Bioc L05 Multifactorial Inheritance Flashcards
What are congential malformations?
malformations present at birth
cleft palate
pyloric stenosis
club food
spina bifida
Multifactorial diseases include congenital malformations as well as many adult diseases including:
coronary artery disease
obesity
alcoholism
diabetes
infatile autism
schizophrenia
Multifactorial diseases occupy a much larger part of our disease burden than what type other type of disorders?
single gene disorders
What is a polygenic or multigenic trait?
Trait in which variation is thought to be caused by a combined effect of multiple genes.
Do polygenic traits have an environmental factor?
No
What is Multifactorial inheritance?
polygenic trait + environmental factors
What are four ways in which Multifactorial inheritance can be distinguised from single-gene?
- Can occur in isolation, no clear Mendelian pattern
- Can occur more in one sex than in another with no clear sex-linked pattern
- Can occur more in a certain ethnic group
- Environmental factors change the risk of the disease
What is the additive polygenic or multigenic model of multifactorial inheritance?
can be applied to quantitative traits
contiuous variation from one extreme to the other, represented by bell shaped curve
ex. human height
How is human height an example of a polygenic model of multifactorial inheritance?
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
What is the Threshold model of multifactorial inheritance?
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
What can change the threshold of liability?
When does the threshold not change?
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)
What are some examples of diseases that fit witht the threshold model of human multifactorial inheritance?
- infantile autism
- neural tube defects
- some forms of congential heart disease
- club food
- isolated cleft palate
- hypertension
How is pyloric stenosis and example of the threshold model?
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
Can you calculate occurence risk polygenic or multifactorial traits?
NO
How do you calculate the recurrence risk for multifactorial diseases?
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
What are three things we know about recurrence risk in multifactorial diseases?
- the more family members affected with the disease, the higher the recurrence risk
- the less the degree of relationship with the proband, the less the recurrence risk
- the more severe the disease in the proband, the higher chance to transmit the disease
- recurrence risk increases if the proband is of the less commonly affected sex
What are two methods used to differentiate between genetic and environmental contribution to disease?
- twin studies
- adoption studies
What is condordance?
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
What is discordance?
if both members of a twin pair do not share a trait
What is heretability?
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
What are some limitations in twin studies?
- differences in uterine environment
- somatic mutations in only one of twins
underestimation of environmental contribution
What are adoption studies based on?
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
What are some limitations of adoption studies?
- 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
Disorders with multifactorial inheritance will be the cause of morbidity and premature mortality in how many individuals during their lifetime?
2/3
