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.
Discover deeper insights
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 through:
- Targeting candidate genes with pre-designed capture panels or long-range PCR to enrich and sequence multi-kilobase fragments.
- Phase alleles and screen for variants including SNPs, complex structural variants like repeat expansions, and long homopolymers.
- Sequence full-length isoforms of disease-relevant genes to characterize the complete landscape of gene-specific transcripts.
- Detect epigenetic signatures for a more complete picture of the underlying biological disease mechanisms.
Spotlight: CRISPR/Cas9 and SMRT Sequencing provide insights into Parkinson’s disease
Scientists used CRISPR/Cas9 in combination with long-read SMRT Sequencing to characterize complete repeat expansions and identify a novel phenotype-genotype correlation between Parkinson’s disease and the ATXN10 repeat expansion. Explore this research further.
Schüle, B. et al., 2017. Parkinson’s disease associated with pure ATXN10 repeat expansion. Parkinson’s Disease, 3(27).
Spotlight: Generating haplotype-specific variant calls in Alzheimer’s disease
Targeted sequencing of 35 candidate genes allowed scientists to detect a broad array of genomic variants in patients with Alzheimer’s disease. Using SMRT Sequencing they uncovered novel transcript isoforms, a novel exon and phased variants to specific alleles and subsequently transcript isoforms. Explore this research further:
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. In 66th Annual Meeting of the American Society of Human Genetics. Vancouver, BC.
For more information about how SMRT Sequencing can advance your neuroscience research, contact us.
- 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
- Kleinman, Claudia L et al. (2014) Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nature Genetics
- Treutlein, Barbara et al. (2014) Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing. Proceedings of the National Academy of Sciences of the United States of America
- Loomis, Erick W et al. (2013) Sequencing the unsequenceable: expanded CGG-repeat alleles of the fragile X gene. Genome Research
- 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: 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
- Ameur, Adam (2017) AGBT Virtual Poster: Analysis method for amplification-free SMRT sequencing and assessment on repeat expansions in Huntington’s disease
- Paulin, Lars (2017) AGBT Virtual Poster: Single-molecule sequencing reveals the presence of distinct JC polyomavirus populations in patients with progressive multifocal leukoencephalopathy
- Korlach, Jonas (2016) ASHG PacBio Workshop: A future of high-quality genomes, transcriptomes, and epigenomes
- Lutz, Michael (2016) ASHG PacBio Workshop: Identification and characterization of informative genetic structural variants for neurodegenerative diseases
- Ashley, Euan (2016) ASHG PacBio Workshop: Towards precision medicine
- Tassone, F. and Olaby, R. and Tang, H. and Hickey, L and Tseng, E. (2016) ASHG Virtual Poster: Alternative splicing in FMR1 premutations carriers
- Wenger, Aaron (2016) Video: Using the Integrative Genomics Viewer (IGV) to visualize PacBio long-read SMRT Sequencing data
- Ekholm, J. and Tsai, Y. and Greenberg, D. and Clark, T. (2016) ASHG Virtual Poster: Enrichment of unamplified DNA and long-read SMRT Sequencing to unlock repeat expansion disorders
- Ashizawa, Tetsuo (2016) Nature Webinar: Large interrupted pentanucleotide repeats of SCA10
- Application Brochure: Amplification-Free Targeted Sequencing (2017)
- Infographic: Structural Variants and Disease (2017)
- PacBio Certified Service Providers (2017)
- Human Biomedical Research Brochure: The most comprehensive view of the human genome (2017)
- Application Brief: Long-read RNA sequencing – Best Practices. (2017)
- SMRT Sequencing Brochure: Revolutionize genomics with SMRT Sequencing. (2017)
- SV Application Brochure: Track the full extent of structural variation in a genome. (2016)
- Isoform Sequencing Application Brochure: Read full-length transcripts – no assembly required. (2016)
- Application Note: Multiplex target enrichment using barcoded multi-kilobase fragments and probe-based capture technologies. (2016)
- Epigenetics Application Brochure: Characterize the epigenetic landscape of your genome. (2016)