Design and evaluation of a panel of single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease

Abstract

MicroRNAs (miRNA) are recognized posttranscriptional gene repressors involved in the control of almost every biological process. Allelic variants in these regions may be an important source of phenotypic diversity and contribute to disease susceptibility. We analyzed the genomic organization of 325 human miRNAs (release 7.1, miRBase) to construct a panel of 768 single-nucleotide polymorphisms (SNPs) covering B1 Mb of genomic DNA, including 131 isolated miRNAs (40%) and 194 miRNAs arranged in 48 miRNA clusters, as well as their 5-kb flanking regions. Of these miRNAs, 37% were inside known protein-coding genes, which were significantly associated with biological functions regarding neurological, psychological or nutritional disorders. SNP coverage analysis revealed a lower SNP density in miRNAs compared with the average of the genome, with only 24 SNPs located in the 325 miRNAs studied. Further genotyping of 340 unrelated Spanish individuals showed that more than half of the SNPs in miRNAs were either rare or monomorphic, in agreement with the reported selective constraint on human miRNAs. A comparison of the minor allele frequencies between Spanish and HapMap population samples confirmed the applicability of this SNP panel to the study of complex disorders among the Spanish population, and revealed two miRNA regions, hsa-mir-26a-2 in the CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, showing geographical allelic frequency variation among the four HapMap populations, probably because of differences in natural selection. The designed miRNA SNP panel could help to identify still hidden links between miRNAs and human disease.

Catalog of MicroRNA Seed Polymorphisms in Vertebrates

“…Nevertheless, our analysis of currently available data revealed a much higher frequency (5.9%) of miR-seed polymorphisms in human than the frequency of >1% reported by Didiano and Hobert [46]. Similarly, Muiños-Gimeno et al [47] also revealed much lower frequencies than our study mapping 24 SNPs within 325 mature miRNAs and detecting only two miR-seed-SNPs. They also estimated the density of SNPs in miRNAs to be 4.5-times lower that in the rest of the genome [47].…”

The role of miR-26 in tumors and normal tissues (Review)

“…Findings of this study also showed 2 miRNA regions, hsa-mir-26a-2 in the The role of miR-26 in tumors and normal tissues (Review) JIE GAO and QING-GUANG LIU CTDSP2 gene and hsa-mir-128-1 in the R3HDM1 gene, among a Spanish population (16). Concomitantly, Diederichs and Haber reported that the expression levels of miRNAs were globally reduced in cancer compared with matched normal tissues.…”

Association ofBSGgenetic polymorphisms with atherosclerotic cerebral infarction in the Han Chinese population

“…The SNP −631 G > T (rs28915400) and −318 G > C (rs4919859) located in the 5 -Flank and 10141 G > A (rs8637), 10826 G > A (rs6758) occurred in the 3 -untranslated region of the BSG gene, the SNP at the 3 -untranslated region or 5 -flanking may affect gene expression at the post-transcriptional level by interfering protein binding, polyadenylation or miRNA binding [34,35]. By compared with the allele frequencies of these BSG polymorphisms in Chinese and other populations as deposited in the Hapmap database, we observed obvious different in allelic and genotype distribution for the polymorphisms, we think the functional significance of these SNP should be deserved further study.…”