Population Genetics Flashcards
Hardy-Weinberg Equation
1 = p^2 + 2pq + q^2
P(AA) =
P(Aa) =
P(aa) =
P(AA) = p^2 P(Aa) = 2pq P(aa) = q^2
Allele frequency
The percentage of alleles in a whole population (2 per person) that are of a particular type
Allele Frequency equation
(# of A alleles in the population)/(Total # of alleles in the population)
Hardy-Weinberg Assumptions
- diploid organism
- sexual reproduction
- nonoverlapping generations
- random mating
- large population size
- equal allele frequencies in the sexes
- no migration
- no mutation
- no selection
If a locus is in HWE, does that mean all the assumptions are true?
No
Penetrance
P(disease/”disease genotype”)
e.g. P(breast cancer/BRCA1 mutation)
q =
sqrt(disease frequency)
Sample 2000 people in the population. Observe 20 with a Mendelian recessive disease. What is the allele frequency?
q = sqrt (20/2000) = 0.1
Sample 1000 people in the population. Observe 60 with a rare Mendelian dominant disease. What is the allele frequency?
p = (disease frequency)/2 = (60/1000)/2 = 0.03
Unilineal relatives (definition and examples)
- Related through only one parent
- Examples: first cousins, aunts/uncles, grandparents
Bilineal relatives (definition and examples)
- Related through both parents
- Examples: siblings, double cousins, inbreeding loop
Identity-by-descent (IBD)
- Two alleles are IBD if they are inherited from a common ancestor (any two alleles of the same variant are not necessarily IBD, they may just be identical by state (IBS))
Coefficient of kinship
- describes the average genetic sharing between 2 people
- Probability that two random alleles in 2 different people are IBD
- Meaning: measure of how closely related two people are
- 0 means that people are unrelated
- 1/2 means people are genetically identical
Coefficient of kinship vs. coefficient of inbreeding
- Coefficient of inbreeding = F
- F is the probability of two alleles IBD in an individual
- F for a person = the coefficient of kinship for the person’s parents
Cotterman’s k
- Describes the average genetic sharing between two people (does not distinguish unilineal vs. bilineal sharing)
True or False: Genotype frequencies at any specific locus are in HWE as long as HWE assumptions hold
True (in particular, random mating)
Why are chromosomes inherited in pretty large chunks?
- Chromosomes are inherited in pretty large chunks due to recombination during meiosis
True or False; when every locus is in HWE, different loci are inherited independently
False: even in a random-mating population with every locus in HWE, different loci are not inherited independently (this is true in families and across the population)
% of offspring that are non-parental types is the _______________
“distance” between the genes
Example:
- Suppose traits A and B have a ‘distance’ of 5%
- Suppose traits B and C have a ‘distance’ of 30%
- What will the distance between A and C be?
A-----B-----C = 35% C-----A-----B = 25%
Genes stay together during meiosis unless there is ______________________
Recombination
Probability of recombination is _________
theta (recombination fraction, Sturtevant’s distance, “Morgans”)
The pace of mixing depends on _______________
the recombination fraction, theta
The larger the theta, means faster mixing
Theta = 0 when ___________
the loci are in the same place
Theta = 1/2 when _________________
the loci are on different chromosomes (or VERY far apart on the same chromosome)
Linkage Disequilibrium (LD) is ______________
correlation between genotypes at different loci (in a population)
2 important sources of LD in human populations
1) Admixture: mixing (interbreeding) of two populations
2) New mutation
Linkage vs. LD
- Linkage: if two genes are “linked,” they are on the same chromosomes (theta
The only relationship between linkage and LD is that _______________________
LD goes away more slowly if linkage is tight (genes are close together)
Addition Rule
If two events are MUTUALLY EXCLUSIVE (can’t both happen at the same time); then their probabilities add
P(A v B) = P(A or B) = P(A) + P(B)
Addition Rule Example
Roll an even number or roll a “1” on a die
P = (1/2) + (1/6) = 2/3
Independence
Two events are independent if one happening does not affect the likelihood of the other happening
Multiplication Rule for Independent Probabilities
P(A ^ B) = P(A and B) = P(A)P(B)
Multiplication Rule Example
- Roll a “1” on the first die and roll an even number on the second
- (1/6) * (1/2) = 1/12
Binomial Distribution
- Experiment with only two outcomes
- n = number of times experiment performed
- X = number of “successes” out of n trials
- The distribution of X is binomial (n,p) where p is the probability of “success” in each experiment
Interpretation of p values
- The p value is NOT the probability that the null hypothesis is true
- A large p value does not necessarily mean the null hypothesis is true. It just means that there isn’t enough evidence to reject the null hypothesis (possibly because of too small of a sample)
When we reject the null hypothesis, we say ________________________________________
the result is statistically significant
Statistically significant does not necessarily mean _________________________________
SCIENTIFICALLY SIGNIFICANT
Definition of drift
- Random changes in allele frequency by chance in finite populations
- Particularly important for small populations
- Due to the random sampling of gametes
- Cause: random sampling of alleles
How does drift operate in real human populations?
- Bottleneck: large population is reduced, then re-expands
- Founder effect: genetic effects on a population started by a small group of individuals (as a result, alleles in the founder group becomes the alleles in the population)
Which processes drive evolution?
- Mutation
- natural selection
- genetic drift
Selection
differing viability and/or fertility of different genotypes
Mutation
- Change in the genetic material
- Significance: mutation changes allele frequencies because it creates new alleles
- mutation is the ultimate source of all genetic variation
