Day 5, Lecture 2 (Aug 26): Genetics VII: Multifactorial Disease Flashcards
Examples of Multifactorial/complex diseases
- Coronary artery disease
- Schizophrenia
- Autism
- Diabetes Mellitus
- Multiple sclerosis
- Epilepsy
- Rheumatoid arthritis
- Alzheimer disease
- Congenital malformations
Spectrum of Genetic disease

What is digenic
induced by two genes to cause phenotype
Difference between Digenic expression and Digenic penetrance
- Digenic expression means that a mutation in two genes makes the expression of disease worse
- Digeneic penetrance means that you need a mutaiton in the second gene to actually express the trait
How can discrete units like genes produce a continuous phenotype?
The cumulative effect of multiple genes can produce a continuous phenotype (polygenic trait)

What is a polygenic trait?
Traits controlled by more than one gene
Difference between a quantitative Trait loci (QTL) and disease susceptibility loci
- if the genes are contributing to a disease they are called disease susceptibility loci
- if they are contributing to a specific trait (such as height) then they are quantitative trait loci (QTL)
Continuous phenotypes are determined by a combination of
- genes and environment
- Example is height
- not alot of genes have changed in the human genome over 100 years but environmental conditions have increased average height
- Example is height

a balance between ___ and ____ factors (and not a specific trigger) = multifactorial disease
Risky and beneficial factors
What is a polygenic threshold
- This is the point were the level of phenotypical expression is high enough that disease is diagnosed

Polygenic traits are
continuous and quantitative
Heritability
The proportion of phenotypic variability explained by genetic variance- varies for different traits
Characteristics of multifactorial diseases
- Familial aggregation w/o defined pattern of inheritance
- Empiric risks help determine the risk fo recurrence
- Recurrence risk is proportional to relatedness
- Recurrence risk is higher with multiple and more severely affected relatives
- There is often a sex-bias; recurrence risk is higher among relatives of the less prevalent sex

Empiric risk
The risk of a condition in a defined situation ascertained from simple observational data.
Recurrence risk
The likelihood that a clinical disorder will occur in additional siblings of the same biological parents


Recurrence risk of mutlifactorial traits depends on


Explain Sex-specific thresholds
- Some diseases have a higher likely hood of being in one sex. This means that if a family member of the sex (which is in the general population is less likely to have the disease) has the disease than the risk goes up in the other members of the family
- ex. Pyloric stenosis is 5 x more likely in men than women
- so if a man has it then his relatives have about a 4% chance of having it but if a woman has it than her relatives have a 9% chance
- ex. Pyloric stenosis is 5 x more likely in men than women


What is an efficient way to analyze conditions that have a stong enviromental component


Familial aggregation
is the clustering of certain traits, behaviours, or disorders within a given family. Family aggregation may arise because of genetic or environmental similarities.