Complex Traits - Lecture 16 Flashcards
What are Mendelian traits?
○ Single gene with high penetrance
○ Predictable mode of inheritance
○ Simple relationship between genotype and phenotype
○ e.g. cystic fibrosis
What are complex traits?
○ Multiple genes with low penetrance
○ Familial clustering but inheritance not predictable
○ Complex relationship between genotype and phenotype
○ Often strongly influenced by environment
What are some complex traits in human medicine?
○ Alzheimer’s disease
○ Crohn’s disease
○ Neural tube defects
○ Asthma
○ Cleft lip
○ Coronary heart disease
○ Type 1 and 2 diabetes
What are discontinuous or discrete traits?
○ The trait or disease is either present or not
○ Blood group or eye colour
○ Few genes and a limited number of phenotypes
○ No in-between
What are continuous traits?
○ No distinct categories
○ Height, blood pressure
○ A lot of genes and environmental factors
○ Range of phenotypes
○ Normal distribution
Equation for phenotypic variance
Total phenotypic variance = genetic variance + environmental variance
What is the equation for heritability?
H^2 = genetic variance/phenotypic variance
What does heritability show?
○ High heritability means that genetic differences in a population explain a high proportion of the phenotypic variation
○ It will be easier to identify genetic variants with the trait if it has high heritability
How is heritability estimated in humans?
Identical twins:
○ Share their environment and alleles
○ relatedness = 1
Non-identical twins:
○ Share their environment but only half of their alleles
○ relatedness = 0.5
For a trait, if identical twins resemble each other more than non-identical twins, then genes contribute to variation in the trait, assuming equal environmental effects
What is concordance?
The probability that if one twin is affected the other twin is also affected by a trait
What do the values of concordance show?
○ Concordance = 1: if one twin is affected the other twin is always affected
○ Concordance = 0.6: if one twin is affected the chance of the second twin being affected is 60%
○ Difference is concordance between MZ and DZ twins can be used to estimate heritability
What are the assumptions when using concordance?
○ Random mating of parents
○ Equal environments on MZ and DZ twins
What are thrifty genes?
Alleles that were advantageous or neutral in the past may confer disease susceptibility in modern societies
What are genome wide association studies (GWAS)?
○ A population level approach to disease gene mapping
○ Odds Ratio: used to calculate the probability of association between each SNP and the disease
- If OR>1.0 = allele gives higher risk of disease
- If OR<1.0 = allele is protective
What does the Manhattan plot show?
○ Variants with highly significant associations with the trait appear as skyscrapers
○ The odds ratio for each variant is calculated & the probability that odds ratio is significantly higher in cases than in controls
