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Genes that shape bones identified, offering clues about our past and future

September 15, 2023
in Science
Genes that shape bones identified, offering clues about our past and future
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Using artificial intelligence to analyze tens of thousands of X-ray images and genetic sequences, researchers, including two NSF Graduate Research Fellows at The University of Texas at Austin and New York Genome Center, have been able to pinpoint the genes that shape our skeletons, from the width of our shoulders to the length of our legs.

The findings, published in Science, pull back a curtain on our evolutionary past and open a window into a future where doctors can better predict patients’ risks of developing conditions such as back pain or arthritis in later life.

“Our research is a powerful demonstration of the impact of AI in medicine, particularly when it comes to analyzing and quantifying imaging data, as well as integrating this information with health records and genetics rapidly and at large scale,” said Vagheesh Narasimhan, an integrative biologist who led the multidisciplinary team of researchers.

Humans are the only large primates to have longer legs than arms, a change in the skeletal form that is critical in enabling our ability to walk on two legs. The scientists sought to determine which genetic changes underlie anatomical differences that are clearly visible in the fossil record leading to modern humans.

The researchers also wanted to find out how these skeletal proportions allowing bipedalism affect the risk of many musculoskeletal diseases such as arthritis of the knee and hip — conditions that affect billions of people in the world and are the leading causes of adult disability in the United States.

The scientists used deep learning models to perform automatic quantification on 39,000 medical images to measure distances between shoulders, knees, ankles and other points in the body. By comparing these measurements to each person’s genetic sequence, they found 145 points in the genome that control skeletal proportions.

The results have implications for our understanding of evolution. The researchers noted several genetic segments that controlled skeletal proportions overlapped more than expected with areas of the genome called human accelerated regions. These are sections of the genome shared by great apes and many vertebrates that diverge significantly in humans. This provides genomic rationale for the divergence in human skeletal anatomy.

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