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

Margarita Muĩos-Gimeno, Magda Montfort, Mònica Bayés, Xavier P. Estivill, Yolanda Espinosa-Parrilla

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 ∼ 1 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.

Original languageEnglish
Pages (from-to)218-226
Number of pages9
JournalEuropean Journal of Human Genetics
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Fingerprint

MicroRNAs
Single Nucleotide Polymorphism
HapMap Project
Nutrition Disorders
Population
Genes
Biological Phenomena
5' Flanking Region
Genetic Selection
Disease Susceptibility
Nervous System Diseases
Gene Frequency
Genome
Psychology

Keywords

  • HapMap
  • MiRNA
  • Population genetics
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Design and evaluation of a panel of single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease. / Muĩos-Gimeno, Margarita; Montfort, Magda; Bayés, Mònica; Estivill, Xavier P.; Espinosa-Parrilla, Yolanda.

In: European Journal of Human Genetics, Vol. 18, No. 2, 02.2010, p. 218-226.

Research output: Contribution to journalArticle

Muĩos-Gimeno, Margarita ; Montfort, Magda ; Bayés, Mònica ; Estivill, Xavier P. ; Espinosa-Parrilla, Yolanda. / Design and evaluation of a panel of single-nucleotide polymorphisms in microRNA genomic regions for association studies in human disease. In: European Journal of Human Genetics. 2010 ; Vol. 18, No. 2. pp. 218-226.
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