Lecture 7 - Multifactorial Inheritance Flashcards
What are polygenic traits?
Traits thought to be caused by multiple genes
What are multifactorial traits?
Polygenic traits that are also influenced by environmental factors. Many quantitative traits are multifactorial (BP, heart rate, etc)
What type of distribution is caused by multifactorial traits?
A normal distribution, as they are caused by additive effects of the environment and genetics
How do genetic diseases compare to environmental diseases?
Genetic diseases in comparison are:
Rare, simple genetics, unifactorial, high recurrence rate
Why would multifactorial disorders have a low recurrence rate?
Because you would need to inherit more genes as they are polygenic, and it is much easier to inherit a single gene
What is the liability model?
It is a model that applies to most multifactorial disorders, which assumes that a threshold must be passed before the disease is expressed.
If the liability model’s threshold is more towards the right for a female than a male, what does this mean?
It means that females will generally need to have more “problems” before they actually show the disease
What factors increase the chance of having a multifactorial disorder?
- Having a close relation to the proband (1st person identified)
- High heritability of disorder
- Proband is of more rarely affected sex (probably more things wrong with them)
- Severe/early onset of disease
- Multiple family members affected
What does it mean if a disease has a high heritability?
It means that the disease is more dependant on genetics, and there aren’t too many genes involved (more chances of passing it on)
How is data gathered about genetic risks for multifactorial diseases?
- Family studies
- Twin studies
- Adoption studies
- Population and Migration studies
Why is it that the more severe the manifestation of a multifactorial condition, the greater the recurrence risk?
Because more genetics are involved and it will be easier to pass them on to the next generation
What is the difference between a monozygotic twin and a dizygotic twin?
In monozygotic twins, there is a single sperm and egg, and a shared placenta.
In dizygotic twins, there are two sperms and two eggs, and 2 placentas
What does concordant and discordant mean?
Concordance is when both twins show the same trait, and when they don’t they are discordant
What is a consideration for determining concordance rates in dizygotic twins?
If the twins are different sex, then there is probably different thresholds for certain diseases, so those need to be considered
Approximately how much of the DNA between twins are similar?
Monozygotic = 100% ; Dizygotic = 50%
What are some complications in concordance studies of twins?
Reduced penetrance
MZ twins are often treated more alike than DZ
Environmental and developmental conditions
Somatic mutations may occur
Methylation patterns based on behaviors
When there is a large percentage of concordance between MZ twins vs. DZ twins, what does it tell you?
It tells you that the disorder is probably heavily genetic
What are some identifiable but uncontrollable risk factors for diseases?
Age, gender, race, family history
What is a phenocopy?
The same phenotype as one that is caused by a disease gene, but it is caused by the environment
Why is it difficult to identify specific genes for a disease?
- Locus heterogeneity
- Interaction between multiple genes
- Decreased penetrance
- Age-dependant onset
- Phenocopies
What is a major, good method to identify disease-causing genes?
Look for markers in people in a diseased population, and we can assume that it is inherited along with the gene
What is an LOD score?
It is the logarithm of the likelihood of the two loci being linked at x% recombination frequency divided by likelihood at 50%.
A score >3 = 1000:1 chance of linkage
A score<-2 = 100:1 chance not linked
What are some ways you can identify a disease-causing gene?
Linkage analysis of family studies
Affected sibling method
GWAS
What is an SNP?
Single nucleotide polymorphism; must occur in 1% of population to be considered an SNP
