Did you know that we humans are 99.9 percent genetically identical? Crazy right? Our DNA plays an important role in determining our appearance, our traits, and our health. Sequence changes in individual genes can determine if we have freckles, can digest lactose, have wet or dry earwax, are red-green colour blind, or are likely to have blue eyes.
Individual genes can help determine if we will develop sickle cell anemia, cystic fibrosis, or Huntington's disease. Multiple genes(segments of DNA) act together with our environment to determine our hair, height, skin colour, weight, blood pressure, risk of developing type 2 diabetes, depression, cancer, and more.
DNA
The smallest genetic unit is a single nucleotide of deoxyribonucleic acid. A DNA nucleotide is composed of sugar, a phosphate group, and one of 4 nitrogenous bases. These bases are Adenine, Thymine, Guanine, and Cytosine.
The bases (ACGT) determine the DNA sequence, while the sugar and phosphate groups serve as the structural backbone of DNA, allowing nucleotides to combine into a long single strand of DNA
The chemical properties of DNA allow bonds to form between the bases, in order to create a double strand. (2 hydrogen bonds pair A and T and 3 hydrogen bonds pair G and T)
Though different types of human cells can be very different in appearance and function they contain the same genome, which consists of about 3 gigabases or 3 billion base pairs of DNA. All the DNA in a cell would be 2m in length if stretched out. In fact, the total length of all the DNA strands in the human body is equal to 6000 times the distance between the moon and the earth.
DNA is first coiled into a canonical helix structure and then wrapped around histone proteins to form a DNA protein structure called a nucleosome. Nucleosomes can be further wound and collide together to create a compact structure that fits into the nucleus.
During cell division, the DNA is organized into tightly wound chromosomes. There are 23 chromosome pairs in total half of the chromosomes from your mom and the other half from your dad. Each new cell carries an exact copy of DNA. There are approximately 20,000 genes which although only correspond to less than 2 percent of all genomic DNA encode all the proteins necessary to build and run a human cell.
What is your genome?
The entire collection of genetic data, or DNA (deoxyribonucleic acid), that makes up a human being’s genetic code is referred to as the human genome. It includes every guide required to construct and sustain a human body. It's the genetic blueprint for a human being.
And your genome is very powerful, it plays a fundamental role in your development and function. Here are your genome's primary roles:
- Genetic blueprint: Your genome encodes all the information necessary for the development and functioning of all your cells, tissues, and organs
- Protein Synthesis: Genes within your genome code for specific proteins. Your proteins are molecules that carry out a wide variety of conditions in the body. For example, they carry out enzymes that catalyze biochemical reactions, and proteins also support cells and determine a cell's function and reaction.
- Genes/Inheritance: Your genome is the basis for the inheritance of traits from one generation to the next. Genetic information is passed on from your parents through the transmission of DNA
- Variation/Diversity: Your genome is responsible for your genetic diversity. These genetic variations include single nucleotide polymorphisms and structural variations that contribute to differences in traits, susceptibility to diseases, and more.
- Regulation: Your genome contains regulatory components that manage the on/off timing and location of genes. These components are essential for the expression of genes and the growth of intricate biological processes.
- Environmental Responses: Your body and genome interact with environmental factors that can influence your health and susceptibility to diseases.
- Evolution: Human evolution has been influenced by alterations to the human genome over time. Modern humans are a result of natural selection favouring genetic variants that improve survival and reproduction.
- Medicine: The development of tailored medicines and advancements in medical genetics have been made possible by our growing understanding of the human genome. Utilizing genomic data, personalized medicine adapts treatments to each patient's unique genetic profile.
- Research: The examination of the human genome continues to reveal new information about human biology, the causes of disease, and prospective treatment targets. It is a crucial topic for genetics and genomics research.
As you see your genome is very important, I mean it does encode the DNA for your whole body! And it has many more purposes than just that. But right now, we are going to focus on how the study of your genome can improve pharmaceutical drugs and save so many lives.
