Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,594 bioRxiv papers from 298,298 authors.
Contribution of non-coding mutations to RPGRIP1-mediated inherited retinal degeneration.
Emily M. Place,
Timothy J. Cherry,
Eric A. Pierce,
Kinga M. Bujakowska
Posted 30 Oct 2017
bioRxiv DOI: 10.1101/211292 (published DOI: 10.1038/s41436-018-0104-7)
Posted 30 Oct 2017
Purpose: With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision making. Yet the genetic cause of disease cannot be identified using exon based sequencing for a significant portion of patients. We hypothesized that noncoding mutations contribute significantly to the genetic causality of IRDs and evaluated patients with single coding mutations in RPGRIP1 to test this hypothesis. Methods: IRD families underwent targeted panel sequencing. Unsolved cases were explored by whole exome and genome sequencing looking for additional mutations. Candidate mutations were then validated by Sanger sequencing, quantitative PCR, and in vitro splicing assays in two cell lines analyzed through amplicon sequencing. Results: Among 1722 families, three had biallelic loss of function mutations in RPGRIP1 while seven had a single disruptive coding mutation. Whole exome and genome sequencing revealed potential noncoding mutations in these seven families. In six, the noncoding mutations were shown to lead to loss of function in vitro. Conclusion: Noncoding mutations were identified in 6 of 7 families with single coding mutations in RPGRIP1. The results suggest that noncoding mutations contribute significantly to the genetic causality of IRDs and RPGRIP1 mediated IRDs are more common than previously thought.
- Downloaded 736 times
- Download rankings, all-time:
- Site-wide: 12,596 out of 67,594
- In genomics: 1,741 out of 4,581
- Year to date:
- Site-wide: 20,521 out of 67,594
- Since beginning of last month:
- Site-wide: 24,560 out of 67,594
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!