Genetics

Question 1

Huntington’s disease (4)

Answer 1

• 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

Question 2

sickle cell anemia (3)

Answer 2

• 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

Question 3

single-gene disorders

Answer 3

• cystic fibrosis, Tay Sachs, sickle-cell anemia, Hungtingtons

Question 4

dominant

Answer 4

• condition expressed in heteroxygote

Question 5

recessive

Answer 5

• condition not expressed in heterozygotes

Question 6

co-dominant

Answer 6

• heterozygotes intermediate between two homozygotes

Question 7

assumptions of Hardy-Weinberg equilibrium (5)

Answer 7

• no selection
• no mutation
• no migration
• random mating
• large population size

Question 8

is the assumptions of H-W equilibrium are met: (3)

Answer 8

• 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

Question 9

H-W equilibrium equation

Answer 9

p^2 + 2pq +q^2 = 1

Question 10

cystic fibrosis (3)

Answer 10

• autosomal recessive
• mucus build up in homozygotes leading to serious infections, digestive problems and early death (before reproductive age)
• early onset (~2)

Question 11

expected equilibrium frequency of deleterious recessive allele under mutation-selection balance equation

Answer 11

q hat = sqrt(mu/s)

Question 12

what does mu mean in the expected equilibrium frequency of deleterious recessive allele under mutation-selection balance

Answer 12

mu = mutation rate

Question 13

what does s mean in the expected equilibrium frequency of deleterious recessive allele under mutation-selection balance (3)

Answer 13

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

Question 14

heterozygote advantage (3)

Answer 14

• when heterozygotes have an advantage for fitness even though the recessive homozygous is deleterious
• cystic fibrosis and sickle cell anemia
• also called overdominance

Question 15

what is the fate of a favoured allele (+) under directional selection

Answer 15

+ will eventually become fixed

Question 16

fate of WT allele (+) under heterozygote advantage/overdominance

Answer 16

+ will reach an intermediate value/stable equilibrium which can be predicted by p hat +

Question 17

predicted freq. of WT allele at equilibrium

Answer 17

p hat+ = (W+s - Wss)/(2W+s - W++ - Wss)

Question 18

long term effects of dominant favoured selection

Answer 18

• dominant allele is fixed

Question 19

long term effects of recessive favoured selection

Answer 19

• dominant allele is lost

Question 20

long term effects of heterozygote disadvantage selection/underdominance (3)

Answer 20

• p hat+ will predict the unstable equilibrium
• starting freq. above this values will fixate +
• starting freq. below this value will lost +

Question 21

why hasn’t natural selection eliminated genetic diseases? (5)

Answer 21

• heterozygote advantage
• genetic drift & founder effects
• recurrent mutation, with, perhaps mutational bias
• late onset
• fitness trade-offs

Question 22

genetic drift & founder effects (3)

Answer 22

• long and mild expansion
• ancient bottleneck + expansion
• strong recent bottleneck + explosive growth

Question 23

hereditary tyrosinemia (3)

Answer 23

• 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

Question 24

genetics of Huntington’s (3)

Answer 24

• dominant mutation on 4th chromosome involving a trinucleotide repeat (CAG CAG …)
• number of repeats determines severity of disease
• mutations exhibit length-dependent bias

Question 25

length of repeats and severity of Huntingtons (3)

Answer 25

• <35 = no disease
• > 35 = disease
• more repeats -> earlier onset

Question 26

mutational bias (Huntingtons) (4)

Answer 26

• 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

Question 27

number of cell divisions leading to gametes in females

Answer 27

• egg precursors divide only 24 times, all but once before birth

Question 28

number of cell divisions leading to gametes in males

Answer 28

• sperm precursors divide 23 times per year after puberty

Question 29

possible areas affected by fitness trade-offs (5)

Answer 29

• sexual selection (adult -> mating pairs)
• fecundity (mating pairs -> gametes)
• gametic selection (gametes -> zygote)
• longevity (zygote -> adult)
• viability (zygote -> adult)

Question 30

fitness trade-offs

Answer 30

• traits that are favoured at some stages of the life cycle may be disfavoured at others

Question 31

possible fitness trade-off in Huntingtons

Answer 31

• heterozygotes may be more fertile prior to onset of disease than WT individuals

Question 32

linkage disequilibrium

Answer 32

• a measure of nonrandom associations among alleles at multiple loci

Question 33

linkage disequilibrium causes (2)

Answer 33

• physical linkage on chromosome (LD decays over time)

- selection favouring particular allelic combinations ( can be enhanced by chromosomal inversions)

Question 34

physical applications of linkage disequilibrium (2)

Answer 34

• estimating alelle age (young -> high LD; old -> low LD)

- detecting positive selection

Question 35

linkage disequilibrium: detecting positive selection

• low freq. of allele
• high LD; young allele

Answer 35

• recent mutation

Question 36

linkage disequilibrium: detecting positive selection

• high freq. of allele
• high LD; young allele (3)

Answer 36

• postive selection
• founder event + population expansion
• involves specific regions within the genome

Question 37

linkage disequilibrium: detecting positive selection

• low freq. of allele
• low LD; old allele

Answer 37

• neutral or low selective advantage

Question 38

linkage disequilibrium: detecting positive selection

• high freq. of allele
• low LD; old allele (2)

Answer 38

• drift

- applies throughout the genome

Question 39

what is the purpose of purifying selection?

Answer 39

• purge deleterious variants

Question 40

what is the purpose of positive selection and balancing selection?

Answer 40

• favour advantageous variants