miRNA-Mediated Relationships between Cis-SNP Genotypes and Transcript Intensities in Lymphocyte Cell Lines

In metazoans, miRNAs regulate gene expression primarily through binding to target sites in the 3′ UTRs (untranslated regions) of messenger RNAs (mRNAs). Cis-acting variants within, or close to, a gene are crucial in explaining the variability of gene expression measures. Single nucleotide polymorphisms (SNPs) in the 3′ UTRs of genes can affect the base-pairing between miRNAs and mRNAs, and hence disrupt existing target sites (in the reference sequence) or create novel target sites, suggesting a possible mechanism for cis regulation of gene expression. Moreover, because the alleles of different SNPs within a DNA sequence of limited length tend to be in strong linkage disequilibrium (LD), we hypothesize the variants of miRNA target sites caused by SNPs potentially function as bridges linking the documented cis-SNP markers to the expression of the associated genes. A large-scale analysis was herein performed to test this hypothesis. By systematically integrating multiple latest information sources, we found 21 significant gene-level SNP-involved miRNA-mediated post-transcriptional regulation modules (SNP-MPRMs) in the form of SNP-miRNA-mRNA triplets in lymphocyte cell lines for the CEU and YRI populations. Among the cognate genes, six including ALG8, DGKE, GNA12, KLF11, LRPAP1, and MMAB are related to multiple genetic diseases such as depressive disorder and Type-II diabetes. Furthermore, we found that ∼35% of the documented transcript intensity-related cis-SNPs (∼950) in a recent publication are identical to, or in significant linkage disequilibrium (LD) (p<0.01) with, one or multiple SNPs located in miRNA target sites. Based on these associations (or identities), 69 significant exon-level SNP-MPRMs and 12 disease genes were further determined for two populations. These results provide concrete in silico evidence for the proposed hypothesis. The discovered modules warrant additional follow-up in independent laboratory studies

Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors

The diversity and distribution of D1 proteins in cyanobacteria

The psbA gene family in cyanobacteria encodes different forms of the D1 protein that is part of the Photosystem II reaction centre. We have identified a phylogenetically distinct D1 group that is intermediate between previously identified G3-D1 and G4-D1 proteins (Cardona et al. Mol Biol Evol 32:1310–1328, 2015). This new group contained two subgroups: D1INT, which was frequently in the genomes of heterocystous cyanobacteria and D1FR that was part of the far-red light photoacclimation gene cluster of cyanobacteria. In addition, we have identified subgroups within G3, the micro-aerobically expressed D1 protein. There are amino acid changes associated with each of the subgroups that might affect the function of Photosystem II. We show a phylogenetically broad range of cyanobacteria have these D1 types, as well as the genes encoding the G2 protein and chlorophyll f synthase. We suggest identification of additional D1 isoforms and the presence of multiple D1 isoforms in phylogenetically diverse cyanobacteria supports the role of these proteins in conferring a selective advantage under specific conditions

A numerical study of the generation and propagation of internal solitary waves in the Luzon Strait

A new composite model, which consists of a generation model of the internal tides and a regularized long wave propagation model, is presented to study the generation and evolution of internal solitary waves in the sill strait. Internal bores in the sill strait are first simulated by the generation model. and then the internal tidal field outside of the sill region is given as input for the propagation model. Numerical experiments are carried out to Study the imposing tide, depth profile. channel width and shoaling effect, etc., on the generation and evolution of internal solitary waves. It is shown that only when the amplitude of internal tide at the forcing boundary of the propagation model is large enough that a train of internal solitary waves would be induced. The amplitude of the imposing tide in the generation model, shoaling effect, asymmetry of the depth profile and channel width have some effects on the amplitude of the induced internal solitary wave. The imposing tidal flow superimposed on a constant mean background flow has a great damping effect on the induced internal waves, especially on those propagate against the background flow direction. The generation and propagation of internal solitary waves in three possible straits among the Luzon Strait are simulated. and the reasons for the asymmetry of their propagation are also explained. (C) 2002 Ifremer/CNRS/IRD/Editions scientifiques of medicales Elsevier SAS. All rights reserved.Un nouveau modèle composite, associant un modèle de génération de marées internes et un modèle de propagation d’ondes longues régularisée est proposé pour l’étude de la génération et de l’évolution d’ondes solitaires internes dans un détroit à seuil. Les ondes de marée internes dans le détroit à seuil sont d’abord simulées par le modèle de génération ; le champ de marée interne à l’extérieur du seuil sert à initialiser le modèle de propagation. Des expériences numériques sont conduites pour étudier les effets de la marée imposée, du profil de profondeur, de la largeur du canal et des haut-fonds, etc. sur la génération et l’évolution des ondes solitaires internes. C’est seulement quand l’amplitude de la marée interne à la limite de forçage du modèle de propagation atteint une certaine valeur qu’un train d’ondes solitaires internes est induit. L’amplitude de la marée initiale dans le modèle de génération, l’effet de haut-fond, l’asymétrie du profil de profondeur et la largeur du canal agissent quelque peu sur l’amplitude de l’onde solitaire interne induite. Le flux de marée surimposé à un courant moyen constant a un effet majeur d’amortissement sur les ondes internes induites, spécialement sur celles qui se propagent contre la direction du courant moyen. La génération et la propagation d’ondes solitaires internes dans trois des seuils du détroit de Luzon sont simulées et les raisons de leur asymétrie de propagation sont également expliquées