Genetic regulatory variation in populations informs transcriptome analysis in rare disease.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
18 10 2019
18 10 2019
Historique:
received:
13
05
2019
accepted:
24
09
2019
pubmed:
12
10
2019
medline:
9
4
2020
entrez:
12
10
2019
Statut:
ppublish
Résumé
Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data showed that this variance estimate is robust and correlated with selective constraint in a gene. Using these variance estimates in a dosage outlier test (ANEVA-DOT) applied to AE data from 70 Mendelian muscular disease patients showed accuracy in detecting genes with pathogenic variants in previously resolved cases and led to one confirmed and several potential new diagnoses. Using our reference estimates from GTEx data, ANEVA-DOT can be incorporated in rare disease diagnostic pipelines to use RNA-sequencing data more effectively.
Identifiants
pubmed: 31601707
pii: science.aay0256
doi: 10.1126/science.aay0256
pmc: PMC6814274
mid: NIHMS1052509
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-356Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001114
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH107666
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH106842
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NHGRI NIH HHS
ID : R15 HG009569
Pays : United States
Organisme : NHGRI NIH HHS
ID : K99 HG009916
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002550
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122924
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Database (Oxford). 2017 Jan 1;2017:
pubmed: 28605766
Nat Genet. 2016 Mar;48(3):245-52
pubmed: 26854917
Neuromuscul Disord. 2015 Dec;25(12):991-1020
pubmed: 27563712
Nat Methods. 2015 Nov;12(11):1061-3
pubmed: 26366987
Nat Genet. 2015 Jan;47(1):88-91
pubmed: 25436857
NPJ Genom Med. 2018 Feb 5;3:5
pubmed: 29423277
PLoS Genet. 2013;9(8):e1003709
pubmed: 23990802
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Nat Rev Genet. 2015 Mar;16(3):172-83
pubmed: 25645873
Nat Med. 2019 Jun;25(6):911-919
pubmed: 31160820
Genome Res. 2014 Jan;24(1):14-24
pubmed: 24092820
NPJ Genom Med. 2018 Apr 4;3:10
pubmed: 29644095
Am J Hum Genet. 2019 Mar 7;104(3):466-483
pubmed: 30827497
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Nat Commun. 2016 Sep 27;7:12824
pubmed: 27670201
Genetics. 2019 Feb;211(2):757-772
pubmed: 30554168
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Genome Res. 2017 Nov;27(11):1872-1884
pubmed: 29021289
Sci Transl Med. 2017 Apr 19;9(386):
pubmed: 28424332
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Genome Biol. 2010;11(10):R106
pubmed: 20979621
Nature. 2017 Oct 11;550(7675):239-243
pubmed: 29022581
Nat Commun. 2019 Jun 28;10(1):2837
pubmed: 31253775
PLoS Genet. 2011 Feb;7(2):e1001317
pubmed: 21383966
Nature. 2013 Sep 26;501(7468):506-11
pubmed: 24037378
Nature. 2015 Mar 12;519(7542):223-8
pubmed: 25533962
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Genome Biol. 2015 Sep 17;16:195
pubmed: 26381377
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Nat Genet. 2018 Mar;50(3):333-337
pubmed: 29483654
PLoS Genet. 2016 Nov 11;12(11):e1006423
pubmed: 27835642
PLoS Genet. 2015 Sep 02;11(9):e1005492
pubmed: 26332131
Nat Genet. 2019 Jan;51(1):88-95
pubmed: 30531870
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427
Genome Res. 2015 Jul;25(7):927-36
pubmed: 25953952
Nat Commun. 2016 Sep 08;7:12817
pubmed: 27605262
Nat Commun. 2017 Jun 12;8:15824
pubmed: 28604674
Science. 2015 Dec 4;350(6265):1262-6
pubmed: 26785492