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Genetics of Autism

Autism is a neurological disorder which, especially in its more severe forms, can severely impair the social interactions and emotional development of those affected by any of the broad range of autism spectrum disorders (ASD). Due to the prevalence of this disorder (approx. 1/300 live births with a 4:1 male-to-female ratio), myriad research has been invested therein, though there is no complete consensus as to the cause of autism, as it is a multifactorial trait for which many promising candidate loci have been identified. Autism is believed to be one of the most genetically heritable of all neurological disorders, with some estimates of heritability as high as 90% (Zhao, Xiaoyue, Leotta, Anthony, et al.) making it an ideal disorder to study from a genetic standpoint. The majority of candidate loci which have been suggested as potentially causative of this disorder were derived via genetic mapping, as was the case with a recent study performed by J.L. McCauley and C. Li et al. which suggests the existence of autism loci on chromosomes 17q and 19p. This study entailed genome-wide linkage screen of 158 autism multiplex families (in which multiple individuals are affected), surveying the karyotypes of said families for levels of mutations at gene loci which were higher than the levels in the control population. These data were also subjected to statistical analysis to determine if there was any statistically significant linkage between possible candidate loci within the experimental population. These results were analyzed using LOD scores, which are based on the probability of a birth with a given linkage value, and while none of the genes noted in this experiment reached the “significant LOD score” of 2.92, 17q11.2 and 19p13 were close enough to merit further study, suggesting the potential for a linkage to autism, with respective LOD scores of 2.30 and 1.92. While this study did not definitively determine genes which are linked to autism, it provided an unbiased genome-wide linkage map of candidate loci, and illustrated the difficulty of pinpointing the causes of ASD. (McCauley, Jacob L, Li, Chun, et al.)

With a number of candidate genes having been identified, it is more easily possible for groups to examine the cellular functions which these genes serve, thereby formulating a more complete view of the causes of autism, presenting researchers with information which may ultimately prove useful in the treatment thereof. A very recent small-scale study by C. M. Durand et al. examined the gene SHANK3, located on chromosome 22q13.3, a region suggested by past studies to be linked to the neurological impairment characteristic of ASD.

The SHANK3 gene “regulates the structural organization of dendritic spines and is a binding partner of neuroligins (neuron-surface proteins)”, indicating its importance in neurological function and thus suggesting why it was selected as the candidate gene of interest. This study examines the presence of SHANK3 in families with members affected by ASD using both direct genomic sequencing and a technique known as FISH (similar to Southern Blotting, but the probe hybridizes with the actual chromosome) designed to more accurately detect genes, which is sometimes necessary due to SHANK3’s location on the telomeric end of 22q. The study ultimately concluded that mutations of the gene in question in studied individuals altered the “function and localization of SHANK3”. In studies of mice, SHANK3 “promotes the maturation and the enlargement of dendritic spine heads”, thereby presenting another hypothesis for future study – that the impaired function of SHANK3 results in alterations in neurological structuring responsible for some of the social and communicative impairment characteristic of ASD. (Durand, CM, Betancur, C, Boeckers, TM, et al.)

The two aforementioned studies indicate the ways in which researchers are gaining increased insight into the causes of ASD, starting from general genome-wide surveys and utilizing the results to examine specific candidate loci in order to determine the ways in which the function of these genes may be causative of autistic behaviors. By determining this information, it becomes increasingly possible to examine different potential ways of treating ASD, with the ultimate goal of curing it or reducing its societal impact. By no means are these studies the only or necessarily the most significant on the genetics of ASD, as there have been over 90 candidate loci identified, including 2q31.1, 3p25.3, 6q14.3, 12q24.23 and 16p13.3, and the exact function and ways in which each of these genes may ultimately affect neurological development is subject to ongoing investigation. (Yang, MS, Gill, M) For example, another recent study of the gene encoding the MET receptor tyrosine kinase on chromosome 7q31, mutations of which, in mice, indicated decreased cerebral organization that may be linked to some of the traits of ASD. (Campbell, DB, Sutcliffe, JS, et al.) Though not all candidate genes will ultimately prove to be causative of autism, the clearly illustrate the ongoing studies into this disorder and suggest that continuous progress is being made toward a more complete genetic theory which accounts for the interactions between the numerous genes affecting ASD.


  • Campbell, Daniel B, Sutcliffe, James S, et al. “A genetic variant that disrupts MET transcription is associated with autism.” PNAS 103(2006): 16834-16839.*
  • Durand, CM, Betancur, C, Boeckers ,TM, et al. “Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.” Nature Genetics 39(2007): 25-27.
  • McCauley, Jacob L, Li, Chun, et al. “Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates.” BMC Medical Genetics (2005):
  • Yang, MS, Gill, M. “A review of gene linkage, association and expression studies in autism and an assessment of convergent evidence.” International Journal of Developmental Neuroscience 25(2007): 69-85.
  • Zhao, Xiaoyue, Leotta, Anthony, et al. “A unified genetic theory for sporadic and inherited autism.” PNAS 104(2007): 12831-12836.

Science | Genetics

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