Abstract
BackgroundSchizophrenia is a severe brain disorder, and SNPs (Single nucleotide polymorphism) in schizophrenia-associated miRNAs are believed to be one of the important reasons for dysregulation which might contribute to the altered expression of genes and ultimately result in the disease. Identification of causal SNPs in associated miRNAs may have certain significance in understanding the mechanism of schizophrenia.ResultsFor the above purposes, a method based on detection of free energy change is proposed for identification of causal SNPs in schizophrenia-associated miRNAs. A miRNA is firstly segmented, and free energy change is computed after adding an SNP into a segment. The method discovers successfully 6 out of 32 known SNPs and some artificial SNPs could cause significant change in free energy, and among which, 6 known SNPs are supposed to be responsible for most cases of schizophrenia in population.ConclusionsThe proposed method is not only a convenient way to discover causal SNPs in schizophrenia-associated miRNAs without any biochemical assay or sample comparison between cases and controls, but it also has high resolution for causal SNPs even if the SNPs are not reported for their very rare cases in the population. Moreover, the method can be applied to discover the causal SNPs in miRNAs associated with other diseases.
Highlights
Schizophrenia is a severe brain disorder, and SNPs (Single nucleotide polymorphism) in schizophrenia-associated miRNAs are believed to be one of the important reasons for dysregulation which might contribute to the altered expression of genes and result in the disease
Identified SNPs associated with schizophrenia We collect 20 schizophrenia-associated miRNAs (SZmiRNA), and add an SNP into them by replacing every nucleotide with any one of the other three letters after dividing each SZmiRNA into 3 segments: terminal loop, mature miRNA duplex and extension duplex
From the schizophrenia-causal SNPs (SZ-SNP), we find that free energy is significantly decreased when nucleotides A and U are changed and free energy is significantly increased when nucleotides C and G are changed
Summary
Schizophrenia is a severe brain disorder, and SNPs (Single nucleotide polymorphism) in schizophrenia-associated miRNAs are believed to be one of the important reasons for dysregulation which might contribute to the altered expression of genes and result in the disease. SNPs usually occur in regions where natural selection is acting and fixating the allele of the SNP that constitutes the most favorable genetic adaptation [2], and most SNPs (93%) discovered by genome-wide association studies (GWAS) over the last decade that appear to contribute to human disease risk are not located in proteincoding regions [3,4,5], suggesting that SNPs regulate gene transcription levels rather than alter the protein-coding sequence or protein structure [4]. SNPs in miRNAs affect gene regulation mainly in two ways: either impairing miRNA/ mRNA interaction or disturbing miRNA biogenesis, both of which result in gene dysregulation
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