MAY 06, 2020 11:58 AM PDT

Advances in Genome Sequencing Technology

WRITTEN BY: Carmen Leitch

The human genome project, which aimed to sequence the human genome in its entirety, was declared complete in 2003, and was celebrated as a major milestone for science. Genetic sequencing tools had gotten more sophisticated, efficient, and inexpensive, which helped make the achievement possible. But behind the scenes, there were some problems. The human genome contains many repetitive regions that don't code for genes and can be extremely challenging to sequence, so there were some gaps. Most of the work was also performed using a genomic sample from one individual, so it was an incomplete picture. The 1000 Genomes Project, completed in 2012, sequenced 1,092 genomes so that we would learn more about variation in the human genome. But that is still an underrepresentation and the data may not be included in reference sequences, potentially because of quality issues.

The nine-day assembly process, broken down by length of time for each step. / Credit: UC Santa Cruz Genomics Institute

Last year, the National Institute of Health announced an initiative to address these problems. Called the “human pangenome reference,” the project aims to sequence the entire genomes of 350 individuals.

"One human genome cannot represent all of humanity. The human pangenome reference will be a key step forward for biomedical research and personalized medicine. Not only will we have 350 genomes representing human diversity, they will be vastly higher quality than previous genome sequences," said David Haussler, professor of biomolecular engineering at UC Santa Cruz and director of the UC Santa Cruz Genomics Institute.

Nobel Laureate Frederick Sanger and colleagues created Sanger sequencing for reading a genetic sequence in 1977. After a DNA sequence has been amplified, each base is labeled and then read from one end. In 1995, pairwise end sequencing was shown to be useful for sequencing whole genomes, and the technology was used to sequence the human genome. A library of fragments is prepared from a genome, and the fragments are read. Computational tools assemble the fragments into longer sequences. Nanopore sequencing, which pushes a molecule through a really tiny pore, detecting the base as it moves through, was created as one of the 'third-generation' sequencing technologies.

With an intensive effort, including 150,000 hours of commuting time, researchers at UC Santa Cruz researchers were able to use nanopore technology for long-read human genome sequencing. Around a year later, the cost was brought down significantly, and the results could were then obtained within about a week. "We sequenced eleven human genomes in nine days, which was unprecedented at the time," said UC Santa Cruz Research Scientist Miten Jain.

It's now been taken even further; an algorithm has been designed that can use long-read sequencing data to assemble as complete human genome in around six hours, and four about $70.

The researchers said they hope their assembler will increase the pace of genomics research and open opportunities. This includes enabling pangenome research to represent the true scale of human diversity, a decidedly more practical pursuit.

"Our new assembler was designed to be cheap and quick, with the goal to be on the cloud," said UC Santa Cruz's Benedict Paten. "It gives us the power to scale nanopore sequencing. Now, I'm confident that we'll be easily assembling hundreds of de novo genomes in the next couple of years."

Sources: AAAS/Eurekalert! via University of California - Santa Cruz, Nature Biotechnology

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
FEB 27, 2021
Cell & Molecular Biology
It's Now Possible to Measure tRNA Levels in Cells
FEB 27, 2021
It's Now Possible to Measure tRNA Levels in Cells
There are different kinds of ribonucleic acids that play essential roles in many aspects of molecular biology, including ...
MAR 08, 2021
Microbiology
Researchers Discover a New Symbiosis
MAR 08, 2021
Researchers Discover a New Symbiosis
A new type of endosymbiosis has been discovered; the organisms are shown in this image by S. Ahmerkamp, Max Planck Insti ...
MAR 15, 2021
Cell & Molecular Biology
When Sample Temperature Matters: How to Keep Your Cool in the Lab
MAR 15, 2021
When Sample Temperature Matters: How to Keep Your Cool in the Lab
Temperature control is critical to many molecular and cellular experiments, but managing sample temperature requires eit ...
MAR 15, 2021
Cell & Molecular Biology
Newly-ID'ed Organelle May Play a Role in Cancer Metastasis
MAR 15, 2021
Newly-ID'ed Organelle May Play a Role in Cancer Metastasis
Cells are packed full of organelles and molecules like proteins floating in a liquid known as cytoplasm. In recent years ...
APR 14, 2021
Genetics & Genomics
The Smell of Home: Insights Into Scent Imprinting
APR 14, 2021
The Smell of Home: Insights Into Scent Imprinting
Right after birth, young animals go through a period in which they 'imprint,' or fixate on sights and smells that they'r ...
MAY 04, 2021
Genetics & Genomics
The Weird World of Flatfish
MAY 04, 2021
The Weird World of Flatfish
Many of us have wondered how fish like sole and flounder ended up with two eyes on one side of their heads, including sc ...
Loading Comments...