Bioc L05 Multifactorial Inheritance

Question 1

What are congential malformations?

Answer 1

malformations present at birth

cleft palate

pyloric stenosis

club food

spina bifida

Question 2

Multifactorial diseases include congenital malformations as well as many adult diseases including:

Answer 2

coronary artery disease

obesity

alcoholism

diabetes

infatile autism

schizophrenia

Question 3

Multifactorial diseases occupy a much larger part of our disease burden than what type other type of disorders?

Answer 3

single gene disorders

Question 4

What is a polygenic or multigenic trait?

Answer 4

Trait in which variation is thought to be caused by a combined effect of multiple genes.

Question 5

Do polygenic traits have an environmental factor?

Answer 5

No

Question 6

What is Multifactorial inheritance?

Answer 6

polygenic trait + environmental factors

Question 7

What are four ways in which Multifactorial inheritance can be distinguised from single-gene?

Answer 7

1. Can occur in isolation, no clear Mendelian pattern
2. Can occur more in one sex than in another with no clear sex-linked pattern
3. Can occur more in a certain ethnic group
4. Environmental factors change the risk of the disease

Question 8

What is the additive polygenic or multigenic model of multifactorial inheritance?

Answer 8

can be applied to quantitative traits

contiuous variation from one extreme to the other, represented by bell shaped curve

ex. human height

Question 9

How is human height an example of a polygenic model of multifactorial inheritance?

Answer 9

if one gene with two alleles (A and a) determine height, there are 3 possible genotypes.

BUT, if there are two genes with two alleles each (A, a, B, b) that contribute in a similar way, 9 genotypes will be possible

All dominant alleles contribute the same, number is what matters

A person would have 0 or 1 or 2 or 3 or 4 tall alleles (A or B)

majority of population will be average height with 2 dominant alleles

many genes = many possible phenotypes = bell shaped curve

Question 10

What is the Threshold model of multifactorial inheritance?

Answer 10

Can be applied to qualitative traits: all or nothing traits, where the disease is present or not

in order to be affected by a certain multifactorial disease, a person must exceed a certain threshold of liability

Question 11

What can change the threshold of liability?

When does the threshold not change?

Answer 11

liability changes depending on genetic and environmental factors. Before threshold, no signs of trait are manifested. After crossing the threshold, the trait appears

The threshold does not change for individuals in the same population, but may change in different populations (ie different genders, different ethnic groups)

Question 12

What are some examples of diseases that fit witht the threshold model of human multifactorial inheritance?

Answer 12

• infantile autism
• neural tube defects
• some forms of congential heart disease
• club food
• isolated cleft palate
• hypertension

Question 13

How is pyloric stenosis and example of the threshold model?

Answer 13

due to hyperplasia of the muscles at the pylorus of the stomach, produces an obstruction of gastric emptying

4 times more prevalent in males, clusters in families

females have a much higher threshold of liability, so it takes more of the disease alleles and/or environmental factors to produce the disease phenotype

Question 14

Can you calculate occurence risk polygenic or multifactorial traits?

Answer 14

NO

Question 15

How do you calculate the recurrence risk for multifactorial diseases?

Answer 15

recurrence risk = empirical risk = empirical recurrenct risk

based on previous observation of similar circumstances and we need info for each multifactorial disease and for a similar population group

Question 16

What are three things we know about recurrence risk in multifactorial diseases?

Answer 16

1. the more family members affected with the disease, the higher the recurrence risk
2. the less the degree of relationship with the proband, the less the recurrence risk
3. the more severe the disease in the proband, the higher chance to transmit the disease
4. recurrence risk increases if the proband is of the less commonly affected sex

Question 17

What are two methods used to differentiate between genetic and environmental contribution to disease?

Answer 17

1. twin studies
2. adoption studies

Question 18

What is condordance?

Answer 18

if both members of a twin pair share a trait

79% of cases two monozygotic twins (genetically idential) share the disorder

24% of cases of dizygotic twins (50% identical) share the disorder

Question 19

What is discordance?

Answer 19

if both members of a twin pair do not share a trait

Question 20

What is heretability?

Answer 20

represents the proportion the variation in a disease trait that can be attributed to genes

h= 2 (C monozygotic twins - C dizygotic twins)

the higher the value, the greater the genetic influence

not universal, applies only to certain population in a given environment

h = .58 means 58% of trait is genetic

concordance says nothing about heritability

Question 21

What are some limitations in twin studies?

Answer 21

• differences in uterine environment
• somatic mutations in only one of twins

underestimation of environmental contribution

Question 22

What are adoption studies based on?

Answer 22

comparing rates of adopted offspring of affected parents vs. adopted offspring of unaffected parents

8-10% of children born into, but adopted out of schizophrenic families will develop the disease

1% of adopted children of normal parents become schizophrenic

Question 23

What are some limitations of adoption studies?

Answer 23

• prenatal environmental influences
• adopted children may have been raised with biological parents
• adoption agency finds adoptive parents with similiar socioeconomic status to the natural parents

Question 24

Disorders with multifactorial inheritance will be the cause of morbidity and premature mortality in how many individuals during their lifetime?

Answer 24

2/3