Huntington’s disease (4)
- genetic autosomal dominant disorder, but rare
- trinucleotide repeat disorder
- late onset (late 30s), but more repeats -> earlier onset
- loss of physical control, emotional changes, mental deterioration, and death
sickle cell anemia (3)
- autosomal recessive genetic disorder, but common in some areas
- single point mutation that causes RBCs to sickle in homozygotes, heterozygotes not affected
- 80% die before reproducing
single-gene disorders
- cystic fibrosis, Tay Sachs, sickle-cell anemia, Hungtingtons
dominant
- condition expressed in heteroxygote
recessive
- condition not expressed in heterozygotes
co-dominant
- heterozygotes intermediate between two homozygotes
assumptions of Hardy-Weinberg equilibrium (5)
- no selection
- no mutation
- no migration
- random mating
- large population size
is the assumptions of H-W equilibrium are met: (3)
- frequencies of alleles and genotypes will remain constant through time
- genotype frequencies can be inferred from allele frequencies and vice versa
- H-W proportions of the genotypes are recovered in a single generation of random mating
H-W equilibrium equation
p^2 + 2pq +q^2 = 1
cystic fibrosis (3)
- autosomal recessive
- mucus build up in homozygotes leading to serious infections, digestive problems and early death (before reproductive age)
- early onset (~2)
expected equilibrium frequency of deleterious recessive allele under mutation-selection balance equation
q hat = sqrt(mu/s)
what does mu mean in the expected equilibrium frequency of deleterious recessive allele under mutation-selection balance
mu = mutation rate
what does s mean in the expected equilibrium frequency of deleterious recessive allele under mutation-selection balance (3)
s = purifying selection coefficient
- number between 0 and 1 reflecting strength of selection against homozygotes for allele
s = 1 - w, where w = relative fitness of the homozygote
heterozygote advantage (3)
- when heterozygotes have an advantage for fitness even though the recessive homozygous is deleterious
- cystic fibrosis and sickle cell anemia
- also called overdominance
what is the fate of a favoured allele (+) under directional selection
+ will eventually become fixed
fate of WT allele (+) under heterozygote advantage/overdominance
+ will reach an intermediate value/stable equilibrium which can be predicted by p hat +
predicted freq. of WT allele at equilibrium
p hat+ = (W+s - Wss)/(2W+s - W++ - Wss)
long term effects of dominant favoured selection
- dominant allele is fixed
long term effects of recessive favoured selection
- dominant allele is lost
long term effects of heterozygote disadvantage selection/underdominance (3)
- p hat+ will predict the unstable equilibrium
- starting freq. above this values will fixate +
- starting freq. below this value will lost +
why hasn’t natural selection eliminated genetic diseases? (5)
- heterozygote advantage
- genetic drift & founder effects
- recurrent mutation, with, perhaps mutational bias
- late onset
- fitness trade-offs
genetic drift & founder effects (3)
- long and mild expansion
- ancient bottleneck + expansion
- strong recent bottleneck + explosive growth
hereditary tyrosinemia (3)
- due to genetic drift & founder effects
- failure to produce enzyme to break down tyrosine aa; autosomal recessive)
- it is much more common in Quebec than worldwide due to defective gene present in founders of Quebec area
genetics of Huntington’s (3)
- dominant mutation on 4th chromosome involving a trinucleotide repeat (CAG CAG …)
- number of repeats determines severity of disease
- mutations exhibit length-dependent bias
