Expression quantitative trait loci (eQTLs) are genomic loci that regulate expression levels of mRNAs or proteins. Expression traits differ from most other classical complex traits in one important respect—the measured mRNA or protein trait almost always is the product of a single gene with a specific chromosomal location. eQTLs that map to the approximate location of their gene-of-origin are referred to as cis eQTLs. In contrast, those that map far from the location of their gene-of-origin gene, often on different chromosomes, are referred to as trans eQTLs. The first genome-wide mapping studies of gene expression were initiated in the late 1980s and early 1990s by Damerval and de Vienne . They exploited then innovative 2D protein separation methods and introduced the term "protein quantity locus" or PQL (now sometimes pQTL). The advent of high-throughput array-based methods to measure mRNA abundance in the early 2000s catalyzed an impressive number of expression QTL studies in plants, animals, and humans.

Some cis eQTLs are detected in many tissue

Tissue (biology)

Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 types but the majority of trans eQTLs are tissue-dependent (dynamic). eQTLs may act in cis (locally) or trans

Trans-acting

In the field of molecular biology, trans-acting , in general, means "acting from a different molecule"...

 (at a distance) to a gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.. The abundance of a gene transcript

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 is directly modified by polymorphism

Polymorphism (biology)

Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...

 in regulatory elements. Consequently, transcript abundance might be considered as a quantitative trait that can be mapped with considerable power. These have been named expression QTLs (eQTLs) The combination of whole-genome genetic association studies

Genome-wide association study

In genetic epidemiology, a genome-wide association study , also known as whole genome association study , is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait...

  and
the measurement of global gene expression

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 allows the systematic identification of eQTLs. By assaying gene
expression and genetic variation

Genetic variation

Genetic variation, variation in alleles of genes, occurs both within and among populations. Genetic variation is important because it provides the “raw material” for natural selection. Genetic variation is brought about by mutation, a change in a chemical structure of a gene. Polyploidy is an...

 simultaneously on a genome-wide basis in a large number of individuals, statistical genetic methods can be used to map the genetic factors that underpin individual differences in quantitative levels of expression of many thousands of
transcripts. Studies have shown that single nucleotide polymorphism

Single nucleotide polymorphism

A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...

s (SNPs) reproducibly associated with complex disorders as well as certain pharmacologic phenotypes are significantly enriched for eQTLs relative to frequency-matched SNPs.

Detecting eQTLs

Mapping eQTLs is done using standard QTL mapping methods that test the linkage between variation in expression and genetic polymorphisms. The only special considerable is that eQTL studies can involve a million or more expression microtraits. Standard gene mapping software packages can be used, although it is often faster to use custom code such as QTL Reaper or the web-based eQTL mapping system Genenetwork

Genenetwork

GeneNetwork is a database and open source bioinformatics software resource for systems genetics. This resource is used to study gene regulatory networks that link DNA sequence variants to corresponding differences in gene and protein expression and to differences in traits such as health and...

. GeneNetwork hosts many large eQTL mapping data sets and provide access to fast algorithms to map single loci and epistatic interactions. As is true in all QTL mapping studies, the final steps in defining DNA variants that cause variation in traits is usually difficult and required a second round of experimentation. This is especially the case for trans eQTLs that do not benefit from the strong prior probability that relevant variants are in the immediate vicinity of the parent gene. Statistical, graphical, and bioinformatic methods are used to evaluate positional candidate genes and entire systems of interactions .