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Updated: May 29, 2026

Ultra-long Read Sequencing for Whole Genomic DNA Analysis
Published on: March 15, 2019
Unravelling ring chromosome structures and formation mechanisms by short-read and long-read genomic sequencing
Mei Ling Chong1, Bruna Burssed2, Chen Zhao1
1Department of Genetics, Yale School of Medicine, New Haven, CT.
Purpose:
Ring chromosomes (RCs) are rare cytogenetic abnormalities involving copy-number variants and chromosome instability. Identifying the breakage-fusion sequences of RCs at nucleotide-level resolution can elucidate the cytogenomic rearrangements and ring formation mechanisms.
Methods:
This study used short-read genomic sequencing (srGS) and long-read genomic sequencing (lrGS) alongside the telomere-to-telomere reference genome to characterize the breakage-fusion events of 17 RC cases.
Results:
Complete RCs without loss of euchromatin by a fusion of subtelomeric or telomeric regions were noted in a RC14 and a RC20. Incomplete RCs with intrachromosomal copy-number variants were noted in 15 cases, including a RC3, a RC4, 4 RC13s, a RC14, 3 RC18s, a RC21, 3 RC22s, and an RCY. srGS defined breakage-fusion sequences in single-copy sequences, and lrGS mapped subtelomeric and pericentric repetitive sequences using the telomere-to-telomere reference genome. The breakage-fusion sequences revealed ring formation mechanisms by intrastrand nonhomology end joining in 5 RCs, microhomology-mediated end joining in 8 RCs, and microhomology-mediated break-induced replication in 4 RCs.
Conclusion:
This study demonstrated the analytic validity and diagnostic utility of srGS and lrGS in delineating the genomic rearrangements in RCs for better interpreting clinico-cytogenomic correlations and further analysis of RC behavior in cell cycles.
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