Nanopore Sequencing: Expediting Your Genome

Written by Christina Young and Edited by Amy Huynh

With the popularity of consumer genomic testing, which is the analysis of characteristic sequences in an individual’s DNA that correspond to high probabilities of developing specific diseases, genes and the roles of DNA are becoming more known to the general public. Although it is not quite a topic to bring up casually over dinner, the idea that DNA is made of four nitrogenous bases —which code for specific genes, traits and characteristics of each individual—is becoming more widespread and understood. Currently, popular genomic sequencing includes Illumina Sequencing and Sanger Sequencing. Illumina Sequencing is the creation of a new strand of DNA by the addition of marked nitrogenous bases (called nucleotides) to create a complementary strand for a specific area of interest, while Sanger Sequencing is the addition of special terminating DNA bases to currently replicating DNA strands.

Both methods then computationally analyze and rearrange the DNA sequences in order, based on the sequence similarity between each small section of the DNA. Researchers spend many hours tracking the bases and their relative locations to each other before a consensus on the actual sequence is reached, even when the relative location of a gene is known. For more extensive mapping and analysis of the entire sequence of DNA in a single person, millions of dollars and thousands of hours would be added to the already large figures, and researchers do not have the time and resources to do so for every person who wants to know exactly what their DNA encodes. Their efforts and methods would go into a recreation of the Human Genome Project, an international expenditure that took 13 years and $2.7 billion to map the full genome, or entire DNA sequence, in a human being [1]. There is no practicality in recreating the venture, especially not when the renewed interest in genetic information is pushing DNA sequencing and testing to become more commonplace and, in necessity, be done at a quicker pace.

On the other hand, nanopore sequencing is a novel genomic sequencing technique that has recently risen to fame in the field of genetics. The eventual goal of geneticists is to systematically sequence an entire genome in less than 24 hours, costing only about $1000; nanopore sequencing is well on its way to reaching that objective. As one of the many systems of third-generation DNA sequencing, nanopore sequencing has the potential to further the next age of genetic research. Currently taking about 48* hours (DNA strand length-dependent), and costing thousands of dollars, nanopore sequencing is a faster and less expensive method of reading a DNA sequence [2]. Utilizing the presence of nanopores, which are holes made in the pore-forming protein α-haemolysin, researchers have created a system that runs a single strand of DNA or RNA through the pore to read it based on the fluctuations in the electrical charge that initiate the movement of DNA or RNA through the protein’s pore [3,4]. Zipping through the pore-like a string running through a bead, the α-haemolysin protein recognizes the signature electrical signals given off by each nucleotide. When analyzed by computers, the electrical signals translate to the particular sequence of bases that ran through the nanopore. As of November 2018, nanopore sequencing has only been used in general trials and testing to determine its accuracy and viability as the next generation of sequencing. In its most recent trial, it is known for having read a total of 2.3 million bases in a study conducted by a research team from Nottingham University, which is the longest sequence of genetic information obtained in a single run [5].

In the short-term, this may not mean much for general medicine, but for new generations of people and the future of tracing age-old diseases over time, this may be a step towards developing improvements of existing methods of preventative care. At the moment, genomic sequencing is the most useful for those associated with the field of genetic counselling, in which the tracking of specific genetic codes is fundamental to the life and death of individual patients and their families. As a practice that looks at the probabilities of getting an inherited disease based on whether or not specific mutated genes are in an individual’s’ DNA, genetic counselors work closely with patients who are stressfully wondering if they have passed down or inherited a “bad” gene that could lead to everything from a debilitating illness, to higher risks of cancer, to costly medical procedures, and to a painful death in the near future. In some cases, patients may wait years, months, or even just weeks to get the results of whether or not those “bad” genes are present, such as in the case of prenatal testing for late-term fetus mortality and the effect on the mother’s probability of survival [6]. Nanopore sequencing can expedite the process, allowing concerned new parents and individuals to receive their results faster and have more time to weigh their options on how to proceed next.

* Sequencing and processing took about 48 hours (2 days) to complete, whereas the raw sequencing was done in about three and a half hours.

References:

6. “Making Sense of Your Genes: A Guide to Genetic Counselling: Prenatal Genetic Counseling.” National Society of Genetic Counselors; Genetic Alliance, NCBI, 2008, https://www.ncbi.nlm.nih.gov/books/NBK115507/

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