Banu Sofia, Mk Kanakavalli, George Joel Kiran, Siby Elizabeth, Bhagat Rakeshpal, Ms Sreelekshmi, Patil Siddaramappa J, Phadke Shubha R, Sowpati Divya Tej, Tallapaka Karthik Bharadwaj
CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Telangana, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Eur J Hum Genet. 2024 Dec 9. doi: 10.1038/s41431-024-01763-z.
Reference genomes serve as a baseline criterion for comparison of personal genomes to deduce clinical variants. The widely used reference genome, GRCh38, contains stretches of gaps and unresolved bases particularly in complex regions which could obscure variant discovery. In contrast, the gapless telomere-to-telomere CHM13 (T2T-CHM13) reference genome can be used to assess difficult regions of the genome. Optical genome mapping (OGM), an imaging technique for structural variation identification has improved resolution compared to traditional cytogenetic methods. Our study showcases the utility of the T2T-CHM13 reference genome for enhanced structural variant (SV) detection in complex regions. We illustrate this through two clinical cases, where improved alignment with T2T-CHM13 led to significantly higher confidence scores for critical SVs. We demonstrate improved clinical diagnostic outcomes with the updated T2T-CHM13 reference and advocate its adoption.
参考基因组作为比较个人基因组以推断临床变异的基线标准。广泛使用的参考基因组GRCh38包含大片段的缺口和未解析的碱基，特别是在复杂区域，这可能会掩盖变异的发现。相比之下，无缺口的端粒到端粒的CHM13（T2T-CHM13）参考基因组可用于评估基因组的困难区域。光学基因组图谱（OGM）是一种用于识别结构变异的成像技术，与传统细胞遗传学方法相比，其分辨率有所提高。我们的研究展示了T2T-CHM13参考基因组在增强复杂区域结构变异（SV）检测方面的实用性。我们通过两个临床病例对此进行了说明，其中与T2T-CHM13的改进比对导致关键SV的置信度得分显著提高。我们证明了更新后的T2T-CHM13参考基因组改善了临床诊断结果，并提倡采用该基因组。
