Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cardiovascular Division, Brigham and Women's Hospital, Harvard University, Boston, Massachusetts 02115, USA.
Nat Commun. 2016 Sep 27;7:12824. doi: 10.1038/ncomms12824.
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.
先天性心脏病（CHD）是一种常见的出生缺陷，在新生儿中的发生率为 1%，可能是由于心脏发育基因的异常表达所致。各种心脏转录因子、发育信号分子和修饰染色质的分子的突变导致至少 20%的疾病，但大多数 CHD 仍然无法解释。我们采用 RNAseq 分析方法，在 144 例接受手术修复的 CHD 患者的 172 个组织样本中评估等位基因特异性表达（ASE）和双等位基因表达缺失（LOE）。结果显示，在具有父源等位基因沉默的已知印记基因中，仅有 5%是单等位基因，而 56%是具有父源等位基因表达的-这种心脏特异性现象似乎与 CHD 无关。此外，与对照组相比，CHD 患者的 LOE 基因和与基因表达改变相关的 ASE 事件负担显著增加。这些研究发现 FGFBP2、LBH、RBFOX2、SGSM1 和 ZBTB16 作为候选 CHD 基因，因为它们的转录表达显著改变。
