paperKB
coga / coga-kb
Help
Sign in

Chunk #19 — RESULTS — Functional dissection of genes highlighted

Source
Gene expression elucidates functional impact of polygenic risk for schizophrenia.
Embedded
yes

Text

post-fertilization (dpf), we assessed the area of the head that contains the forebrain and midbrain structures (Fig. 3A, B). Relative to control embryos, overexpression of TSNARE1 or CNTN4 resulted in a significant decrease in head size, 9.5% (P < 0.001) and 3.5% (P = 0.018), respectively, while SNAP91 or CLCN3 showed no statistically significant effect (Fig. 3A, B). Body length and somitic structures were similar across all embryos, suggesting that our observations were unlikely due to gross developmental delay. For FURIN, we sought to mimic the transcriptional down-regulation in human brains associated with SCZ risk. A reciprocal BLAST search of the zebrafish genome revealed a FURIN ortholog with two potential paralogs; both copies were expressed at ~40–60 counts per million reads in mRNA from heads of 3 dpf zebrafish embryos36. We depleted furin_a, the isoform most closely resembling the human ortholog, using a splice blocking morpholino (sbMO) that almost completely extinguished expression of the endogenous message by triggering the inclusion of intron 7 (Supplementary Fig. 8). Suppression of furin_a led to a 24% decrease in head size (Fig. 3A, B); this observation was replicated in CRISPR/Cas9 mutants (Supplementary Fig. 8) and in embryos injected with a second sbMO targeting exon