Complex Traits Flashcards
Simple Trait (Mendelian)
one gene has one distinct biological effect; equal risk for everyone with the mutation
Complex Trait
variations in multiple genes contribute to a single effect; individuals can have different levels of risk
Is red/green colorblindness simple or complex?
simple (X-linked)
Examples of complex traits?
hair color, litter size, breast cancer development
Polygenic Trait
trait influenced by the effects of more than one gene; many alleles each with a small effect that are subject to environmental factors
ex: susceptibility to disease (heart disease, obesity)
Multi-Locus Traits
alleles at a few loci interact to determine phenotype with no ennvironmental effect
ex: coat color
Oligogenic Trait
several alleles interact to determine phenotype, subject to overall g3enetics and environmental effects
ex: milk yield
Can you determine whether a complex trait is polygenic, multi-locus, or oligogenic?
Not unless you know the alleles that underlie its expression
Complex Traits and Variable Expression
Complex traits are ALWAYS variably expressed; can result in different phenotypes or discrete difference in expression
ex: height; osteoporosis in horse breeds (which joints are affected)
Overall Genetic Risk
coombination of multiple risk alleles, which can vary between and within groups resulting in different expression and different overall risk
Examples of traits with Multiple Risk Alleles
hip dysplasia in dogs, osteochondrosis in horses
Role of the Enivronment
diet/nutrition, exercise, exposure to toxins, trauma, biomechanics, hormones, infectious disease
Linkage Analysis
looking for haplotypes that are shared by affected individuals, not unaffected individuals, in order to narrowdown our region of interest
Are linkage studies more useful for simple or complex traits?
simple (Mendelian), or Mendelian-like, or family
Why do we use large unrelated populations in GWAS?
we need to limit false positives; difficult to distinguish what alleles you share because you are related and what alleles you share because you are affected
Genome-Wide Association Studies (GWAS)
look for a statistical association between allele frequency and trait/disease of interest in a large population of unrelated individuals
3 Steps of Linkage Analysis
- Identify loci with alleles shared by affected individuals
- Eliminate loci that also appear in unaffected individuals
- Boom, you have your loci of interest
Most important step for a good GWAS?
Accurate Phenotypes!!!
Linkage Disequilibrium
the idea that markers that are close together are more likely to continue to be inherited together than those that are far apart
Linkage Disequilibrium Diagram
use lots of known nearby SNPs in hopes of finding variants close by
Manhattan Plots
how to visualize GWAS and see the difference in allele frequency between cases and controls (if anything is misphenotyped, your results are completely useless)
plots chromosomal position vs. statistical significance
Is segregation analysis a perfect solution in complex traits?
No, each locus more than likely only accounts for a small amount of variability in the trait
Coat Color as a Multi-Locus Trait
individual loci that affetc color can have Mendelian inheritance when considered alone, but it is truly the interaction of multiple loci that determines phenotype
Horse Coat Color: Grey (STX17)
trumps ALL other color loci - a big G means the horse WILL be grey
Horse Coat Color: Extension locus (MCR1)
responsible for the production of eumelanin (black) and pheomelanin (red)
Horse Coat Color: Agouti locus (ASIP)
determines distribution of black hair, only in presence of a big E from the extension locus
Do all variants found via GWAS explain all the variation in a trait?
NO, so many to find and there’s still environmental factors!
ex: human height - 10 genes found so far but only explain ~30% of human height variance
