小柯机器人

美国哈佛大学Peter V. Kharchenko等研究人员合作对948名个体的镶嵌染色体改变进行泛组织调查。相关论文于2023年10月30日在线发表在《自然—遗传学》杂志上。

研究人员介绍了基因型-组织表达项目对948名健康人的镶嵌染色体变异（mCA）进行的泛组织调查，通过单倍型分期增强了基于RNA的等位基因不平衡估计。研究人员发现，约四分之一的个体至少在一个组织中携带克隆扩增的mCA，其发生率与年龄密切相关。不同组织类型中mCA的发生率和全基因组模式差异很大，这表明组织特异性诱变暴露和选择压力。正常肾上腺和垂体中的mCA形态与这些组织中的肿瘤形态相似，而食管和皮肤中的mCA形态则不尽相同。

总之，这些研究结果表明，在正常人体组织中，mCA的出现广泛依赖于年龄，并与肿瘤发生有着错综复杂的联系。

据了解，基因突变会在生物体的一生中不断累积。虽然体细胞单核苷酸变异在人体中已经得到了很好的描述，但正常组织中大的染色体改变的模式和后果在很大程度上仍不为人所知。

附：英文原文

Title: A pan-tissue survey of mosaic chromosomal alterations in 948 individuals

Author: Gao, Teng, Kastriti, Maria Eleni, Ljungstrm, Viktor, Heinzel, Andreas, Tischler, Arthur S., Oberbauer, Rainer, Loh, Po-Ru, Adameyko, Igor, Park, Peter J., Kharchenko, Peter V.

Issue&Volume: 2023-10-30

Abstract: Genetic mutations accumulate in an organism’s body throughout its lifetime. While somatic single-nucleotide variants have been well characterized in the human body, the patterns and consequences of large chromosomal alterations in normal tissues remain largely unknown. Here, we present a pan-tissue survey of mosaic chromosomal alterations (mCAs) in 948 healthy individuals from the Genotype-Tissue Expression project, augmenting RNA-based allelic imbalance estimation with haplotype phasing. We found that approximately a quarter of the individuals carry a clonally-expanded mCA in at least one tissue, with incidence strongly correlated with age. The prevalence and genome-wide patterns of mCAs vary considerably across tissue types, suggesting tissue-specific mutagenic exposure and selection pressures. The mCA landscapes in normal adrenal and pituitary glands resemble those in tumors arising from these tissues, whereas the same is not true for the esophagus and skin. Together, our findings show a widespread age-dependent emergence of mCAs across normal human tissues with intricate connections to tumorigenesis.

DOI: 10.1038/s41588-023-01537-1

Source: https://www.nature.com/articles/s41588-023-01537-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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