Population Genetics

Lab No (5)
Population genetics Outline
What is population genetics?
Calculate
Why is genetic variation important?
- genotype frequencies
- allele frequencies
How does genetic structure change?


Population
A population is a group of organisms of
the same species that reproduce with
each other.

The gene pool is the collection of all the
alleles present within a population.

Population geneticists generally examine
many different genes simultaneously
Gene: A sequence of nucleotides coding for a protein (or, in
some cases, part of a protein); a unit of heredity
Allele: A variant segment of the genetic material
( alternative form of the gene)
Genotype: The set of DNA variants found at one or more
loci in an individual. (More generally, the genetic profile of an
individual)
Phenotype: The outward expression of a genotype
(length, color etc..)
Haplotype: A set of genes at more than one locus
inherited by an individual from one of its parents. It is the multi-
locus analog of an allele.

Polymorphism
A locus is defined as polymorphic if the
frequency of one of its alleles is less than or
equal to 0.95 or 0.99


A gene is called polymorphic if there is more
than 1 allele present in at least 1% of the
population.

Genes with only 1 allele in the population are
called monomorphic. Some genes have 2
alleles: they are dimorphic.

Heterozygosity
Heterozygosity is the percentage of
heterozygotes in a population

The average H
e
over all loci is an estimate of the
extent of genetic variability in the population
What is Population Genetics?

The genetic study of the process of evolution
Evolution is the changes in the gene pool of the
population over time.
The forces that cause changes and maintain
diversity are:
1-Genomic: mutation and recombination
2-Evolutionary: natural selection, genetic drift,
non random mating and migration.
Mutation:
A gene mutation is an alteration in the
nucleotide sequence of it.
It can be caused by mutagenes or
spontaneous.
It produces new allele.

Recombination:
It can directly affect the level of variation
by decreasing variation.
It can increase the genetic variance. If
beneficial fitness alleles are not randomly
distributed among population members
and are found in different individuals more
often than expected by chance.
cont

Genetic drift
It is the random fluctuation of gene
frequencies from one generation to
another as a result of random sampling of
the gametes.

Ideally, a population must infinitely large
for genetic drift to be ruled out completely
as an agent for evolution.

Genetic drift, which changes gene
frequencies at random, may cause a
favored allele to be lost. cont
Natural Selection:
It can be identified with the popular phrase survival
of the fittest provided one define the word fit as
the capacity to leave fertile progeny.

It acts directly on the phenotypes, but it acts on
genotypes in an indirect fashion, depending on the
extent to which phenotype is determined by
genotype.

It is the only evolutionary factor that has direct
adaptive consequences. cont


Other factors That can Affect the
population diversity
Migration: When migration takes
place in one direction (i.e. from one
group to another) it is referred to as
gene flow.
Non Random Mating: There are two
types of non-random mating:
assortative mating and inbreeding.
cont
Allele frequency is the concept used to quantify
genetic variation.

It is defined as a measure of the commonness of a
given allele in a population, that is, the
proportion of all alleles of that locus in the
population that are specifically this type.

Allele and Genotype Frequencies
Each diploid individual in the population
has 2 copies of each gene. The allele
frequency is the proportion of all the genes
in the population that are a particular allele.

The genotype frequency of the proportion
of a population that is a particular
genotype.


Statistical Population
Genetics
For example: consider the MN blood group. In a
certain population there are 60 MM individuals,
120 MN individuals, and 20 NN individuals, a
total of 200 people.

The genotype frequency of MM is 60/200 = 0.3.
The genotype frequency of MN is 120/200 = 0.6
The genotype frequency of NN is 20/200 = 0.1

In an infinitely large, randomly mating
population in which selection,
migration, and mutation do not occur,
the frequencies of alleles and genotypes
do not change from generation to
generation.

The Hardy-Weinberg equilibrium

Allele Frequency: The proportion of all alleles in all
individuals in the group in question which are of a
particular type.
Genotype Frequency: The proportion of individuals in a
group with a particular genotype.


For a gene with just two alleles A and a, if the frequency of allele:
A is p, a is q

The sum of the frequencies of the alleles must equal 1; (p + q = 1)

After one generation of Random mating the genotype frequencies
would remain fixed in and would be in the ratio:
Hardy Weinberg frequencies

Genotype

frequency

AA

p
2


Aa

2pq

aa

q
2


And accordingly:
p+ 2pq + q = 1
This is called Hardy-Weinberg equation
which is used for calculating the genotype
frequencies.
X is used to determine the probability
that the observed number differs from the
expected number due to chance alone.
Standardized statistical charts have been
developed which correlate the P value
and degrees of freedom (the number of
independent variables) with probability
values (p).


