Multifactorial Inheritance Flashcards
(35 cards)
How do you identify that a condition has a genetic component?
- family studies
- twin studies
- adoption studies
How do family studies work?
Compare the incidence of a disease amongst the relatives of an affected individual with the general population.
What factors influence the risk of inheriting a multifactorial disease (from family studies)?
- risk varies directly with degree of relationship
- risk varies with severity of the proband’s illness
- risk varies with the number of relatives affected
Who is the proband?
Proband - the first family member affected by a multifactorial genetic condition
What is a twin study?
Compares genetically identical twins with genetically non-identical twins.
What does monozygotic mean?
Identical twins
What does dizygotic mean?
Non-identical twins
What is the concordance rate?
The % of twin pairs studied that both have the condition.
What would you expect from the concordance rate if a condition has a genetic component?
Concordance rate is higher in monozygotic twins than in dizygotic twins.
What is the significance of a high risk of disease for monozygotic twins even when they are reared apart?
Genetic component of disease is more significant than environmental factors.
What is an adoption study?
Compare:
- adopted children with a biological parent who has the disease, but their adoptive parents do not
- adopted children with biological parents who do not have the disease, but one of their adoptive parents does
Or look at the rates of the condition in biological and adoptive families when the adopted individual has the disease.
What do adoption studies show?
Adopted children with a biological parent who has the disease, but with adoptive parents who don’t, have a high risk.
Adopted children with biological parents who do not have the disease, but with an adoptive parent who does, have a low risk.
Where an adopted individual has the disease, the risk is low in the adoptive families but high in the biological families.
This shows that the genetic component is more significant than environmental factors.
What does aetiology mean?
The cause of a disease.
What does hereditability mean?
The proportion of the aetiology that can be ascribed to genetic factors rather than environmental factors.
Expressed as a percentage.
What is one way that you can calculate hereditability?
The concordance rate in monozygotic twins.
What are 3 characteristics of multifactorial inheritance?
- incidence is greatest amongst relatives of the most severely affected patients
- if there is more than one affected close relative then the risks for other relatives are increased
- relatives of an affected individual of the less frequently affected sex are at higher risk
What does the threshold signify in the liability / threshold model?
The combination of environmental and genetic factors that will cause the disease. Above the threshold the abnormal phenotype is expressed.
What does liability mean?
The genetic and environmental factors that influence the development of a multifactorial disease.
What distribution does liability have?
Normal distribution
How does the liability curve for relatives of an affected individual compare to the curve for the general population?
Curve shifts to the right for relatives.
How do you work out what the genetic component of a disease is?
Genome wide association studies.
What is a GWAS?
- compares frequency of markers (e.g. SNPs) in a sample of patients and a sample of healthy controls
- look for markers seen more frequently in the disease population
- sequence the area in which the marker is found to identify the particular gene / allele associated with the disease
What is a neural tube defect?
Defective closure of the developing neural tube during the first month of embryonic life.
What are recurrence risks for neural tube defects without treatment? For which ethnicity are they highest?
(Without treatment)
- 4 - 5 % in affected families
- 1 - 2 % in general population
Highest in people of Celtic origin.
