Cardiovascular Health Lecture 2.2 : Interrogating the Coding and Non - Coding Genome

Question 1

What percentage of genes and environment contribute to blood pressure?

Answer 1

~30% from genes, and ~70% from environment.

Question 2

What is genomics? What does it use to predict shit?

Answer 2

Looking at genes, explaining genetic causes and mechanisms of disease. Can predict using biomarkers.

Question 3

What is the most common genetic variation?

Answer 3

SNPs

Single nucleotide polymorphisms

Question 4

What are SNPs?

Answer 4

Changes in DNA at one base pair.

Question 5

Where can SNPs occur?

Answer 5

Both coding and non coding regions.

Question 6

How can SNPs be used in relation to dieases? Give an example.

Answer 6

Look at SNP of 2k people with no diease (hypertension)
Do the same with 2k people with disease.
Compare SNP prevalence percentages to form an assocation.

Question 7

How can SNPs be analysed?

Answer 7

Using microarrays, which is covered by SNPs.

Amplify genome, fragment and allow to anneal.

Question 8

Besides an assocation with disease, what else can SNPs tell us?

Answer 8

Can associate a disease to a locon/chromosomal location.

Question 9

What needs to be done to form a strong association using SNPs?

Answer 9

A lot of data is obtained using SnPs, so a very strict p-value is needed to remove false positives.

Question 10

What percentage of the total heritability does SNPs contribute to? What does this suggest?

Answer 10

Only ~10%. Suggests other factors are aside from SNPs are at play, such as gene expression differences and epigenetics.

Question 11

What is a copy number variation? What percentage of the genome do they account for?

Answer 11

Large segments of DNA that are bulk changes to the DNA. Account for up to 12%.

Question 12

Give an example of a copy number variation.

Answer 12

4 segments - ABCD - normal
CNV is ABBCD
one segment is repeated, can also be deleted
BCD

Question 13

How are copy number variations detected, and how do they appear?

Answer 13

Using microarrays.

Duplicated segments appear brighter while deletions are less so, or an absence.

Question 14

What are two forms of non-coding RNA?

Answer 14

lncRNA - long

miRNA - small

Question 15

what are the functions of non-coding RNAs?

Answer 15

Full function not known, but might be involved in chromatin maintenance and DNA folding, as well as splicing and DNA editing.

Question 16

What is needed to study RNA effects?

Answer 16

Tissue of the associated region.

ie. to study hypertension/bp, kidney tissue needed.

Question 17

Can RNA be sequenced?

Answer 17

Yes, reverse transcriptase, to form cDNA.

Question 18

Can RNA expression levels be detected?

Answer 18

Yes, microarrays. Intensity of dots suggest expression levels.

Question 19

How big are miRNAs and where are they found?

Answer 19

20bp long, and float freely in the nucleus. Also found in plasma.

Question 20

What do miRNA bind to? What do they do?

Answer 20

They bind to mRNA via complementarity and can degrade it as a signalling molecule, but can also block translation.

Question 21

What is the use of RNA sequencing?

Answer 21

Can be sequenced to cDNA using reverse transcriptase then aligned to the genome.