Multifactorial Inheritance

Question 1

Frequency of multifactorial disease

Answer 1

5% incidence at birth
60% population prevalence

Question 2

Examples of multifactorial congenital malformations

Answer 2

Cleft lip and palate
Neural tube defects
Heart defects

Question 3

Examples of multifactorial adult-onset diseases

Answer 3

Diabetes
Heart disease
Epilepsy
Affective Disorders

Question 4

Examples of multifactorial traits in general population

Answer 4

Height
Intelligence
Blood pressure

Question 5

Genetics factors involved in multifactorial inheritance

Answer 5

Susceptibility genes
Modified genes
Epigenetic modifications

Question 6

Environmental factors in multifactorial conditions

Answer 6

Diet
Exercise
Teratogens
Infections
Smoking
Trauma
Stress
Pollutants

Question 7

Continuous multifactorial traits

Answer 7

Quantitative traits
Bell shaped distribution (example: height)

Question 8

Discontinuous multifactorial traits

Answer 8

Qualitative traits
Threshold effect
Trait is present or absent (example: CHD)

Question 9

Twin studies

Answer 9

Probability that one twin will have a trait given that the other twin has the trait
Large difference in concordance between monozygotic (MZ) and dizygotic (DZ)

Question 10

Concordance rates for MZ twins for
Epilepsy
Diabetes type I
Schizophrenia
Cleft lip +/- cleft palate

Answer 10

70
40
53
30

Question 11

Concordance rates for DZ twins for
Epilepsy
Diabetes type I
Schizophrenia
Cleft lip +/- cleft palate

Answer 11

6
4.8
15
5

Question 12

Liability

Answer 12

genetic and environmental factors involved in the occurrence of a MF tait

Question 13

What model can explain the presentation of discontinuous traits

Answer 13

Threshold

Question 14

Correlation

Answer 14

Tendency for values of a physiological measurement to be more similar among relatives than among general population

Question 15

Heritability

Answer 15

Fraction of the total phenotypic variance of a quantitative trait caused by genes

Question 16

Candidate gene studies

Answer 16

disease association studies
Sibling pairs

Question 17

Multifactorial inheritance recurrence risks

Answer 17

Based on empiric data
Risk to first degree relatives is often ~2-5%
Depends on number of affected relatives and degree of relatedness
RR to 1st degree relatives is increased above general population risk
RR increases proportionately to the number of affected individuals in family
RR typically higher if disorder is in the more severe range of the phenotype
RR is higher if the proband is of the less commonly affected sex
RR quoted are averages
RR can vary on population

Question 18

Population incidence of cleft palate per 1000

Answer 18

.4

Question 19

Population incidence of cleft palate +/- CP per 1000

Answer 19

.4-1.7

Question 20

Population incidence of hip dysplasia per 1000

Answer 20

2

Question 21

Population incidence of CHD per 1000

Answer 21

1.7

Question 22

Population incidence of neural tube defects per 1000

Answer 22

2-10

Question 23

Population incidence of pyloric stenosis per 1000

Answer 23

1 (female), 5 (male)

Question 24

Pyloric stenosis

Answer 24

narrowing of pylorus
More common in males
Higher liability in females (stronger genetic and environmental factors needed to cross threshold)

Question 25

Pyloric stenosis recurrence risk

Answer 25

affected female - RR higher for male first degree relatives than female

Question 26

Half siblings are what degree of relatives

Answer 26

2nd

Question 27

What increases recurrence risk for multifactorial inheritance

Answer 27

Close relationship to proband
High heritability
Multiple affected relatives
Severe form or early onset
Proband is the less frequently affected gender

Question 28

Population risk of CL/P

Answer 28

1:500-1000
Native Americans: 3.6/1000 (1/277)
Japanese: 1/476
Chinese: 1/714
White: 1/1000
Black: 1/3333