The distribution of common genetic variants in the human genome (PGP meeting 2008).
Cis-regulatory sequences in the genome are responsible for the sequential activation and deactivation of all the genes during development, therefore clusters of cis-regulatory elements define a large number of logic modules required for orderly growth and pattern formation [1]. Of the estimated 10 million common single nucleotide polymorphisms (SNPs) in human, more than 98% are expected to fall in the non-coding region[2]. While several promoter and transcription factor binding site databases are available, it is difficult to measure the exact number of function cis-regulatory sites present in the human genome. It is even more difficult to know how many of them are affected by SNPs although some estimates are available [3].
While most deleterious genetic disorders are caused by non-synonymous coding-variants, cis-regulatory polymorphisms are thought to be important for normal evolutionary divergence of growth, function and phenotype.[4, 5, 6]. Thus, the majority of normal human traits and their wide (or narrow, depending on your point of view) spectrum may be due to subtle changes in cis-regulatory elements and in gene expression.
Various cis-regulatory SNPs are known to play a role is a small number of common and rare human diseases.[4, 5, 6, 7, 8, 9, 10] Studies and plants and mice have shown that a large measure of gene expression variation is may be due to a surprisingly common cis-regulatory SNPs/genetic variations. Cis-regulatory SNPs are attractive also because it can readily identify the associated signaling and transcription cascade and biological pathways, and become a target for selective pharmacological agents.
So far, vast majority of genetic studies have focused on the coding SNPs mainly due to the limitations in technology. With the arrival of affordable full genome sequencing and capture technologies, this relatively unexplored area in human genetics is about to explode. This page will be dedicated to groups and laboratories interested in developing and applying methods for exploring functional non-coding, cis-regulatory SNPs.
