Human Genetics of Atrial Septal Defect.

Although atrial septal defects (ASD) can be subdivided based on their anatomical location, an essential aspect of human genetics and genetic counseling is distinguishing between isolated and familiar cases without extracardiac features and syndromic cases with the co-occurrence of extracardiac abnormalities, such as developmental delay. Isolated or familial cases tend to show genetic alterations in genes related to important cardiac transcription factors and genes encoding for sarcomeric proteins. By contrast, the spectrum of genes with genetic alterations observed in syndromic cases is diverse. Currently, it points to different pathways and gene networks relevant to the dysregulation of cardiomyogenesis and ASD pathogenesis. Therefore, this chapter reflects the current knowledge and highlights stable associations observed in human genetics studies. It gives an overview of the different types of genetic alterations in these subtypes, including common associations based on genome-wide association studies (GWAS), and it highlights the most frequently observed syndromes associated with ASD pathogenesis.

Improving the efficiency of estrus synchronization in cows.

Objective: This study aimed to determine the effects of biologically active substances and electrical stimulation of the uterus in cows on the effectiveness of estrus synchronization. Materials and Methods: Ninety (n = 90) Kazakh white-headed cows were synchronized with two injections of gonadotropin-releasing hormone on days 0 and 9 and prostaglandin F2α on day 7. The cows were divided into six groups and, during the protocol, treated with biologically active substances (Tetramag, Selevetum, antiseptic-stimulator Dorogov 2 fraction, groups 2, 3, and 4). Cows in groups 5 and 6 were treated with the same substances but additionally had electrical stimulation of the uterus, while cows in group 1 were left untreated and served as a control. Results: The results have shown that on Day 0, no differences were observed in E2 concentrations between the groups. However, on the 10th day, a significant disparity was noted in the E2 level among cows in group 6 compared to groups 2, 3, 4, and the control group. Conversely, no significant differences were observed between groups 5 and 6. Likewise, the fertility rate in cows from group 6 was significantly higher compared to groups 2, 3, 4, and the control group, with no significant differences between groups 5 and 6. Conclusion: It can be concluded that the utilization of electrical stimulation of the uterus and the inclusion of certain biological substances during the estrus synchronization protocol demonstrate a positive effect on the reproductive performance of beef cattle in Kazakhstan.

ALG-1 Influences Accurate mRNA Splicing Patterns in the Caenorhabditis elegans Intestine and Body Muscle Tissues by Modulating Splicing Factor Activities.

MicroRNAs (miRNAs) are known to modulate gene expression, but their activity at the tissue-specific level remains largely uncharacterized. To study their contribution to tissue-specific gene expression, we developed novel tools to profile putative miRNA targets in the Caenorhabditis elegans intestine and body muscle. We validated many previously described interactions and identified ∼3500 novel targets. Many of the candidate miRNA targets curated are known to modulate the functions of their respective tissues. Within our data sets we observed a disparity in the use of miRNA-based gene regulation between the intestine and body muscle. The intestine contained significantly more putative miRNA targets than the body muscle highlighting its transcriptional complexity. We detected an unexpected enrichment of RNA-binding proteins targeted by miRNA in both tissues, with a notable abundance of RNA splicing factors. We developed in vivo genetic tools to validate and further study three RNA splicing factors identified as putative miRNA targets in our study (asd-2, hrp-2, and smu-2), and show that these factors indeed contain functional miRNA regulatory elements in their 3'UTRs that are able to repress their expression in the intestine. In addition, the alternative splicing pattern of their respective downstream targets (unc-60, unc-52, lin-10, and ret-1) is dysregulated when the miRNA pathway is disrupted. A reannotation of the transcriptome data in C. elegans strains that are deficient in the miRNA pathway from past studies supports and expands on our results. This study highlights an unexpected role for miRNAs in modulating tissue-specific gene isoforms, where post-transcriptional regulation of RNA splicing factors associates with tissue-specific alternative splicing.

Switch-like regulation of tissue-specific alternative pre-mRNA processing patterns revealed by customized fluorescence reporters.

Alternative processing of precursor mRNAs (pre-mRNAs), including alternative transcription start sites, alternative splicing and alternative polyadenylation, is the major source of protein diversity and plays crucial roles in development, differentiation and diseases in higher eukaryotes. It is estimated from microarray analyses and deep sequencing of mRNAs from synchronized worms that up to 25% of protein-coding genes in Caenorhabditis elegans undergo alternative pre-mRNA processing and that many of them are subject to developmental regulation. Recent progress in visualizing the alternative pre-mRNA processing patterns in living worms with custom-designed fluorescence reporters has enabled genetic analyses of the regulatory mechanisms for alternative processing events of interest in vivo. Expression of the tissue-specific isoforms of actin depolymerising factor (ADF)/cofilin, UNC-60A and UNC-60B, is regulated by a combination of alternative splicing and alternative polyadenylation of pre-mRNA from a single gene unc-60. We recently found that muscle-specific splicing regulators ASD-2 and SUP-12 cooperatively switch the pre-mRNA processing patterns of the unc-60 gene in body wall muscles. Here I summarize the bichromatic fluorescence reporter system utilized for visualizing the tissue-specific alternative processing patterns of the unc-60 pre-mRNA. I also discuss the model for the coordinated regulation of the UNC-60B-type pre-mRNA processing in body wall muscles by ASD-2 and SUP-12.