Regulatory SNPs and their widespread effects on the transcriptome.

Currently, it is generally accepted that the cis-acting effects of noncoding variants on gene expression are a major factor for phenotypic variation in complex traits and disease susceptibility. Meanwhile, the protein products of many target genes for the identified cis-regulatory variants (rSNPs) are regulatory molecules themselves (transcription factors, effectors, components of signal transduction pathways, etc.), which implies dramatic downstream effects of these variations on complex gene networks.

Regulatory single nucleotide polymorphisms at the beginning of intron 2 of the human KRAS gene.

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 greater than A, rs12226937: G greater than A, and rs61761074: T greater than 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.