[caption id="attachment_24559" align="alignright" width="300"] The coast of Panay Island in the Philippines. U.S. Navy photo by Jennifer S. Kimball[/caption] In an exciting new Cell paper, scientists report identification of an intronic structural variant that causes a neurodegenerative Mendelian disorder that primarily affects people on the island of Panay in the Philippines. The team used a number of approaches, including SMRT Sequencing and the Iso-Seq method, to solve the medical mystery. “Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly” comes from lead authors Tatsiana Aneichyk, William Hendriks, Rachita Yadav, David Shin, and Dadi Gao; senior authors Cristopher…
The last day of February each year is designated as Rare Disease Day, a unique opportunity to recognize people who sometimes seem to be forgotten by the mainstream medical community. Once again PacBio is an official sponsor of the day, which will be marked with awareness-raising events in 80 countries around the world. It’s a beautiful way to remember the hundreds of millions of people affected by a rare disease, as well as the caretakers, researchers, and clinicians who work so hard to make their lives better. The thing about rare diseases is that, while each individual disease might affect…
The SOLVE-RD research program, a collaboration of 21 participant organizations in 10 nations, announced it has received a €15 million grant from the European Union’s Horizon 2020 initiative. SOLVE-RD aims to improve the diagnosis and treatment of rare diseases, which in total affect millions of Europeans. The program is applying novel diagnostic tools to around 19,000 cases unsolved by prior short-read exome sequencing. Prominent among the planned “multi-omics” approach is long-read genome sequencing, which will reveal the large amount of potentially disease-causing genetic variation that is not accessible with short-read DNA sequencing. SOLVE-RD plans to apply long-read genome sequencing to 500…
The annual meeting of the American Society of Human Genetics kicked off with a splash yesterday in Orlando, Fla. The PacBio team was thrilled that the opening talks in the presidential address and plenary session included a significant focus on increasing diversity in genetic studies to better characterize underrepresented populations. Nancy Cox, ASHG president, highlighted a number of excellent efforts to address this but noted, “Compared with what we need, what we’ve done so far is really just a drop in the bucket.” As regular blog readers know, we work closely with groups around the world to build population-specific reference…
Sniffles and NGMLR, structural variant detection and alignment algorithms developed in the Schatz lab for long-read sequence data, are already familiar to many in the PacBio community. Now, a preprint is available so users can see how these open-source tools perform in a variety of conditions. “Accurate detection of complex structural variations using single molecule sequencing” comes from lead author Fritz Sedlazeck at Baylor College of Medicine, senior author Michael Schatz at Johns Hopkins University, and collaborators. The team notes that long-read sequencing has introduced a much more comprehensive means of discovering structural variants, many of which are missed by…
In an effort to improve precision medicine in Chinese populations, Novogene announced plans to build a database of structural variants in 1,000 Chinese individuals using PacBio SMRT Sequencing. Databases which catalog SNVs and small indels have proven invaluable for precision medicine, serving as population controls for rare disease research and providing a list of variants for genetic association studies. Yet, most of the base pairs that differ between two human genomes are in structural variants which are not adequately represented in current databases. Furthermore, current databases do not represent the genetic background of all ethnic populations, particularly the Chinese who…
An article published today in Genetics in Medicine from Jason Merker, Euan Ashley, and colleagues at Stanford University reports the first successful application of PacBio whole genome sequencing to identify a disease-causing mutation. (Check out Stanford's news release here.) The authors describe an individual who presented over 20 years with a series of benign tumors in his heart and glands. The individual satisfied the clinical criteria for Carney complex, but after eight years of genetic evaluation, including whole genome short-read sequencing, experts were still unable to pinpoint the underlying genetic mutation and confirm a diagnosis. Ultimately, the authors turned to the…
