Uncovering complexity
To identify the genetic drivers of neurological, neuromuscular, and neurodegenerative disorders scientists must have access to the complete genomic landscape, including regions previously deemed impossible to sequence, and the tools to examine the full range of genomic variation.
The PacBio Systems using Single Molecule, Real-Time (SMRT) Sequencing provide exceptionally long reads, uniform coverage and high consensus accuracy. This technology enables scientists to gain a more comprehensive understanding of the genetic basis of neurological disease.
Explore the Range of Applications
 |
Targeting Sequencing of candidate genes with pre-designed capture panels or long-range PCR to enrich and sequence multi-kilobase fragments |
 |
Variant Detection to phase alleles and screen for variants including SNPs, complex structural variants like repeat expansions, and long homopolymers |
 |
RNA Sequencing of full-length isoforms of disease-relevant genes to characterize the complete landscape of gene-specific transcripts |
 |
Epigenetics for a more complete picture of the underlying biological disease mechanisms |
Spotlight: Alzheimer’s Study Reveals First Somatic Gene Recombination Found in Human Neurons
Using an impressive array of novel and cutting-edge technologies, the scientists found evidence of significant recombination in the APP gene, which encodes amyloid precursor protein in neurons and has been associated with Alzheimer’s. Explore this research further.
Lee, M.-H. et al. 2018. Somatic APP gene recombination in Alzheimer’s disease and normal neurons. Nature 563(7733):639-645.
Spotlight: Sequencing ALS-causing repeat expansion using No-Amp targeted sequencing method
Scientists used both whole genome long-read sequencing and amplification-free targeted sequencing using the CRISPR/Cas9 system to gain base-level resolution of the notoriously challenging C9orf72 repeat expansion causing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Ebbert, M. T. W. et al. 2018. Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease. Molecular Neurodegeneration, 13(1):46.
Learn more about the No-Amp targeted sequencing method.
Selected Resources
- Takeshi Mizuguchi et al. (2021) Pathogenic 12-kb copy-neutral inversion in syndromic intellectual disability identified by high-fidelity long-read sequencing Genomics
- Mitsuhashi, Satomi et al. (2019) Long-read sequencing for rare human genetic diseases. Journal of human genetics
- Manek, Rachna et al. (2019) 5’UTR-mediated regulation of Ataxin-1 expression. Neurobiology of disease
- Ishiura, Hiroyuki et al. (2019) Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease. Nature genetics
- Mizuguchi, Takeshi et al. (2019) Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases. Journal of human genetics
- Mizuguchi, Takeshi et al. (2019) A 12-kb structural variation in progressive myoclonic epilepsy was newly identified by long-read whole-genome sequencing. Journal of human genetics
- Zablotskaya, Alena et al. (2018) Mapping the landscape of tandem repeat variability by targeted long read single molecule sequencing in familial X-linked intellectual disability. BMC medical genomics
- Lee, Ming-Hsiang et al. (2018) Somatic APP gene recombination in Alzheimer’s disease and normal neurons. Nature
- Cumming, Sarah A et al. (2018) De novo repeat interruptions are associated with reduced somatic instability and mild or absent clinical features in myotonic dystrophy type 1. European journal of human genetics
- Hughes, Timothy et al. (2018) Elevated expression of a minor isoform of ANK3 is a risk factor for bipolar disorder. Translational psychiatry
- Kondratyev, Nikolay et al. (2018) Prediction of smoking by multiplex bisulfite PCR with long amplicons considering allele-specific effects on DNA methylation. Clinical epigenetics
