Genetic Basis of Multifactorial Disease Flashcards
What are examples of diseases mainly caused by environmental factors?
Trauma, Infection
What are examples of diseases mainly caused by genetic factors?
Cystic fibrosis, Huntington disease, Chromosome abnormalities
How do genetic and environmental factors contribute to a phenotype?
They interact together, with both playing a role in determining the phenotype.
What is the nature of complex traits in genetic risk?
They are probabilistic, and influenced by many genes and environmental factors.
What model is used to describe genetic and environmental contributions in complex diseases?
Liability threshold model
What two main study types are used to determine genetic contribution?
Family studies and Twin studies
What does a family study investigate?
Whether a disease is more common among relatives of affected individuals
What does a twin study compare?
Concordance rates of disease between monozygotic and dizygotic twins
What is heritability?
The proportion of total variance in a trait that is due to genetic factors
Name some conditions with high heritability estimates.
Schizophrenia (85%), Asthma (80%), Pyloric stenosis (75%)
What is a polymorphism?
A variation in the genome present in more than 1% of the population
What is an association study?
A method to compare frequency of polymorphisms in affected vs unaffected individuals
What is a common limitation of association studies?
Population stratification and difficulty in identifying the correct gene or variant
What approach is used to overcome the gene-targeting problem in association studies?
Genome-wide association studies (GWAS)
What does a significant association in a study imply?
It may indicate a genetic contribution, but needs replication and functional relevance
How does family history help in assessing genetic risk?
More affected members or younger onset suggests inherited predisposition
Are most common diseases caused by single gene mutations?
No, they are typically multifactorial
What is the role of genetic testing in multifactorial disease?
Limited; clinical management usually targets modifiable factors
What is the clinical approach to conditions like heart disease with genetic predisposition?
Use empirical risk and treat based on clinical factors (e.g., cholesterol, BP)
Why is recurrence risk higher if a female is affected in a sex-biased condition like pyloric stenosis?
Because she likely carries more susceptibility genes due to higher threshold for expression
