Rxivist logo

Single-cell RNA-seq of mouse dopaminergic neurons informs candidate gene selection for sporadic Parkinson's disease

By Paul W. Hook, Sarah A. McClymont, Gabrielle H. Cannon, William D. Law, A. Jennifer Morton, Loyal A. Goff, Andrew S. McCallion

Posted 09 Jun 2017
bioRxiv DOI: 10.1101/148049 (published DOI: 10.1016/j.ajhg.2018.02.001)

Genetic variation modulating risk of sporadic Parkinson′s disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research.

Download data

  • Downloaded 2,182 times
  • Download rankings, all-time:
    • Site-wide: 5,046 out of 116,126
    • In genetics: 272 out of 5,126
  • Year to date:
    • Site-wide: 30,799 out of 116,126
  • Since beginning of last month:
    • Site-wide: 27,926 out of 116,126

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News