Genetic Basis of Multifactorial disease Flashcards
Describe the contribution of genetic and environmental factors
Some diseases are almost exclusively genetic (eg, cystic fibrosis) some diseases are a combination of both genetic and environmental (eg, heart disease) and some are almost exclusively environmental (eg, trauma) but still has some genetic factors
What is quantitative inheritance?
Complex disorders and continuous traits which are influenced by multiple genes and multiple environmental factors
What are single gene disorders?
Deterministic
What are complex traits?
Even if you have all susceptibility alleles, disease still depends on environmental hazards.
What is the liability threshold model?
Where all the factors which influence the development of a multifactorial trait/disorder can be considered as a single entity
What is to the right of the threshold on a liability curve?
The incidence of disease in the general population
What is the familial incidence?
The proportion above the threshold on a liability curve
What is heritability of a trait/disease?
It is the proportion of the total variance that is genetic
What is the overall variance of a phenotype?
The sum of the environmental and genetic variance.
What is polymorphism?
Any variation in the human genome that does not cause a disease on its own but can predispose to a common disease.
What is synonymous polymorphism?
Changes in DNA sequence that doesn’t change the amino acid or subsequent protein
What is non-synonymous missense polymorphism?
Changes in the DNA sequence and amino acid and protein produced
What is non-synonymous nonsense polymorphism?
Changes to DNA sequence to code for a premature stop codon.
What are some of the limitations of family studies?
It does not take into account the risk caused by shared environment such as a familial predilection for hamburgues in siblings
How will the liability curve appear for affected relatives?
It will shift to the right as the familial incidence is higher than the general population
Describe why 1st degree relatives of an affected person who in the lower risk group are more likely to get the disease?
For the person in the lower risk group to be affected they would have to have had a greater number of risk factors therefore their relatives are more likely to also have a greater number of risk factors.
What are some of the limitations of twin studies?
It doesn’t take into account that being a monozygotic twin can be a predisposing factor for a disease
What are the ways of working out if a disease phenotype has genetic contribution?
By recurrence risk in siblings and twin studies
What are some of the limitations of association studies?
Difficult if you don’t know what gene or polymorphism to look at and association could be due to chance or to population stratification.
How can you find out if a polymorphism contributes to a disease?
Via association study methods - looks at the affected individuals and what polymorphism is increased. Or test the whole genome - Analyse the polymorphisms in a disease and control population.
When can you suspect a single gene disorder
If you see a really severe version of a disease that is usually multifactorial
For multifactorial conditions there is a higher recurrence risk if?
There are more affected family members and more severely affected family members.
What informations does heritability provide
Liability / susceptibility for a certain disorder: example
What should we do for multifactorial conditions
