Blog 2: What is DNA Sequencing?

Did you know that every cell in your body holds a 3-billion-letter instruction manual? As crazy as that sounds, it was only recently that we've developed the tools to actually read and understand what it's telling us. 

The instruction manual I'm talking about is the 3 billion base pairs of deoxyribonucleic acid (DNA) inside each human cell. Each of these base pairs are formed by specific pairings of the 4 nucleotide bases: adenine (A) with thymine (T), and guanine (G) with cytosine (C). Anything from growing your hair to fighting diseases can be accounted for by this code. 

However, even with its importance, trying to read and understand DNA code proved complicated and expensive. Think about it like this, a computer codes using 0s and 1s. The human body codes using A, T, C, and G, which is infinitely more complex. Sophisticated machines, called sequencers were needed to decode the DNA into useful information.

The first sequencers used Sanger Sequencing, which at the time was game-changing, but had some serious limitations.  Only very short sequences of DNA could be read at one time making it time consuming and not cost effective but then came Next Generation Sequencing (NGS).

What is Next Generation Sequencing (NGS)?

NGS is a powerful, high-throughput technology that revolutionized genome sequencing. Instead of reading one piece of DNA at a time, NGS can read millions of fragments simultaneously. Scientifically speaking, this ability, known as massively parallel sequencing, gives scientists the ability to decode entire genomes with much greater speed and efficiency. 

How it works:

1. DNA Fragmentation                                                                                                              The process begins by breaking long strands of DNA into smaller fragments. This makes it easier for the sequencer to read the DNA.

2. Adapter Ligation                                                                                                                 Short, synthetic DNA sequences called adapters are added to the ends of each DNA fragment. These adapters help the fragments attach to the sequencing platform and serve as the starting points for reading the DNA.

3. Amplification                                                                                                                         The adapter-added DNA fragments are then copied many times through Polymerase Chain Reaction (PCR). This process creates groups of identical DNA fragments to help improve the accuracy of the system. 

4. Sequencing
Then we get into the actual reading of the DNA. The instruments used for NGS label the nucleotides (A,T,C, and G) to read one base at a time. 

5. Data Analysis & Assembly                                                                                             Finally, powerful technology takes millions of short sequences and pieces them back together. The result of this puzzle-like creation is a full or partial DNA sequence that scientists can analyze for any answers they need. 

Importance and Implications:

Now that I’ve covered how NGS works, let me tell you why it's important and how it will affect our future. 

NGS opens the doors to solving some of the most complex challenges in science and medicine. For rare diseases, it can be used to uncover the genetic causes of an illness that was previously undiagnosable. Also, it improves agriculture by identifying genes that make crops more resilient and sustainable, which is incredibly important with growing food demands and concerns for global warming. Not to mention, NGS also plays a huge role in tracking infectious diseases, personalizing cancer treatments, and even protecting biodiversity. 

Not to mention, because genome sequencing is so much cheaper than it's been in the past, it's become much more achievable.  

From the graph, back in 2001 it would cost around $100 million to sequence a single human genome. However, through innovations like NGS, this price tag has lowered significantly, costing less than $1000 today. This dramatic drop in cost means that powerful genetic systems are now accessible to hospitals, clinics, and all of healthcare. Its widespread use will lead to faster diagnoses, better treatments for all diseases, and breakthroughs in all fields. 

Anyway, that's all I have for this blog. Just remember that genetic sequencing is the building block of all synthetic biology. All of my future topics will build upon this one.

Thanks!

– Aidan Kincaid