Powering genetic discovery
Advanced exploration of human genomes requires reference-quality assemblies of diverse populations. We must look beyond single nucleotides to include comprehensive structural variant mapping of individuals and large cohorts to fully understand the complexity of human health and disease.
Single Molecule, Real-Time (SMRT) Sequencing is informing population-specific reference genomes around the world by uncovering regions of the genome not previously sequenced and enabling detection of all variant types. With the PacBio System scientists can:
- Generate de novo assemblies of population-specific reference genomes
- Utilize low-coverage, long-read whole genome sequencing to detect structural variants
- Conduct targeted sequencing for novel allele-discovery for genes of interest
Population-Specific Human Genome Assemblies
PacBio long-read sequencing is being used to develop population-specific reference genomes as part of international research efforts. To learn more about these projects and explore detailed assembly information view the interactive map.
Spotlight: Structural variant discovery with PacBio long-read sequencing
Explore human genetic variation and learn how SMRT Sequencing uncovers the full spectrum of structural variants to advance understanding of genetic disease and broaden our knowledge of human diversity.
Infographic: Structural Variants and Disease
Explore the types of human genomic variation and the diseases known to be caused by structural variants.
Whitepaper: Structural variation in the human genome
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.
Structural Variation Project Calculator
Use this calculator to estimate the time and materials needed for structural variant discovery on the Sequel System.
Spotlight: SMRT Sequencing delivers a Chinese reference genome
Scientists used PacBio long-read sequencing to construct a de novo assembly of a Chinese genome (HX-1). This high-quality assembly filled 247 N-gaps in the GRCh38 reference sequence and shed light on 12.8 Mb of Chinese population-specific sequences and novel structural variants. Explore this research further:
Shi, L. et al., 2016. Long-read sequencing and de novo assembly of a Chinese genome. Nature Communications, 7, p.12065.
Spotlight: Long-read sequencing sheds light on MHC diversity in Africa
Martin Pollard presents his research to better represent natural variation in the major histocompatibility complex (MHC) among African populations. PacBio long reads provided full-length sequences of the human leukocyte antigen haplotypes, enabling improved understanding of genetic diversity.
Pollard, M., 2016. ASHG Virtual Poster: The MHC Diversity in Africa Project (MDAP) pilot – 125 African high-resolution HLA types from 5 populations. 66th Annual Meeting of the American Society of Human Genetics.
Selected Resources
- Reiner, Jennifer et al. (2018) Cytogenomic identification and long-read single molecule real-time (SMRT) sequencing of a Bardet-Biedl Syndrome 9 (BBS9) deletion. NPJ Genomic Medicine
- Chaisson, Mark J.P. et al. (2017) Multi-platform discovery of haplotype-resolved structural variation in human genomes BioRxiv
- Nakano, Kazuma et al. (2017) Advantages of genome sequencing by long-read sequencer using SMRT technology in medical area. Human Cell
- Merker, Jason D et al. (2017) Long-read genome sequencing identifies causal structural variation in a Mendelian disease. Genetics in medicine
- Roe, D. et al. (2017) Revealing complete complex KIR haplotypes phased by long-read sequencing technology Genes and immunity
- Koren, Sergey et al. (2017) Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome research
- Huddleston, John et al. (2017) Discovery and genotyping of structural variation from long-read haploid genome sequence data. Genome research
- Seo, Jeong-Sun et al. (2016) De novo assembly and phasing of a Korean human genome. Nature
- Suzuki, Yuta et al. (2016) AgIn: Measuring the landscape of CpG methylation of individual repetitive elements. Bioinformatics
- Ashley, Euan A et al. (2016) Towards precision medicine. Nature reviews. Genetics
- Steinberg, Karyn Meltz et al. (2016) High-quality assembly of an individual of Yoruban descent BioRxiv
- Shi, Lingling et al. (2016) Long-read sequencing and de novo assembly of a Chinese genome. Nature communications
- Huddleston, John et al. (2016) An incomplete understanding of human genetic variation. Genetics
- Chaisson, Mark J P et al. (2015) Genetic variation and the de novo assembly of human genomes. Nature reviews. Genetics
- Pendleton, Matthew et al. (2015) Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nature methods
- Editorial et al. (2015) Whole genome? Nature genetics
- Berlin, Konstantin et al. (2015) Assembling large genomes with single-molecule sequencing and locality-sensitive hashing. Nature biotechnology
- English, Adam C et al. (2015) Assessing structural variation in a personal genome-towards a human reference diploid genome. BMC genomics
- Chaisson, Mark J P et al. (2015) Resolving the complexity of the human genome using single-molecule sequencing. Nature
- Yasuda, Jun et al. (2018) Genome analyses for the Tohoku Medical Megabank Project toward establishment of personalized healthcare. Journal of biochemistry
- Hickey, Luke et al. (2017) Hunting structural variants: Population by population Front line genomics magazine
- Hickey, L. et al. (2017) Structural variation offers new home for disease associations and gene discovery Drug discovery and development magazine
- Schneider, Valerie A et al. (2017) Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly. Genome research
- Novak, Adam M et al. (2017) Genome graphs BioRxiv
- Kojima, Kaname et al. (2016) STR-realigner: a realignment method for short tandem repeat regions. BMC genomics
- Cho, Yun Sung et al. (2016) An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes. Nature communications
- Liljegren, Mikkel Meyn et al. (2016) Microsatellite length scoring by Single Molecule Real Time Sequencing – Effects of sequence structure and PCR regime. PloS one
- Garg, Shilpa et al. (2016) Read-based phasing of related individuals. Bioinformatics
- Poster: Audano, Peter A. et al. (2018) Improving the reference with a diversity panel of sequence-resolved structural variation
- Poster: Vogelsang, R. et al. (2018) Population-scale discovery of structural variants with PacBio SMRT Sequencing
- (2018) Tutorial: Structural variant calling [SMRT Link v6.0.0]
- Korlach, Jonas and Lleras, Roberto (2018) User Group Meeting: Structural variant calling in SMRT Link 6.0
- Ameur, A. and Graves-Lindsay, T. and Peluso, P. (2018) Webinar: Assembling high-quality human reference genomes for global populations
- Korlach, Jonas (2018) Podcast: Why the diversity of genomic data matters
- Sedlazeck, Fritz (2018) Webinar: Size Matters: Accurate detection and phasing of structural variations
- Hoischen, A. and Wenger, A (2018) Webinar: Sequencing structural variants for disease gene discovery and population genetics