Genetic Risk
Monogenic disorders
genes have large effects
high penetrance
sporadic cases are rare
increased risk to biological relatives depending on position in pedigree
mode of transmission is easy to recognize
Complex disorders
genes have small effects (additive effect)
low penetrance
many sporadic cases
increased risk to relatives; risk decreases with decreasing kinship
no recognizable pattern of inheritance
complex model: disease phenotype is product of many genes (major and minor), environment, random variation
Genetic Susceptibility
classic Mendelian trait is all or none Þ if you have the gene, you get the trait
susceptibility states that genes predispose, but do not guarantee a phenotype
genes may predispose to a disease, protect from a disease, or make a person more or less susceptible to
environmental exposures, other genes, etc
types of genetic susceptibility
- susceptible to disease
- susceptible to the natural history of the disease
- susceptible to differences in the response to therapy
disorders of susceptibility: hypertension, atherosclerosis, diabetes, cancer, osteoporosis
Estimation of Risk
risk is not an absolute value - it is an estimation
interpretation of risk is dependant on the clinical context
how to do it
identify the disorder and mode of inheritance Þ construct a pedigree
determine exactly what risk is to be calculated (risk of allele, risk of both alleles, risk of disease)
use punnet square for Mendelian conditions
calculate risks
- probabilities multiplied if the events are independent
- probabilities are added if the events are not independent of each other