants,” or genetic changes found in less than one percent of the population.” 15 These findings have led scientists to notice that “a large number of these mutations affect the genes already associated with autism or with intellectual disabilities.” 16


The Future of the Autism Genome Project
Although research into the genetic causes of autism is promising, science is years away from developing new drugs that target the genes that influence or cause autism spectrum disorder.7 According to the Autism Genome Project website the study is presently awaiting the necessary funds to undergo phase 3. Currently, the AGP has received only received enough funds to supports its core Consortium activities.12 However, according to Autism Speaks the preparations for the next phase of the AGP are threefold:

  • Complete additional analyses, including a collaborative effort with investigators from the Simons Simplex Collection that will pool from both datasets
  • Pilot joint analysis of CNV and sequencing data
  • Finalize research plan for the phase 3 project focusing on translation 17

The worldwide collaboration of the Autism Genome Project dedicated to the study of how genetics affect the incidence of autism is unprecedented. If you are interested in learning about how to become an active participant in the AGP study, please visit the about section of the Autism Genome Project website here: Autism Genome Project (AGP)




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