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It’s About the Genes … It’s Personal

Imagine that your close friend has recently been diagnosed with depression. But before your friend’s whole world started falling apart, imagine a world in which he would go to the doctor’s office, where they would pull up a copy of your friend’s genetic records, and then simply hand him an over-the-counter drug that completely cured his depression.

This reality may be closer than we think.

Perhaps one would think that “diseases” or “medical conditions” are caused by malfunction or misbehavior in your body. Surely, cancer is an uncontrolled division of cells, cardiovascular diseases are blocked blood flow in your tissues, and allergic reactions are your immune system’s triggered reception to a particular factor. Aren’t all health problem in the world caused by common internal or external factors that lead to a “common” misbehavior in our bodies?

But our bodies may be more unique and more special than what most people would think.

You see, humans – and all living things, too – are miraculous creatures. We have tens of thousands of proteins, and billions of gene base pairs that work together in an infinite number of combinations to code for every single movement of our body. And what’s more miraculous is that every single person who has ever lived on earth – all the hundreds of billions of people to have ever been more in the universe – have a genetically unique profile. Aren’t we such special beings?

What makes each individual so special is, scientifically, our genome. And what makes our genome so powerful is the applications our genome has on today’s world. The human genome project was completed decades ago, but it was only until very recently that scientists have discovered a whole new way of approaching medicine through genetics: personalized medicine [1].

Let’s say there are two elementary students in the same class. These two kids have both been struggling with language arts this year. However, one is having trouble with spelling. The other is having trouble with reading. Today’s society would try to help these students develop their language arts skills in exactly the same way; either both would practice reading more books, or both would practice writing stories. But what if we took a more personalized approach to helping these students? What if the kid who struggles with spelling has a diagnostic test that reveals that the student is weak with spelling double vowels (i.e., “oo” vs “ou”), and the other kid’s diagnostic test reveals that this student is struggling with reading words with silent consonants (i.e., “kn”)? Now, the solution becomes much more easier to fix, because we can personalize each student’s solutions to their problems; one student can practice spelling only words with double vowels, while the other can practice studying all words that have silent consonants.

Medicine is not much different. By personalizing medicine and tailoring it to fit each person’s needs, diseases, disorders, and health concerns may be fixed in the cleanest, most effective way. How does this work? By examining and observing exactly what part of each individual body is malfunctioning: the genetics.

Depression, with more than 3 million people affected per year in the US, is a brain disorder that causes feelings of sadness and loss of interest, interfering with and impairing everyday life. According to a study done in 2014, patients with depressive showed genetic modifications that differed from patients without depression [2].

This study, dubbed ‘GSE54566’ and publically available in the  National Center for Biotechnology Information (NCBI) database, examined genetic characteristics that differentiated depressed patients from non-depressed patients. Containing genetic samples from the amygdala, 14 control variable samples and 14 obtained from Major Depressive Disorder (MDD) patients were analyzed. Figure 1 shows the top 250 significantly expressed genes in these patients, and the result is pretty surprising. Almost all of these genes were actively interacting with each other, signifying that one possible alteration of even just one of these genes can heavily affect the functions of these proteins [3].

figure-1

Figure 1: Top 250 Genes found to be significant in study [3]

The findings in further analysis of these genes is even more surprising. Out of the genes that were found to be significant among the samples from the study, one gene stood out in particular: ADCY7. As you can see in figure 2, ADCY7 was directly interacting with 25 other proteins in the amygdala samples [3].

 

figure-2

Figure 2: String Protein Network of ADCY7 and interconnected proteins [3]

Based on the GEO2R analysis, as shown in figure 3, ADCY7 had a positive logFC value of 0.5895, indicating its upregulation in MDD patients [4]. ADCY7 is a gene coding for a protein enzyme with key regulatory roles, including ATP release [5]. The upregulation of ADCY7 in MDD patients and its correlation with ATP suggests that the gene is involved in neural circuit activity; multiple forms of adenylyl cyclase (ADC) is found to exist in the brain, which metabolizes the release of ATP. ATP, in turn, regulates serotonin, dopamine and other neurotransmitters [6]. ADCY7, then, regulates the activity of neurotransmitters in neural circuits throughout the central nervous system. The overexpression of ADCY7 in MDD patients indicates uncontrolled, abnormal activity in neural circuits and the central nervous system, as found in depression.

figure-3

Figure 3: ADCY7 expression in major depressive disorder vs. control sample

We can see that ADCY7 is an important protein necessary for proper nervous system function. Personalizing medicine to reduce the expression of ADCY7 or other genes that are found to be abnormally expressed in depressive disorder patients may potentially lead to prevention of the abnormal neural circuit behavior, providing for a possible solution of depression.

This is just one example of how personalized medicine may work. The possibilities are endless; from not just depression but also from cancer to diabetes to Alzheimer’s, personalized medicine that targets an individual’s own genes may ultimately be the key to a risk-free, healthy future.


References

[1] Human genome project (HGP). The Dictionary of Genomics, Transcriptomics and Proteomics. 2015:1-1. doi:10.1002/9783527678679.dg05804.

[2] Chang LC, Jamain S, Lin CW, Rujescu D et al. Expression data from human brain amygdala. National Center for Biotechnology Information, PLoS One. 2014;9(3):e90980. PMID: 24608543

[3] STRING Protein Network. STRING: Functional Protein Association Networks, http://string-db.com

[4] Gene Expression Omnibus. National Center for Biotechnology Information, U.S. National Library of Medicine, http://www.ncbi.nlm.nih.gov/geo/.

[5] ADCY7 Gene, ADCY7 Protein, ADCY7 Antibody. GeneCards. OMIM: 600385

[6] Verkhratsky A, Krishtal O. Adenosine Triphosphate (ATP) as a Neurotransmitter. Encyclopedia of Neuroscience. 2009:115-123. doi:10.1016/b978-008045046-9.01245-6.

 

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