Figure 1

The Fmrp targets are highly expressed in the brain, and highly brain-expressed genes overlap with autism candidate genes. (A) Histogram of P21 mouse brain RNAseq of Fmrp targets (purple) compared to random selection brain-expressed genes (grey). Fmrp targets are significantly higher expressed, longer than random, brain-expressed genes (P < 2.2e − 16, t test). (B) Gene expression levels correlate moderately with Fmrp HITS-CLIP counts (0.64). (C) Forest plot of the odds ratio and 95% confidence intervals for Fisher’s exact test results. The Fmrp targets significantly overlap with a database of autism candidate genes (SFARI db, OR = 3.4, P < 1.2e − 11), recently characterized rare de novo variant genes in autism (rDNV, OR = 3.65, P < 6.1e − 12). Likewise, a sample of random genes selected to match the expression of the Fmrp targets also significantly overlap with the rDNV and SFARIdb (OR = 1.8-2.2) (D) Histogram of the P values resulting from 1,000 Fisher’s exact tests using random gene sets, each sampled to match the Fmrp target’s expression levels, compared to SFARIdb (top panel) or rDNV genes (bottom panel). Randomly sampled sets were generally less significant than the true Fmrp target list (red arrow, P < 1.2e − 11, P < 6.1e − 12), but most were more than nominally significant (blue line, P < 0.05).