AA

Aa

aa

Total

# of
individuals

40

47

13

100

# of A alleles

80

47

0

127

# of a alleles

0

47

26

73

Total # of
alleles







200

Review of Hardy-Weinberg

Allele frequency:
pA (p) = ((40 x 2) + 47) /200) = 127/200 = 0.635
pa (q) = ((13 x 2)+47) /200) = 73/200 = 0.365 ( = 1- Pa)
Genotype Frequency:
40 AA- 47 Aa -13 aa Total =100 individuals
pAA = 40/100 = 0.4
pAa = 47/100 = 0.47
paa = 13/100 = 0.13

Statistical test for deviations from HWE.
It is done by calculating the P-value from Chi-square
(X): X = (O-E) / E
P is significant when it is < 0.05.

e.g.. Among 1000 people: MM: 298, MN: 489, NN: 213
P = fre of M
Q = fre of N

Total no of alleles = 1000 x 2 = 2000

No of M = (298 x 2) + 489
No of N = (213 x2) + 489


Allele frequencies are estimated to be:
p=(596+489)/2000=0.5425
q=(426+489)/2000=0.4575
from the equation: p + 2pq + q = 1
The expected genotype frequencies under HWE:
P=p 2 =0.5425 0.5425=0.2943
Q=2pq=2 0.5425 0.4575=0.4964
R=q 2 =0.4575 0.4575=0.2093


Observed Expected (O-E) (O-E)/E
MM: 298 294.3 13.69 0.234
MN: 489 496.4 54.76 0.110
NN: 213 209.3 13.96 0.065

X= (O-E)/E = 0.409
http://faculty.vassar.edu/lowry/tabs.html#csq.
P = 0.8151
Which means that this population is in HWE.




Example continued from Hardy-
Weinberg discussion above




In the above example, the P value
of X =27.77 is < 0.0001 which
correlates to a greater than 99% chance
that the difference between the
observed and the expected is NOT due
to chance alone. This high probability
indicates that some external factor (i.e.,
migration, selection, inbreeding, or drift)
is influencing the frequencies of alleles

The allele frequencies can be determined
by adding the frequency of the homozygote
to 1/2 the frequency of the heterozygote.

The allele frequency of M is 0.3 (freq of
MM) + 1/2 * 0.6 (freq of MN) = 0.6
The allele frequency of N is 0.1 + 1/2 * 0.6
= 0.4
Note that since there are only 2 alleles
here, the frequency of N is 1 - freq(M).

Hardy-Weinberg Equilibrium
Early in the 20th century G.H. Hardy and Wilhelm
Weinberg independently pointed out that under ideal
conditions you could easily predict genotype frequencies
from allele frequencies, at least for a diploid sexually
reproducing species.

For a dimorphic gene (two alleles, which we will call A
and a), the Hardy-Weinberg equation is based on the
binomial distribution:
p
2
+ 2pq + q
2
= 1
where p = frequency of A and q = frequency of a, with p +
q = 1.
p
2
is the frequency of AA homozygotes
2pq is the frequency of Aa heterozygotes
q
2
is the frequency of aa homozygotes


Necessary Conditions for Hardy-
Weinberg Equilibrium
The relationship between allele frequencies and
genotype frequencies expressed by the H-W equation
only holds if these 5 conditions are met.

If a population is not in equilibrium, it takes only 1
generation of meeting these conditions to bring it into
equilibrium. Once in equilibrium, a population will stay
there as long as these conditions continue to be met.

1. no new mutations
2. no migration in or out of the population
3. no selection (all genotypes have equal fitness)
4. random mating
5. very large population
Testing for H-W Equilibrium
If we have a population where we can distinguish all
three genotypes, we can use the chi-square test once
again to see if the population is in H-W equilibrium. The
basic steps:
1. Count the numbers of each genotype to get the observed
genotype numbers, then calculate the observed genotype
frequencies.
2. Calculate the allele frequencies from the observed genotype
frequencies.
3. Calculate the expected genotype frequencies based on the H-
W equation, then multiply by the total number of offspring to get
expected genotype numbers.
4. Calculate the chi-square value using the observed and
expected genotype numbers.
5. Use 1 degree of freedom (because there are only 2 alleles).

Example
Data: 26 MM, 68 MN, 106 NN, with a total population of 200 individuals.
1. Observed genotype frequencies:
MM: 26/200 = 0.13
MN: 68/200 = 0.34
NN:106/200 = 0.53
2. Allele frequencies:
M: 0.13 + 1/2 * 0.34 = 0.30
N: 0.53 + 1/2 * 0.34 = 0.70
3. Expected genotype frequencies and numbers:
MM: p
2
= (0.30)
2
= 0.09 (freq) x 200 = 18
MN: 2pq = 2 * 0.3 * 0.7 = 0.42 (freq) * 200 = 84
NN: q
2
= (0.70)
2
= 0.49 (freq) * 200 = 98
4. Chi-square value:
(26 - 18)
2
/ 18 + (68 - 84)
2
/ 84 + (106 - 98)
2
/ 98
= 3.56 + 3.05 + 0.65
= 7.26
5. Conclusion: The critical chi-square value for 1 degree of freedom is
3.841. Since 7.26 is greater than this, we reject the null hypothesis that the
population is in Hardy-Weinberg equilibrium.

Levels of Variation
Expected Heterozygosity (H
exp
) = 1- p
i
2
, where
p
i
= frequency of ith allele
Estimated from allele frequencies
Observed Heterozygosity (H
obs
) = direct count of
proportion of heterozygotes in sample
Estimated from genotypes
Differences between H
exp
and H
obs
estimate
deviations from H-W due to a variety of factors
Population genetic is concerned with:
Gene and genotype frequencies and their fluctuation over
time.
The factors that tend to keep them constant
The factors that tend to change them in populations.
It is largely concerned with the study of polymorphisms.
It directly impacts counseling, forensic medicine, and
genetic screening.



Neis Genetic Distance/ Identity