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

Deaminase associated single nucleotide variants in blood and saliva-derived exomes from healthy subjects

View ORCID ProfileNathan E. Hall, View ORCID ProfileJared Mamrot, Christopher M.A. Frampton, Prue Read, Edward J. Steele, Robert J. Bischof, Robyn A. Lindley
doi: https://doi.org/10.1101/807073
Nathan E. Hall
1GMDx Group Ltd, Melbourne, 3000, Victoria, AUSTRALIA
2Department of Animal, Plant and Soil Sciences, La Trobe University, Melbourne, Victoria, AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nathan E. Hall
  • For correspondence: nathan.hall@gmdxgroup.com
Jared Mamrot
1GMDx Group Ltd, Melbourne, 3000, Victoria, AUSTRALIA
3The Ritchie Centre, Hudson Institute of Medical Research, Clayton, 3168 Victoria, AUSTRALIA
4Monash University, Clayton, Victoria, AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jared Mamrot
Christopher M.A. Frampton
5Department of Medicine, University of Otago, Christchurch, NEW ZEALAND
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Prue Read
1GMDx Group Ltd, Melbourne, 3000, Victoria, AUSTRALIA
6Five Corners Pty Ltd 13/76 Reserve Road, Artarmon, NSW AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Edward J. Steele
7CYO’Connor ERADE Village Foundation, 24 Genomics Rise, Piara Waters, Perth, AUSTRALIA
8Melville Analytics Pty Ltd, Melbourne, Victoria, AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert J. Bischof
3The Ritchie Centre, Hudson Institute of Medical Research, Clayton, 3168 Victoria, AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robyn A. Lindley
1GMDx Group Ltd, Melbourne, 3000, Victoria, AUSTRALIA
9Department of Clinical Pathology, The Victorian Comprehensive Cancer Centre, Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Victoria, AUSTRALIA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Background Deaminases play an important role in shaping inherited and somatic variants. Disease related SNVs are associated with deaminase mutagenesis and genome instability. Here, we investigate the reproducibility and variance of whole exome SNV calls in blood and saliva of healthy subjects and analyze variants associated with AID, ADAR, APOBEC3G and APOBEC3B deaminase sequence motifs.

Methods Samples from twenty-four healthy Caucasian volunteers, allocated into two groups, underwent whole exome sequencing. Group 1 (n=12) analysis involved one blood and four saliva replicates. A single saliva sample was sequenced for Group 2 subjects (n=12). Overall, a total of 72 whole exome datasets were analyzed. Biological (Group 1 & 2) and technical (Group 1) variance of SNV calls and deaminase metrics were calculated and analyzed using intraclass correlation coefficients. Candidate somatic SNVs were identified and evaluated.

Results We report high blood-saliva concordance in germline SNVs from whole exome sequencing. Concordant SNVs, found in all subject replicates, accounted for 97% of SNVs located within the protein coding sequence of genes. Discordant SNVs have a 30% overlap with variants that fail gnomAD quality filters and are less likely to be found in dbSNP. SNV calls and deaminase-associated metrics were found to be reproducible and robust (intraclass correlation coefficients >0.95). No somatic SNVs were conclusively identified when comparing blood and saliva samples.

Conclusions Saliva and blood both provide high quality sources of DNA for whole exome sequencing, with no difference in ability to resolve SNVs and deaminase-associated metrics. We did not identify somatic SNVs when comparing blood and saliva of healthy individuals, and we conclude that more specialized investigative methods are required to comprehensively assess the impact of deaminase activity on genome stability in healthy individuals.

Footnotes

  • Author Information: Nathan E. Hall nathan.hall{at}gmdxgroup.com, Jared Mamrot jared.mamrot{at}gmdxgroup.com, Christopher M.A. Frampton chris.frampton{at}otago.ac.nz, Prue Read pruef{at}optusnet.com.au, Edward J. Steele e.j.steele{at}bigpond.com, Robert J. Bischof robert.bischof{at}hudson.org.au, Robyn A. Lindley robyn.lindley{at}gmdxgroup.com

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 4.0 International license.
Back to top
PreviousNext
Posted October 16, 2019.
Download PDF

Supplementary Material

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.
Deaminase associated single nucleotide variants in blood and saliva-derived exomes from healthy subjects
(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
Deaminase associated single nucleotide variants in blood and saliva-derived exomes from healthy subjects
Nathan E. Hall, Jared Mamrot, Christopher M.A. Frampton, Prue Read, Edward J. Steele, Robert J. Bischof, Robyn A. Lindley
bioRxiv 807073; doi: https://doi.org/10.1101/807073
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Deaminase associated single nucleotide variants in blood and saliva-derived exomes from healthy subjects
Nathan E. Hall, Jared Mamrot, Christopher M.A. Frampton, Prue Read, Edward J. Steele, Robert J. Bischof, Robyn A. Lindley
bioRxiv 807073; doi: https://doi.org/10.1101/807073

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

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2430)
  • Biochemistry (4791)
  • Bioengineering (3332)
  • Bioinformatics (14676)
  • Biophysics (6637)
  • Cancer Biology (5168)
  • Cell Biology (7425)
  • Clinical Trials (138)
  • Developmental Biology (4365)
  • Ecology (6873)
  • Epidemiology (2057)
  • Evolutionary Biology (9918)
  • Genetics (7346)
  • Genomics (9527)
  • Immunology (4554)
  • Microbiology (12684)
  • Molecular Biology (4945)
  • Neuroscience (28325)
  • Paleontology (199)
  • Pathology (808)
  • Pharmacology and Toxicology (1391)
  • Physiology (2024)
  • Plant Biology (4497)
  • Scientific Communication and Education (977)
  • Synthetic Biology (1299)
  • Systems Biology (3914)
  • Zoology (726)