L15-17 Heritability + Pharmogenomics Flashcards
define infectious disease
caused by pathogenic microorganisms (can be a complex disease)
define non communication disease
condition non infectious
= chronic
what is the pattern of morality of infect/chrnoic diseases in low/high income countries
low income more infectious, chronic more middle/high income
why is life expectancy lower in low income countries
• 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
what is a complex disease
environmental + genetic
what is polygenic and pleiotrphy
Simple= polygenic: multiple genes to a single effect
Complex: pleiotropy (one gene= multiple effect)
how to determine how much of a disease is due to genetics and how much to environment (analysis of complex diseases)`
- familial aggregation? (twin studies, adoption, risk ratio)
- susceptibility genetic? (heritability)
- type and frequency of susceptibility allele?
- identify disease gene (linkage, association, GWAS)
Describe risk ratio
• 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
if risk ratio = 1?
no risk
if risk ratio higher than 1
= risk
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 ?
VP =VG +VE
• Heritability = H =VarG /VarP = VG /VP
• H can take any value between 0 and 1
• Within a population
// what is H in heritability formual
proportion of phenotypic variation in a population that is attributable to genetic variation among individuals.
what does a heribtriality closer to 1 mean
greater effect of genes (Vg)
why are twin studies problematic
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
how is speed effected by heritability
Speed of selection is proportional to heritability
= o Greater genetic variation contributes to the phenotype = faster selection occurs
how is rate of change influenced by mode of expression + strength
if recessive= slower selection
if highly favoured genotype= fast selection
what is linkage studies
• Seeks to identify chromosomal segments shared by affected (family) members
o What is shared between individuals
what is association studies
• Measures preferential segregation of a particular allele with a phenotype across families
what is GWAS
an sample variation across genome and compare ‘control’ and ‘disease’ subjects
- Compare freq of variant b/w 2 groups
what are the green spots in manhattan plot
• Green = genetic hot spots
o Likely to contain candidate genes that influence that particular phenotype
describe correlation of IFNL3 with HCV recovery rates
- low freq= low recovery
- changes in different ethnic groups i.e. african americans
what determines if a disease gene is easy to find
- Penetrance:
- Frequency:
• If common= use genome wide
what is penetrance
if penetrance if high = have genetic varient and have disease
• Low penetrance = have gentic varient + don’t develop (may tag as controlled)
sample size requirements finding rare/common disease varients
• To find low freq = high sample, if high freq= lower sample needed
define phamcogenomics
study of genetic variations that affect an individual’s responses to drugs.
what drug issues are significant to phamcogenomics
drug metabolism
drug target
how does phamcogenomics tailor treatments
• Reflects dosage in response to varients
