Asset Tag: Variant detection
Quick Reference Card — Loading and Pre-Extension Recommendations for the Sequel II and IIe Systems
SFAF NGS Tech Panel (Teaser 2)
The COVID-19 pandemic has brought new focus and resources to pathogen surveillance of all kinds. HiFi sequencing, which combines high accuracy, long read lengths, and single-molecule sequencing, is unique in…
Computational Advances in Genome and Transcriptome Using HiFi Sequencing
PacBio HiFi sequencing has been used to generate the latest and most complete version of the human genome, characterize population-level structural variations, diplotype pharmacogenetic loci, and elucidate complex alternative splicing at the…
Germline mosaicism of a missense variant in KCNC2 in a multiplex family with autism and epilepsy
Currently, protein-coding de novo variants and large copy number variants have been identified as important for ∼30% of individuals with autism. One approach to identify relevant variation in individuals who lack these types of events is by utilizing newer genomic technologies. In this study, highly accurate PacBio HiFi long-read sequencing was applied to a family with autism, treatment-refractory epilepsy, cognitive impairment, and mild dysmorphic features (two affected female full siblings, parents, and one unaffected sibling) with no known clinical variant. From our long-read sequencing data, a de novo missense variant in the KCNC2 gene (encodes Kv3.2 protein) was identified in both affected children. This variant was phased to the paternal chromosome of origin and is likely a germline mosaic. In silico assessment of the variant revealed it was in the top 0.05% of all conserved bases in the genome, and was predicted damaging by Polyphen2, MutationTaster, and SIFT. It was not present in any controls from public genome databases nor in a joint-call set we generated across 49 individuals with publicly available PacBio HiFi data. This specific missense mutation (Val473Ala) has been shown in both an ortholog and paralog of Kv3.2 to accelerate current decay, shift the voltage dependence of activation, and prevent the channel from entering a long-lasting open state. Seven additional missense mutations have been identified in other individuals with neurodevelopmental disorders (p = 1.03 × 10−5). KCNC2 is most highly expressed in the brain; in particular, in the thalamus and is enriched in GABAergic neurons. Long-read sequencing was useful in discovering the relevant variant in this family with autism that had remained a mystery for several years and will potentially have great benefits in the clinic once it is widely available.
PacBio HiFiViral SARS-CoV-2 Kit
We created the HiFiViral SARS-CoV-2 Kit for labs working on the front line of the COVID-19 pandemic — tracking and identifying the spread of novel variants in their communities. The…
Brochure — SMRT Sequencing: Delivering highly accurate long reads to drive discovery in life science
Learn how Single Molecule, Real-Time (SMRT) Sequencing and the Sequel IIe System and will accelerate your research by delivering highly accurate long reads to provide the most comprehensive view of genomes, transcriptomes and epigenomes.
Application brochure — What can you do with one SMRT Cell?
With PacBio Single Molecule, Real-Time (SMRT) Sequencing on the Sequel IIe System you can characterize whole genomes and transcriptomes with just one SMRT Cell. Explore our applications and pricing to get your sequencing project started.
Uncovering Neurological Disorders Through an Examination of VNTRs
Many neurological diseases result from expansion of unstable variable nucleotide tandem repeats (VNTRs) that influence gene transcription of neighboring genes. In this talk, Dr. Henne Holstege presents research that investigated…
HiFi Sequencing: See What You’ve Been Missing
PacBio Vice President of Segment Marketing, Dr. Jennifer Stone, demonstrates how HiFi sequencing is changing the game in human genetics by sharing some of the exciting milestones and seminal publications…
Integrated Rare Disease using Long-Read Genome Sequencing
Genomic variation beyond single nucleotide variants, including structural variation (SV), copy number variants (CNV), and repeat expansions, plays a significant role in rare disease. However, current technologies require multiple tests…
Resolving Highly Diverse HLA and CYP2D6 Alleles Using HiFi Sequencing for Long-Range Amplicon Data with a New Clustering Algorithm
Targeted amplification of difficult pharmacogenetic loci with PacBio HiFi reads can resolve complex alleles in a single direct assay without imputation.
HiFiViral SARS-CoV-2: A Kitted Solution for Genome Surveillance that is Robust Across Sample Input Quantities and New Variants
The COVID-19 pandemic continues to be a major global epidemiological challenge with the ongoing emergence of new strain lineages that are more contagious, more virulent, drug resistant and in some cases evade vaccine-induced immunity. In response, the HiFiViral SARS-CoV-2 kit (PacBio; Menlo Park, California) was developed as a scalable solution for the Sequel II and Sequel IIe systems. The HiFiViral SARS-CoV-2 is an easy to perform solution for surveillance of variants to support pandemic response by public health. With 80% of samples yielding complete genome coverage in a 96-plex run, the combination of long read lengths and a differentiated probe design provides highly accurate results and robust genome coverage across a range of Ct values.
Simplified and Robust Library Construction for High-Throughput HiFi Sequencing for Human Variant Detection
New workflow for preparing SMRTbell libraries from <4ug gDNA input using AMPure PB bead purification. This workflow requires samples with high molecular weight gDNA with minimal presence of <5kb fragments.
Long-Read Amplicon Sequencing of the Polymorphic CYP2D6 Locus
With PacBio Single Molecule, Real-Time (SMRT) Sequencing on the Sequel IIe System you can characterize highly polymorphic CYP2D6 locus from 384 or more samples with just one SMRT Cell. Explore our applications and pricing to get your sequencing project started.