We’re excited to be heading to Washington, DC, for the annual meeting of the American Association for Cancer Research. The PacBio team always enjoys hearing about the latest in cancer translational research at AACR, along with thousands of leading scientists in the field. Many of those scientists have already learned that SMRT Sequencing provides a unique view into cancer, revealing structural variation, phasing distant variants, and delivering full-length isoform sequences. With uniform coverage, industry-leading consensus accuracy, and reads extending to tens of kilobases, PacBio long-read sequencing gives researchers the ability to monitor and make sense of even the most complex…
Scientists from Rutgers University and the University of California, Davis, used SMRT Sequencing to study structural variation in maize. They found that this approach delivered more complete information at lower cost than standard methods and generated new findings that could be important for crop breeding. From lead author Jiaqiang Dong, senior author Jo Messing, and collaborators, “Analysis of tandem gene copies in maize chromosomal regions reconstructed from long sequence reads” was published in PNAS recently. They chose to evaluate SMRT Sequencing for copy number detection as an alternative to short-read sequencing, which doesn’t span long repeats, and BAC cloning, which…
At Cold Spring Harbor Laboratory, scientists used SMRT® Sequencing to decode one of the most challenging cancer genomes ever encountered. Along the way, they built a portfolio of open-access analysis tools that will help researchers everywhere make structural variation discoveries with long-read sequencing data. When Mike Schatz realized a few years ago that his PacBio® System had reached the throughput needed to process human genomes, he decided to give it a real challenge: the incredibly complicated, massively rearranged SK-BR-3 breast cancer cell line. The genome consists of 80 chromosomes, and that’s just the tip of the complexity iceberg. “We were…
Much like the “sharpen” tool in Photoshop brings a picture into tighter focus and enhances the fine detail, long-read sequencing offers enhanced resolution of genomic information, according to Cold Spring Harbor Laboratory colleagues Mike Schatz and Maria Nattestad. The scientists spoke with Mendelspod’s Theral Timpson about how long-read sequencing is advancing their research in unique and powerful ways; a brief recap of their conversation follows. Schatz uses PacBio sequencing to establish incredibly accurate assemblies of microbial, crop, animal, and human genomes. Indeed, SMRT technology has significantly improved his work on the flatworm Macrostomum lignano, an organism with regenerative powers. With…
During the Wednesday afternoon sessions of last week's ASHG conference, several speakers provided helpful insights about their use of SMRT Sequencing for a range of applications. Highlights included the following: Yao Yang, a researcher at the Icahn School of Medicine at Mount Sinai, discussed the development of an assay to genotype the CYP2D6 gene to inform drug dosing in patients. CYP2D6 metabolizes 20-25% of all medications, including antidepressants, anti-psychotics, and opiates. There are more than 100 known variants, which include gene deletions and duplications. Variants can have profound impacts on how patients metabolize drugs, with some individuals being ultra-rapid metabolizers…
In the first podcast of a new series on the applications of long-read sequencing, Mendelspod host Theral Timpson interviewed Marc Salit, leader of the Genome Scale Measurements Group at the National Institute of Standards and Technology. Their conversation focused on how and why NIST is involved in establishing baseline measurements for the human genome.Salit, along with Justin Zook and their team at NIST, are managing the Genome in a Bottle (GIAB) Consortium to develop reference materials, data, and methods needed to assess whole human genome sequencing. Their goal is to establish a physical reference genome as a standard against which…
At the inaugural Festival of Genomics event in Boston, more than 1,500 people turned out to see what was billed as a conference unlike any other. The meeting was indeed unique, featuring a play (starring well-known scientists), a giant chess board, and a Genome Dome, in addition to the more familiar lineup of excellent speakers and workshops. To help kick off the festival, genomic luminaries Craig Venter and James Lupski presented plenary talks on day 1 and set the stage for some exciting science to follow. Lupski’s talk was particularly impactful, as he described how his team at Baylor recently…
Scientists from Argentina and Brazil published the results of a study comparing long-read approaches to characterize the genome structure of a highly complex region of the Y chromosome in Drosophila melanogaster. They found that Single Molecule, Real-Time (SMRT®) Sequencing outperformed synthetic long reads in accurately representing tandem repeats. The study aimed to resolve the structure of the autosomal gene Mst77F, which had previously been found to have multiple tandem copies; the region, however, was known to be grossly misassembled in the reference. The scientists, from Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas and Universidade Federal…