Elena Yu Leberfarb
Articles written in Journal of Biosciences
Volume 40 Issue 5 December 2015 pp 873-883 Articles
Elena V Antontseva Marina Yu Matveeva Natalia P Bondar Elena V Kashina Elena Yu Leberfarb Leonid O Bryzgalov Polina A Gervas Anastasia A Ponomareva Nadezhda V Cherdyntseva Yury L Orlov Tatiana I Merkulova
There are two regulatory single nucleotide polymorphisms (rSNPs) at the beginning of the second intron of the mouse 𝐾-𝑟𝑎𝑠 gene that are strongly associated with lung cancer susceptibility. We performed functional analysis of three SNPs (rs12228277: T>A, rs12226937: G>A, and rs61761074: T>G) located in the same region of human 𝐾𝑅𝐴𝑆. We found that rs12228277 and rs61761074 result in differential binding patterns of lung nuclear proteins to oligonucleotide probes corresponding two alternative alleles; in both cases, the transcription factor NF-Y is involved. G>A substitution (rs12226937) had no effect on the binding of lung nuclear proteins. However, all the nucleotide substitutions under study showed functional effects in a luciferase reporter assay. Among them, rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer (NSCLC). Taken together, the results of our study suggest that a T>G substitution at nucleotide position 615 in the second intron of the KRAS gene (rs61761074) may represent a promising genetic marker of NSCLC.
Volume 43 Issue 5 December 2018 pp 1069-1075 Review
Currently, it is generally accepted that the cis-acting effects of noncoding variants on gene expression are a major factor forphenotypic variation in complex traits and disease susceptibility. Meanwhile, the protein products of many target genes forthe identified cis-regulatory variants (rSNPs) are regulatory molecules themselves (transcription factors, effectors, componentsof signal transduction pathways, etc.), which implies dramatic downstream effects of these variations on complexgene networks. Here, we brief the results of recent most comprehensive studies on the role of rSNPs in transcriptionalregulation across the genome.