Multifactorial inheritance Flashcards
Familial aggregation
Affected individuals tend to cluster in families; disorders occur more frequently in some families than in the rest of the population
*does NOT mean disease has a genetic contribution
Relative risk λr
assess familial aggregation
frequency of disease in relatives/ general population
Case-Control studies
asses familial aggregation
Compare individual with others without disease with respect to family history of disease, geographical location, parity, environmental exposures, and previous illness (spouses often used)
Genetics & environmental factors
Environment can influence expression of what appears to be primarily a genetic disorder (PKU - control w/ diet)
Genetic bkgd influences susceptibility to environmentally caused disease (sickle cell anemia are more susceptible to pneumonia but resistant to malaria)
Twin studies
- Pure genetics conditions: MZ concordance rate is 100%; DZ concordance rate is similar to siblings
- Pure environmental: equal concordance rate btwn MZ and DZ twins
- Multifactorial conditions: concordance rate is higher for MZ > DZ, but not 100%
Concordance & discordance
Concordance: two related ppl have the same disease
Discordance: one member of the pair of relatives is affected
Heritability
Percentage of population variation in a trait that is due to genes
h=2(cmz-cdz)
*height has high heritability; contagious disease has low
Gaussian curve of variation
Bell-shaped distribution in populations
-concentrated in mid-range; few at extremes
Threshold model
Applies to many multifactorial diseases
-Assumes there is an underlying liability distribution in a population and that a threshold on this distribution must be passed before a disease is expressed
Degree of relationship (alleles in common)
MZ: 1
first-degree relative: 1/2
second-degree: 1/4
third degree: 1/8
Recurrence risk for 1st degree relatives
sq root (prevalence)
- Increased by:
1. multiple affected family members
2. severe form, early onset
3. consanguineous marriages
