An expression quantitative trait locus (eQTL) is a type of

quantitative trait locus A quantitative trait locus (QTL) is a locus (section of DNA) that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers (such as SNPs or AFLPs) ...

(QTL), a genomic locus (region of DNA) that is associated with

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

variation for a specific, quantifiable trait. While the term QTL can refer to a wide range of phenotypic traits, the more specific eQTL refers to traits measured by

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

, such as mRNA levels. Although named "expression QTLs", not all measures of gene expression can be used for eQTLs. For example, traits quantified by protein levels are instead referred to as protein QTLs (pQTLs).

Distant and local, trans- and cis-eQTLs, respectively

An expression quantitative trait is an amount of an

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

transcript or a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

. These are usually the product of a single

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

with a specific chromosomal location. This distinguishes expression quantitative traits from most

complex traits Complex traits are phenotypes that are controlled by two or more genes and do not follow Mendel's Law of Dominance. They may have a range of expression which is typically continuous. Both environmental and genetic factors often impact the variat ...

, which are not the product of the expression of a single gene. Chromosomal loci that explain variance in expression traits are called eQTLs. eQTLs located near the gene-of-origin (gene which produces the transcript or protein) are referred to as local eQTLs or cis-eQTLs. By contrast, those located distant from their gene of origin, often on different chromosomes, are referred to as distant eQTLs or trans-eQTLs. The first genome-wide study of gene expression was carried out in yeast and published in 2002. The initial wave of eQTL studies employed microarrays to measure genome-wide gene expression; more recent studies have employed massively parallel

RNA sequencing RNA-Seq (named as an abbreviation of RNA sequencing) is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also kn ...

. Many expression QTL studies were performed in plants and animals, including humans, non-human primates and mice. Some cis eQTLs are detected in many tissue types but the majority of trans eQTLs are tissue-dependent (dynamic). eQTLs may act in cis (locally) or

trans Trans- is a Latin prefix meaning "across", "beyond", or "on the other side of". Used alone, trans may refer to: Sociology * Trans, a sociological term which may refer to: ** Transgender, people who identify themselves with a gender that di ...

(at a distance) to a

. The abundance of a gene transcript is directly modified by polymorphism in

regulatory elements A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and vir ...

. 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 and the measurement of global

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

genetic variation Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources ...

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 In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...

s (SNPs) reproducibly associated with complex disorders as well as certain pharmacologic phenotypes are found to be significantly enriched for eQTLs, relative to frequency-matched control SNPs. The integration of eQTLs with

GWAS GWAS may refer to: *Genome-wide association study, study of mutations' correlations with disease or other phenotypic expressions *''gwas'', a Welsh term for a valet * Great Western Ambulance Service, the ambulance service serving Somerset, Gloucest ...

has led to development of the transcriptome-wide association study (TWAS) methodology.

Detecting eQTLs

Mapping eQTLs is done using standard QTL mapping methods that test the linkage between variation in expression and genetic polymorphisms. The only considerable difference 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 hosts many large eQTL mapping data sets and provide access to fast algorithms to map single loci and

epistatic Epistasis is a phenomenon in genetics in which the effect of a gene mutation is dependent on the presence or absence of mutations in one or more other genes, respectively termed modifier genes. In other words, the effect of the mutation is depe ...

interactions. As is true in all QTL mapping studies, the final steps in defining DNA variants that cause variation in traits are usually difficult and require 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. The development of single cell technologies, and parallel advances in statistical methods has made it possible to define even subtle changes in eQTLs as cell-states change.

References

{{DEFAULTSORT:Expression Quantitative Trait Loci Classical genetics Statistical genetics Quantitative trait loci

Distant and local, trans- and cis-eQTLs, respectively

Detecting eQTLs

See also

References