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Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR‐140
Author(s) -
Li Ling,
Meng Tian,
Jia Zhonglin,
Zhu Guiquan,
Shi Bing
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33236
Subject(s) - single nucleotide polymorphism , genetics , polymorphism (computer science) , medicine , biology , genotype , gene
Nonsyndromic oral cleft is a common developmental malformation of humans. Embryonic development is regulated by microRNAs. MicroRNA‐140‐5p (miR‐140‐5p) was found to regulate palatal development. As sequence variants in miRNA genes are likely to affect miRNA expression and/or maturation, we investigated the miRNA‐140 gene and identified a SNP (rs7205289: C>A) located in precursor miRNA‐140. We carried out a case–control analysis in 557 patients with nonsyndromic oral clefts and 306 unaffected controls from west China and found that the frequency of minor allele (A allele) was significantly increased ( P = 0.003 after Bonferroni correction) in nonsyndromic cleft palate (NSCP) patients in comparison with that in controls. We constructed expression vectors of primary miRNA‐140 (pri‐miR‐140) with the major and minor alleles of rs7205289. The vectors were transfected into HEK293 cells, and the mature forms of miR‐140 were detected by Northern blot. Compared to the vector with the C allele, the vector with the A allele was found to influence the miR‐140 processing, resulting in a significant decrease of miR‐140‐5p and an increase of miR‐140‐3p. These results suggest that the SNP located in pre‐miR‐140 contributes to NSCP susceptibility by influencing the processing of miR‐140. © 2010 Wiley‐Liss, Inc.