Population genetics

Question 1

Population Genetics =

Answer 1

the study of allele frequencies and changes in allele frequencies in ‘populations’

Question 2

Basic Pop Gen Principles:

Answer 2

– mutation rates, fitness, consangunity

Question 3

mutation:

Answer 3

any change in the DNA sequence or arrangement

Question 4

germline

Answer 4

in gonadal tissue (usually in all cells) can be passed onto next generation

Question 5

polymorphism

Answer 5

any genetic variant (mutation) found in >1% of population

Question 6

forces affecting allele frequencies

Answer 6

1. mutation: new mutations
2. Natural selection: survival of the fittest
3. genetic drift: random changes
4. gene flow: addition/subtraction

Question 7

Heterozygous advantage:

Answer 7

deleterious mutation in homozygous state, maintained as an “advantage” in heterozygous state (protect against malaria for heterozygous for sickle cell anemia)

Question 8

New mutations rate

Answer 8

1.18 x10^-8

Question 9

we transmit ______ novel SNPs per genome per generation

Answer 9

74

Question 10

diseases due to novel mutatiosn

Answer 10

schinzel-Giedion,
Kabuki
Bohring–Opitz

Question 11

Fitness (f)

Answer 11

the probability of transmitting one’s genes to the next generation
f=1 (same as normal population)
f=0 (gene is not passed on)

Question 12

coefficient of selection

Answer 12

a measure of forces that reduces fitness

s=1 - f

Question 13

mutation rate (u)

Answer 13

frequency of new mutations at a given genetic locus, expressed as mutations/generation

Question 14

how to measure autosomal dominant

Answer 14

1. direct method

2. indirect method

Question 15

direct method

Answer 15

fully penetrant (no hidden mutations)–> count the cases with no family history (the new mutations)

Question 16

indirect method

Answer 16

if f=0, then all cases represent new mutations –> then use incidence (I) of disease to calculate u –> I = 2 u, since each of us inherits two alleles

if f/=/ 0, then can estimate u using u = 1/2/ F (1 - f)

Question 17

autosomal recessive equation

Answer 17

u = F (1 - f)

Question 18

X-linked recessive equation

Answer 18

u = 1/3 F (1-f)

u=mutation rate/gene/generation
F= frequency of the disease
f= reproduction fitness

Question 19

Hardy-Weinberg Law

Answer 19

p + q = 1 = p2 + 2pq + q2

Question 20

Hardy weinberg assumptions

Answer 20

1. population is large and matings are random
2. allele frequencies remain constant over time
3. no appreciable rate of mutation
4. all genotypes are equally fit
5. equal chance to pass allele to the next generation
6. no significant immigration/emigration of individuals with different allele frequencies

Question 21

Hardy weinburg do not appear in reality, but cane used because

Answer 21

Populations are large enough

Question 22

how is hardy weinberg used

Answer 22

1. used in genetic counseling to predict risks for a couple to have an affected child
2. prevalence of disease is approximately: q^2
3. freom q^2, you can calculate q, p, and then the carrier frequency 2pq

Question 23

for rare autosomal recessive disease, 2q can estimate

Answer 23

2pq

Question 24

genome mutation

Answer 24

mechanism: chromosome missegregation
Frequency: 2-4 x 10 ^-2 per cell division
example: aneuploidy (e.g. trisomy 21)

Question 25

chromosome mutation

Answer 25

mechanism: chromosome rearrangement
Frequency: 6 x 10^ -4
example: translocation

Question 26

gene mutation

Answer 26

mechanism: base pair mutation
Frequency: 10^ -5 – 10^-6 per locus/generation
example: point mutation

Question 27

mutation

Answer 27

any change in nucleotide sequence and arrangemtn of DNA

Question 28

polymorphism

Answer 28

a genetic variant (mutation) which is common (>1%) in the populations

Question 29

founder effects

Answer 29

a high frequency of mutant allele in a population founded by a small ancestral group when one or more original founders was a carrier of the mutant allele

Question 30

genetic drift

Answer 30

random fluctuation of allele frequencies, usually in small populations

Question 31

selection

Answer 31

active selection of favorable alleles over non favorable ones

Question 32

selection depends on

Answer 32

fitness

Question 33

fitness is

Answer 33

a measure of the chance an allele will be transmitted to the next generation
Scale of 0-1

Question 34

Fitness 0

Answer 34

lethal and severe disorders that have low fitness because an individual doesn’t live long enough or is not healthy enough to reproduce and pass on the disease allele

Question 35

fitness measures

Answer 35

reproductive success

Question 36

reproductive success

Answer 36

means survival is not the only consideration (e.g. your fitness is still low if you possess superhuman strength and health, but suffer from infertility or are an intolerable egomaniac and are unable to have biological children)

Question 37

Natural selection generally occurs only when the trait is _______, which means that even severe recessive alleles are not selected against in the ______. Exceptions to this statement could occur if _______

Answer 37

expressed

heterozygous state

genetic testing of asymptomatic persons identifies heterozygotes persons who then elect to not have children or terminate an affected pregnancy for instance.

