Genetics Flashcards
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
length of repeats and severity of Huntingtons (3)
- <35 = no disease
- > 35 = disease
- more repeats -> earlier onset
mutational bias (Huntingtons) (4)
- number of repeats more likely to increase than decrease
- mutated alleles transmitted to offspring if occurring in germ line cells (genetic anticipation)
- fathers more likely to transmit mutated alleles than mother
- number of mutations (repeats) increases with father’s age
number of cell divisions leading to gametes in females
- egg precursors divide only 24 times, all but once before birth
number of cell divisions leading to gametes in males
- sperm precursors divide 23 times per year after puberty
possible areas affected by fitness trade-offs (5)
- sexual selection (adult -> mating pairs)
- fecundity (mating pairs -> gametes)
- gametic selection (gametes -> zygote)
- longevity (zygote -> adult)
- viability (zygote -> adult)
fitness trade-offs
- traits that are favoured at some stages of the life cycle may be disfavoured at others
possible fitness trade-off in Huntingtons
- heterozygotes may be more fertile prior to onset of disease than WT individuals
linkage disequilibrium
- a measure of nonrandom associations among alleles at multiple loci
linkage disequilibrium causes (2)
- physical linkage on chromosome (LD decays over time)
- selection favouring particular allelic combinations ( can be enhanced by chromosomal inversions)
physical applications of linkage disequilibrium (2)
- estimating alelle age (young -> high LD; old -> low LD)
- detecting positive selection
linkage disequilibrium: detecting positive selection
- low freq. of allele
- high LD; young allele
- recent mutation
linkage disequilibrium: detecting positive selection
- high freq. of allele
- high LD; young allele (3)
- postive selection
- founder event + population expansion
- involves specific regions within the genome
linkage disequilibrium: detecting positive selection
- low freq. of allele
- low LD; old allele
- neutral or low selective advantage
linkage disequilibrium: detecting positive selection
- high freq. of allele
- low LD; old allele (2)
- drift
- applies throughout the genome
what is the purpose of purifying selection?
- purge deleterious variants
what is the purpose of positive selection and balancing selection?
- favour advantageous variants
