Fig. 2: Characterization of the complex rearrangement involving MLH1 and LRRFIP2.
From: Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador
A Visualization of WGS data with Integrative Genomics Viewer (IGV). Germline short reads from WGS allowed the detection of three SVs involving the 3’-ends of MLH1 and LRRFIP2. Representative paired reads with discordant pair orientation (RR, LL and RL) and aberrant mapping distance are depicted. A schematic map of the area of the rearrangement shows the three SVs and the six breakpoints, resulting in a five-segment map (A to E). The size of each segment in bp is indicated. The overlapped SVs are defined as a small inversion in MLH1 of 0.91 kb (fragments A and B, deep blue), a big inversion of 22.8 kb involving MLH1 and LRRFIP2 (fragments C and D, turquoise blue) and a tandem duplication of 37.88 kb in the LRRFIP2 gene (fragments D and E, green). B Characterization of the breakpoints of the SVs and proposed map of the rearrangement. IGV simplified coverage plot (IGV Count tool with an average read density window of 300 bp) allowed the characterization of the breakpoints and duplicated areas. The proposed map of the actual rearrangement fits the WGS coverage and the SV calling. Sanger sequencing profiles of the three PCRs (arrows) validated the breakpoints.