- Song, Janet H T et al. (2018) Characterization of a human-specific tandem repeat associated with bipolar disorder and schizophrenia. American journal of human genetics
- Höijer, Ida et al. (2018) Detailed analysis of HTT repeat elements in human blood using targeted amplification-free long-read sequencing. Human mutation
- Ebbert, Mark T W et al. (2018) Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease. Molecular neurodegeneration
- Ardui, Simon et al. (2018) Detecting AGG interruptions in females with a FMR1 premutation by long-read Single-Molecule Sequencing: A 1 year clinical experience. Frontiers in genetics
- Aneichyk, Tatsiana et al. (2018) Dissecting the causal mechanism of X-linked Dystonia-Parkinsonism by integrating genome and transcriptome assembly. Cell
- Ardui, Simon et al. (2018) Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics. Nucleic acids research
- Jacob-Hirsch, Jasmine et al. (2018) Whole-genome sequencing reveals principles of brain retrotransposition in neurodevelopmental disorders. Cell research
- Tseng, Elizabeth et al. (2019) The landscape of SNCA transcripts across synucleinopathies: New insights from long reads sequencing analysis BioRxiv
- Tseng, Elizabeth et al. (2017) Altered expression of the FMR1 splicing variants landscape in premutation carriers. Biochimica et Biophysica Acta
- Schüle, Birgitt et al. (2017) Parkinson’s disease associated with pure ATXN10 repeat NPJ Parkinson's Disease
- Korlach, Jonas et al. (2017) De novo PacBio long-read and phased avian genome assemblies correct and add to reference genes generated with intermediate and short reads. GigaScience
- Seppälä, Hanna et al. (2017) Single-molecule sequencing revealing the presence of distinct JC polyomavirus populations in patients with progressive multifocal leukoencephalopathy. The Journal of infectious diseases
- Ardui, Simon et al. (2017) Detecting AGG interruptions in male and female FMR1 premutation carriers by single-molecule sequencing. Human mutation
- Brykczynska, Urszula et al. (2016) CGG repeat-induced FMR1 silencing depends on the expansion size in human iPSCs and neurons carrying unmethylated full mutations. Stem cell reports
- Hartley, Stephen W et al. (2016) Alternative isoform analysis of Ttc8 expression in the rat pineal gland using a multi-platform sequencing approach reveals neural regulation. PloS one
- Tombácz, Dóra et al. (2016) Full-length isoform sequencing reveals novel transcripts and substantial transcriptional overlaps in a herpesvirus. PloS one
- Ashley, Euan A et al. (2016) Towards precision medicine. Nature reviews. Genetics
- Chaisson, Mark J P et al. (2015) Genetic variation and the de novo assembly of human genomes. Nature reviews. Genetics
- McFarland, Karen N. et al. (2015) SMRT Sequencing of long tandem nucleotide repeats in SCA10 reveals unique insight of repeat expansion structure. PloS one
- Koskinen, Lotta L E et al. (2015) Identification of a common risk haplotype for canine idiopathic epilepsy in the ADAM23 gene. BMC genomics
- You, Xintian et al. (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nature neuroscience
- Chaisson, Mark J P et al. (2015) Resolving the complexity of the human genome using single-molecule sequencing. Nature
- Doolan, Kyle M et al. (2015) Conformation dependent epitopes recognized by prion protein antibodies probed using mutational scanning and deep sequencing. Journal of molecular biology
- Pretto, Dalyir I et al. (2015) Differential increases of specific FMR1 mRNA isoforms in premutation carriers. Journal of medical genetics
- Poster: McLaughlin, Ian et al. (2021) Targeting Clinically Significant Dark Regions of the Human Genome with High-Accuracy, Long-Read Sequencing
- Poster: Zhu, Lei et al. (2021) Full-Length Sequencing of CYP2D6 Locus with HiFi Reads Increasing Genotypes Accuracy
- Poster: McLaughlin, Ian et al. (2021) Targeting Clinically Significant Dark Regions of the Human Genome with High-Accuracy, Long-Read Sequencing
