Scope
This concept covers repetitive regions, segmental duplications, sequencing dead zones, complex medically relevant loci, and rearrangements whose structure matters as much as their presence.
Current position in this corpus
- This is one of the strongest justification zones for long-read WGS.
- Long reads help not only by detecting more events, but by resolving structure, phasing, and breakpoint relationships.
Supporting sources
Current takeaways
- Complex rearrangements are often underdescribed by copy-number summaries alone.
- Medically relevant hard loci remain a major weakness of short-read WGS.
- Even long-read workflows still struggle in centromeres, high-identity segmental duplications, some large inversions, and multiallelic repeat-rich regions.
Open questions
- Which hard-region problems are now mostly solved by routine long-read WGS, and which still need specialized or multi-platform analysis?
- How should clinical pipelines report uncertainty when a locus remains structurally ambiguous even after long-read sequencing?