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DNA ‘Switches’ Determine Your Height

S u m m a r y :
Switches governing genes associated with height play a role in determining how tall you’ll be, says a new study published in eLife.

Your height isn’t just a random number: rather, it is determined by a combination of factors, from genetics and pre- and post-natal health to nutrition. However, what remains unknown is how these elements interact with each other, culminating to one’s specific height. This is where the new research, conducted by investigators from Harvard University, comes in: the findings constitute an attempt to clarify the processes behind establishing height.

According to lead author Associate Professor of Human Evolutionary Biology Terence D. Capellini, 700 genetic regions are linked with height. Then, within those regions are tens of thousands of DNA variants connected together. From this pool of information, the team wanted to identify the specific variants that actually influence height. The researchers were, ultimately, able to sieve through hundreds of genetic ‘switches’ that play a role in determining height, singling out one particular switch that modifies the function of an important gene involved in height differences.

As part of their ‘filtering’ process, Capellini and his colleagues identified genetic variants likely to be functional in the cartilage growth plates of bones of mice: they found regulatory ‘switches’, the DNA sequences that turn nearby genes on and off. Then, to separate switches involved in bone growth from those that are not, the investigators performed the same test on another type of cell, and then identified open sequences in both.

“If we find a common sequence that’s open in a brain cell and in a cartilage cell, we can say it likely turns on some gene that may be important for cells to live,” Capellini said. “So we filtered those out, but we didn’t ignore them completely, because they may actually be important. While we first concentrated on the bone-specific switches, we know there are a lot of inputs to height—it’s about the length of our bones, but we also know hormones trigger height, malnutrition can impact height, among other inputs so there may be general genetic factors that influence height.”

Then, study author Michael Guo identified 900 genetic variants associated with height in the on/off switches for bone. A number of other tests were done to ensure that they had narrowed their search down to the correct variants.

“We took genome-wide analyses from other studies that had nothing to do with height and looked to see if we saw the same signal, and we didn’t, which makes sense,” he said. “We also looked at switches from other cell types to see if these genetic variants appeared, and they didn’t. That really suggests to us that the signals we’re seeing are very strong, it’s not just a property of the genome or a property of identifying these switches.”

The next step is to now understand the role played by all the variants in determining height.

These findings not only help us demystify human height but also show how genetics can be used to understand conditions linked with both genetic and environmental factors like diabetes and heart disease.

“For any disease or trait, being able to say here is a switch that turns a gene on or off, and here is the mutation in that switch that can effect it dramatically…that’s pretty powerful,” Capellini said. “That will allow us figure out what are the biological pathways that are worth targeting. The future of personalised medicine will rely on knowing what specific pieces of DNA are doing in the body, and this is one way to do that.”

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