Lecture 7: Multifactorial Inheritance

Question 1

True or False: Multifactorial traits tend to cluster in families but do not follow a recognizable inheritance pattern

Answer 1

True

Question 2

Multifactorial traits can either be ____ or ____

Answer 2

quantitative (continuous) or qualitative (discontinous)

Question 3

Which traits exhibit phenotypic variability due to additive contribution of genetic and environmental factors?
A. Continuous (quantitative)
B. Discontinuous (qualitative)

Answer 3

A. Continuous (quantitative)

Question 4

Which traits are expressed as “all or none” once a threshold of predisposing insults is exceeded?
A. Continuous (quantitative)
B. Discontinuous (qualitative)

Answer 4

B. Discontinuous (qualitative)

Question 5

True or False: If a condition is common in a population AND an affected individual’s relatives have a LOWER incidence of the disease than for a single gene disorder but a HIGHER risk than the general population, this suggest complex inheritance

Answer 5

True

Question 6

A proband’s siblings and offspring have similar incidence of a disease. Dose this suggest complex inheritance?

Answer 6

Yes!

Question 7

If a disease incidence in a proband’s relatives increases rapidly with every degree of separation, does this suggest complex inheritance?

Answer 7

No! - If it were a complex disease, you would expect disease incidence in a proband’s relatives to DECREASE rapidly with every degree of separation

Question 8

The disease incidence of X condition in relatives of a proband is LOWER when the proband is of the LEAST commonly affected sex. Does this suggest complex inheritance?

Answer 8

No - if condition X was inherited complexly, you would expect the disease incidence of X condition in relatives of a proband to be HIGHER when the proband is of the LEAST commonly affected sex

Question 9

True or False: In complex inheritance, observed risk rises following birth of two affected children

Answer 9

True

Question 10

True or False: In complex inheritance, disease incidence in a proband’s relatives INCREASES with the severity of phenotypic manifestation in the proband

Answer 10

True

Question 11

The more closely two people are relayed, the more ___ they share

Answer 11

alleles

Question 12

The higher the frequency of shared alleles between proband and their relatives , the higher the correlation to the expression of the ___

Answer 12

trait

Question 13

Height, body weight, BP, serum cholesterol are all examples of:
A. Continuous/quantitative traits
B. Discontinuous/qualitative traits

Answer 13

A. Continuous/quantitative traits

Question 14

True or False: Continuous/quantitative traits are determined by the additive effects of multiple genes AND environmental factors

Answer 14

True
“Multiple additive locus model”

Question 15

True or False: Qualitative traits tend to follow a normal Gaussian Curve in populations

Answer 15

False - quantitative traits do!

Question 16

True or False: In quantitative traits, each predisposing gene allele (quantitative trait loci - QTL) and environmental factor contributes a small degree to overall expression of the trait

Answer 16

True

Question 17

True or False: There is phenotypic variability in multifactorial complex inheritance

Answer 17

True

Question 18

True or False: Multifactorial traits with complex inheritance are monogenic

Answer 18

False - polygenic

Question 19

____ twins have same allele at every locus while first degree relatives have about ___

Answer 19

100%; 50%

Question 20

Siblings and dizygotic twins share an average of __ of alleles across all loci

Answer 20

50%

Question 21

True or False: Multiple additive locus model is associated with qualitative traits

Answer 21

False - quantitative!

Question 22

Do discontinous/threshold traits follow a normal Gaussian distribution in populations?

Answer 22

No! - you either have it or don’t

Question 23

In Discontinuous (Threshold) Traits, additive effects of genes and environment ___ to variable expression of a trait
A. Do
B. Do NOT

Answer 23

B. do NOT

Question 24

In Discontinuous (Threshold) Traits, additive effects of genes and environment accumulate until a ___ is met

Answer 24

threshold

Question 25

True or False: Discontinuous (threshold) traits applies to most common multifactorial disorders

Answer 25

True

Question 26

In discontinuous (threshold) traits, additive effects of multiple gene alleles and environmental influences accumulate until a certain threshold level is exceeded. What happens once it is exceeded?

Answer 26

Disease phenotype is expressed

Question 27

True or False: Once disease threshold is reached in discontinuous (threshold) traits, additive effects of multiple genes alleles and environmental influences can cause INCREASED severity of disease manifestation

Answer 27

True

Question 28

____: Combined influences of multiple genetic and environmental insults are a person's

Answer 28

Liability

Question 29

True or False: The liability for a given multifactorial disorder does follow a normal gaussian distribution

Answer 29

True

Question 30

Individuals on the high end of the liability distribution carry ___ genetic and environmental risk factors and are at ___ risk of developing the disease

Answer 30

high

Question 31

True or False: There is familial aggregation in quantitative traits

Answer 31

False - qualitative traits

Question 32

In qualitative traits, why does the risk to family members of expressing the disease phenotype remain higher than the general population?

