Complex Genetic Disorders Flashcards
Characteristics of MFDs (5)
- Relatively common
- Non-Mendelian
- Cluster in families
- Chronic or later onset
- Cont or discontinuous
MFD Rules (7)
- if one relative affected other relatives at higher risk
- risk is same for all first degree relatives of affected person (2-7%)
- Incidence higher in first degree than second than third
- incidence is higher in more severely affected patients
- If disease is more common in males than relatives of affected female have higher risk than relatives of affected male (because female must have more severe form)
- risk of recurrence in first degree relatives is roughly square root of risk of general population
- Risk of recurrence in subsequent pregnancies depends on # ids already affected (1 kid affected «_space;2 kids affected because more kids suggests more bad gene load)
Concordance v Discordance
- 2 related individuals in family have same disease (suggests genetic basis)
- *100% concordance means fairly certain disease is all genetic
-1 relative affected while other is not (suggests environmental factors involved)
Relative Risk
(prev of disease in relatives of affected person)/(prev of disease in relatives of control person)
-If RR=1 then relatives of proband are no more likely to develop disease than random person in population
2 Ways to Determine Relative Contributions of Genetics v Environment
1- Relatives/unrelated family members (higher concordance among truly related family members than w/ spouse or adopted sibs) **controls for same environmental exposure
2- TWINS (if MZ concordance > DZ concordance…likely genetic component)
Twins Studies
MZ (identical) DZ (fraternal)
-If R=1 for MZ then 100% concordance and purely genetic
- If R of MZ = R of DZ then environmental factors
- If R of MZ»_space; R of DZ then genetic factors
Heritability
- Percentage of phenotypic variance explained by genotypic variance
- h^2= (var in DZ twins - var in MZ twins)/Var in DZ twins
