Genetics of skeletal shape identified for the first time

July 21 () –

By using artificial intelligence to analyze tens of thousands of X-ray images and genetic sequencesresearchers from the University of Texas at Austin and the New York Genome Center (United States) have been able to identify the genes that shape our skeletonsfrom the width of the shoulders to the length of the legs, as published in the magazine ‘Science’.

The research provides information on our evolutionary past and opens a window to a future in which doctors will be able to better predict the risk of patients developing conditions such as back pain or arthritis later in life, the authors emphasize.

“Our research is a powerful demonstration of the impact of AI in medicine, especially when it comes to analyzing and quantifying imaging data, as well as integrating this information with medical histories and genetics quickly and on a large scale.”says Vagheesh Narasimhan, an associate professor of integrative biology, as well as statistics and data science, who led the multidisciplinary team of researchers to provide the genetic map of skeletal proportions.

Humans are the only large primates to have legs longer than arms, a change in skeletal shape that is critical to enabling the ability to walk on two legs. The scientists aimed to determine what genetic changes underlie the anatomical differences that are clearly visible in the fossil record leading up to modern humans, from Australopithecus to Neanderthals.

They also wanted to find out how these skeletal proportions that allow for bipedalism affect the risk of many musculoskeletal diseases such as knee and hip arthritis, conditions that affect billions of people worldwide and are the leading causes of disability in adults in the United States.

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

“Our work provides a roadmap that connects specific genes to the skeletal lengths of different parts of the body, allowing developmental biologists to systematically investigate them.“, says Tarjinder (TJ) Singh, a co-author of the study, an associate member of the NYGC and an adjunct professor in the Department of Psychiatry at Columbia University.

The team also examined how skeletal proportions are associated with major musculoskeletal diseases. and showed that individuals with a greater hip width-to-height ratio were more likely to develop osteoarthritis and hip pain. Similarly, people with a higher femur (thigh bone) length to height ratio were more likely to develop knee arthritis, knee pain, and other knee problems. People with a higher torso length to height ratio were more likely to develop back pain.

“These disorders are due to biomechanical stresses placed on the joints throughout life,” says Eucharist Kun, a biochemistry student at the University of Austin and lead author of the study. Skeletal proportions affect everything from our gait to how we sit, and it makes sense that they are risk factors for these disorders.”

The results of their work also have implications for our understanding of evolution. The researchers found that several gene segments that control skeletal proportions coincided 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, but diverge significantly in humans. This genomically explains the divergence of our skeletal anatomy.they point out.

One of the most enduring images of the Rennaisance — Leonardo Da Vinci’s “Vitruvian Man” — contained similar conceptions of the proportions and lengths of limbs and other elements that make up the human body.

“In a way, we are faced with the same question as Da Vinci. Narasimhan stresses. What is the basic human form and its proportion? But now we use modern methods and we also wonder how these proportions are determined genetically“.