Pharmaceuticals
In the US alone pharmaceuticals is a 1.48 trillion dollar industry. Yet there are so many gaps and problems. More than 50 percent of adults use at least one prescription drug prescribed by their doctor. Yet due to the negative side effects over 100,000 people in the US alone die because of prescription drugs.
And now you may be asking, well what does your genome have to do with this problem? Well, we’re getting there, firstly let us understand how your genome interacts with the medicine you take, and then I’ll explain how this has the potential to save millions of lives.
How your genome determines how your body interacts with medicine
In order to understand the relationship between your genome and prescription medicine we are going to go down a little journey called protein synthesis.
Your body manufactures proteins through a very intricate process. Every cell has a genome and the DNA in your genome works alongside tRNA and mRNA to encode for your proteins.
Once protein synthesis begins (the making of proteins). A gene then gets activated(a section of DNA). Once this section of DNA is activated the DNA starts to open up or “unzip”. Now that this DNA strand is open the nucleotides are now free bases.
The RNA polymerase now enters the picture. During the transcription process, this enzyme is in charge of copying the DNA sequence into an RNA sequence.
The RNA polymerase is attached to the open DNA, this enzyme moves along the DNA. As it moves along the DNA a strand of messenger RNA (mRNA) is made. The role of this mRNA is to pair with DNA so it can transport protein information.
Once this mRNA strand is made it leaves the nucleus where the DNA is and then travels to the cytoplasm. In the cytoplasm is located the ribosome.
Ribosomes are composed of two subunits, a small subunit and a large subunit, each of which is made up of ribosomal RNA and protein molecules. These subunits come together when the ribosome is actively engaged in protein synthesis and dissociate when the process is complete.
In the ribosome is tRNA which links the mRNA to the amino acids, which becomes a polypeptide chain, and then a protein.
So so far what basically happened is that you DNA in your genome has been translated into a protein. Now this protein is where the magic happens.
These proteins give instructions to your cells, determine their functions, and how they interact with your medicine.
For example, the ABCA3 gene is usually found in chromosome 16. Once this segment of DNA is activated and the protein is made, the protein determines the functions of your cells and causes your body to be more resistant to drugs.
So now that you know what your genome is and how it can encode for proteins, and interact with the medicine you take. How can we use this information to improve our prescription drugs?
Pharmacogenomics
The answer to this is pharmacogenomics, pharmacogenomics is the study of your genome(genes) and their effects on the medicine you take. Pharmacogenomics allows doctors to personalize their patients' treatments to their genes/genome.
To explain simply what this does, I am going to use a clothing metaphor. Imagine if every day everyone wore the same sized clothes. No matter if you were 3ft or 7ft, 600 pounds or 100 pounds. That would be bizarre right? Yeah, it's crazy because all these people are so different. Well so is our genome, but yet when we go to the doctor's office we get given the same prescriptions.
So what aspects of your genome does pharmacogenomics study? By studying your genome pharmacogenomics can understand and predict everything that happens when u take medicine. From the moment it enters your body to the moment it leaves it. Pharmacogenomics encompasses two main factors, pharmacokinetics and pharmacodynamics.
Pharmacokinetics is the study of a drug’s movement and distribution inside the body. This procedure begins by entering the body, moving to the bloodstream, and then distributing to the desired location. The drug must subsequently be digested and broken down (through metabolism), and then the body must expel it (by excursion).
The most challenging aspect of pharmacogenetics is pharmacodynamics. due to the fact that it examines every aspect of the drug’s effects on the patient’s body and its efficacy. This comprises receptor binding and its subsequent effects, as well as molecular, physiological, metabolic, and other effects.
Direct Example Of Your Genes And A Protein
Going back to the ABCA3 gene and protein, if one of the genes in your genome encoded for this protein, the whole course of a prescription could be changed. The DNA and mRNA of these genes would look like this:
A simple gene in your genome that looks similar to this creates a protein that causes great multi-drug resistance. An example of this is chemotherapy. In cancer tumours, this protein is found and has been seen to make the treatment process longer. In one study the median expression of the ABCA3 was three times higher in patients who had failed to achieve remission.
