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

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.

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.


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Also Published In

Nature Communications

More About This Work

Academic Units
Systems Biology
Biomedical Informatics
Nature Publishing Group
Published Here
October 29, 2016