Did you know that neural tube defects are among the most
common form of human birth defects? These defects result in the abnormal
development of the brain, spine, or spinal cord. Often, this occurs within the
first month of pregnancy, and the reasons behind these disorders are unclear. There
are about 8 babies born in the U.S. each day that are affected and 300,000
cases identified each year. Among neural tube defects, spina bifida is one of
the most common. Spina bifida occurs when the neural tube does not close properly
during fetal development (image 1). This can then leave a bulge in the skin in
the area that is affected, or in severe cases, the skin could be open with the
nerves exposed.
The development of spina bifida is due to alterations in genes both in
the fetus and the placenta that encode for the development of the neural tube. As
most of us know, the placenta controls the environment and nourishes the fetus,
so its proper development is vital. The placenta is responsible for gas
exchange, supplying the fetus with nutrients, production of hormones, and
protection from infection. All of these important functions of the placenta are
under control of placental genes. A quick overview of the term genes: genes are
made of DNA, and genes code for proteins to be made. The expression of genes (and
thus the formation of proteins) can be controlled by what is called DNA
methylation. This is a form of regulation for genes, and a methyl group, -CH3,
is added to the DNA (image 2). The addition of this methyl group turns genes
off, so there is less protein made. So in simpler terms, if there are methyl
groups on the gene, that gene will make less protein. In contrast, if there are
less methyl groups, more protein will be made. This seems pretty simple, but
changes in the amount of methyl groups can have great consequences!
Previous studies have located two placental genes that
are important in neural tube development; TRIM26 and GNAS. TRIM26 is a gene
that is involved in the regulation of neural
system function, and GNAS is important in the development of the fetus and
placenta. In an experiment conducted by Zhang et. al, they looked at the amount
of methyl groups on these two genes in spina bifida placentas. They found that
the spina bifida placentas had less DNA methylation on these two genes than normal
placentas. As stated before, the lower amount of methyl groups on the DNA, the
more protein will be made from the gene. So this allowed for higher amounts of
TRIM26 and GNAS protein in spina bifida placentas. This is an important discovery
since high levels of these proteins could be a major cause of the development
of spina bifida. Who would most have thought that such a small molecule could
have such a profound impact? There is now evidence that these methyl groups
could be one reason for neural tube defects.
The high amount of TRIM26 and GNAS proteins is associated
with the deformity of the neural tube. Since the development of spina bifida is
still unclear, these findings provide great insight into possible ways to
decrease neural tube defects. Even though this knowledge just scratches the
surface, it is a great area to keep researching and these findings were a huge
breakthrough.
Their research was very credible and it is exciting to see new
advances being made! A question I have for the next researchers is: do you have
a specific idea that could decrease the amount of these proteins? If there is a
way to prevent abnormal neural tube development in the future, the number of
newborns with birth defects could be greatly decreased.
Works Cited
Zhang, Xiaojuan et. al. 2015. Spina bifida in fetus
is associated with an altered pattern of
DNA methylation in
placenta. Journal of Human Genetics.
1-7. doi:
10.1038/jhg.2015.80.
Images used:
Spina Bifida-web. Image by Center for Disease Control and
Prevention, made available under the Creative Commons CC0 1.0 Universal Public
Domain Dedication.
DNA Methylation. Image by Christopher Bock, made
available under Creative Commons Attribution- Share Alike 3.0 Unported license.
Is there a way to increase DNA methylation in regards to TRM26 and GNAS specifically? I wonder if this could be possible, especially in light of the strides made in genetic engineering. Such control and manipulation is not an easy feat, however recently new methods have dramatically improved our ability to edit DNA. When treatment is necessary with Spina Bifida, it's done through surgery to close the defect. Other treatments focus on managing complications. How great would it be if we could prevent the issue from ever occurring? Research like this brings us closer to the answers as we discover more about the genetic controls and switches that lead to disorders and defects.
ReplyDeleteIt is always interesting to learn about disorders I've heard of at a more cellular level. I've heard of Spina Bifida but I never knew about the causes, such as abnormalities in the placenta. I agree when you say this is a great step in hopefully discovering a way to stop Spina Bifida before it occurs. My question would be similar to Natalie's, I wonder if there is a way to increase the methylation on TRM26 and GNAS? I also wonder if there is a test that could be done in utero to detect the high levels of TRM26 and GNAS? Development is such a delicate process. It is things like this that make me realize how many things have to go the right way for each person to develop correctly. Two genes I've never even heard of play a huge part in the development of the neural system function, placenta and fetus. Development is so detailed and fragile!
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ReplyDeleteThis article was surprising and interesting! I never would have thought that two genes could have such an impact on possibly causing birth defects. However, this new research seems very promising in regards to new forms of treatment, especially preventative. As others have mentioned, if there was a way to either add more methyl groups or limit the amount of protein production, it seems likely that this would have an affect on the development. Finding ways to prevent these defects would be very helpful, as they are somewhat common as you mentioned.
ReplyDeleteI really enjoyed your article because like Hannah said, it is always so fascinating to learn the deeper workings of disorders I've heard in passing before but have never really taken the time to investigate further myself. I was surprised to learn how many newborns were affected by neural tube defects. I guess I knew it was a problem but didn't really comprehend the severity of the issue. I think your emphasis on the placental role in development and this disorder specifically was really crucial in your explanation. Perhaps the in utero test Hannah suggested could somehow use placenta samples to test the DNA methylation levels as opposed to fetal samples to ensure the safety of the developing child.
ReplyDeleteSpina bifida is one of the most common neural tube defects. It is interesting that too much of a protein can cause a deformity in the neural tube. Is there a way to add methyl groups to the genes? Also, could less methyl groups to the genes TRIM26 and GNAS also cause other neural tube defects?
ReplyDeleteJust as other have mentioned above, I enjoyed reading your post because although I have heard of spina bifida before, I have never fully understood what it entails. Just as how methylation prevents proteins from being made, by tightly coiling DNA into heterochromatin, acetylation helps to unwind the DNA into euchromatin to increase protein production. Since methylation was low, causing the amount of TRIM26 and GNAS proteins to be high, I wonder if acetylation of the DNA could be looked at to see if there was a high amount of acetylation in the DNA of babies with spina bifida.
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