Expression QTLs

Question 1

What are the characteristics of Qualitative traits?

Answer 1

• discrete, one-or-the-other phenotypes, no in between
• typically Mendelian inheritance
• E.g. ABO blood groups
• sometimes called discontinuous characters
• genotype can be inferred from phenotype

Question 2

What are the characteristic of Quantitative traits?

Answer 2

• continuous characteristic or continuously-variable trait
• called quantitative because they must be measured
• complex characteristics or phenotypes
• polygenic trait
• multifactorial inheritance
• e.g. height
• genotype cannot be inferred from phenotype

Question 3

What is discrete versus continuous variable phenotypes?

Answer 3

Discrete (or discontinuous)

• 1 loci = 3 phenotypes
• 2 loci = 5 phenotypes
• 5 loci = 11 phenotype

Continuously variable
- many loci = many phenotypes

Question 4

Disease versus healthy is a discontinuous or continuous phenotype?

Answer 4

Discontinuous - only 2 phenotypes (healthy or not).

Susceptibility to disease considered a continuum (so many disease can be treated as quantitative

Question 5

What is heritability?

Answer 5

The proportion of phenotypic variation (Vp) that is due to variation in genetic values (Vg)

H2 = Vg/Vp

Question 6

What is broad sense heritability?

Answer 6

The proportion of phenotypic variance due to all genetic factors (as opposed to narrow sense which is due to additive genetic factors only)

Question 7

What does a H2 value of 0 mean?

Answer 7

Means phenotypic variance is due to environment only, whereas H2 value of 1 means phenotype variance due to genotypes only

Question 8

What does gene mapping do?

Answer 8

Determines how far apart genes are on a chromosome, as well as their locations on chromosomes

Question 9

What are quantitative trait loci (QTL)?

Answer 9

Spots on chromosomes that influences quantitative traits - we use QTL mapping to connect the phenotypes with the genetic markers (genes or regions of the genome). There may be many QTLs that influence a single trait

Question 10

What does QTL mapping look for?

Answer 10

For genetic markers that correlate with a specific trait.

Question 11

What is an eQTL?

Answer 11

Similar to QTL except specifically referring to gene expression (frequently mRNA expression levels) as the quantitative trait. So, loci that regulate expression levels of mRNA or proteins. Pinpointing the region/s in the genome which controls the expression of a specific gene. Measured mRNA trait is the product of a single gene with a specific chromosomal location

Question 12

What is integrative genomics?

Answer 12

The study of the genetic basis of gene expression. Combination of gene expression studies (microarrays, RNAseq transcriptomics) with linkage analysis or GWAS. Gene expression levels are treated as QTLs and the genetic variation responsible can be mapped

Question 13

What is a 2-parent cross?

Answer 13

Uses recombinant inbred lines (RIL) to map gene expression levels. Because you have population of essentially identical individuals (RIL) differences between RILs can be mapped to either parental chromosome. After segregation of population –> microarray/RNAseq to correlate

Question 14

What are the steps in QTL mapping?

Answer 14

1. select or create a population of genetically different individuals showing a relevant phenotypic variation in the environment of interest (e.g. backcrosses, RILs)
2. Use molecular markers to genotype individuals throughout the genome
3. Determine the molecular profile of each individual in the population
4. Treat molecular abundance levels for each transcript/protein as a quantitative trait and associate this variation to genotype variation to identify regulating loci
5. Reconstruct regulatory networks based on patterns of QTL co-localisation and independent biological knowledge

Question 15

What can QTL data be used for?

Answer 15

• understanding gene regulation in specific contexts and the relationships between genotype and phenotype
• identify genes causal in particular phenotype
• identify modifier loci, those that influence the severity of disease
• identify gene networks and novel pathways involved in disease
• identify novel drug targets and understand disease pathobiology