Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Differential variant calling in mutants from diverse genetic backgrounds: A case study in the nematode Pristionchus pacificus

View ORCID ProfileChristian Rödelsperger, Eduardo Moreno
doi: https://doi.org/10.1101/138479
Christian Rödelsperger
1Department for Integrative Evolutionary Biology, Max Planck Institute for Developmental Biology, Spemannstr. 35, 762076, Tübingen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christian Rödelsperger
  • For correspondence: christian.roedelsperger@tuebingen.mpg.de
Eduardo Moreno
1Department for Integrative Evolutionary Biology, Max Planck Institute for Developmental Biology, Spemannstr. 35, 762076, Tübingen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Genome sequencing of mutants is one of the most widely used techniques to identify genes that control traits of interest including human diseases. Traditionally, variants are called against reference genomes and various filtering techniques are applied to reduce the number of candidate mutations. However, if the genetic background of the mutant is different from the reference genome, the number of background variants may exceed the number of true mutations by several orders of magnitude resulting in candidate lists that cannot be effectively reduced.

We introduce the problem of differential variant calling in mutants from diverse genetic backgrounds. In the example of a mutant strain of the nematode Pristionchus pacificus, where the genetic background is not identical to the reference genome (≈1% genome-wide divergence), we show that simple intersection filtering does not effectively reduce the list of candidate mutations due to the combined effect of high number of background mutations, missing coverage in the wildtype sample, and problematic regions in the genome assembly. Although restriction to sites with coverage in mutant and wildtype sample greatly reduced the number of candidate sites, we further improved this candidate set by implementing a customized variant calling procedure. This takes the mutant sample and the control sample of same genetic background as input and calls variants exhibiting strong discriminative signals across the two samples. Intersecting the candidate mutations with an interval identfied from mapping by RAD-seq revealed a likely splice-site mutation in the P. pacificus dpy-1 gene, which has been previously shown to cause the associated morphological phenotype.

Our study shows that combined analysis of mutant and wildtype samples drastically increases the potential to find true mutations. We hope that these results may be helpful for other model systems, where the identification of candidate mutants is complicated by assembly errors, lab-derived mutations, or different genetic backgrounds.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted May 16, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Differential variant calling in mutants from diverse genetic backgrounds: A case study in the nematode Pristionchus pacificus
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Differential variant calling in mutants from diverse genetic backgrounds: A case study in the nematode Pristionchus pacificus
Christian Rödelsperger, Eduardo Moreno
bioRxiv 138479; doi: https://doi.org/10.1101/138479
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Differential variant calling in mutants from diverse genetic backgrounds: A case study in the nematode Pristionchus pacificus
Christian Rödelsperger, Eduardo Moreno
bioRxiv 138479; doi: https://doi.org/10.1101/138479

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3504)
  • Biochemistry (7346)
  • Bioengineering (5321)
  • Bioinformatics (20259)
  • Biophysics (10013)
  • Cancer Biology (7742)
  • Cell Biology (11298)
  • Clinical Trials (138)
  • Developmental Biology (6437)
  • Ecology (9950)
  • Epidemiology (2065)
  • Evolutionary Biology (13318)
  • Genetics (9360)
  • Genomics (12581)
  • Immunology (7700)
  • Microbiology (19016)
  • Molecular Biology (7439)
  • Neuroscience (41029)
  • Paleontology (300)
  • Pathology (1229)
  • Pharmacology and Toxicology (2135)
  • Physiology (3157)
  • Plant Biology (6860)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1895)
  • Systems Biology (5311)
  • Zoology (1089)