This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: In metazoan, miRNAs regulate gene expression primarily through binding to the target sites on the 3'UTR of messenger RNAs (mRNAs). Cis variants within, or close to, a gene are crucial in explaining the variability of the gene expression measures. Single nucleotide polymorphisms (SNPs) in the 3'UTRs of genes can affect the base-pairing between the miRNAs and mRNAs, and hence disrupt existing target sites (in the reference sequence) or create novel target sites, suggesting a promising 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 that, 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. Results: We herein performed an association analysis of the documented cis-SNP markers and the inter-population SNPs located in the miRNA target sites on the 3'UTRs of various human genes. By systematically integrating multiple information sources, we found 58 significant gene-level SNP-involved post-transcriptional regulation modules (SNP-PTRMs) in the form of SNP-miRNA-mRNA triplets from the CEU and YRI populations. Among the cognate genes, seven including CHL1, CTSB, GNA12, KLF11, LRPAP1, MTRR and P2RY1 are related to multiple genetic diseases such as depressive disorder and type-II diabetes. Moreover, we found that ~35% of cis-associated SNPs (~950) within documented transcripts are identical to, or in linkage disequilibrium (LD) (p 0.01) with, one or multiple SNPs located in miRNA target sites. Based on these associations (or identities), over 100 exon-level SNP-PTRMs were further determined for each population. Conclusion: SNPs inside miRNA target sites may provide a promising explanation to the individual and population variability of gene expression measures, and these site variants potentially function as bridges linking the documented cis-SNP markers to the expression of the associated genes. We provided solid in silico evidence for this hypothesis by identifying genome-wide SNP-involved miRNA-mediated post-transcriptional regulation modules in lymphocyte cells.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Exploratory Grants (P20)
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Louisiana State University A&M Col Baton Rouge
Schools of Veterinary Medicine
Baton Rouge
United States
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El-Saadi, Madison Wynne; Williams-Hart, Tara; Salvatore, Brian A et al. (2015) Use of in-silico assays to characterize the ADMET profile and identify potential therapeutic targets of fusarochromanone, a novel anti-cancer agent. In Silico Pharmacol 3:6
Babu, Sainath; Uppu, Sannihith N; Martin, Brittany et al. (2015) Unusually high levels of bisphenol A (BPA) in thermal paper cash register receipts (CRs): development and application of a robust LC-UV method to quantify BPA in CRs. Toxicol Mech Methods 25:410-6
Ibrahim, Sulaimon; Chowriappa, Pradeep; Dua, Sumeet et al. (2015) Classification of diabetes maculopathy images using data-adaptive neuro-fuzzy inference classifier. Med Biol Eng Comput 53:1345-60
Gu, Ying; Barzegar, Mansoureh; Chen, Xin et al. (2015) Fusarochromanone-induced reactive oxygen species results in activation of JNK cascade and cell death by inhibiting protein phosphatases 2A and 5. Oncotarget 6:42322-33
Pogue, A I; Dua, P; Hill, J M et al. (2015) Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic mice. J Inorg Biochem 152:206-9
Zhang, Cheng; Rissman, Robert A; Feng, June (2015) Characterization of ATP alternations in an Alzheimer's disease transgenic mouse model. J Alzheimers Dis 44:375-8
Pasluosta, Cristian F; Chiu, Alan W L (2015) Modulation of grasping force in prosthetic hands using neural network-based predictive control. Methods Mol Biol 1260:179-94
McFerrin, Harris E; Olson, Scott D; Gutschow, Miriam V et al. (2014) Rapidly self-renewing human multipotent marrow stromal cells (hMSC) express sialyl Lewis X and actively adhere to arterial endothelium in a chick embryo model system. PLoS One 9:e105411
Fontana, Juan M; Chiu, Alan W L (2014) Analysis of electrode shift effects on wavelet features embedded in a myoelectric pattern recognition system. Assist Technol 26:71-80
Zheng, Shilong; Zhong, Qiu; Xi, Yulan et al. (2014) Modification and biological evaluation of thiazole derivatives as novel inhibitors of metastatic cancer cell migration and invasion. J Med Chem 57:6653-67

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