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Tseng E, Rowell WJ, Glenn OC, et al. The Landscape of . Front Genet. 2019;10:584doi: 10.3389/fgene.2019.00584.
Tseng, E., Rowell, W. J., Glenn, O. C., Hon, T., Barrera, J., Kujawa, S., & Chiba-Falek, O. (2019). The Landscape of . Frontiers in genetics, 10584. https://doi.org/10.3389/fgene.2019.00584
Tseng, Elizabeth, et al. "The Landscape of ." Frontiers in genetics vol. 10 (2019): 584. doi: https://doi.org/10.3389/fgene.2019.00584
Tseng E, Rowell WJ, Glenn OC, Hon T, Barrera J, Kujawa S, Chiba-Falek O. The Landscape of . Front Genet. 2019 Jul 09;10:584. doi: 10.3389/fgene.2019.00584. eCollection 2019. PMID: 31338105; PMCID: PMC6629766.
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Front Genet. 2019 Jul 09;10:584. doi: 10.3389/fgene.2019.00584. eCollection 2019.

The Landscape of .

Frontiers in genetics

Elizabeth Tseng, William J Rowell, Omolara-Chinue Glenn, Ting Hon, Julio Barrera, Steve Kujawa, Ornit Chiba-Falek

Affiliations

  1. Pacific Biosciences, Menlo Park, CA, United States.
  2. Department of Neurology, Duke University Medical Center, Durham, NC, United States.
  3. Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, United States.

PMID: 31338105 PMCID: PMC6629766 DOI: 10.3389/fgene.2019.00584

Abstract

Dysregulation of alpha-synuclein expression has been implicated in the pathogenesis of synucleinopathies, in particular Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Previous studies have shown that the alternatively spliced isoforms of the SNCA gene are differentially expressed in different parts of the brain for PD and DLB patients. Similarly, SNCA isoforms with skipped exons can have a functional impact on the protein domains. The large intronic region of the SNCA gene was also shown to harbor structural variants that affect transcriptional levels. Here, we apply the first study of using long read sequencing with targeted capture of both the gDNA and cDNA of the SNCA gene in brain tissues of PD, DLB, and control samples using the PacBio Sequel system. The targeted full-length cDNA (Iso-Seq) data confirmed complex usage of known alternative start sites and variable 3' UTR lengths, as well as novel 5' starts and 3' ends not previously described. The targeted gDNA data allowed phasing of up to 81% of the ~114 kb SNCA region, with the longest phased block exceeding 54 kb. We demonstrate that long gDNA and cDNA reads have the potential to reveal long-range information not previously accessible using traditional sequencing methods. This approach has a potential impact in studying disease risk genes such as SNCA, providing new insights into the genetic etiologies, including perturbations to the landscape the gene transcripts, of human complex diseases such as synucleinopathies.

Keywords: Iso-Seq; PacBio; Parkinson’s Disease; alternative splicing; isoforms; long read sequencing; targeted sequencing

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