Figure 3.

Scheme of PAX5 intragenic amplification (PAX5 iAmp). (A) PAX5 iAmp detected by RNA-seq and whole genome sequencing (WGS (16)). The most frequently affected exons are e2-5, which are shown with increased expression levels (by RNA-seq) compared to the adjacent exons. The amplified region on the genomic level is reflected by abruptly elevated depth from WGS, which corroborates the affected exons identified from RNA-seq. (B) PAX5 iAmp leads to an extended isoform of PAX5. Using optical genomic mapping, 4-5 extra copies of PAX5 e2-5 were determined in the PAX5 iAmp cases. The tandem multiplication of PAX5 paired box DNA binding domain may change its binding activity, thus altering its transcription program and disrupting B cell differentiation (68).