An Everyday DNA blog article
Written by: Sarah Sharman, PhD
Illustrated by: Cathleen Shaw
Summer is in full swing, and what better way to beat the heat than with a delicious scoop of ice cream? From classic vanilla to rocky road, there’s a flavor for everyone. And just like ice cream, the world of genetic sequencing offers a delightful array of “flavors,” each with its own unique characteristics and applications.
In the world of DNA, understanding these different “flavors” of sequencing is key to unlocking new insights into human health, agriculture, and even the environment around us. So grab your favorite cone, and let’s dig into the many methods of genetic discovery.
The Original Scoop: Sanger Sequencing
Not too long ago, genetic testing felt like something out of a sci-fi movie. Sequencing an entire human genome was a monumental task, taking years and costing billions of dollars. The groundbreaking technique that started it all was Sanger sequencing, often called the “chain-termination method.”
Think of Sanger sequencing as the classic vanilla of the genetic world. It was the foundational method that paved the way for everything that came after. Developed by Frederick Sanger in the 1970s, this method allowed scientists to determine the precise order of nucleotides (A, T, C, and G) in a DNA strand. While it was revolutionary for its time, it was a relatively slow and labor-intensive process, best suited for sequencing shorter DNA fragments. But every great innovation has to start somewhere, and Sanger sequencing was the essential first step.
Even with newer technologies, Sanger sequencing remains highly relevant for specific tasks due to its high accuracy. Today, scientists use it to confirm critical findings from next-generation sequencing, especially in clinical diagnostics. It’s also used to diagnose conditions caused by mutations in single, known genes, like cystic fibrosis and BRCA1-related breast cancer, and to identify specific bacteria and fungi in research and clinical settings.
The Next-Gen Swirl: High-Throughput Sequencing
As our understanding of genetics grew, so did the need for faster, more efficient sequencing methods. Enter the next-generation sequencing (NGS) technologies. Imagine trying to read a massive library one book at a time versus having thousands of people reading different books all at once. The power of NGS allows millions of DNA fragments to be sequenced simultaneously.
This was a game-changer for the genetics community. These advancements drastically reduced the time and cost of sequencing, making it possible to sequence entire genomes in days, not years, and for thousands, not billions, of dollars.
NGS has truly revolutionized biological sciences and medicine, enabling a broad, unbiased approach to genetic analysis. With NGS, scientists can sequence an individual’s entire genome to diagnose rare genetic disorders, identify predisposition to certain diseases, and tailor treatments based on a person’s unique genetic makeup. In agriculture, NGS helps identify desirable traits in crops and livestock, leading to improved yield, disease resistance, and more sustainable farming practices.
The Specialized Scoops: Targeted Sequencing and Exome Sequencing
While whole-genome sequencing (WGS) gives us the entire genetic blueprint, sometimes we’re only interested in specific parts of the genome, or we want a more focused look. This is where more specialized sequencing comes into play.
Targeted Sequencing: Sometimes, scientists only need to look at specific genes or regions of interest. This is like choosing a specific flavor swirl in your ice cream; you know exactly what you want. Targeted sequencing allows researchers and clinicians to focus their efforts and resources on genes known to be associated with particular diseases or traits. It’s more cost-effective and faster than sequencing an entire genome when only a few genes are relevant.
For example, sequencing panels of genes known to be mutated in various cancers helps oncologists choose the most effective targeted therapies for patients. It also identifies genetic variations that influence how individuals respond to certain drugs, allowing for personalized medication dosages.
Exome Sequencing: The exome is the protein-coding portion of our genome, making up about one percent of our entire DNA. Despite its small size, the exome contains the vast majority of disease-causing mutations. Exome sequencing is a highly efficient way to identify genetic variants that could be responsible for Mendelian diseases or contribute to complex conditions. It offers a powerful balance between the comprehensiveness of whole-genome sequencing and the focus of targeted sequencing.
Exome sequencing is a primary tool for diagnosing rare genetic disorders, especially in children with undiagnosed conditions. It often uncovers the genetic cause after years of searching. It’s also used to identify rare genetic variants that contribute to the risk of complex disorders like autism or neurological conditions.
The Future Forecast: Long-Read Sequencing and Beyond
Just when you think you’ve tried all the flavors, new and exciting options emerge. The world of genetic sequencing is constantly evolving, with new technologies promising even greater insights.
While NGS is excellent for short pieces of DNA, sometimes we need to see longer stretches of DNA to resolve complex genomic regions, understand structural variations, or accurately assemble genomes. Long-read sequencing technologies, like those from Pacific Biosciences (PacBio) and Oxford Nanopore Technologies, give us a much more extensive, continuous view of the DNA. These technologies are crucial for understanding highly repetitive regions of the genome and for de novo genome assembly (building a genome from scratch).
Long-read sequencing is ideal for sequencing highly repetitive regions of the genome that are challenging for short-read technologies, helping to complete human reference genomes. It can more accurately identify large-scale genomic changes like insertions, deletions, inversions, and translocations, which can be implicated in various diseases, including some cancers and developmental disorders.
The constant evolution of genetic sequencing is what drives much of the work at the HudsonAlpha Institute for Biotechnology. Our scientists are at the forefront of developing new sequencing technologies and applying them to unravel the complexities of human health, plant biology, and more, pushing the boundaries of what’s possible.
