Genes Lecture 8- Complex Traits Flashcards
complex traits (quantitative traits )
more than one gene that contributes to phenotype and is influenced by environmental factors
mendelian traits are also known as
multifactoral traits
Mendelian vs complex traits
Mendelian traits
single gene (monogenic) with high penetrance
predictable mode of inheritance
simple relationship between genotype and phenotype
e.g. cystic fibrosis
Complex traits
multiple genes (polygenic) with low penetrance
familial clustering but inheritance not predictable
complex relationship between genotype and phenotype
often strongly influenced by environment
examples of complex traits in humans
-Alzheimer’s disease
-Crohn’s disease
-Neural tube defects
-Asthma
-Cleft Lip
-Coronary heart disease
-Type 1 and Type 2 Diabetes’s
prevalence of complex diseases
600/1000
% of pop with type 2 diabetes
6-8%
discontinuous traits
the trait or disease is either present or not
For example: gender, blood group, eye colour
continuous traits
quantitative or continuous traits e.g. height, blood pressure, serum cholesterol, body mass index (BMI), crop yield
what graph is usually used for discrete/ discontinuous traits
bar
what graph is used for continuous traits
normal distribution: bell or Gaussian curve
total phenotypic variance formula
VP (or VT) = VG + VE
total phenotypic variance= genetic variance + environmental variance
heritability
H2 = VG/ VP
heritability= genetic variance /total phenotypic variance
-statistical measure of how much genetic variance is present within a phenotypic trait
high heritability
genetic differences in the population explain a high proportion of the phenotypic variation
-it’s easier to identify genetic variants associated with the trait than for a trait with low heritability
relatedness of MZ twins
r=1
relatedness of DZ twins
r=0.5
concordance
the probability that if one twin is affected, the other twin is also affected by a trait
concordance = 1.0: 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 0.6 (60%)
what is differences in concordance used to measure
heritability
heritability formula in terms of MZ and DZ twins
H^2 = 2(MZ-DZ)
assumptions when using MZ and DZ twins for heritability
Random mating of parents
Equal environments on MZ and DZ twins
Why should disease-associated alleles be common?
Alleles that were advantageous or neutral in the past may confer disease susceptibility in modern societies (‘thrifty gene’)
Disease causing alleles can be maintained at high frequency by balancing selection
Late onset diseases have little effect on fitness (weak purifying selection)
purifying selection
removal of alleles that are deleterious
Genome wide association studies (GWAS)
a population level approach to disease gene mapping
Odds ratio
used to calculate the probability of association between SNP and the disease
OR > 1.0
allele gives higher risk of disease
OR < 1.0
allele is protective
Manhattan Plot
graphical representation of P-values for genetic variants across the genome
x-axis: Variants are arranged according to their position on chromosomes.
y-axis: The -log10(P-value) is plotted showing the probability of association
skyscrapers in the Manhattan plot
Variants with highly significant associations with the trait
haplotypes
Closely linked SNPs on the same chromosomeh
haplotype blocks
Closely linked SNPs on the same are often inherited together
-regions without crossing over
how are haplotype blocks defined
by a small number of tag SNPs: ~1 million tag SNPs represent all 10 million common SNPs
