DNA: How the Alphabet of Our Genes Spells Out Disease 

(Image Credit: ASHG)

October 18, 2023

Lily Sharkey

11th Grade

Dominican Academy



Discovered in 1869, deoxyribonucleic acid (DNA) is an organic chemical that is the basis of life. Found in all prokaryotic and eukaryotic cells (and even some virus cells), DNA codes for the genetic information that is responsible for the expression of inherited traits. Traits such as hair color, freckles, nose shape, and height are coded for by DNA. DNA is structured as a double-helix polymer, or in other words, two strands of DNA wound around each other. Each strand of DNA is composed of monomer nucleotides (compounds of nitrogenous bases joined with a sugar and a phosphate), which are held together by covalent bonds. The two strands of DNA are connected by hydrogen bonds. During the DNA replication process, the two strands “unzip” into individual strands, with each strand serving as a template for new nitrogenous bases to bond to. The result is two new molecules, each containing one strand of the original DNA. This means that whatever trait is coded for on the original DNA will be perpetually replicated, allowing diseases like cancer to persist and spread throughout the body.

      

What causes these diseases such as cancer? A genetic disorder is caused by a mutation in the DNA sequence that results in the coding of a new trait. Some mutations include the deletion of a section of the genome or a substitution of nitrogenous bases, which can change what trait the gene is coding for. Mutations can be inherited from the parents or be caused during a person’s life by environmental factors. One way to see if a person has a genetic disease is through DNA testing, which analyzes the DNA for mutations or variations in the sequence. Many different kinds of genetic tests are focused on different samples and performed at different stages of life. DNA testing uses a patient sample of blood, skin, hair, or other body tissue to analyze the DNA for any atypicality that may lead to genetic disease. Some methods include FISH, aCGH, and PCR. 

Fluorescence In Situ Hybridization (FISH) is used to find genetic deletions in the genome. It also helps scientists pinpoint where on the chromosome a specific gene is located. To use FISH, a short sequence of single-strand DNA that pairs with a section of the genome is created, called a probe. The probes are then tagged by coloring them with fluorescent dye. Because these probes are single-stranded, they will seek the complementary strand of DNA, thus revealing its location to the researcher. To find deletions, two probes are sent into the genome: one control probe that seeks both chromosomes by using a portion of the genome that is not suspected to be deleted, and another probe that seeks the suspected deleted portions on the chromosome. If only one probe shows up on a chromosome (the control probe), that means that a portion of the chromosome is deleted. 

(Image Credit: CSI Laboratories)

Array Comparative Genomic Hybridization (aCGH) detects chromosomal rearrangements, deletions, and duplications. It compares the chromosomal information of an individual against a group or array of people. aCGH is similar to FISH in that it uses control and test probes to determine whether there are any anomalies. Scientists analyze the deletions and duplications on a chromosome and then compare that data to an array of other patients. If the deletions and duplications are found commonly throughout the array, then they are not irregular. However, if the deletions or duplications are atypical, then it may be the cause of a disease or disorder.

Polymerase Chain Reaction (PCR) is a test that gained renown during the COVID-19 pandemic. It works by utilizing recombinant DNA technology. In many DNA tests, a major issue is being unable to detect early signs of disease because there are not enough pathogens in the sample. PCR takes a small sample of DNA and replicates it using an enzyme called polymerase. If there is an anomaly in the DNA, the amplification of the sample will make it easier to see. Additionally, as many people know from frantic COVID-19 tests, PCR tests are much faster than other DNA tests. It only takes one hour to make a billion copies of DNA.


DNA tests are very helpful for taking the next step in the treatment of disease. But DNA also has a more revolutionary use– it can be used to genetically modify humans and prevent disease. Gene therapy is the introduction of functional DNA into the genome of a patient’s cell to rectify the way it produces proteins. Essentially, gene therapy edits a patient’s genome to instruct it to produce proteins in a different way. Gene therapy utilizes vectors to deliver the genetic material to the DNA of a cell. Vectors are small vehicles that carry the material to the correct cell. Viruses are very effective vectors because they can easily infect cells. Scientists are able to remove the viral genes from the virus and replace them with the genetic material that needs to get into the cell. The virus then carries the material to the cell, where it will be inserted into the genome and begin to produce proteins as they typically should. Gene therapy is undergoing clinical trials and has been approved for limited diseases such as melanoma and spinal muscular atrophy in children under two years. 

Gene therapy is a promising treatment for aggressive diseases such as cancer. Glioblastoma (GBM) is the most prevalent brain tumor in adults. Ineffective drug transfer across the blood-brain barrier (BBB), an immunosuppressive tumor microenvironment (TME), and drug resistance are all obstacles that make treating GBM very difficult. Gene therapy can be used to increase the effectiveness of natural tumor antigens, edit the TME in order to stop immunosuppression caused by glioma, and overcome the BBB to allow drug treatment to penetrate. Another use of gene therapy is to introduce oncolytic viruses using viro-immunotherapy. Oncolytic viruses can kill tumor cells and activate an anti-tumor response.

(Image Credit: genome.gov)

DNA is one of the most fundamental elements of natural existence, and further study is required to discover how scientists can utilize DNA to effectively diagnose diseases and manipulate genomes to create effective one-time treatments, but it is a promising field that is the future of chronic illness diagnosis and treatment.

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