Balanced Translocation Disrupting JAG1 Identified by Optical Genomic Mapping in Suspected Alagille Syndrome

Figure 1

Reciprocal translocation disrupting JAG1 identified in P1. (a) Circos plot demonstrated a translocation between chromosomes 4 and 20. The Circos plot is composed of four circles (viz., four tracks). The outmost track with number (1,2,3…X, Y) stands for simulated cytoband on each chromosome; the second track with colorful dots represents SVs (including InDel, inversion, and duplication); the third track with a central purple line exhibits CNVs (purple marks a baseline; outward blue and inward red indicate CNV gain and CNV loss segments, individually); the inmost track with purple circle and crossed lines shows translocation (intra- and intermolecules). (b) Reciprocal translocation presented in genome browser view of OGM. The top and bottom two grass green bars represent reference chr20 and chr4, respectively. The ice green bar in the middle represents the patient’s derivative chromosome as matched to reference chr4 and chr20 (gray lines between grass green bar and ice green bar show alignment; purple line suggests breakpoint junction). The number on the reference chromosome corresponding to the two sides of the breakpoint junction represents the position on the chromosome. Ref: GRCh38/hg38 reference sequence of chromosome; LF and LR were primer pairs designed for long-range (L) PCR; chr: chromosome. Schematic derivative chromosome rightmost (chr4 in orange and chr20 in green). (c) Visualization of breakpoints identified by targeted next-generation sequencing. Arrow with dotted line indicates breakpoint. Breakpoints for derivative chr4, left, and for chr20, right. (d) Results of the Sanger sequencing confirming breakpoints for derivative chr4 and chr20. (e) Schematic of JAG1 and FAM13A rearrangement and corresponding damage to JAG1. E: exon; E-R: reverse strand of exon.