Complex Genetic Disorders

Question 1

Characteristics of MFDs (5)

Answer 1

• Relatively common
• Non-Mendelian
• Cluster in families
• Chronic or later onset
• Cont or discontinuous

Question 2

MFD Rules (7)

Answer 2

• 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)

Question 3

Concordance v Discordance

Answer 3

• 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)

Question 4

Relative Risk

Answer 4

(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

Question 5

2 Ways to Determine Relative Contributions of Genetics v Environment

Answer 5

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)

Question 6

Twins Studies

Answer 6

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

Question 7

Heritability

Answer 7

• Percentage of phenotypic variance explained by genotypic variance
• h^2= (var in DZ twins - var in MZ twins)/Var in DZ twins