Answer 32

Threshold remains

Question 33

True or False: Pyloric stenosis is a multifactorial condition with unequal sex ratios

Answer 33

True (male:female, 5:1) - Therefore, different liability thresholds for male and females

Question 34

The disease risk of what type of traits rises with affected siblings? A. Continuous B. Discontinuous

Answer 34

B. Discontinuous

Question 35

In pyloric stenosis, disease risk rises if affect relative is of _____ sex A. most often affected sex B. less often affected sex

Answer 35

B. less often affected sex

Question 36

True or False: In pyloric stenosis, the least commonly affects sex must acquire more ____ (gene mutations) to express disease phenotype

Answer 36

liability factors

Question 37

True or False: In pyloric stenosis, close relatives if an affected female share the HIGHER mutations burden and are more apt to acquire the disorder

Answer 37

True

Question 38

Which of the following couples has the highest risk of a having a baby affected with pyloric stenosis? A. Couples in which the father was affected with pyloric stenosis in infancy B. Couples in which mother was affected with pyloric stenosis in infancy

Answer 38

B. Couples in which mother was affected with pyloric stenosis in infancy

Question 39

RA is a multifactorial disorder affecting girls 3x more often than boys. Which of the following is at the highest risk of being affected? A. Boy with affected male cousin B. Boy with affected brother C. Girl with affected uncle D. Girl with affected brother E. Girl with affected niece

Answer 39

D. Girl with affected brother

Question 40

Hypertrophy and thickening of pylorous muscles, which blocks food from entering small intestine from the stomach is a feature of which condition?

Answer 40

Pyloric Stenosis

Question 41

The recurrence risk for first degree relatives of a proband of a multifactorial disease can be approximated by calculating the ____ of disease incidence of the general population

Answer 41

square root

Question 42

True or False: Cleft lip and palate arises due to both genetic and environmental mechanisms

Answer 42

True

Question 43

Which type of CL/P occurs if the cause is: - Single gene mutation - Chromosomal disorders - Teratogens A. Non-Syndromic B. Syndromic

Answer 43

B. Syndromic

Question 44

Which type of CL/P occurs if the cause is due to environmental causes (folic acid deficient during pregnancy, uncontrolled maternal diabetes, maternal smoking) A. Non-Syndromic B. Syndromic

Answer 44

A. Non-Syndromic

Question 45

True or False: ~2/3 of Non-Syndrome CL/P patients are male

Answer 45

True

Question 46

Non-syndromic patients are often sporadic cases with complex ____

Answer 46

inheritance

Question 47

Which two factors increased risk of CL/P?

Answer 47

1. Disease severity in affected relatives 2. # of affected parents or relatives - disease risk rises with increased phenotypic severity of affected proband

Question 48

True or False: The more severe the manifestation of a multifactorial condition, the greater the probability of its recurrence in the family

Answer 48

True

Question 49

How can you determine the risk of recurrence in multifactorial diseases for 1st degree relatives?

Answer 49

Take the square root of the disease incidence in the general population

Question 50

The overall incidence of CL/P is 1/1000. For a family with no history of CL/P, what is the probability that any pregnancy will result in an affect child?

Answer 50

Occurrence risk is the same as the overall incidence in general population (1/1000)

Question 51

For a family in which a child is born with CL/P, what is the result that any subsequent pregnancy will result in an affected child?

Answer 51

Square root of 1/1000 = 1/32 = 3.1%

Question 52

_____: assesses the extent to which one's genetic makeup influences expression of a trait

Answer 52

Heritability

Question 53

What are examples of non-genetic factors that can impact the heritability of complex traits?

Answer 53

1. Environmental exposures (diet, infection) 2. Somatic mutation 3. Epigenetic gene expression changes

Question 54

How do you estimate heritability from concordance rates in twins?

Answer 54

Question 55

True or False: The higher the heritability, the greater role genetic background plays in developing traits

Answer 55

True

Question 56

Answer 56

Question 57

Which of the following is inherited according to the discontinuous model of muti-factorial inheritance? A. BP B. Duchenne Muscular Dystrophy C. Height D. Non-syndromic cleft lip/palate E. Body weight

Answer 57

D. Non-syndromic cleft lip/palate

Question 58

The concordance rate for MS in MZ twins is 0.28 and in dizygotic twins it is 0.03. What is the heritability of MS? A. 1 B. 0 C. 0.25 D. 0.5 E. 2.0

Answer 58

D. 0.5