Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
14 Mar 2022
14 Mar 2022
Historique:
received:
10
08
2021
accepted:
04
02
2022
entrez:
15
3
2022
pubmed:
16
3
2022
medline:
16
3
2022
Statut:
epublish
Résumé
Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10
Identifiants
pubmed: 35288587
doi: 10.1038/s41525-022-00288-y
pii: 10.1038/s41525-022-00288-y
pmc: PMC8921194
doi:
Types de publication
Journal Article
Langues
eng
Pagination
18Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/M009203/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009203/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_14089
Pays : United Kingdom
Investigateurs
J C Ambrose
(JC)
P Arumugam
(P)
E L Baple
(EL)
M Bleda
(M)
F Boardman-Pretty
(F)
J M Boissiere
(JM)
C R Boustred
(CR)
H Brittain
(H)
M J Caulfield
(MJ)
G C Chan
(GC)
C E H Craig
(CEH)
L C Daugherty
(LC)
A de Burca
(A)
A Devereau
(A)
G Elgar
(G)
R E Foulger
(RE)
T Fowler
(T)
P Furió-Tarí
(P)
A Giess
(A)
J M Hackett
(JM)
D Halai
(D)
A Hamblin
(A)
S Henderson
(S)
J E Holman
(JE)
T J P Hubbard
(TJP)
K Ibáñez
(K)
R Jackson
(R)
L J Jones
(LJ)
D Kasperaviciute
(D)
M Kayikci
(M)
A Kousathanas
(A)
L Lahnstein
(L)
K Lawson
(K)
S E A Leigh
(SEA)
I U S Leong
(IUS)
F J Lopez
(FJ)
F Maleady-Crowe
(F)
J Mason
(J)
E M McDonagh
(EM)
L Moutsianas
(L)
M Mueller
(M)
N Murugaesu
(N)
A C Need
(AC)
C A Odhams
(CA)
A Orioli
(A)
C Patch
(C)
D Perez-Gil
(D)
M B Pereira
(MB)
D Polychronopoulos
(D)
J Pullinger
(J)
T Rahim
(T)
A Rendon
(A)
P Riesgo-Ferreiro
(P)
T Rogers
(T)
M Ryten
(M)
K Savage
(K)
K Sawant
(K)
R H Scott
(RH)
A Siddiq
(A)
A Sieghart
(A)
D Smedley
(D)
K R Smith
(KR)
S C Smith
(SC)
A Sosinsky
(A)
W Spooner
(W)
H E Stevens
(HE)
A Stuckey
(A)
R Sultana
(R)
M Tanguy
(M)
E R A Thomas
(ERA)
S R Thompson
(SR)
C Tregidgo
(C)
A Tucci
(A)
E Walsh
(E)
S A Watters
(SA)
M J Welland
(MJ)
E Williams
(E)
K Witkowska
(K)
S M Wood
(SM)
M Zarowiecki
(M)
Informations de copyright
© 2022. The Author(s).
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