Question 38

Doctors theoretically affect fitness through _______. If medical care improves the health (and reproductive fitness) of persons with disease X then mutation frequencies for disease X may _______. Rate of increase depend on the _____

Answer 38

through improving health and altering one’s chances of reproductive success

rise

inheritance (as well as the severity of the disease and the absolute increase in fitness).

Question 39

Recessive diseases:

Answer 39

mutant allele increases are slow

Question 40

Dominant diseases / X-linked diseases

Answer 40

the rates could be higher

Question 41

Hardy-Weinberg useful in _____________

Answer 41

recessive conditions for calculating carrier rates

Question 42

By observing the number of cases of disease in a population it is possible to calculate ________

Answer 42

rates of mutation for different conditions

Question 43

NextGeneration DNA sequencing will determine _________

Answer 43

whether the ‘estimates’ of mutation rates turn out to be correct

Question 44

Forces affecting allele frequencies

Answer 44

1. Natural selection – Survival of fittest
2. Genetic drift – Random changes
3. Mutation
   – New mutations
4. Gene flow
   – Addition/Subtraction

Question 45

Autosomal Dominant Polycystic Kidney Disease

Answer 45

1. Prevalence estimated at 1
   in 400
2. ~400,000 affected in US
3. ~10% of cases are due to novel mutations

Question 46

Population sampling by phenotype can lead to estimates of ________if the underlying _______ is known.

Answer 46

allele frequency

underlying genetic mechanism (i.e. dominant vs. recessive // autosomal vs. sex-linked)

Question 47

Population genetics is important for understanding _____________

Answer 47

allele frequency in populations (and how those frequencies change)

Question 48

direct method is used for

Answer 48

autosomal dominant conditions with 100% penetrance.

You can count the new cases that occur with no family history. Since each child has 2 alleles, multiple that by two.

Question 49

‘mutation-rate’ (μ)

Answer 49

the number of alleles for each new cases with no family history

Question 50

Indirect method is used for

Answer 50

For an autosomal dominant condition where the reproductive fitness (f) is zero (i.e. affected persons do not survive to reproduce and/or are infertile) then all cases represent new mutations.

Question 51

Incidence

Answer 51

2 alleles for autosomal dominant where fitness is zero

Question 52

when the fitness is not 0, Autosomal dominant=

Answer 52

μ= 1/2 F (1-f)

Question 53

when the fitness is not 0, Autosomal recessive=

Answer 53

μ= F (1-f)

Question 54

When fitness is not 0, X-linked recessive=

Answer 54

μ= 1/3 F (1-f)

Question 55

Hardy-Weinberg principle describes the________

Answer 55

the frequency of two alleles in a population in terms of allele frequency and genotype frequency. It is useful to physicians because it can predict expected frequencies for the next generation

Question 56

q is the

Answer 56

q is usually reserved for the less common (minor allele)

Question 57

Hardy Weinberg assumes the absence of:

Answer 57

1. Non-random mating
2. mutation
3. selection
4. migration/drift
5. small population size

Question 58

The major use of Hardy-Weinberg in medical genetics is in __________

Answer 58

genetic counseling for autosomal recessive disorders.

Question 59

Cystic fibrosis (CF) is an autosomal _______ lung disease with a prevalence of _______

Answer 59

recessive

1/2,500.

Question 60

rarer diseases (< 1/10,000) 2pq = ________

Answer 60

2q

Question 61

Random Mating does not always occur:

Answer 61

1. Stratification
2. Assortive Mating
3. Consanguity

Question 62

Stratification:

Answer 62

refers to populations containing 2 or more subgroups which tend preferentially mate within their own subgroup. Mate selection is not dependent on the trait/disease or interest.

Question 63

Stratification example

Answer 63

Example: sickle cell anemia in African Americans (AAs) has higher incidence social stratification favoring mating of AAs with other AAs, than is predicted by HWE

Question 64

Assortive mating:

Answer 64

refers to when the choice of mate is dependent (in part) on a particular trait (or sometimes a disease).

Question 65

Assortive mating has been observed for:

Answer 65

for congenital short stature (previously called ‘dwarfism’), blindness, and deafness.

Question 66

Consanguinity increases matings between _______, thereby increasing the __________ in the population.

Answer 66

carriers of autosomal recessive diseases,

number of cases of autosomal recessive diseases