The Identification of Cis-Regulatory Sequence Motifs in Gene Promoters Based on SNP Information

Conservation of particular molecular sequence motifs throughout evolution is a strong indicator of their functional relevance as selective pressure likely prevented the accumulation of mutations. Known as "phylogenetic footprinting", this rationale has been exploited for the identification of novel functional motifs using sequence information from sequence alignments of diverse species, in particular transcription factor binding site motifs in aligned gene promoter sequences of orthologous genes. With the rapid advances of sequencing technologies, whole genome sequence information is accumulating not only across different species, but increasingly for variants of the same species exhibiting relatively little sequence variability, primarily present as single nucleotide polymorphisms (SNPs). Here, we lay out the basic strategy for the identification of functional cis-regulatory motifs in gene promoter regions based on SNP information.