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Pacific Biosciences

Researchers Use PacBio Sequencing to Create More Complete Human Genome Reference and Discover New Forms of Structural Variation; Paper Published in Nature

Monday, November 10, 2014

MENLO PARK, Calif., Nov. 10, 2014 (GLOBE NEWSWIRE) — Pacific Biosciences of California, Inc., (Nasdaq:PACB) provider of the PacBio® RS II Sequencing System, announced that a paper published online today in Nature1 entitled “Resolving the complexity of the human genome using single-molecule sequencing” demonstrates how researchers used Single Molecule, Real-Time (SMRT®) Sequencing technology to identify and resolve missing or misassembled regions of the human genome and to access more complex forms of variation not covered by other sequencing technologies.

Despite extensive efforts in human genome sequencing, more than 160 gaps remain in the human genome reference, and aspects of the structural architecture of human genomes are poorly understood due to limitations of the Sanger and short-read technologies. Researchers at the University of Washington led by Dr. Evan Eichler, Professor of Genome Sciences, collaborating with scientists from the University of Bari Aldo Moro, the University of Pittsburgh, and Pacific Biosciences used SMRT Sequencing data from a human genome cell line that is designated as a target for a ‘platinum genome’ reference assembly to close or extend 55% of the remaining gaps in the human GRCh37 reference genome. The team also resolved at the base-pair level the complete sequence of more than 26,000 structural variants-75% of which have not been previously reported—and discovered and validated other categories of complex variation that have been difficult to assess.

“The characteristics of the data produced by SMRT Sequencing technology differ significantly from other sequencing platforms,” said Dr. Eichler. “With read lengths up to two orders of magnitude longer than second-generation sequencing technologies, we achieved high-confidence mapping across a greater percentage of the genome as well as accurate reconstruction of more complex genetic variation. More comprehensive access to human genetic variation is likely key to understanding disease and disease susceptibility.”

Dr. Eichler’s laboratory has also been using SMRT Sequencing to interrogate specific regions of human and chimpanzee genomes associated with rapid evolution and certain diseases. Xander Nuttle, a graduate student of Dr. Eichler, recently reported at the American Society of Human Genetics annual meeting on their work to resolve regions that are deleted, duplicated, or repeated in some humans and are associated with predisposition to one of the most common causes of autism. Critical to their discoveries was the use of the PacBio RS II Sequencing System, which allowed the team to accurately sequence and assemble these complex stretches of the human genome.

This paper joins other recent publications that highlight the power of SMRT Sequencing to elucidate the complex structure of human genomes and gene products, and their importance for understanding disease. A team of scientists from Brown University and the Icahn School of Medicine at Mt. Sinai reported in the journal Bioinformatics2 the development of new algorithms to detect structural genetic variation with high sensitivity and specificity. In another recent study, Dr. Flora Tassone and colleagues from the UC Davis MIND Institute reported in the Journal of Medical Genetics3 that different RNA isoforms of the FMR1 gene, which is responsible for Fragile X syndrome (the most common heritable form of cognitive impairment), premature menopause, ataxia syndrome and other disorders, can be directly sequenced and quantified using PacBio’s Iso-Seq™ approach. This study provides, for the first time, a comprehensive map of the complex landscape of full-length FMR1 gene products, providing new insights that could play relevant roles in the pathology of these important disorders.

“A growing body of scientific evidence supports the use of SMRT Sequencing to obtain the most comprehensive view of the human genome, facilitating the most detailed understanding of the genetics of complex human diseases at both the DNA and RNA level,” said Jonas Korlach, Chief Scientific Officer for Pacific Biosciences. “We are very excited by the success of our users who are uncovering important missing information in genomes and better characterizing genetic variation, which will benefit researchers, and ultimately patients, worldwide.”

About the PacBio RS II and SMRT Sequencing

Pacific Biosciences’ SMRT Sequencing technology achieves the industry’s longest read lengths, highest consensus accuracy, and the least degree of bias. These characteristics, combined with the ability to detect many types of DNA base modifications (e.g., methylation) as part of the sequencing process, make the PacBio RS II an essential tool for many scientists studying genetic and genomic variation. The PacBio platform provides a sequencing solution that can address a growing number of complex medical, agricultural, and industrial problems.

About Pacific Biosciences

Pacific Biosciences of California, Inc. (Nasdaq:PACB) offers the PacBio RS II DNA Sequencing System to help scientists solve genetically complex problems. Based on its novel Single Molecule, Real-Time (SMRT) technology, the company’s products enable: targeted sequencing to more comprehensively characterize genetic variations; de novo genome assembly to more fully identify, annotate, and decipher genomic structures; and DNA base modification identification to help characterize epigenetic regulation and DNA damage. By providing access to information that was previously inaccessible, Pacific Biosciences enables scientists to increase their understanding of biological systems. More information is available at www.pacb.com 

1Huddleston et al. (2014) Resolving the complexity of the human genome using single-molecule sequencing. Nature https://dx.doi.org/10.1038/nature13907.

2Ritz et al. (2014) Characterization of Structural Variants with Single Molecule and Hybrid Sequencing Approaches. Bioinformatics doi:10.1093/bioinformatics/btu714.

3Pretto et al. (2014) Differential increases of specific FMR1 mRNA isoforms in premutation carriers. Journal of Medical Genetics https://dx.doi.org/10.1136/jmedgenet-2014-102593.


         Nicole Litchfield

         Trevin Rard

Source: Pacific Biosciences of California, Inc.

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