What does this entail, though, if a patient arrives with a cold and is given cold medicine? The dosage of this cold medication is now determined by the patient’s weight and age. The issue is that the physician is unaware of the patient’s genes and the precise dosage of medication that their body actually requires. More particularly, it’s unclear how much of the medication will truly work to treat the cold. Since the patient’s genes have not been examined, it is likely that the patient may have high amounts of ABCA3, necessitating greater dosages.
A patient with high ABCA3 levels will exhibit greater medication resistance. As a result, less medication can enter the vascular system. Drugs are metabolized differently by the liver, and as a result, less of the medication will reach the target region. The transporter and bonding process will also be impacted after it reaches the target spot.
What Does This Mean?
So what does this all mean? Let's recap what we’ve been over:
- Every cell has a genome that contains all your genetic data/DNA
- This DNA encodes for proteins
- Your proteins determine your cell's functions and reactions
- These proteins and cells interact with the medicine you take
- Pharmacogenomics studies your DNA and these interactions
If we implement pharmacogenomic studies on your DNA/genome we can drastically improve the world of prescription drugs.
What Is Stopping Us?
So if this testing is possible and can improve so many lives why haven't we implemented it yet? There are two main factors stopping this from happening.
The first is GINA. The GINA law was enacted on May 21st, 2008. Congressmen passed the Genetic Information Nondiscrimination Act (GINA) to shield Americans from genetic prejudice. This aims to stop genetic prejudice between patients and medical professionals. It states that it is unlawful to make patients submit to genetic testing. This forbids insurance companies from modifying premiums, denying coverage, or placing limits based on preexisting conditions. Some scientists are raising moral concerns with pharmacogenomics because of this law and its intended use.
The second is education. Medicine can be so advanced and the technology can be there but not all doctors know how to implement it. If all doctors who gave out prescriptions knew about pharmacogenomics and genome testing making this more mainstream would be so much easier.
Imagine that now instead of just getting your prescribed medication to be personalized to your weight, height, and symptoms. It is now personalized to your genome, the thing that makes you you.
Companies working on this
- Genelex is a new and evolving pharmacogenomic testing company. “YouScript,” a pharmacogenomic software platform, is one of Genelex’s well-known products. By examining a patient’s genetic data and detecting potential interactions and dangers related to particular medications, YouScript hopes to help medical professionals make better judgments about administering pharmaceuticals. Based on the genetic information of the patient, the software can suggest substitute medications or different dosages. The tests and software developed by Genelex are intended to increase the effectiveness and safety of medications, lessen negative drug reactions, and improve patient care in general. When many medications are provided and there are worries about drug-drug interactions or individual response variability, healthcare providers frequently employ their services to customize treatment plans for patients.
- The biotechnology firm Pacific Biosciences, also known as PacBio, is renowned for its cutting-edge DNA sequencing technology. In particular, PacBio is a pioneer in single-molecule, real-time (SMRT) sequencing, a technique for accurately and thoroughly decoding DNA’s genetic code. Third-generation sequencing is another name for this technology.
- A pioneering organization in the fields of customized medicine and genetics is the Mayo Clinic Center for Individualized Medicine. It is a component of the Mayo Clinic, a prestigious American medical facility noted for its dedication to patient care, research, and education. The Mayo Clinic’s Center for Individualized Medicine is dedicated to modifying patient care to take into account each person’s particular genetic and molecular traits. The center carries out pharmacogenomics research, which entails figuring out how a person’s genetic makeup impacts how they react to pharmaceuticals. This information can assist medical professionals in selecting the most efficient and secure drugs for their patients.
What's Next?
Genetic testing is difficult and not as convenient as people may think. So, my next article will be about how we can create a saliva or urine testing stick that is made to test for one specific gene that can impact prescription medicine. If you are interested in this be sure to follow my medium to read the article once it's out!