- Poster: Zhu, Lei et al. (2021) Full-Length Sequencing of CYP2D6Variants with PacBio HiFi Reads
- Poster: Ekholm, Jenny et al. (2020) Amplification-free targeted enrichment powered by CRISPR-Cas9 and long-read Single Molecule Real-Time (SMRT) Sequencing can efficiently and accurately sequence challenging repeat expansion disorders
- Poster: Underwood, Jason et al. (2020) A complete solution for full-length transcript sequencing using the PacBio Sequel II System
- Poster: Tsai, Yu-Chih et al. (2020) Amplification-free protocol for targeted enrichment of repeat expansion genomic regions and SMRT Sequencing
- Poster: Tseng, E. et al. (2019) Full-Length RNA-seq of Alzheimer brain on the PacBio Sequel II System
- Poster: Ekholm, J. M. et al. (2019) Structural variant in the RNA Binding Motif Protein, X-Linked 2 (RBMX2) gene found to be linked to bipolar disorder
- Poster: Ekholm, J. et al. (2019) Sequencing the previously unsequenceable using amplification-free targeted enrichment powered by CRISPR/Cas9
- Poster: McLaughlin, Ian et al. (2018) No-amp targeted SMRT sequencing using a CRISPR-Cas9 enrichment method
- Poster: Ekholm, J. et al. (2018) Amplification-free, CRISPR-Cas9 targeted enrichment and SMRT Sequencing of repeat-expansion disease causative genomic regions
- Poster: Clark, Tyson A. et al. (2018) Amplification-free targeted enrichment and SMRT Sequencing of repeat-expansion genomic regions
- Poster: Chakraborty, Shreyasee et al. (2018) Mitochondrial DNA sequencing using PacBio SMRT technology
- Poster: Ekholm, J. et al. (2017) Screening for causative structural variants in neurological disorders using long-read sequencing
- Poster: Ekholm, Jenny et al. (2017) Screening and characterization of causative structural variants for bipolar disorder in a significantly linked chromosomal region onXq24-q27 in an extended pedigree from a genetic isolate
- Poster: Clark, T. A. et al. (2017) Targeted SMRT Sequencing of difficult regions of the genome using a Cas9, non-amplification based method
- Poster: Eng, K. et al. (2016) Target enrichment using a neurology panel for 12 barcoded genomic DNA samples on the PacBio SMRT Sequencing platform
- Poster: Tassone, F. et al. (2016) Alternative splicing in FMR1 premutations carriers
- Poster: Kujawa, S. et al. (2016) A method for the identification of variants in Alzheimer’s disease candidate genes and transcripts using hybridization capture combined with long-read sequencing
- Poster: Sethuraman, A. et al. (2016) Characterization of the Poly-T variants in the TOMM40 gene using PacBio long reads
- Poster: Ekholm, J. et al. (2016) Enrichment of unamplified DNA and long-read SMRT Sequencing to unlock repeat expansion disorders
- Poster: Jenny Gu, Kevin Eng, Anand Sethuraman, Steve Kujawa et al. (2016) Multiplex target enrichment using barcoded multi-kilobase fragments and probe-based capture technologies
- Poster: Ekholm, Jenny et al. (2016) Candidate gene screening using long-read sequencing
- Poster: Ekholm, Jenny et al. (2016) Enrichment of unamplified DNA and long-read SMRT Sequencing in unlocking the underlying biological disease mechanisms of repeat expansion disorders
- Poster: Baybayan, Primo et al. (2016) Application specific barcoding strategies for SMRT Sequencing
- Henry, Christian and Shen, Richard and Stone, Jennifer (2021) With Long Reads and Short Reads, the Possibilities are Endless – PacBio ASHG 2021 Fireside Chat
- Stone, Jennifer (2021) HiFi Sequencing: See What You’ve Been Missing
- Hiatt, Susan and Korlach, Jonas (2021) Long-Read Genome Sequencing for the Molecular Understanding of Neurodevelopmental Disorders
- Wenger, Aaron (2021) Complete and Accurate Human Genomes with HiFi Reads
- Hoischen, Alexander (2021) Long Reads to Identify Hidden Structural Variants in Rare Disease
- Matsumoto, Naomichi (2021) The Utility of HiFi Long-Read WGS in Solving Patients with Rare Diseases
