complex disease and pharmacogenetics

Question 1

• What is meant by a Mendelian trait?

Answer 1

A trait controlled by a single gene

Their inheritance follows Mendel's principle

Question 2

• How did the results of his research, lead to Mendel’s theory of inheritance?

Answer 2

He deduced that genes come in pairs and are inherited as distinct units, one from each parent.

Mendel tracked the segregation of parental genes (of peas) and their appearance in the offspring as dominant or recessive traits

Question 3

• What is meant by a complex trait?

Answer 3

Controlled by multiple genes

Effect of environment also involved in the presentation of complex traits as well

Question 4

• What is the best way to study Mendelian disease?

Answer 4

Family studies - Pedigrees

Question 5

• How can you study Complex diseases?

Answer 5

Collect data from people suffering from Complex disease in interest

Compare them to that of the healthy individuals

Question 6

• What is a Single Nucleotide Polymorphism (SNP)?

Answer 6

DNA sequence variations that occur when a single nucleotide is changed

Question 7

• How do you carry out an association analysis (e.g - for SNP prevalence)?

Answer 7

Stratify population according to genotype and specific SNP (TT, TG, GG)

Look at the number of disease cases in each group

For 1 SNP the statistical P value must be 0.05

Question 8

• Why might there be false positives when looking at over 10,000,000 SNPs?

Answer 8

Larger sample, more of a likelihood that diseases occur purely by chance

Question 9

• Explain the concept of multiple testing

Answer 9

To correct the effect of false positives, the new P value for a genome wide association study is 5x10^-8

This means a much larger sample size is required than normal

This allows robust findings

Question 10

• What is meant by a risk allele?

Answer 10

An allele that is more frequently observed in individuals who are suffering from disease

Question 11

• Give some examples of the modifiable factors affecting CVD

Answer 11

Drinking habits

Eating habits

Smoking

High blood pressure

Sedentary lifestyle

Question 12

• Give some examples of the non-modifiable factors affecting CVD

Answer 12

Sex

Age

Genetic factors

Question 13

what is the benefit of genetic studies on CVD

Answer 13

understand biology of CVD
can predict CVD
identify high risk groups
preventative methods intensified for high risk groups

Question 14

What is heritability

Answer 14

how much the phenotype varies due to genetic differences

Question 15

• Give one way we can compare Heritability and describe why this can be done

Answer 15

Compare Monozygotic (MZ) and Dizygotic (DZ) twins

MZ twins share 100% of DNA

DZ twins share 50% genetic component

MZ twins twice as identical as DZ twins

Question 16

• What is missing heritability?

Answer 16

The gap between the known heritability of a gene and the GWAs loci for that phenotype
eg if known heritability is 40% but GWAs loci is only 5-10%

Question 17

• Give suggested reasons for missing heritability

Answer 17

Rare variants (SNPs)

Low frequency variants with intermedeiate effect

Interactions

Miscalculated estimation of heritability

Diagnosis (accuracy and precision)

Question 18

• What is meant by pharmacogenetics and what is its purpose?

Answer 18

Study of variability in drug response due to genetic differences

To improve drug therapy and prescribing in the future

Question 19

• How does metabolism affect the effect of a drug?

Answer 19

Increased metabolism = Less effect of drug as it is quickly removed

Reduced metabolism = More effect of drug as it may cause overdose

Question 20

• What is the ideal scenario for a drug to be in and how could studies of genetics help this?

Answer 20

Increased efficacy

Decreased adverse effects

Find genes that increase efficacy and decrease the adverse effects

Question 21

• What is meant by personalised medicine?

Answer 21

Tailoring treatment to patients depending on specific characteristics of their disease