School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, 650500, China; Yunnan Environmental Mutagen Society, Kunming, Yunnan, 650500, China.
School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, 650500, China.
Mutat Res Rev Mutat Res. 2021 Jul-Dec;788:108389. doi: 10.1016/j.mrrev.2021.108389. Epub 2021 Jul 5.
As human life expectancy increases substantially and aging is the primary risk factor for most chronic diseases, there is an urgent need for advancing the development of post-genomic era biomarkers that can be used for disease prediction and early detection (DPED). Mosaic loss of Y chromosome (LOY) is the state of nullisomy Y in sub-groups of somatic cells acquired from different post-zygotic development stages and onwards throughout the lifespan. Multiple large-cohort based epidemiology studies have found that LOY in blood cells is a significant risk factor for future mortality and various diseases in males. Many features intrinsic to LOY analysis may be leveraged to enhance its use as a non-invasive, sensitive, reliable, high throughput-biomarker for DPED. Here, we review the emerging literatures in LOY studies and highlight ten strengths for using LOY as a novel biomarker for genomics-driven DPED diagnostics. Meanwhile, the current limitations in this area are also discussed. We conclude by identifying some important knowledge gaps regarding the consequences of malsegregation of the Y chromosome and propose further steps that are required before clinical implementation of LOY. Taken together, we think that LOY has substantial potential as a biomarker for DPED, despite some hurdles that still need to be addressed before its integration into healthcare becomes acceptable.
随着人类预期寿命的大幅延长，衰老成为大多数慢性疾病的主要风险因素，因此迫切需要推进后基因组时代生物标志物的发展，以便用于疾病预测和早期检测 (DPED)。Y 染色体镶嵌缺失 (LOY) 是指从不同的合子后发育阶段开始，在整个生命周期中，亚群体细胞中获得的无 Y 染色体单体状态。多项基于大型队列的流行病学研究发现，血细胞中的 LOY 是男性未来死亡率和各种疾病的重要危险因素。LOY 分析的许多内在特征可被利用，以增强其作为非侵入性、敏感、可靠、高通量生物标志物用于 DPED 的用途。在这里，我们回顾了 LOY 研究的新兴文献，并强调了将 LOY 用作基于基因组的 DPED 诊断的新型生物标志物的十个优势。同时，还讨论了该领域目前的局限性。我们最后确定了关于 Y 染色体错分的后果的一些重要知识空白，并提出了在 LOY 临床应用之前需要采取的进一步措施。总之，尽管在将 LOY 整合到医疗保健中之前仍需要解决一些障碍，但我们认为 LOY 作为 DPED 生物标志物具有很大的潜力。
