Genome-Wide Analysis in the Study of the Fetal Growth Restriction Pathogenetics

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Abstract

Fetal growth restriction is a complication of pregnancy that defined as the inability of the fetus to realize its genetically determined growth potential. Despite the high social and medical significance of this problem the exact pathogenesis of fetal growth restriction is not known by now. Therefore, the analysis of the molecular genetics mechanisms of this pathology within the framework of approaches using modern high-performance technologies of next generation sequencing is of undoubted interest. In this review we focused on the analysis of data obtained in studies of the fetal growth restriction genetics component. The authors of these researches used next generation sequencing technologies and carried out whole transcriptome profiling. The results of the genes expression genome-wide analysis in placental tissue allow us to identify 1430 differentially expressed genes between fetal growth restriction and normal pregnancy, of which only 1% were found in at least two studies. These differentially expressed genes are involved in the Wnt/β-catenin signaling pathway that plays an important role in cell migration, neural pattern formation and organogenesis during embryonic development. Common genes are associated with both obstetric and gynecological diseases, as well as with various somatic conditions from the groups of neurodegenerative, cardiovascular diseases and mental disorders, which probably reflects their involvement in the development of postnatal consequences of fetal growth restriction. The results of our work don‘t point only to potential molecular mechanisms and key genes underlying fetal growth restriction, but also indicate the important role of gene-gene communications in this pathology implementation: about 30% of all identified differentially expressed genes products interact with each other within the same gene network. In general, genome-wide RNA sequencing combined with the analysis of protein-protein interactions represents a promising direction in research on the development and functioning of the placenta, as well as the identification of placental insufficiency diseases genetics mechanisms, including fetal growth restriction.

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M. M. Gavrilenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center

Author for correspondence.
Email: maria.gavrilenko@medgenetics.ru
Russian Federation, Tomsk, 634050

E. A. Trifonova

Research Institute of Medical Genetics, Tomsk National Research Medical Center

Email: maria.gavrilenko@medgenetics.ru
Russian Federation, Tomsk, 634050

V. A. Stepanov

Research Institute of Medical Genetics, Tomsk National Research Medical Center

Email: maria.gavrilenko@medgenetics.ru
Russian Federation, Tomsk, 634050

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2. Fig. 1. Venn diagram showing the commonality and specificity of DEGs identified in whole-transcriptome studies of IRR.

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3. Fig. 2. Association analysis of 16 DEGs with various diseases according to literature data and the DisGeNet database. RML – recurrent pregnancy loss; POF – premature ovarian failure; PCOS – polycystic ovary syndrome. The DisGeNET score takes into account the number of sources reporting the association, the type of curation of each of these sources, the animal models in which the association was studied, and the number of supporting publications. The score ranges from 0 to 1 and gives the highest value to associations reported by multiple databases and with a large number of supporting publications. A score > 0.3 is considered high.

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4. Fig. 3. Enrichment analysis for the total array of 1430 DEGs from whole-transcriptome studies of IRR.

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5. Fig. 4. Network of protein-protein interactions of products of differentially expressed genes in placental tissue in IUGR (red color – central genes of the network; purple, lilac, light blue and blue colors – genes from studies by Awamleh [35], Majewska [36], Li [37], Gong [38], respectively).

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