March 24, 2022  |  

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…

December 20, 2021  |  

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.

November 16, 2021  |  

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…

October 28, 2021  |  

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.

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