Direct and inverted duplications.

(A) In this example, modeled after the Factor 8 locus on the X chromosome in humans, additional repeats provide other opportunities for rearrangements of the triplicated locus that remove the centromere-proximal junction. The telomeric-proximal junction is removed by NHEJ or MMBIR at short regions of microhomology. This pattern of palindrome erosion results in a deletion and an inverted duplication separated by a copy-neutral segment of chromosome. (B) A failed recombination/MMBIR attempt to erode the centromere-proximal junction leaves a dsDNA break that acquires or captures a new telomere. It results in the complete loss of sequences from the point of the inverted duplication to the end of the chromosome. See S1 Fig for alternate illustrations of the 2 rearrangement events. MMBIR, microhomology-mediated break-induced replication; NHEJ, non-homologous end joining.