Scoliosis- A Complex and Mysterious Disease Daryn PetersBIO 1080 010December 7, 2017 INTRO: Adolescent Idiopathic Scoliosis also known as AIS, is the most common pediatric spinal deformity, affecting around 3% of children worldwide.
AIS is a condition where the spine grows curved in the C-Shape or an S-Shape The word Idiopathic means that the cause is unknown, and is a disease or condition that emerges spontaneously. To try and get to the bottom of this complex and mysterious disease, The American Society of Human Genetics did a study of over twenty-thousand people total, 4,332 of them being affected by Scoliosis, and 15,864 people who are not affected by this disease. The study was able to find some correlation between a Scoliosis and a gene located on the ninth chromosome. Below is a picture of my personal spine, before and after spinal fusion surgery. HYPOTHESIS/ PREDICTIONS: It was hard for the researchers to make a prediction about the study, because there has been no known cause of Scoliosis up to this point, but they were hopefully to find some correlation between a gene and this disease. Before this study, they had previously hypothesized that genes played a major role in rare disorders involving Scoliosis and may be important in the idiopathic forms AIS.
Disorders like this typically involve duplication, deletion or other variations of a gene. While conducting the study they were able to find a connection between those who had Scoliosis and the protein BNC2 and hypothesized that if there were higher levels of BNC2 during the development of a fetus that there could be a higher chance of having AIS. METHODS/CONTROLS/EXPERIMENT DESIGN: The study began with a genome-wide association study, containing over ten thousand participants with and without Scoliosis. The participants who volunteered in this study were seen by a medical professional who specializes in spine deformities beforehand to confirm that a person was affected or not affected by the disease. They started out with a control group- the participants who were not affected by Scoliosis- and an experimental group -those who were affected. The study took blood from all of the volunteers and looked for slight difference amongst their genes – specifically at single nucleotide polymorphisms or SNP’s – that occur in more frequently in people with certain diseases. The researchers were able to link a particular SNP and concluded that is located closely to the part of DNA that codes for protein BNC2, a protein that is associated with facial pigmented spots. They used a RT-PCR also known as a Real-Time PCR is used to qualitatively detect gene expression through creation of a complementary strand of DNA transcripts from RNA, to find where BNC2 is expressed in humans.
To confirm the association of the loci and the BNC2 the team took the genes of another 958 Scoliosis participants and 3,551 control participants. BNC2 is also found in a variety of other animals, and to test the effects of a large quantity of BNC2 they gave it to Zebrafish embryos and tested how it affected them. RESULTS/DATA: The team was able to pinpoint where the protein BNC2 is expressed in humans, and found that it highly appears in the uterus, spinal cord, bone, and cartilage. Since, a significant amount of BNC2 was found in the spinal cord, bone and cartilage it showed a strong correlation. The SNP variation that was connected to Scoliosis was also to discover that those with the disease also had increased levels of BNC2 expression and that this specific single nucleotide polymorphism has the chance to regulate the expression of the protein BNC2. This lead the team to believe that the large quantities of BNC2 in the spine and bones make it more likely that adolescents with the SNP that is associated with AIS may begin to make excess amount of BNC2 once they reach puberty if genetic or environmental factors are also present. When the researchers presented the BNC2 to the Zebrafish embryos, as stated above, the results were seen that the Zebrafish had deformities and severe body curvature that positively correlated with the high amounts of BNC2. Below is a scatter plot of the ninth chromosome and where the most amounts of BNC2 are located on the chromosome.
You can see that there is a jump of recombination rate near the 16.7 Mb on the ninth chromosome. CONCLUSION: This study was able to begin to find a specific protein that is expressed through a specific gene. The team hypothesized after looking at genomes of a plethora of people that there was a connection between the protein BNC2 and Scoliosis. The narrowed it down and associated that a large amount of BNC2 was located in areas such as the spinal cord and bone, and have seen an increase of BNC2 in those with the disease once they hit puberty. ALTERNATIVE EXPLANATIONS/LIMITATIONS OF DESIGN: There could be different explanations for Scoliosis, that scientist and researchers have not developed yet. Since this disease is idiopathic it is difficult to locate an exact cause which makes it hard to know if a finding is correct or just a correlation.
SIGNIFICANCE: Scoliosis is a not uncommon in population around the world, especially children. It affects 3% of children and adolescents around the globe. This topic is significant because before this study there was no real clue on what was the cause of Scoliosis. Whether that was genetics or the environment researchers had no insight, this is the step in the right direction. This also opens up the door to other idiopathic disease, it can lead researchers in the direction of looking into a group of people’s genomes and comparing it to others to see if there is a discrepancy and see if they can find a link between a disease and a certain gene or loci. Citations”Adolescent Idiopathic Scoliosis – Genetics Home Reference.” U.
S. National Library of Medicine, National Institutes of Health, ghr.nlm.
nih.gov/condition/adolescent-idiopathic-scoliosis#synonyms.RIKEN. (2015, July 23). Genetic roots of adolescent scoliosis. ScienceDaily. Retrieved December 5, 2017 from www.
sciencedaily.com/releases/2015/07/150723125238.htmSuzuki, Teppi, and Shiro Ikegwa. “A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.” The American Journal of Human Genetics, Cell Press, 23 July 2015, www.sciencedirect.
com/science/article/pii/S000292971500275X?via%3Dihub.Wise, Carol A, et al. “Understanding Genetic Factors in Idiopathic Scoliosis, a Complex Disease of Childhood.” Current Genomics, Bentham Science Publishers Ltd., 9 Mar.