Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Genetics, Kitasato University Hospital, Sagamihara 252-0375, Japan.
Department of Pediatrics, Tokyo Metropolitan Kita Medical Rehabilitation Center for the Handicapped, Kita-ku, Tokyo, 114-0033, Japan.
Genomics. 2024 Sep;116(5):110894. doi: 10.1016/j.ygeno.2024.110894. Epub 2024 Jul 15.
Technologies for detecting structural variation (SV) have advanced with the advent of long-read sequencing, which enables the validation of SV at a nucleotide level. Optical genome mapping (OGM), a technology based on physical mapping, can also provide comprehensive SVs analysis. We applied long-read whole genome sequencing (LRWGS) to accurately reconstruct breakpoint (BP) segments in a patient with complex chromosome 6q rearrangements that remained elusive by conventional karyotyping. Although all BPs were precisely identified by LRWGS, there were two possible ways to construct the BP segments in terms of their orders and orientations. Thus, we also used OGM analysis. Notably, OGM recognized entire inversions exceeding 500 kb in size, which LRWGS could not characterize. Consequently, here we successfully unveil the full genomic structure of this complex chromosomal 6q rearrangement and cryptic SVs through combined long-molecule genomic analyses, showcasing how LRWGS and OGM can complement each other in SV analysis.
随着长读测序技术的出现，检测结构变异（SV）的技术得到了发展，该技术能够在核苷酸水平上验证 SV。基于物理图谱的光学基因组图谱（OGM）技术也可以提供全面的 SV 分析。我们应用长读全基因组测序（LRWGS）技术，准确地重建了一名复杂 6q 染色体重排患者的断裂点（BP）片段，而传统的核型分析对此仍然难以捉摸。虽然所有的 BP 都通过 LRWGS 精确地识别出来，但根据其顺序和方向，有两种可能的方法来构建 BP 片段。因此，我们还使用了 OGM 分析。值得注意的是，OGM 能够识别超过 500kb 的整个倒位，而 LRWGS 无法对其进行特征化。因此，在这里，我们通过结合长分子基因组分析成功揭示了这种复杂的 6q 染色体重排和隐匿性 SV 的完整基因组结构，展示了 LRWGS 和 OGM 如何在 SV 分析中相互补充。
