Thermo ebook on eQTL - 19

Figure 1. How eQTLs affect expression levels of genes. (A) In a wild type individual, a transcription factor (TF) binds to the controlling region of two genes,
resulting in normal transcript levels. (B) An individual with a cis-eQTL can
have a SNP in the region bound by the transcription factor that reduces (but
may not eliminate) transcript levels of gene B while leaving levels of gene A
unaffected. (C) In an individual with a trans-eQTL, a SNP in the DNA-binding
motif of the transcription factor reduces (but may not eliminate) its affinity to
all binding sites, resulting in reduced expression of multiple genes.
Proximity is variably defined, but
typically cis-eQTLs fall within 200
kb-1 Mb of the transcriptional
start site of a gene. Thus, these
are usually thought of as SNPs
that fall within the promoter, enhancer, or other transcriptional
regulatory sequences. The other
type of eQTL, trans-eQTLs, are
usually genetically unlinked and
are thought to regulate expression of a locus from a distance. For
example, a trans-eQTL could be a
SNP in a transcriptional activating protein that lowers, but does
not eliminate, the DNA-binding
affinity of the protein to all binding sites (Figure 1C). eQTLs can
also be tissue specific: a SNP that

affects the expression of a gene
in one tissue may have no effect
in a different tissue. eQTL data are
often deposited into publicly accessible databases. One of these,
arising from the GTEx project,5 is
rapidly becoming the gold-standard repository for eQTL data.
To be useful in contributing to
disease research, SNPs that are
eQTLs need to be linked to GWAS
of phenotypes or pathologies.
Several tools have been developed that look for overlaps of
eQTLs and GWAS-identified SNPs.
For example, the Sherlock software tool provides a statistical
basis for finding SNPs common

to GWAS and eQTL studies.6 A
link between the GWAS-identified SNP locus and eQTL suggests
that differential expression of the
gene affected by the eQTL could
contribute to the trait. Once a putative link has been established,
verification of the link is needed.
This could be done by screening
the transcriptome and genome
of even more samples; however, this could become unwieldy
and expensive. Alternatively, an
orthogonal technology, such
as qPCR, could be used to confirm the association of the SNP
genotype and mRNA levels of
the affected gene in a targeted
manner. This method has the potential to deliver information on
targeted associations in a cost-effective manner.
In this document, we provide
short descriptions of how to
navigate the GTEx database. We
use the GTEx database to introduce some example case studies that illustrate how qPCR using TaqMan Assays can be used
to verify GWAS and eQTL analysis results.

Navigating the GTEx
database
The GTEx database is accessed
through the GTEx portal URL
(gtexportal.org, Figure 2). There
is a large amount of information
deposited in this database. Five

http://www.gtexportal.org

Thermo ebook on eQTL

Table of Contents for the Digital Edition of Thermo ebook on eQTL