Long Read Genetic Sequencing Gives Insight Into Gorilla Genome

Long read genetic sequencing technology has been applied to the Western Lowland Gorilla, a level of quality now comparable to the human and mouse genomes. The new technique is a combination of Single Molecule, Real Time (SMRT) sequencing technology, assembly tools Falcon and QUIVER and other techniques to produce longer sequence reads. This new and accurate sequenced genome has the potential to give us more insight into human disease and how our ancestors split from the other ape species.

Previous assembly of the gorilla genome was roughly 400,000 broken pieces of short stretches of sequence called "reads." The reads were originally pieced together with assembly technology that left numerous gaps at the sites of large sequence repeats. University of Washington professor of genome sciences and lead researcher Evan Eichler comments that, "Some assemblies can be like Swiss cheese, with a lot of missing biological information in the gaps." Essentially, bioinformatic technology is now advancing to the point of more sophisticated genome sequencing for all species. This research in particular completes the picture of overall genetic comparison among apes.

The new long read genome sequence for the gorilla was assembled from 1,800 fragments as opposed to the previous 400,000 fragmented genome. Average size of the fragments were a reported 800 times larger and approximately 90 percent of the gaps in the original were closed. Scientists found "tens of thousands" of new structural variants of introns and exons and dissimilarities in genes between humans and gorillas that code for: sensory perception, keratin production, insulin regulation, immunity, reproduction and cell signaling. Researchers also found that humans are closer to the gorilla in some ways more than the chimpanzee, for example ear shape and hearing perception.

Overall, longer read sequencing technology gives a greater insight into genetic variation. Genome sequencing being done on gorillas and other animals can contribute to medical research. While the long read sequencing is still extremely expensive ($80,000) further advances in technology and cost reduction is expected to allow the technique to be available in medical diagnosis in years to come.

Above, a zoo gorilla sits and observes his surroundings.

Credit: Alice C. Gray

Thousands of Never-Before-Seen Human Genome Variations Uncovered

     A new genome sequencing process known as Single-Molecule, Real-Time sequencing (SMRT) has been developed and used to discover thousands of genetic variants and close numerous mapping gaps in the human genome. Through this sequencing method, it is possible to determine which genetic mutations are responsible for certain conditions, most of which have yet to be discovered. According to what scientists call the “missing heritability problem”, the genetic cause for only about half of the inherited conditions has been determined. However, the main reason for this problem is the fact that the standard methods of genome sequencing are not as precise as SMRT. These methods analyze millions segments of DNA that are approximately 100 bases long and use this information to create a genome map. By looking for the replacement of a single nucleotide base, known as a single-nucleotide polymorphism or SNP, genetic variations in the human genome can be identified.

     Due to the limitations in technology, DNA sequences of 5,000 bases or more were unable to be sequenced using the standard methods of genome sequencing. However, through the use of SMRT, DNA sequences of more than 5,000 base pairs can be analyzed and sequenced. Therefore, through the use of this new sequencing technology, much more detailed genome maps can be created. A study was conducted upon a hydatidiform mole, which is when an egg that lacks the DNA of the mother is fertilized by a sperm and only carries one copy of each gene. Due to this, the search for genetic variation becomes easier when analyzing the hydatidiform genome. It was concluded that 26,079 segments differed from a reference human genome when using the SMRT method, 22,000 of which had never been reported before. 

     I thought this article was interesting because it shows how quickly genome research is advancing and how more detailed maps of the human genome can be used to determine the causes of hereditary conditions. In the future it may be possible to sequence a patient’s genome at the doctor’s office and tell him that the presence of particular SNPs or variations may make him more susceptible to a specific disease. Advances like these will make it easier to not only cure diseases and conditions that occur in the human body, but also prevent them before they arise.

Source: Thousands of Never-Before-Seen Human Genome Variations Uncovered

New DNA Sequencing Method

     Genetics has come a long way in the past few years, but a new discovery by Evan Eichler, a professor of genome sciences at the University of Washington, and his colleagues, have discovered many new genetic variants by using new genome sequencing technology. The technique is called single-molecule, real time DNA sequencing (SMRT). Researchers may now be able to identify the genes and genetic mutations in some portions of genome mapping that have eluded scientists. Ultimately, this advancement in genetic mapping may explain the underlying genetic causes of some diseases and conditions.

Example of SMRT sequencing for 5-hmC gene.

     Standard genome sequencing methods are able to map about half of the genome precisely enough to know the genes related to about half of all known heritable diseases. The current way of mapping DNA involves cutting out small snippets of the DNA sequence and overlapping the segments and analyzing the sequence to map the genome. Even though this methods is very accurate and scientists have been able to identify many variation this way, they have been unable to use this method to detect variation that are 50-5,000 bases in length, leaving this part of the genome unknown to everyone.

      SMRT technology allowed Eichler and his colleagues to sequence and read DNA segments that are longer than 5,000 bases, something that cannot be done with standard gene sequencing technology. This technique allows researcher to create a much higher resolution and more well-structured map which leads to being able to detect more structure variation in base pairs. The researchers tested their new approach by doing the genome sequence of a mole. They were able to identify and sequence 26,079 segments that were different from the human genome and 22,000 of these variants had not been reported before. These results show that there is a lot of variation in the human genome that researchers can currently be missing. They were also able to identify 160 genome gaps that were not known before, close 50 gaps, and narrowed 40 others.

      I think that this is a very big advancement in DNA sequencing that will prove be extremely useful in the years to come. Being to to be more specific and uncover hidden genetic variants that can help identify the causes of certain diseases will be extremely helpful to the public, researchers, and doctors. The identification of more genetic variants will help us achieve and even better understanding of the human genome and will have very important, valuable implications for the future of disease diagnosis and prevention.

Original Article :New technology closes many human genome mapping gaps that have long resisted sequencing