Understanding how DNA tests or Whole Genome Sequencing works is very complex. One of the main hindrances people encounter is understanding the basic terminology used to describe genomic sciences. When a scientist, or medical professional, explains DNA tests and genome sequencing, they often look at how the base pairs Adenine, Thymine, Cytosine, and Guanine align.
So what are these base pairs? In the easiest of terms, they are what form the building blocks of the double helix ladder structure for DNA. This structure is the carrier of all the genetic material that adds up to a living organism.
A base pair is connected by hydrogen bonds that form a coiled ladder shape. This shape in and of itself is of great importance. The double helix provides enough stability for delicate genetic material to translate into DNA within each cell in the body. There are an estimated 3 billion base pairs in each human cell. To understand just how big that is, if you were to unravel all the base pairs in your body, it would be long enough to reach the sun and back close to 70 times. That is why it has taken so long to fully sequence the human genome, simply because it is so big.
When sequencing the genome, the total of all the base pairs in the body, scientists look at the order in which the bases Adenine, Thymine, Cytosine, and Guanine are arranged. Adenine (A), Thymine (T), Cytosine (C), and Guanine (G) each serve their own function but have a strict manner in which they can pair up. Adenine will only pair with Thymine, while Cytosine will only pair with Guanine. Once bonded into base pairs, forming the ladder rungs, nearly all human DNA is identical. It is the 0.01% differentiation of the alignment of the base pairs that make each human different (with the exception of identical multiples).
In the 1890s, German biochemist Albrecht Kossel was the first to isolate and identify ATCG. In 1910, Albrecht’s work in genomics earned him the Noble Prize in Physiology or Medicine. His research led to a further understanding of how ATCG works together to support cellular life, and thus DNA.
Adenine and Thymine are bonded by two hydrogen bonds. Cytosine and Guanine are bonded by three hydrogen bonds. The importance of being able to read the sequence of how these base pairs arrange within a cell can be vital in understanding how cells can become mutated, leading to genetic or environmental diseases.
Cytosine is the most unstable of the four base pairs. When it is arranged next to Thymine, a kink or mutation in DNA can occur. In some situations, this arrangement is inherited from a relative and can lead to genetic cancers such as breast cancer. In other cases, the cell becomes damaged by an outside force, causing Cytosine and Thymine to form a mutation. The damage to the cell can be from environmental stressors like cigarette smoke or other pollutants.
When a patient comes to a doctor complaining of a chronic ailment, sequencing the patient’s genes can help lead to what is causing the ailment. Often the doctor will have clues pointing them in the right direction for diagnoses, such as being the relative of someone with a genetic disorder, or someone who has been exposed to environmental factors like smoke.
In either situation, the doctor now has a starting point on how to search the patient’s cells for the mutations. By collecting a DNA sample, a lab can replicate and magnify the cells in order to sequence the base pairs. Once the base pairs, ATCG, are sequenced, a confirmed diagnosis can be made.
Going even further, scientists can do the same procedure to study cancerous cells and see how they become mutated in the first place. What happens to the arrangement of ATCG in these cells can provide preventive measures as well as treatment options.
It may still be a bit confusing. In a DNA test, the basic genetic markers found in the arrangement of a section of base pairs are studied. For Whole Genome Sequencing, all 3 billion base pairs are sequenced to create a complete data set of an individual person.