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Loss of RNA expression and allele-specific expression associated with congenital heart disease

David M. McKean; Jason Homsy; Hiroko Wakimoto; Neil Patel; James S. Ware; Steven R. DePalma; Joshua Gorham; Samir Zaidi; Wenji Ma; Nihir Patel; Yufeng Shen; Wendy K. Chung; Richard P. Lifton; Richard Kim; Martina Brueckner; Elizabeth Goldmuntz; Andrew J. Sharp; Christine E. Seidman; Bruce D. Gelb; J. G. Seidman

Title:
Loss of RNA expression and allele-specific expression associated with congenital heart disease
Author(s):
McKean, David M.
Homsy, Jason
Wakimoto, Hiroko
Patel, Neil
Ware, James S.
DePalma, Steven R.
Gorham, Joshua
Zaidi, Samir
Ma, Wenji
Patel, Nihir
Shen, Yufeng
Chung, Wendy K.
Lifton, Richard P.
Kim, Richard
Brueckner, Martina
Goldmuntz, Elizabeth
Sharp, Andrew J.
Seidman, Christine E.
Gelb, Bruce D.
Seidman, J. G.
Date:
Type:
Articles
Department(s):
Systems Biology
Pediatrics
Biomedical Informatics
Volume:
7
Persistent URL:
Book/Journal Title:
Nature Communications
Publisher:
Nature Publishing Group
Abstract:
Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression.
Subject(s):
Gene expression
Abnormalities, Human
RNA
Congenital heart disease
Genetics
Publisher DOI:
https://doi.org/10.1038/ncomms12824
Item views
112
Metadata:
text | xml
Suggested Citation:
David M. McKean, Jason Homsy, Hiroko Wakimoto, Neil Patel, James S. Ware, Steven R. DePalma, Joshua Gorham, Samir Zaidi, Wenji Ma, Nihir Patel, Yufeng Shen, Wendy K. Chung, Richard P. Lifton, Richard Kim, Martina Brueckner, Elizabeth Goldmuntz, Andrew J. Sharp, Christine E. Seidman, Bruce D. Gelb, J. G. Seidman, , Loss of RNA expression and allele-specific expression associated with congenital heart disease, Columbia University Academic Commons, .

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