Multifactorial Inheritance

Question 1

What is a polygenic trait?

Answer 1

Polygenic trait: variation is caused by combined effect of multiple genes

Question 2

What is a multifactorial trait?

Answer 2

Multifactorial trait: polygenic + environmental factors

Question 3

What are the seven characteristics of a multifactorial trait?

Answer 3

• There can be multiple occurrences in family with no clear Mendelian pattern of inheritance
• Affected children can be born to unaffected parents
• Disease can occur more in one sex than the other, but no clear sex-linked pattern (no X or Y link)
• Disease occurs more frequently in a specific ethnic group
• Large amount of variation in the severity of the condition
• Environmental factors change the risk of disease
• Degree of relatedness change the risk of disease

Question 4

What is the Additive Polygenic Model (2 parts)?

Answer 4

Multiple genes are involved in the development of a trait AND the number of phenotypic classes increases as the number of genes controlling a trait increases

Question 5

What type of traits is the Additive Polygenic Model applied to? How is this model represented graphically?

Answer 5

Additive Polygenic Model is applied to quantitative (measurable) traits
- Represented by a bell-shaped curve

Question 6

What is the Threshold Model?

Answer 6

Threshold Model: in order to be affected by the multifactorial disease, a person must excess a threshold of liability

Question 7

What type of traits is the Threshold Model applied to?

Answer 7

Threshold Model is applied to qualitative traits (either have the disease or you don’t)

Question 8

Under what circumstances might the Threshold of Liability be different?

Answer 8

Threshold of Liability may be different in different populations

Question 9

Does threshold or liability change within a specific population?

Answer 9

Threshold does not change with a specific population but liability can change

Question 10

What is a disease example of application of the Threshold Model? Based on the Threshold Model, how are occurrence risk and recurrence risk affected with this disease?

Answer 10

Pyloric Stenosis

• Occurrence risk: higher in males due to a lower threshold of liability
• Recurrence risk: higher in females due to a higher threshold of liability (females must be exposed to more disease-causing liability factors in order to develop the disease)

Question 11

What are the four factors affecting recurrence risk?

Answer 11

• More family members affected with a multifactorial disease, the higher the recurrence risk
• Closer the degree of relationship with the proband, the higher the recurrence risk
• Recurrence risk increases if the proband is of the less commonly affected sex
• The more severe the disease is in the proband, the higher the recurrence risk

Question 12

What two study types are used to differentiate between nature versus nurture?

Answer 12

• Twin studies

- Adoption studies

Question 13

What two twin types are compared in twin studies? Describe each in terms of amount of genetic information shared and placental sharing/not sharing

Answer 13

Monozygotic twins (identical twins)

• Genetically identical (100%)
• May share a placenta or have separate placentas

Dizygotic twins (fraternal twins)

• Genetically similar but not identical (50% like with any other siblings)
• Have separate placentas

Question 14

Differentiate between concordance and discordance

Answer 14

• Concordance: both members of the twin pair share a trait

- Discordant: both members of a twin pair do not share a trait

Question 15

Theoretically, why are twin studies used? (hint: think genes versus environment)

Answer 15

Influence of environment is similar in monozygotic twins and dizygotic twins (raised together), but they are genetically different

Question 16

What is heritability? What is the equation to evaluate for heritability, and what does a value closer to 1.0 indicate?

Answer 16

Heritability (h): represents the proportion of variation in a disease trait that can be attributed to genes

(h) = 2 (CMZ - CDZ)
- Higher the (h) value is to 1.0, the greater the genetic influence

Question 17

What are the three limitations of a twin study?

Answer 17

• Differences in uterine environment not accounted for (shared versus separate placentas)
• Somatic mutations can occur in only one twin
• There is an underestimation of environmental contribution (MZ twins often treated more similarly than DZ twins)

Question 18

What are the two hypotheses associated with adoptive studies?

Answer 18

• Adopted children coming from biological parents affected with disease: if the children still develop disease in their adoptive environment, then the disease may have a strong genetic component
• Adopted children coming from biological parents unaffected with disease: if the children develop disease in their adoptive environment, then the disease may have a strong environmental component

Question 19

What are the four limitations of adoptive studies?

Answer 19

• Prenatal environmental influences may be confused with genetics
• Adopted children are not always adopted as newborns and may have been influenced by their biological parents early in life
• Many children are adopted by relatives so environment may be similar to biological parents environment
• Health/behavioral data from birth parents may not be available

Question 20

What is the take home message regarding twin/adoption studies in evaluating multifactorial inheritance?

Answer 20

Twin and adoption studies only provide a preliminary indication of the extent of genetic versos environmental influence on multifactorial diseases