Intrachromosomal homologous recombination between inverted amplicons on opposing Y-chromosome arms

- We molecularly characterize four structural rearrangements of the human Y chromosome.
- Rearrangements arise by ectopic homologous recombination between Y chromosome arms.
- Repeat pairs located on opposing arms of the Y chromosome can undergo recombination.
- Fifty such rearrangements are predicted to arise on common Y chromosome structures.

Amplicons - large, nearly identical repeats in direct or inverted orientation - are abundant in the male-specific region of the human Y chromosome (MSY) and provide targets for intrachromosomal non-allelic homologous recombination (NAHR). Thus far, NAHR events resulting in deletions, duplications, inversions, or isodicentric chromosomes have been reported only for amplicon pairs located exclusively on the short arm (Yp) or the long arm (Yq). Here we report our finding of four men with Y chromosomes that evidently formed by intrachromosomal NAHR between inverted repeat pairs comprising one amplicon on Yp and one amplicon on Yq. In two men with spermatogenic failure, sister-chromatid crossing-over resulted in pseudoisoYp chromosome formation and loss of distal Yq. In two men with normal spermatogenesis, intrachromatid crossing-over generated pericentric inversions. These findings highlight the recombinogenic nature of the MSY, as intrachromosomal NAHR occurs for nearly all Y-chromosome amplicon pairs, even those located on opposing chromosome arms.