Autism Spectrum Disorders (ASD) is a spectrum of highly heritable neurodevelopmental disorders in which known mutations contribute to disease risk in 20% of cases. Here, we report the results of the largest blood transcriptome study to date that aims to identify differences in 170 ASD cases and 115 age/sex-matched controls and to evaluate the utility of gene expression profiling as a tool to aid in the diagnosis of ASD. The differentially expressed genes were enriched for the neurotrophin signaling, long-term potentiation/depression, and notch signaling pathways. We developed a 55-gene prediction model, using a cross-validation strategy, on a sample cohort of 66 male ASD cases and 33 age-matched male controls (P1). Subsequently, 104 ASD cases and 82 controls were recruited and used as a validation set (P2). This 55-gene expression signature achieved 68% classification accuracy with the validation cohort (area under the receiver operating characteristic curve (AUC): 0.70 [95% confidence interval [CI]: 0.62–0.77]). Not surprisingly, our prediction model that was built and trained with male samples performed well for males (AUC 0.73, 95% CI 0.65–0.82), but not for female samples (AUC 0.51, 95% CI 0.36–0.67). The 55-gene signature also performed robustly when the prediction model was trained with P2 male samples to classify P1 samples (AUC 0.69, 95% CI 0.58–0.80). Our result suggests that the use of blood expression profiling for ASD detection may be feasible. Further study is required to determine the age at which such a test should be deployed, and what genetic characteristics of ASD can be identified.

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This paper presents data and modelling results from a crustal and upper mantle wide‐angle seismic transect across the Salton Trough region in southeast California. The Salton Trough is a unique part of the Basin and Range province where mid‐ocean ridge/transform spreading in the Gulf of California has evolved northward into the continent. In 1992, the U.S. Geological Survey (USGS) conducted the final leg of the Pacific to Arizona Crustal Experiment (PACE). Two perpendicular models of the crust and upper mantle were fit to wide‐angle reflection and refraction travel times, seismic amplitudes, and Bouguer gravity anomalies. The first profile crossed the Salton Trough from the southwest to the northeast, and the second was a strike line that paralleled the Salton Sea along its western edge. We found thin crust (∼21–22 km thick) beneath the axis of the Salton Trough (Imperial Valley) and locally thicker crust (∼27 km) beneath the Chocolate Mountains to the northeast. We modelled a slight thinning of the crust further to the northeast beneath the Colorado River (∼24 km) and subsequent thickening beneath the metamorphic core complex belt northeast of the Colorado River. There is a deep, apparently young basin (∼5–6 km unmetamorphosed sediments) beneath the Imperial Valley and a shallower (∼2–3 km) basin beneath the Colorado River. A regional 6.9‐km/s layer (between ∼15‐km depth and the Moho) underlies the Salton Trough as well as the Chocolate Mountains where it pinches out at the Moho. This lower crustal layer is spatially associated with a low‐velocity (7.6–7.7 km/s) upper mantle. We found that our crustal model is locally compatible with the previously suggested notion that the crust of the Salton Trough has formed almost entirely from magmatism in the lower crust and sedimentation in the upper crust. However, we observe an apparently magmatically emplaced lower crust to the northeast, outside of the Salton Trough, and propose that this layer in part predates Salton Trough rifting. It may also in part result from migration of magmatic spreading centers associated with the southern San Andreas fault system. These spreading centers may have existed east of their current locations in the past and may have influenced the lower crust and upper mantle to the east of the current Salton Trough.

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally-regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene-environment interactions underlying complex behavior in health and disease. Synaptic function is a main target of A-to-I editing, which can selectively recode key amino acids in synaptic genes, directly altering synaptic strength and duration in response to environmental signals. Here we performed a high-resolution survey of synaptic A-to-I RNA editing in a human population, and examined how it varies in autism, a neurodevelopmental disorder in which synaptic abnormalities are a common finding. Using ultra-deep (>1000×) sequencing, we quantified the levels of A-to-I editing of 10 synaptic genes in postmortem cerebella from 14 neurotypical and 11 autistic individuals. A high dynamic range of editing levels was detected across individuals and editing sites, from 99.6% to below detection limits. In most sites, the extreme ends of the population editing distributions were individuals with autism. Editing was correlated with isoform usage, clusters of correlated sites were identified, and differential editing patterns examined. Finally, a dysfunctional form of the editing enzyme ADARB1 was found more commonly in postmortem cerebella from individuals with autism. These results provide a population-level, high-resolution view of A-to-I RNA editing in human cerebella, and suggest that A-to-I editing of synaptic genes may be informative for assessing the epigenetic risk for autism.