Gladstone研究所的科学家揭示了一项新的遗传机制：仅失去一个TBX5基因副本就足以导致心脏细胞的DNA错误折叠，破坏基因组的三维结构。[1]这项发表在《Science》杂志上的研究表明，当TBX5含量降至正常水平的一半时，就能够破坏DNA折叠并引发心脏缺陷。[1]
TBX5蛋白在这一过程中发挥关键作用，充当DNA的"建筑师"，指导称为cohesin的分子马达创建染色体环。[1]研究团队使用不同的计算模型分析了数千个单细胞的结果，发现这种DNA三维结构的改变与出生缺陷的产生相关。[1]
这一发现具有更广泛的意义。研究人员指出，TBX5只是一个更广泛的基因类别的例子，当仅失去一个副本时就会导致出生缺陷。[1]由于先天性心脏病影响约1/100婴儿出生，[1]这项研究表明许多出生缺陷可能由DNA三维结构的错误折叠引起，而非仅源于基因指令本身的改变。
Scientists at the Gladstone Institute have discovered that losing just a single copy of the TBX5 gene causes heart cells' DNA to fold incorrectly, disrupting the three-dimensional structure of the genome.[1] The finding, published in Science on July 23, 2026, reveals a mechanism that may explain why patients carrying the same gene mutation develop different heart defects.[1]
The TBX5 protein functions as a DNA "architect," directing molecular motors called cohesin to create chromosomal loops that organize genetic material.[1] When TBX5 levels drop to just half their normal amount, the disruption to DNA folding is sufficient to trigger heart abnormalities.[1] This suggests that many birth defects may stem from incorrect three-dimensional DNA folding rather than solely from changes in genetic instructions themselves.[1] Congenital heart disease affects approximately one in 100 infants at birth.[1]
Researchers analyzed results from thousands of individual cells using multiple computational models to reach their conclusions.[1] According to Benoit Bruneau, one of the investigators, "TBX5 is just an example of a broader class of genes that cause birth defects when only one copy is lost."[1]