- Rowell, William and LIeras, Roberto (2021) A Bioinformatics Workflow for Comprehensive Detection and Prioritization of Variants with PacBio HiFi Reads
- Pastinen, Tomi (2021) Genomic Answers for Kids
- Ekholm, Jenny (2021) Increasing Solve Rates in Rare and Mendelian Disease Research with Long-Read Sequencing
- Lambert, Christine (2021) Scalable Workflow for Constructing HiFi Libraries
- Wenger, Aaron (2021) The Present and Future of HiFi Whole-Genome Sequencing for Rare Disease
- Blethrow, Justin and Smith, Melissa L. and Vinnere Pettersson, Olga (2021) Webinar: Unleashing the Power of HiFi Sequencing – How the Sequel IIe System Removes Barriers and Empowers Life Scientists
- Becker, Aaron and Ekholm, Jenny and Harris, Charlotte and Kingham, Brewster and Vinnere Pettersson, Olga (2021) SMRT Sequencing as a Service – How to Bring Long-Read Technology to Your Core Lab
- Korlach, Jonas (2021) AGBT Presentation: Increasing the Solve Rate of Rare and Undiagnosed Genetic Diseases with HiFi Sequencing
- Tassone, Flora (2020) Altered Alternative Splicing Process in FMR1 Premutation Carriers
- Tome, Stephanie (2020) Improving the Prognosis and Genetic Counseling in DM1 Patients
- Schuele, Birgitt (2020) Long-read Sequencing and Optical Mapping of ATXN10 Repeat Expansion
- van Blitterswijk, Marka (2020) Long-read Sequencing to Assess an Expanded Repeat in C9orf72
- McEachin, Zachary (2020) Multiplex, Long-Read Sequencing of Ataxia Repeat Expansions
- Course, Meredith (2020) The Evolution and Function of a Large Tandem Repeat Associated with ALS
- Holstege, Henne (2020) Uncovering Neurological Disorders Through an Examination of VNTRs
- (2020) Application Tutorial: Introduction to Full-Length RNA Sequencing with HiFi Reads
- (2020) Introduction to highly accurate long-read sequencing (HiFi Sequencing)
- Latham, Gary (2020) Virtual Global Summit: Long-range PCR meets long-read sequencing: Tandem technologies for tackling the toughest genes in carrier screening
- Aro, Lori (2020) Virtual Global Summit: When Accuracy Matters – SMRT Sequencing in clinical research and diagnostics
- Korlach, Jonas (2020) ASHG PacBio Workshop: Latest product and application updates
- Tilgner, Hagen (2020) ASHG PacBio Workshop: Single-cell isoform analysis of the nervous system
- Tsai, Yu-Chih and McLaughlin, Ian and Hon, Ting and Ekholm, Jenny and Ziegle, Janet (2020) Video Poster: A new approach to Thalassemia and Ataxia carrier screening panels using CRISPR-Cas9 enrichment and long-read sequencing
- (2020) Video: HiFi Sequencing – Unlock your next great discovery
- Ameur, Adam (2020) Webinar: SMRT Sequencing applications for human genomics and medicine
- Ekholm, Jenny (2020) Video Poster: Full-length RNA sequencing of Alzheimer brain sample using long reads reveals complex alternative splicing patterns
- Sund, Kristen and Wenger, Aaron (2020) Webinar: Increasing solve rates for rare and Mendelian diseases with long-read sequencing
- Gharbi, Karim (2020) Customer Experience: Advancing UK genomics research with the PacBio Sequel II System
- Schmutz, Jeremy and Conesa, Ana and Gharbi, Karim and Kuo, Richard (2020) Customer Experience: HiFi reads help scientists explore genomes and transcriptomes
- Conesa, Ana (2020) Customer Experience: Improving transcriptome research with PacBio HiFi reads
- SMRT Sequencing Brochure: Delivering highly accurate long reads to drive discovery in life science (2021)
- Application Brief: No-Amp targeted sequencing – Best Practices (2020)
- Product Brochure: Sequel IIe System – Sequencing evolved (2020)
- Informational Guide: Understanding accuracy in DNA sequencing (2020)
- Application Brochure: HiFi reads for highly accurate long-read sequencing (2020)
- PacBio Certified Service Providers (2020)
- Application Brief: Long-read RNA sequencing – Best Practices (2019)
- Infographic: Structural variants and disease (2017)