Fig. 1: Genetic and functional characterization of the DHX40 c.710_713delTCAG variant. | Leukemia

Fig. 1: Genetic and functional characterization of the DHX40 c.710_713delTCAG variant.

From: Identification of DHX40 as a candidate susceptibility gene for colorectal and hematological neoplasia

Fig. 1

A Pedigree of F32. Numbers below the symbols are patient identifiers. Arrow denotes the index person. Tumor manifestations and age at diagnosis (years) are given below patient symbols. Non-essential pedigree features have been excluded or modified to protect confidentiality. A plus sign (+) denotes the presence of the variant in a heterozygous state and a minus sign (-) the absence of the variant. Sequence chromatogram on the right displays the normal (top) and altered sequence (bottom), where arrowhead denotes the site of the germline change. Lollipop diagram (bottom) indicates location of the predisposing variant against the main functional domains of the encoded protein. The functional domains of DHX40 are: DEAD, DEAD/H box helicase domain; Helicase_C, Helicase conserved C-terminal domain; HA2, Helicase associated domain; OB_NTP bind, Oligonucleotide/oligosaccharide-binding (OB)-fold. B Consequences of siRNA-mediated knockdown of DHX40. Workflow of siRNA experiments on CCD841CoN, HEK293, and K562 cell lines is shown on the left. Results from analyses of RNA-sequencing data for differential transcript expression (DTE) and novel splicing events (by the ASGAL tool) (see Supplementary Materials and Methods) are depicted on the right. The bar graph of DTE analysis displays top 20 differentially expressed genes among 71 unique transcripts shared between the three cell lines. Genes whose products participate in RNA metabolism are in bold (see Supplementary Fig. 3 for all 71 genes). The ASGAL analysis shows the number of novel splicing events detected after treatment with DHX40-siRNA, GAPDH-siRNA, or non-target siRNA, vs. untreated cells, and stratified by the type of splicing alteration (A3, alternative 3’ site; A5, alternative 5’ site; ES, exon skipping; IR, intron retention). Splicing events for all three cell lines (HEK293, K562, and CCD841CoN) were combined. Asterisk denotes statistically significant differences (p < 0.0001 for ES and p < 0.05 for all other events, by pairwise chi-square test with FDR correction) in the number of specific types of splice events after DHX40-siRNA treatment vs. GAPDH-siRNA or non-target siRNA treatment.

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