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The Importance of DNA Crossovers
A Recent Study Reveals New Insights into Aneuploidy
December 7, 2020
As you may already know, DNA crossovers occur during the stage of meiosis, in which DNA mixes and matches into a series of combinations that are completely unique. But, what is it about this process that’s so important to fertility science?
One key feature of meiosis is that the DNA crossovers occur so that the swapped DNA segments are spaced apart. Additionally, the resulting DNA would ideally have the same number of chromosomes as when meiosis started. However, when this process goes wrong, we begin to see negative repercussions.
Faulty crossover formation can lead to aneuploidy, or the quality of cells to have either too many or too few chromosomes. It’s aneuploidy that makes DNA crossovers so important in the study of fertility and reproduction, as it can lead to infertility, miscarriages, and even conditions such as Down syndrome. In fact, according to Science Daily, “learning how crossovers are regulated is key to understanding human reproduction and improving reproductive health.”
While we know that DNA crossovers can lead to fertility problems, research is still being conducted on what exactly the details are behind aneuploidy. In two new studies from the Blavatnik Institute at Harvard Medical School, researchers were able to shed further light on this process.
Understanding Aneuploidy in Sperm Cells
The first study was concerned with the analysis of crossovers and aneuploidy. In this study, researchers simultaneously analyzed aneuploidy and crossovers on over 30,000 sperm cells. From that analysis, the researchers proposed that a single biological process helps regulate the number, location, and spacing of crossovers.
Researchers wanted to know exactly how often aneuploidy occurs in sperm, and get a better baseline for male fertility. In order to conduct the study, HMS developed a new technology to analyze sperm cells. To do so, they took an existing technology from DNA analysis and adapted it into a new process, dubbed Sperm-seq.
Sperm-seq allowed them to detect DNA crossovers in sperm on a whole new scale. In total, the team were able to analyze over 30,000 sperm cells- meaning over 800,000 DNA crossovers!
In their analysis of the sperm cells, HMS researchers found that the number of aneuploid sperm ranged from one percent to five percent, with an average of 2.5 percent. Additionally, in cells with a lot of crossovers, the crossovers tended to be closer together. Plus, they had a tendency to be located proportionally more in the central regions of the chromosomes than the ends, which suggests an underlying regulation in aneuploidy.
After the success of their experiment, HMS is also allowing other labs to utilize Sperm-seq in their study, which is fantastic news for future research on male fertility.
Aneuploidy in Worm Egg Cells
The second study from the Blavatnik Institute was concerned with why they were seeing crossovers more often in some chromosome locations than others. In order to study this phenomenon, researchers examined meiosis in developing worm egg cells.
Scientists knew that during meiosis, proteins deliberately snap the double strands of DNA at many sites along the chromosome. Additionally, they had previously observed that these breakage points on the arms of the chromosomes often turn into crossover repair sites. However, breakage points in other locations (such as the chromosome centers and ends) did not feature the same transformation.
So, in their study, scientists broke DNA at different positions along chromosomes in developing Caenorhabditis elegans worm egg cells. That way, they could observe whether the crossovers at the manual breakage points proceeded normally or not. In that study, they found that location does determine the success of crossovers. The crossovers on the centers and ends of the chromosomes concluded poorly, while the crossovers on the arms did not. It was the egg itself that played a key role in minimizing crossovers in specific regions.
As a result of this study, scientists believe that some parts of the chromosome resist crossovers due to the fact that they cannot support healthy chromosome organization. So, in order to avoid aneuploidy, the chromosome tightly regulates where its crossovers can occur.
When it comes to understanding DNA crossovers, the research on aneuploidy in eggs has been mostly covered. This is partly due to the fact that eggs are known to have higher rates of aneuploidy than sperm do, but also because there is a lack of research on sperm cells. Previously, sperm samples had been evaluated on the basis of sperm count and motility only. It’s only now that we’re beginning to see more complex analyses of sperm and male fertility, such as this one.
While the research in these studies is still in its early stages, they are both promising for the future. By understanding aneuploidy and why it occurs, we will surely be able to make great advancements in fertility science a bit further down the line.
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