W5L1 Describing and measuring diversity in gene expression

Question 1

Fluctuation of gene expression in different level

Answer 1

1. Across genes within a single individual/organ/cell
2. Across individuals/organs/cells within a single gene
3. Across individuals/organs/cells and genes both

Question 2

is biological process deterministic and predictable

Answer 2

• Stochasticity, genetic variation and environmental variation can all substantially alter outcomes of cellular processes…for better and for worse

Question 3

Quantifying variation with molecular quantitative trait locus mapping (molQTLs)

Answer 3

• A QTL is a genetic region(locus) associated with a particular quantitative phenotype
• QTL mapping has been transformed by the resolution of high-throughput sequencing
• In some organisms, we map things to a specific SNP.
• Most common: linking genetic variants to mRNA expression levels: eQTLs (expression QTLs)

Question 4

eQTL discovery and math

Answer 4

• To identify eQTLs, test each SNP near a gene for a linear association between genotype and expression levels of the gene
  -If genotype is significantly associated (in a statistical sense) with expression, that SNP is an eQTL for that gene

Question 5

assumption on alleles effect

Answer 5

• We often make one additional assumption: allelic effects are additive:
• Values in heterozygotes will be ~halfway between the values in either homozygote

Question 6

Making eQTL maps

Answer 6

To map eQTLs in anything we need two things:
1. RNA expression data from a lot of individuals
* From what tissues should we map? All tissues? Some tissues? Which tissues? What’s a tissue, anyhow?
* Are eQTL effects shared across tissues or are they tissue-specific?
2. Whole genome genotype data from the same individuals
* Which individuals should we use

Question 7

Quantifying gene expression in human tissues: the GTEx project

Answer 7

An ongoing effort to build a comprehensive public resource to study tissue-specific gene expression and regulation
v8 (2020): RNA-seq on 49 human tissues across 838 people
-showed that human tissue are transcriptionally distinct

Question 8

eQTL in human genome

Answer 8

eQTLs are ubiquitous(everywhere) in the genome, as the number of sample increase, more QTL they find. so far 12k gene
-but not all eQTLs have equal effect size (differences in expression levels between genotype class)

Question 9

when is eQTLs have the largest effectsize

Answer 9

• eQTLs that disrupt splice sites or introduce early stop codons have the largest effect, but they are rare
  Upstream regulatory eQTLs are a much more common means of regulating expression

Question 10

cis(local) vs trans eQTLs

Answer 10

• A cis QTL affects expression of the focal gene in an allele specific manner.
• A trans QTL impacts expression of both alleles of the focal gene equally.