Open questions: What has genetics told us about autism spectrum disorders?

Abstract

Some of the most interesting questions in biology today, in my view, derive from the real advances in neuropsychiatry that have come largely from human genetics. Research in autism spectrum disorders (ASDs) has been leading the way, mainly because it has become especially well funded and has recently attracted many outstanding scientists. (I must make it clear that I am an outsider in this field, as I have never worked on any neuropsychiatric disorder).

Empirical approaches to the study of language evolution

“…But there are many other disorders with genetic bases where genomes of afflicted individuals shed light on genes involved in language (I will call these Blanguage-related genes,^or LRGs). Relevant disorders can either be rather specific to components of language, like FOXP2, specific language impairment (van der Lely & Pinker, 2014), or dyslexia (Mozzi et al, 2016;St Pourcain et al, 2014;Wang, Chen, et al, 2015), or they can be broader disorders like autism, which have important consequences for, but are not specific to, language (Graham & Fisher, 2015;Raff, 2014;RodenasCuadrado, Ho, & Vernes, 2014). A particularly interesting result involves CNTNAP2, a gene coding for a neurexin specifically expressed in the human cortex and involved in cortical development.…”

Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis

“…Multiple genes, several cellular pathways and disordered molecular pathways (Pinto et al, 2014) have been implicated in the development of autism. Furthermore, environmental factors may also contribute to the risk of ASD (Banerjee et al, 2014;Persico and Bourgeron, 2006;Raff, 2014).…”

Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia

“…ASD is considered a heritable disorder, with some studies showing heritability rates as high as 90% [Bailey et al, ; Bauer and Msall, ; Heger, ; Gürkan and Hagerman, ; Prasad et al, ; Constantino et al, ; Craig, ; Hogenson, ; Stein et al, ; Berg and Dobyns, ; Brandler and Sebat, ; Chen et al, ; Yuen et al, ]. However, a recently completed Swedish population‐based longitudinal study estimates heritability to be closer to 50% [Sandin et al, ], implying that environmental and epigenetic factors also contribute to disease manifestations [Smith and Mill, ; Genuis, ; Newschaffer et al, ; Smith and Ehlers, ; Ecker et al, ; Nardone et al, ; Raff, ]. The diverse phenotypic and genotypic presentations of ASD speak against a purely genetic cause [Rossignol and Frye, ].…”

“…There is mounting evidence that links decreases during synaptic consolidation and pruning in early childhood with ASD [Fahim et al, ; Kubota et al, ; Spooren et al, ; Crespi, ; Das, ; Raff, ; Stoner et al, ; Tang et al, ; Zhan et al, ; Zhu et al, ; Khan et al, ; Szyf, ; Volmar and Wahlestedt, ; Washbourne, ] and SCZ [Millan et al, ; Spooren et al, ; Crespi, ; Millan, ; Zhan et al, ; Cocchi et al, ; Szyf, ; Volmar and Wahlestedt, ; Washbourne, ]. Synaptic plasticity is a principal means by which sensory experience affects cortical development [Greenhill et al, ].…”