Copy number variants in Ebstein anomaly
PLOS ONE
Authors: Giannakou, Andreas; Sicko, Robert J.; Zhang, Wei; Romitti, Paul; Browne, Marilyn L.; Caggana, Michele; Brody, Lawrence C.; Jelliffe-Pawlowski, Laura; Shaw, Gary M.; Kay, Denise M.; Mills, James L.
Abstract
Background Ebstein anomaly (EA) is a rare congenital defect characterized by apical displacement of the septal tricuspid leaflets and atrialization of the right ventricle. The etiology of EA is unclear; however, recurrence in families and the association of EA with genetic syndromes and copy number variants (CNVs) suggest a genetic component. Objective We performed a population-based study to search for recurrent and novel CNVs in a previously unreported set of EA cases. Methods We genotyped 60 EA cases identified from all live births (2,891,076) from selected California counties (1991-2010) using the Illumina HumanOmni 2.5-8 array. We identified 38 candidate CNVs in 28 (46%) cases and prioritized and validated 11 CNVs based on the genes included. Results Five CNVs (41%) overlapped or were close to genes involved in early myocardial development, including NODAL, PDLIM5, SIX1, ASF1A and FGF12. We also replicated a previous association of EA with CNVs at 1p34.1 and AKAP12. Finally, we identified four CNVs overlapping or in close proximity to the transcription factors HES3, TRIM71, CUX1 and EIF4EBP2. Conclusions This study supports the relationship of genetic factors to EA and demonstrates that defects in cardiomyocytes and myocardium differentiation may play a role. Abnormal differentiation of cardiomyocytes and how genetic factors contribute should be examined for their association with EA.
High-throughput transcriptome analysis reveals potentially important relationships between lncRNAs and genes in broilers affected by Valgus-varus Deformity (Gallus gallus)
GENE
Authors: Guo, Yaping; Tang, Hehe; Li, Zhuanjian; Zhang, Yanhua; Li, Donghua; Li, Wenting; Sun, Guirong; Kang, Xiangtao; Han, Ruili
Abstract
Valgus-varus Deformity (VVD) is an outward or inward deviation of the tibiotarsus or tarsometatarsus, which results in physical distress of chickens and economic loss in poultry industry. While the etiology and pathogenesis of VVD at the molecular level are still not fully understood so far. Here, based on a case/control design with VVD birds and normal birds, we identified genes and lncRNAs which associated with VVD using RNA sequencing. Transcriptome analysis revealed 231 differentially expressed mRNAs and 23 differentially expressed lncRNAs between case and control of leg cartilage. We identified the cis- and trans-regulatory targets of the differentially expressed lncRNAs, and we constructed a functional 1ncRNA-mRNA co-expression network. Analysis of the network showed that the differentially expressed mRNAs and the target genes of the differentially expressed lncRNAs were enriched in the signaling pathways associated with bone development, including p53, MAPK, Toll-like receptor, Jak-STAT, Hedgehog, and PPAR. The expression levels of DENND4A, FGF10, FGF12 and BMP3 were also determined in cartilage and other six tissues. Overall, our study predicted the mRNAs and lncRNAs related with leg diseases by transcriptome analyses, which might contribute to understand the etiology and pathogenesis of VVD. It established the foundation for the further research on the function of -mRNAs and lncRNAs in skeleton development.