Complex Traits

Question 1

Simple Trait (Mendelian)

Answer 1

one gene has one distinct biological effect; equal risk for everyone with the mutation

Question 2

Complex Trait

Answer 2

variations in multiple genes contribute to a single effect; individuals can have different levels of risk

Question 3

Is red/green colorblindness simple or complex?

Answer 3

simple (X-linked)

Question 4

Examples of complex traits?

Answer 4

hair color, litter size, breast cancer development

Question 5

Polygenic Trait

Answer 5

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)

Question 6

Multi-Locus Traits

Answer 6

alleles at a few loci interact to determine phenotype with no ennvironmental effect
ex: coat color

Question 7

Oligogenic Trait

Answer 7

several alleles interact to determine phenotype, subject to overall g3enetics and environmental effects
ex: milk yield

Question 8

Can you determine whether a complex trait is polygenic, multi-locus, or oligogenic?

Answer 8

Not unless you know the alleles that underlie its expression

Question 9

Complex Traits and Variable Expression

Answer 9

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)

Question 10

Overall Genetic Risk

Answer 10

coombination of multiple risk alleles, which can vary between and within groups resulting in different expression and different overall risk

Question 11

Examples of traits with Multiple Risk Alleles

Answer 11

hip dysplasia in dogs, osteochondrosis in horses

Question 12

Role of the Enivronment

Answer 12

diet/nutrition, exercise, exposure to toxins, trauma, biomechanics, hormones, infectious disease

Question 13

Linkage Analysis

Answer 13

looking for haplotypes that are shared by affected individuals, not unaffected individuals, in order to narrowdown our region of interest

Question 14

Are linkage studies more useful for simple or complex traits?

Answer 14

simple (Mendelian), or Mendelian-like, or family

Question 15

Why do we use large unrelated populations in GWAS?

Answer 15

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

Question 16

Genome-Wide Association Studies (GWAS)

Answer 16

look for a statistical association between allele frequency and trait/disease of interest in a large population of unrelated individuals

Question 17

3 Steps of Linkage Analysis

Answer 17

1. Identify loci with alleles shared by affected individuals
2. Eliminate loci that also appear in unaffected individuals
3. Boom, you have your loci of interest

Question 18

Most important step for a good GWAS?

Answer 18

Accurate Phenotypes!!!

Question 19

Linkage Disequilibrium

Answer 19

the idea that markers that are close together are more likely to continue to be inherited together than those that are far apart

Question 20

Linkage Disequilibrium Diagram

Answer 20

use lots of known nearby SNPs in hopes of finding variants close by

Question 21

Manhattan Plots

Answer 21

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

Question 22

Is segregation analysis a perfect solution in complex traits?

Answer 22

No, each locus more than likely only accounts for a small amount of variability in the trait

Question 23

Coat Color as a Multi-Locus Trait

Answer 23

individual loci that affetc color can have Mendelian inheritance when considered alone, but it is truly the interaction of multiple loci that determines phenotype

Question 24

Horse Coat Color: Grey (STX17)

Answer 24

trumps ALL other color loci - a big G means the horse WILL be grey

Question 25

Horse Coat Color: Extension locus (MCR1)

Answer 25

responsible for the production of eumelanin (black) and pheomelanin (red)

Question 26

Horse Coat Color: Agouti locus (ASIP)

Answer 26

determines distribution of black hair, only in presence of a big E from the extension locus

Question 27

Do all variants found via GWAS explain all the variation in a trait?

Answer 27

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