近日，美国德克萨斯大学奥斯汀分校Vagheesh M. Narasimhan等研究人员合作揭示人类骨骼的遗传结构与演化。相关论文发表在2023年7月21日出版的《科学》杂志上。

研究人员将深度学习模型应用于英国生物库中的31221张X光片，提取了一组全面的骨骼比例（SP），这些SP与全基因组范围内的145个独立基因位点相关。结构方程建模表明，肢体比例具有很强的遗传共享性，但与宽度和躯干比例无关。多基因评分分析确定了骨关节炎与髋关节和膝关节SP之间的特定关联。

与其他性状不同的是，SP位点富集在人类加速区域以及人类和类人猿之间表达不同的基因的调控元件中。因此，这项工作确定了影响骨骼形态的特定基因变异，并将人类解剖学变化的一个主要演化方面与发病机制联系起来。

据介绍，人类的骨骼形态是两足行走的基础，但SP的遗传基础却没有得到很好的描述。

附：英文原文

Title: The genetic architecture and evolution of the human skeletal form

Author: Eucharist Kun, Emily M. Javan, Olivia Smith, Faris Gulamali, Javier de la Fuente, Brianna I. Flynn, Kushal Vajrala, Zoe Trutner, Prakash Jayakumar, Elliot M. Tucker-Drob, Mashaal Sohail, Tarjinder Singh, Vagheesh M. Narasimhan

Issue&Volume: 2023-07-21

Abstract: The human skeletal form underlies bipedalism, but the genetic basis of skeletal proportions (SPs) is not well characterized. We applied deep-learning models to 31,221 x-rays from the UK Biobank to extract a comprehensive set of SPs, which were associated with 145 independent loci genome-wide. Structural equation modeling suggested that limb proportions exhibited strong genetic sharing but were independent of width and torso proportions. Polygenic score analysis identified specific associations between osteoarthritis and hip and knee SPs. In contrast to other traits, SP loci were enriched in human accelerated regions and in regulatory elements of genes that are differentially expressed between humans and great apes. Combined, our work identifies specific genetic variants that affect the skeletal form and ties a major evolutionary facet of human anatomical change to pathogenesis.

DOI: adf8009

Source: https://www.science.org/doi/10.1126/science.adf8009