Flashcards in Cardiovascular Health Lecture 2.3 : Searching for Genetic Clues Deck (24):
What is a first pass look?
Analysing the entire gene by mapping it, searching for points associated with disease.
What is fine mapping?
Done after a first pass look, you focus on a particular area, using denser markers to pinpoint signals for diseases.
Where are disease associated points of DNA found? What must be done with them?
In the non-coding region. They need to be tested to be sure they are the functional candidate.
What is endothelin?
What happens with an endothelin knockout? What happens if a copy is added?
In a knockout, blood pressure is expected to decrease.
With an extra copy, blood pressure is expected to rise.
In practice, this doesn't happen.
How is endothelin associated with the lung? What does this say about abnormal levels?
Has lung development in utero. Abnormal levels therefore affect lung pathology more than cardiovascular health.
What are the 5 types of linkage mapping?
What is Ld mapping?
What is transcriptomics?
What is proteomics?
What is computational biology?
Modelling biological data
What is systems analysis?
Do non-coding regions affect RNA expression?
Can genes themselves alter RNAs?
Yes, there are some genes specific to the expression of some RNAs.
What is linkage disequilibrium?
There is a physical proximity between the marker used and a causative variant. LD means they are close enough that the distance doesn't change following recombination.
How does recombination play a role in linkage equilibrium?
Normally, they align and swap chromosomal regions, in doing so, chance that a non causative variant from one parent becomes associated with a marker to a causative variant from the other parent post recombination. Ie. Marker for diabetes found on dad chromosome. After recombination, this marker becomes associated with a non causative variant in the mother’s genome (wherever it may be). LD is that theyre close enough that this doesn't happen.
What are the most common variants?
What kind of mutations can SNPs be?
Can be siltent mutations, and wont change the amino acid
Can also cause direct protein mutation, or mutate region controlling expression level.
What is linkage analysis?
Use of pedigrees to track a marker and associate it with a disease.
What effect does linkage disequilibrium have on a marker's association to a disease?
Strengthens further down the generation.
What is association analysis?
Create groups of interest that gives information on genetic markers being carried with the disease. Compares groups with the disease, to those without, and relatve percentages of SNP prevalence.
How much of the blood pressure loci found to date account for the total heritability of blood pressure? Why is this so (name 3 reasons)?
Less than 5%. Not just in blood pressure, but most phenotypes assessed. Possibly due to synergy between the different systems affecting the phenotype.
ie with blood pressure, NO, renin and (para)symp might synergise, as well as epigenetics. SNPs also miss the rare variants.
Human population was ~10k when it first left Africa. What is the effect of an ancient mutation in this population? Why is this useful?
The mutation will be present widely dispersed in the current population. It can be used as a marker or could be causing a disease.