Fla. — Why one person gets a disease, and another remains untouched, can often be traced to their genetic code, the vast set of instructions that tells human cells how to function
That’s because errors in this code can cause cells to misbehave
University of Florida Health researchers in a new study have identified 92 genetic variants that might contribute to adolescent idiopathic scoliosis, a spinal curvature that affects 3% of children worldwide. The findings, researchers said, help them better understand the condition’s mysterious underpinnings
That list of genetic suspects is a milestone that might, with more research, eventually allow genetic tests to identify those at high risk of developing the condition
“Earlier risk identification could allow closer monitoring and timely intervention before a spinal curve progresses to the point of requiring surgery,” said Nadja Makki, Ph.D., the study’s senior author and an assistant professor in the UF College of Medicine’s Department of Physiology and Aging
UF Health researchers collaborated with Anat Kreimer, Ph.D., and her bioinformatics lab at Rutgers University on the study published Aug. 17 in Genome Research. UF doctoral student Darius Ramkhalwan also played a key role in the investigation
Scientists started with 1,664 variants in 26 regions of the human genome previously associated with scoliosis risk. They narrowed the pool to 92 and ranked them by the extent to which each variant altered DNA’s control of gene activity. Genes are segments of DNA that carry instructions used by the body. More change provided stronger evidence that the variant might be important in scoliosis
“This is quite a big deal in the scoliosis research community,” Makki said. “This allows us to focus on very specific regions in the genome that we can now analyze in more detail.”
The genome is the complete set of DNA in an organism’s cells. The human genome contains about 3.2 billion pairs of chemical building blocks, each represented by the letters A, T, C and G
Genetic variants are differences in the DNA sequence from one person to another. Often, a variant involves a difference of just a single DNA letter, as is the case for most variants in the study. Generally, most variants are harmless, while others can increase disease risk
Previous genetic studies compared the DNA of people with and without scoliosis and identified 26 regions of DNA associated with increased risk. But those studies could not tell scientists which DNA variations in those regions were important or what they did
“Genome-wide studies gave us the neighborhood where a risk variant might be located,” Makki said. “Our study helps identify the specific address and begins to explain what is happening there.”
The relatively new method used in the study is called a massively parallel reporter assay. It enables simultaneous testing of thousands of genetic sequences
Researchers created short DNA fragments containing either the common or the scoliosis-associated version of each variant and introduced them into living cartilage cells in the lab. They then measured whether the two versions differed in their ability to increase or decrease gene activity
More research is needed to confirm whether any of the variants affect scoliosis development
Makki was particularly encouraged by one variant located near a gene essential for cartilage health and spinal alignment. Loss of the gene can lead to a condition in mice similar to scoliosis
The study comes on the heels of another landmark scoliosis paper by Makki and UF Health researchers
That earlier research began with spinal cartilage and muscle tissue samples collected from people with and without scoliosis and compared gene activity between the two groups. Researchers focused on which genes are unusually active or inactive in scoliosis
The new study starts at the other end of the problem, namely with inherited variants already statistically linked to scoliosis. It asks which of them can alter the switches that control gene activity
Together, the studies begin to connect DNA changes with abnormal gene activity
Related topics
- College of Medicine
- UF Health
- University of Florida
About the author
For the media
Media contact
Peyton WesnerCommunications Manager for UF Health External Communications
pwesner@ufl.edu(352) 273-9620
Related assets
Download images from this story
