Fig. 1
PDCD6IP deletion detected by CoNIFER with confirmed effects on gene expression and support for pathogenicity from a zebrafish knock-down model defines a new gene for CP. a Composite plot showing genomic context of the PDCD6IP deletion. The ideogram for chromosome 3 at the top of the plot shows the genomic location of the CNV boxed in red. Base pair positions of the CNV from the hg19 build of the human genome are shown below the ideogram. Data from CoNIFER (Exome SVD-ZRPKM values) are shown in blue with the zero baseline indicated by a grey line. PennCNV Log R ratios are shown in khaki with the zero baseline indicated by a grey line. RNA Seq outlier gene expression for each gene in its genomic context is plotted as a heat map; purple indicates upregulation and green indicates down regulation, grey or light shading indicates the gene is below the cut off of −2 to 2. Haploinsufficency percentile scores (HI scores) from DECIPHER are shown as a heatmap with genes with the darkest orange the most sensitive to copy number variation. GENCODE v28 gene models are shown at the bottom of the plot. b Average turning angle of zebra fish injected with the PDCD6IP-AUGMO at concentrations of 62.5 μM (red, n = 21) compared to a control injected group (blue, n = 37) over three trials stimulating movement with a tap in the first two trials and light in the final trial. PDCD6IP-AUGMO treated fish moved with significantly greater turning angles, p < 0.05 Student’s two-tailed T-test assuming equal variances. c Quantification of phenotypes with increasing concentration of the PDCD6IP-AUGMO. Larvae were classified as having mild, moderate or severe developmental abnormalities depending on whether they had one, two to three, or more than four of the following phenotypes: loss of pigment in eye, decreased eye size, grey matter hindbrain, small head, domed cranium, cardiac abnormality, decreased body size and tail curvature or kinking
