Principles of multifactorial inheritance

Question 1

What are traits in which variation is thought to be caused by multiple genes called?

Answer 1

Polygenic traits

Polygenic means ‘many genes’ and often involves environmental factors.

Question 2

What term is used when environmental factors are believed to cause variation in a trait?

Answer 2

Multifactorial

Multifactorial traits involve both genetic and environmental influences.

Question 3

What shape does the distribution of multifactorial traits often follow?

Answer 3

Normal or bell-shaped distribution

Question 4

In the example of height determined by a single gene with two alleles, what are the three possible phenotypes?

Answer 4

• Tall
• Intermediate
• Short

Question 5

How many possible genotypes are there when height is determined by two loci with two alleles each?

Answer 5

Nine possible genotypes

Question 6

What are the loci underlying variation in a quantitative trait such as height called?

Answer 6

Quantitative trait loci (QTL)

Question 7

Is height considered a multifactorial trait or a single-gene trait?

Answer 7

Multifactorial trait

Question 8

What is an example of a multifactorial trait besides height?

Answer 8

Blood pressure

Question 9

What does the threshold model suggest about diseases that do not follow a normal distribution?

Answer 9

There is an underlying liability distribution

Question 10

What is required to express a multifactorial disease according to the threshold model?

Answer 10

Crossing a threshold of liability

Question 11

What disorder is used as an example of the threshold model?

Answer 11

Pyloric stenosis

Question 12

What is the prevalence of pyloric stenosis among whites?

Answer 12

About 3/1000 live births

Question 13

How does the liability threshold concept explain sibling recurrence risks for pyloric stenosis?

Answer 13

Males have a lower threshold, hence higher risk than females

Question 14

What other congenital malformations are thought to correspond to the threshold model?

Answer 14

• Isolated cleft lip and/or cleft palate
• Neural tube defects
• Club foot
• Some forms of congenital heart disease

Question 15

What is the relationship between the number of affected family members and recurrence risk in multifactorial diseases?

Answer 15

The recurrence risk is higher if more than one family member is affected

Question 16

How does the severity of disease expression relate to recurrence risk?

Answer 16

Higher severity leads to higher recurrence risk

Question 17

What happens to recurrence risk as the relationship to the affected individual becomes more remote?

Answer 17

Recurrence risk decreases rapidly

Question 18

What is the general rule for sibling recurrence risk in relation to disease prevalence in the population?

Answer 18

Approximately equal to the square root of the prevalence

Question 19

What do neural tube defects (NTDs) include?

Answer 19

• Anencephaly
• Spina bifida
• Encephalocele

Question 20

What is the estimated heritability of neural tube defects?

Answer 20

Approximately 70%

Question 21

What is the typical prevalence of neural tube defects in most populations?

Answer 21

Approximately 1 per 1000 births

Question 22

What is the recurrence risk for siblings of individuals with neural tube defects?

Answer 22

Ranges from 2% to 5%

Question 23

How does the occurrence of anencephaly affect the recurrence risk for spina bifida?

Answer 23

Increases the recurrence risk

Question 24

What is the main reason for the increasing prevalence of neural tube defects in some populations?

Answer 24

Combination of genetic and environmental factors

Question 25

What are the sibling recurrence risks for NTDs after one, two, and three affected offspring?

Answer 25

3%, 12%, 25% ## Footnote Recurrence risks are slightly lower in populations with lower NTD prevalence rates

Question 26

How can NTDs be diagnosed prenatally?

Answer 26

By ultrasound and elevation in α-fetoprotein (AFP) ## Footnote AFP can be detected in maternal serum or amniotic fluid

Question 27

What is the difference between open and closed spina bifida?

Answer 27

Open spina bifida is not covered with skin, while closed spina bifida is covered ## Footnote Open spina bifida is more likely to be detected by an AFP assay

Question 28

What dietary supplement is associated with a reduced likelihood of NTDs?

Answer 28

Folic acid ## Footnote Approximately 50% to 70% of NTDs can be avoided with dietary folic acid supplementation

Question 29

What is the effect of traditional prenatal vitamin supplements on NTD prevention?

Answer 29

They do not have an effect because administration usually begins after neural tube closure ## Footnote Folic acid intake before conception is critical

Question 30

What nongenetic factor contributes to familial clustering of NTDs?

Answer 30

Dietary folic acid ## Footnote Genetic variation in response to folic acid may explain differences in NTD occurrence

Question 31

Which gene product is mentioned as being involved in folic acid metabolism?

Answer 31

Methylene tetrahydrofolate reductase ## Footnote Associations between NTDs and variants in genes related to folic acid metabolism are being tested

Question 32

What is the prevalence of cleft lip/palate in the general population?

Answer 32

0.001 ## Footnote Recurrence risks vary among first, second, and third-degree relatives

Question 33

What distinguishes multifactorial diseases from single-gene diseases?

Answer 33

Multifactorial diseases are caused by multiple genetic and environmental factors; single-gene diseases require a single mutation ## Footnote Locus heterogeneity allows for different mutations at multiple loci to cause the same disease

Question 34

What is an example of a trait influenced by both a major gene and multifactorial background?

Answer 34

Height ## Footnote Variation in height can be attributed to both genetic and environmental factors

Question 35

What is the overall distribution of height described as?

Answer 35

Bell-shaped ## Footnote This distribution results from the superposition of variations from different genotypes

Question 36

Can diseases like colon cancer and breast cancer be caused by both major genes and multifactorial inheritance?

Answer 36

Yes ## Footnote These diseases may have subsets where single-gene inheritance contributes to disease susceptibility

Question 37

What is the importance of identifying responsible major genes in multifactorial diseases?

Answer 37

They provide important clues to the pathophysiology and treatment of the disease ## Footnote Identifying these genes can help in understanding disease mechanisms