Fig. 3

Schematic representation of mechanisms leading to gross simple unbalanced translocations in case 1, 2 and 3. Donor chromosome pair is in yellow, recipient chromosome pair is in blue, the telomeric sequences are in grey, the red line indicates the breakage event, the sticky terminal portion of deleted chromosome that will stabilize in different ways is indicated in red. Mechanism A (upper sequence): The trisomy (A1) normalizes by anaphase lagging with chromothripsis of the supernumerary chromosome in the micronucleus (A2, right); a breakage event in the recipient chromosome (either in p or in q arm) with loss of the terminal portion (A3), the deleted chromosome stabilizes by telomere (p or q) capture from the fragmented chromosome leading to the simple unbalanced translocation (A4). This mechanism presupposes a second chromosomal breakage event at the same initial breakpoint in the recipient chromosome (A4) for the onset of the second cryptic derivative chromosome, either by a second chromothripsis event and smaller segments recapture (case 1 and 2) or by loss of the translocated portion and neo-telomere formation (case 3) (see the text for the details). Mechanism B (lower sequence): a breakage event in the recipient chromosome (either in p or in q arm) with loss of the terminal portion leads to the deleted chromosome (B1) which stabilizes in different independent ways in the two daughter cells during early embryonic development, by telomere (p or q) capture from donor chromosome in one cell (B2, the result is the simple unbalanced translocation) and by de novo telomere synthesis in the other cell (B3, the result is the cryptic derivative)