Validation of low-coverage whole-genome sequencing for mitochondrial DNA variants suggests mitochondrial DNA as a genetic cause of preterm birth.
human genetics
low-coverage whole-genome sequencing
mitochondrial disease
mitochondrial genome
preterm birth
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
17
07
2021
received:
06
05
2021
accepted:
29
08
2021
pubmed:
2
9
2021
medline:
1
4
2022
entrez:
1
9
2021
Statut:
ppublish
Résumé
Preterm birth (PTB), or birth that occurs earlier than 37 weeks of gestational age, is a major contributor to infant mortality and neonatal hospitalization. Mutations in the mitochondrial genome (mtDNA) have been linked to various rare mitochondrial disorders and may be a contributing factor in PTB given that maternal genetic factors have been strongly linked to PTB. However, to date, no study has found a conclusive connection between a particular mtDNA variant and PTB. Given the high mtDNA copy number per cell, an automated pipeline was developed for detecting mtDNA variants using low-coverage whole-genome sequencing (lcWGS) data. The pipeline was first validated against samples of known heteroplasmy, and then applied to 929 samples from a PTB cohort from diverse ethnic backgrounds with an average gestational age of 27.18 weeks (range: 21-30). Our new pipeline successfully identified haplogroups and a large number of mtDNA variants in this large PTB cohort, including 8 samples carrying known pathogenic variants and 47 samples carrying rare mtDNA variants. These results confirm that lcWGS can be utilized to reliably identify mtDNA variants. These mtDNA variants may make a contribution toward preterm birth in a small proportion of live births.
Identifiants
pubmed: 34467602
doi: 10.1002/humu.24279
pmc: PMC9290920
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1602-1614Informations de copyright
© 2021 The Authors. Human Mutation Published by Wiley Periodicals LLC.
Références
Genome Med. 2019 Nov 26;11(1):74
pubmed: 31771638
Nature. 2015 Aug 13;524(7564):234-8
pubmed: 26176921
Pediatr Res. 2009 Jan;65(1):1-9
pubmed: 18787421
J Inherit Metab Dis. 2020 Jan;43(1):36-50
pubmed: 31021000
Proc Natl Acad Sci U S A. 2015 Feb 24;112(8):2491-6
pubmed: 25675502
Genetics. 1996 Dec;144(4):1835-50
pubmed: 8978068
Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15212-6
pubmed: 22932870
Mitochondrion. 2008 Mar;8(2):130-5
pubmed: 18082471
Mitochondrial DNA. 2015 Jun;26(3):445-51
pubmed: 24102597
J Genet Genomics. 2020 Mar 20;47(3):167-169
pubmed: 32317151
Cell Metab. 2016 Aug 9;24(2):283-94
pubmed: 27425585
Mitochondrion. 2020 Jul;53:38-47
pubmed: 32361035
BMC Pregnancy Childbirth. 2020 Apr 6;20(1):201
pubmed: 32252663
BMC Pregnancy Childbirth. 2019 Feb 6;19(1):57
pubmed: 30727983
Pediatr Res. 2012 Nov;72(5):539-44
pubmed: 22902432
Nature. 2010 Oct 28;467(7319):1061-73
pubmed: 20981092
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6616-6621
pubmed: 32156736
Obstet Gynecol Int J. 2014;1(3):
pubmed: 25905109
Biotechniques. 2010 Apr;48(4):287-96
pubmed: 20569205
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Development. 2017 Jul 1;144(13):2490-2503
pubmed: 28576772
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10654-9
pubmed: 25002485
Ann Neurol. 2015 May;77(5):753-9
pubmed: 25652200
Am J Epidemiol. 2013 Aug 15;178(4):543-50
pubmed: 23568591
Ann Neurol. 2008 Jan;63(1):35-9
pubmed: 17886296
BMC Genomics. 2020 Dec 9;21(1):882
pubmed: 33297960
J Cell Physiol. 1988 Sep;136(3):507-13
pubmed: 3170646
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Cells. 2019 Jun 18;8(6):
pubmed: 31216686
Pediatr Res. 2019 Mar;85(4):422-431
pubmed: 30353040
PLoS One. 2016 Sep 13;11(9):e0162506
pubmed: 27622562
PLoS One. 2013 Apr 24;8(4):e62005
pubmed: 23637946
Hum Genet. 2015 Jul;134(7):803-8
pubmed: 25920518
N Engl J Med. 2017 Sep 21;377(12):1156-1167
pubmed: 28877031
Nat Ecol Evol. 2019 Feb;3(2):213-222
pubmed: 30643241
Sci Rep. 2019 Apr 2;9(1):5501
pubmed: 30940880
BJOG. 2019 Oct;126(11):1380-1389
pubmed: 30801962
Am J Hum Genet. 2008 Aug;83(2):254-60
pubmed: 18674747
Hum Mutat. 2021 Dec;42(12):1602-1614
pubmed: 34467602
J Genet Genomics. 2018 Jun 6;:
pubmed: 29910094
Hum Genet. 2014 Jul;133(7):861-8
pubmed: 24488180
J Pediatr. 2018 Mar;194:40-46.e4
pubmed: 29249523
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Chin Med J (Engl). 2017 Oct 20;130(20):2435-2440
pubmed: 29052564
Biomarkers. 2014 Jun;19(4):269-74
pubmed: 24773072
Am J Epidemiol. 2009 Dec 1;170(11):1358-64
pubmed: 19854807
Curr Protoc Hum Genet. 2011 Oct;Chapter 19:Unit19.8
pubmed: 21975941
Mitochondrion. 2015 Nov;25:98-103
pubmed: 26455484
BMJ. 2004 Sep 18;329(7467):675-8
pubmed: 15374920
Am J Obstet Gynecol. 2006 Sep;195(3):643-50
pubmed: 16949395
PLoS One. 2014 Oct 03;9(10):e109470
pubmed: 25279731
Cold Spring Harb Perspect Biol. 2013 Nov 01;5(11):a021220
pubmed: 24186072
Curr Protoc Bioinformatics. 2013 Dec;44:1.23.1-26
pubmed: 25489354