Regulatory Variation Flashcards
Where most SNPs identified by GWAS for common diseases are located
Noncoding DNA (promoters, enhancers, introns, etc.)
How SNPs in noncoding DNA influence GWAS traits
Altering gene expression
Expression quantitative trait loci (eQTLs)
Regions of the genome that contain one or more DNA variants that are associated with expression level of one or more genes
Mapping eQTLs for a given gene along the genome
- Collect RNA levels and genotypes from a group of individuals
- For each gene, scan the genome for associations between mRNA levels and genotype
- Repeat process for every gene that is expressed in the tissue
Local eQTLs
eQTLs that are located close to the gene they influence (50 kb to 1 Mb)
Distant eQTLs
eQTLs that are located far from their target gene (usually on different chromosomes)
Cis-eQTLs
Influence expression of the allele on the same strand of DNA as the variant
Usually located close to target gene
Allele specific expression and cis-eQTLs
One allele in a person is expressed more than the other allele
Trans-eQTLs
Alter protein sequence of a trans regulator or alter the abundance of a trans regulator
Relationship between distance of eQTLs and whether eQTL is cis or trans acting
Most local eQTLs act in cis
Some local eQTLs act in trans- trans regulator is close to target gene or variant influences autoregulatory feedback
Distant eQTLs always act in trans
Most of the genetic portion of expression heritability is due to which type of eQTLs?
Trans-eQTLs
Why are distant eQTLs not well understood in humans?
Large samples are hard to get: require studying gene expression in tissues
Must correct for multiple tests (more so than normal GWAS): number of SNPs times number of expressed genes
Do eQTLs act in one tissue, or multiple?
Can be either one or multiple tissues
Genotype-Tissue Expression (GTEx)
Studying using eQTLs (RNA sequencing) to map gene expression to tissues
Which two organs express the most genes?
Brain
Testes
