Highly Accurate Long-Read Sequencing of Human Genomes Leads to Discovery of Disease-Causing Variants
June 13 2019 - 7:30AM
While DNA sequencing tools have been useful for determining the
genetic cause of many diseases, there remain a large number that
are left unexplained. Recently, scientists have adopted Single
Molecule, Real-Time (SMRT®) Sequencing from Pacific Biosciences of
California, Inc. (Nasdaq:PACB), a leading provider of high-quality
sequencing of genomes, transcriptomes and epigenomes, to study
previously unsolved diseases. Many high-impact research
publications report expanded variant detection in human genomes,
leading to discovery of disease-causing variants and genes
underlying rare and Mendelian disorders.
In a Nature Communications publication, scientists report that
most structural variants (SVs) and large indels are undetected in
today’s human genetic studies, which likely accounts for some
of the missing heritability of genetic disease1. Meanwhile, several
studies have demonstrated that these missing variants can be
discovered routinely using highly accurate long reads (HiFi reads)
generated by the PacBio® Sequel II® System2,3. A review article
from scientists at Radboud University Medical Center summarizes
many of these findings, including genetic discovery results for
ALS, Huntington’s disease, Parkinsonism, epilepsy, ataxias,
myotonic dystrophy, and Fragile X disorders4.
For example, scientists in Japan turned to SMRT Sequencing to
explain a familial form of epilepsy that had not been solved with
whole exome sequencing. PacBio whole genome sequencing data allowed
the team to detect more than 17,000 SVs and quickly identify the
12.4 kb deletion responsible for the family’s condition5. The
team determined that “long-read sequencing ensures unbiased
coverage even in GC-rich repetitive sequences, which enables the
identification of previously unidentified pathogenic SVs.”
“Far too many genetic diseases have gone unsolved in the genomic
era, and it’s becoming clear that some of the answers were simply
not conducive to detection with previous technologies,” said Jonas
Korlach, Chief Scientific Officer of Pacific Biosciences. “It’s
been tremendously gratifying to see the flurry of recent
publications reporting the discovery of underlying causes for some
of these diseases through the use of SMRT Sequencing systems.”
Additional studies describing novel disease-causing variant
detection with SMRT Sequencing will be presented at the European
Society of Human Genetics (ESHG) 2019 Annual Meeting, taking place
June 15-18 in Gothenburg, Sweden. To learn more, please visit
PacBio in ESHG booth #560 or download a flyer with a list of
featured presentations at:
https://www.pacb.com/wp-content/uploads/2019-ESHG-Program-Flyer.pdf.
References
- Chaisson, M. J. P., et al. (2019) Multi-platform discovery of
haplotype-resolved structural variation in human genomes. Nature
Communications, 10(1), 1784.
- Wenger, A. M., et al. (2019) Highly-accurate long-read
sequencing improves variant detection and assembly of a human
genome. bioRxiv, doi:10.1101/519025.
- Vollger, M. R., et al. (2019) Improved assembly and variant
detection of a haploid human genome using single-molecule,
high-fidelity long reads. bioRxiv, doi:10.1101/635037.
- Mantere, T., et al. (2019) Long-read sequencing emerging in
medical genetics. Frontiers in Genetics, 10, 426.
- Mizuguchi, T., et al. (2019) A 12-kb structural variation in
progressive myoclonic epilepsy was newly identified by long-read
whole-genome sequencing. Journal of Human Genetics, 64,
359–368.
About Pacific Biosciences
Pacific Biosciences of California, Inc. (NASDAQ:PACB)
offers sequencing systems to help scientists resolve genetically
complex problems. Based on its novel Single Molecule, Real-Time
(SMRT®) technology, Pacific Biosciences’ products enable: de
novo genome assembly to finish genomes in order to more fully
identify, annotate and decipher genomic structures; full-length
transcript analysis to improve annotations in reference genomes,
characterize alternatively spliced isoforms in important gene
families, and find novel genes; targeted sequencing to more
comprehensively characterize genetic variations; and real-time
kinetic information for epigenome characterization. Pacific
Biosciences’ technology provides high accuracy, ultra-long reads,
uniform coverage, and the ability to simultaneously detect
epigenetic changes. PacBio® sequencing systems, including
consumables and software, provide a simple, fast, end-to-end
workflow for SMRT Sequencing. More information is
available at www.pacb.com.
Forward-Looking Statements
All statements in this press release that are not historical are
forward-looking statements, including, among other things,
statements relating to the attributes of the Sequel II System, the
future availability, uses, accuracy, quality or performance of, or
benefits of using, products or technologies, the suitability or
utility of methods, products or technologies for particular
applications, studies or projects, the importance of long-read
sequencing data, the expected benefits of sequencing projects, and
other future events. You should not place undue reliance on
forward-looking statements because they involve known and unknown
risks, uncertainties, changes in circumstances and other factors
that are, in some cases, beyond Pacific Biosciences’ control and
could cause actual results to differ materially from the
information expressed or implied by forward-looking statements made
in this press release. Factors that could materially affect actual
results can be found in Pacific Biosciences’ most recent filings
with the Securities and Exchange Commission, including Pacific
Biosciences’ most recent reports on Forms 8-K, 10-K and 10-Q, and
include those listed under the caption “Risk Factors.”
Pacific Biosciences undertakes no obligation to revise or update
information in this press release to reflect events or
circumstances in the future, even if new information becomes
available.
Contacts
Media: Nicole Litchfield415.793.6468nicole@bioscribe.com
Investors:Trevin Rard650.521.8450ir@pacificbiosciences.com
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