Structural variation accounts for much of the variation among human genomes. Structural variants of all types are known to cause Mendelian disease and contribute to complex disease. Learn how long-read sequencing is enabling detection of the full spectrum of structural variants to advance the study of human disease, evolution and genetic diversity.
Explore the types of human genomic variation and the diseases known to be caused by structural variants.
Explore how long-read sequencing enables solving of rare and mendelian diseases.
Application Brochure: Scalable human whole genome HiFi sequencing for rare and inherited disease research
PacBio highly accurate long reads – HiFi reads – offer a single-platform solution for rare and inherited disease research, elucidating suspected genetic causes of disease in up to ~50% of cases that have not previously been explained using short-read exome or whole genome sequencing. PacBio offers an efficient workflow, developed in collaboration with Children’s Mercy Kansas City, which provides a scalable solution for sequencing 100s to 1000s of whole human genomes per year on the Sequel II and Sequel IIe Systems.
With highly accurate long reads (HiFi reads) from the Sequel II or IIe Systems you can comprehensively detect variants in 100s to 1000s of genomes in a year. HiFi reads provide high precision and recall for single nucleotide variants (SNVs), indels, structural variants (SVs), and copy number variants (CNVs), including in difficult-to-map repetitive regions.
Learn how PacBio highly accurate long reads enable an improved approach to whole genome sequencing to understand the genetic origins of rare diseases.
2015 SMRT Informatics Developers Conference Presentation Slides: Ali Bashir of Mount Sinai School of Medicine discussed methods for characterizing structural variation in human genomes across a variety of coverage levels.
High-quality de novo genome assembly and intra-individual mitochondrial instability in the critically endangered kakapo
The kakapo (Strigops habroptila) is a large, flightless parrot endemic to New Zealand. It is highly endangered with only ~150 individuals remaining, and intensive conservation efforts are underway to save this iconic species from extinction. These include genetic studies to understand critical genes relevant to fertility, adaptation and disease resistance, and genetic diversity across the remaining population for future breeding program decisions. To aid with these efforts, we have generated a high-quality de novo genome assembly using PacBio long-read sequencing. Using the new diploid-aware FALCON-Unzip assembler, the resulting genome of 1.06 Gb has a contig N50 of 5.6 Mb (largest contig 29.3 Mb), >350-times more contiguous compared to a recent short-read assembly of a closely related parrot (kea) species. We highlight the benefits of the higher contiguity and greater completeness of the kakapo genome assembly through examples of fully resolved genes important in wildlife conservation (contrasted with fragmented and incomplete gene resolution in short-read assemblies), in some cases even providing sequence for regions orthologous to gaps of missing sequence in the chicken reference genome. We also highlight the complete resolution of the kakapo mitochondrial genome, fully containing the mitochondrial control region which is missing from the previous dedicated kakapomitochondrial genome NCBI entry. For this region, we observed a marked heterogeneity in the number of tandem repeats in different mtDNAmolecules from a single bird tissue, highlighting the enhanced molecular resolution uniquely afforded by long-read, single-molecule PacBio sequencing.
Structural variants (SVs) – genomic differences =50 base pairs – are few by count compared to single nucleotide variants (SNVs) and indels but include most of the base pairs that differ between two humans.
Explore human genetic variation and learn how SMRT Sequencing uncovers the full spectrum of structural variation to advance understanding of genetic disease and broaden our knowledge of human diversity.
Most of the basepairs that differ between two human genomes are in intermediate-sized structural variants (50 bp to 5 kb), which are too small to detect with array CGH but…
In this ASHG 2017 presentation, Jonas Korlach, the CSO of PacBio shared updates on three applications featuring SMRT Sequencing on the Sequel System, highlighting structural variant detection, targeted sequencing and…
In this ASHG 2017 presentation, Han Brunner of Radboud University Medical Center presented research using SMRT Sequencing to detect structural variants to uncover the genetic causes of intellectual disability. He…
Structural variants (SVs, differences >50 base pairs) account for most of the base pairs that differ between two human genomes, and are known to cause over 1,000 genetic disorders including…
In this presentation Fritz Sedlazeck describes his latest work to obtain comprehensive genomes leveraging long-read sequencing and linked reads.