Blood and saliva-derived exomes from healthy Caucasian subjects do not display overt evidence of somatic mosaicism.


Journal

Mutation research
ISSN: 1873-135X
Titre abrégé: Mutat Res
Pays: Netherlands
ID NLM: 0400763

Informations de publication

Date de publication:
Historique:
received: 29 02 2020
revised: 07 04 2020
accepted: 27 04 2020
pubmed: 23 6 2020
medline: 15 12 2020
entrez: 23 6 2020
Statut: ppublish

Résumé

Somatic mosaicism is a normal occurrence during development in the tissues and organs. As part of establishing a "healthy population "(HP) background or base-line, we investigated whether such mosaicism can be routinely detected in the circulating DNA secured from a rigorously designed healthy human liquid biopsy clinical trial (saliva, blood). We deployed next generation (NG) whole exome sequencing (WES) at median exome coverage rates of 97.2 % (-to-30x) and 70.0 % (-to-100x). We found that somatic mosaicism is not detectable by such standard bulk WES sequencing assays in saliva and blood DNA in 24 normal healthy Caucasians of both sexes from 18 to 60 years of age. We conclude that for circulating DNA using standard WES no novel somatic mutational variants can be detected in protein-coding regions of normal healthy subjects. This implies that the extent within normal tissues of somatic mosaicism must be at a lower level, below the detection threshold, for these circulating DNA WES read depths.

Identifiants

pubmed: 32569906
pii: S0027-5107(20)30038-5
doi: 10.1016/j.mrfmmm.2020.111705
pii:
doi:

Substances chimiques

Cell-Free Nucleic Acids 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111705

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Nathan E Hall (NE)

GMDxCo Pty Ltd, Melbourne, Victoria, Australia; Department of Animal, Plant and Soil Sciences, La Trobe University, Melbourne, Victoria, Australia. Electronic address: nathan.hall@gmdxgroup.com.

Jared Mamrot (J)

GMDxCo Pty Ltd, Melbourne, Victoria, Australia; Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Monash University, Clayton, Victoria, Australia. Electronic address: jared.mamrot@gmdxgroup.com.

Chris Frampton (C)

Department of Medicine, University of Otago, Christchurch, New Zealand. Electronic address: chris.frampton@otago.ac.nz.

Prue Read (P)

Five Corners Pty Ltd, 13/76 Reserve Road, Artarmon, NSW Australia. Electronic address: pruef@optusnet.com.au.

Edward J Steele (EJ)

CYO'Connor ERADE Village Foundation, 24 Genomics Rise, Piara Waters, 6112, Perth, Australia; Melville Analytics Pty Ltd, Melbourne, Victoria, Australia. Electronic address: e.j.steele@bigpond.com.

Robert J Bischof (RJ)

Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; School of Health and Life Sciences, Federation University, Berwick, Victoria, Australia. Electronic address: r.bischof@federation.edu.au.

Robyn A Lindley (RA)

GMDxCo Pty Ltd, Melbourne, Victoria, Australia; Melville Analytics Pty Ltd, Melbourne, Victoria, Australia; Department of Clinical Pathology, The Victorian Comprehensive Cancer Centre, Faculty of Medicine, Dentistry & Health Sciences, University of Melbourne, Victoria, Australia. Electronic address: robyn.lindley@gmdxgroup.com.

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Classifications MeSH