Multifactorial Inheritance Flashcards
What is a polygenic trait?
Polygenic trait: variation is caused by combined effect of multiple genes
What is a multifactorial trait?
Multifactorial trait: polygenic + environmental factors
What are the seven characteristics of a multifactorial trait?
- 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
What is the Additive Polygenic Model (2 parts)?
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
What type of traits is the Additive Polygenic Model applied to? How is this model represented graphically?
Additive Polygenic Model is applied to quantitative (measurable) traits
- Represented by a bell-shaped curve
What is the Threshold Model?
Threshold Model: in order to be affected by the multifactorial disease, a person must excess a threshold of liability
What type of traits is the Threshold Model applied to?
Threshold Model is applied to qualitative traits (either have the disease or you don’t)
Under what circumstances might the Threshold of Liability be different?
Threshold of Liability may be different in different populations
Does threshold or liability change within a specific population?
Threshold does not change with a specific population but liability can change
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?
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)
What are the four factors affecting recurrence risk?
- 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
What two study types are used to differentiate between nature versus nurture?
- Twin studies
- Adoption studies
What two twin types are compared in twin studies? Describe each in terms of amount of genetic information shared and placental sharing/not sharing
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
Differentiate between concordance and discordance
- Concordance: both members of the twin pair share a trait
- Discordant: both members of a twin pair do not share a trait
Theoretically, why are twin studies used? (hint: think genes versus environment)
Influence of environment is similar in monozygotic twins and dizygotic twins (raised together), but they are genetically different
What is heritability? What is the equation to evaluate for heritability, and what does a value closer to 1.0 indicate?
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
What are the three limitations of a twin study?
- 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)
What are the two hypotheses associated with adoptive studies?
- 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
What are the four limitations of adoptive studies?
- 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
What is the take home message regarding twin/adoption studies in evaluating multifactorial inheritance?
Twin and adoption studies only provide a preliminary indication of the extent of genetic versos environmental influence on multifactorial diseases
