L15-17 Heritability + Pharmogenomics

Question 1

define infectious disease

Answer 1

caused by pathogenic microorganisms (can be a complex disease)

Question 2

define non communication disease

Answer 2

condition non infectious

= chronic

Question 3

what is the pattern of morality of infect/chrnoic diseases in low/high income countries

Answer 3

low income more infectious, chronic more middle/high income

Question 4

why is life expectancy lower in low income countries

Answer 4

• Earlier death= greater effect on life expectancy
o // lower life for low income as more infectious die at lower age
o Despite total people dying being the same
o But as in higher income = people die later

Question 5

what is a complex disease

Answer 5

environmental + genetic

Question 6

what is polygenic and pleiotrphy

Answer 6

Simple= polygenic: multiple genes to a single effect

Complex: pleiotropy (one gene= multiple effect)

Question 7

how to determine how much of a disease is due to genetics and how much to environment (analysis of complex diseases)`

Answer 7

1. familial aggregation? (twin studies, adoption, risk ratio)
2. susceptibility genetic? (heritability)
3. type and frequency of susceptibility allele?
4. identify disease gene (linkage, association, GWAS)

Question 8

Describe risk ratio

Answer 8

• If brother or sister affected, risk ratio is what is YOUR risk compared to general population
o Genetics= risk higher as share more genetic similarity

Question 9

if risk ratio = 1?

Answer 9

no risk

Question 10

if risk ratio higher than 1

Answer 10

= risk

Question 11

how to determine •for complex traits how much of the variation between people is due to genetic differences between them and how much is due to them experiencing different environments ?

Answer 11

VP =VG +VE
• Heritability = H =VarG /VarP = VG /VP
• H can take any value between 0 and 1
• Within a population

Question 12

// what is H in heritability formual

Answer 12

proportion of phenotypic variation in a population that is attributable to genetic variation among individuals.

Question 13

what does a heribtriality closer to 1 mean

Answer 13

greater effect of genes (Vg)

Question 14

why are twin studies problematic

Answer 14

can be problematic in determining genetic contribution (as H is not constant but affected in environments)
o Mono= 100% of DNA , dizo= 50%
o concordance of DNA = allows to determine genetic probability
o Complications: shared environment = overcompensates for genetic contribution // adoption studies more accurate

Question 15

how is speed effected by heritability

Answer 15

Speed of selection is proportional to heritability

= o Greater genetic variation contributes to the phenotype = faster selection occurs

Question 16

how is rate of change influenced by mode of expression + strength

Answer 16

if recessive= slower selection

if highly favoured genotype= fast selection

Question 17

what is linkage studies

Answer 17

• Seeks to identify chromosomal segments shared by affected (family) members
o What is shared between individuals

Question 18

what is association studies

Answer 18

• Measures preferential segregation of a particular allele with a phenotype across families

Question 19

what is GWAS

Answer 19

an sample variation across genome and compare ‘control’ and ‘disease’ subjects
- Compare freq of variant b/w 2 groups

Question 20

what are the green spots in manhattan plot

Answer 20

• Green = genetic hot spots

o Likely to contain candidate genes that influence that particular phenotype

Question 21

describe correlation of IFNL3 with HCV recovery rates

Answer 21

• low freq= low recovery

- changes in different ethnic groups i.e. african americans

Question 22

what determines if a disease gene is easy to find

Answer 22

1. Penetrance:
2. Frequency:
   • If common= use genome wide

Question 23

what is penetrance

Answer 23

if penetrance if high = have genetic varient and have disease
• Low penetrance = have gentic varient + don’t develop (may tag as controlled)

Question 24

sample size requirements finding rare/common disease varients

Answer 24

• To find low freq = high sample, if high freq= lower sample needed

Question 25

define phamcogenomics

Answer 25

study of genetic variations that affect an individual’s responses to drugs.

Question 26

what drug issues are significant to phamcogenomics

Answer 26

drug metabolism

drug target

Question 27

how does phamcogenomics tailor treatments

Answer 27

• Reflects dosage in response to varients