Lecture 2: Hardy-Weinberg Equilibrium Population Genetics

Hardy-Weinberg Principle
Hardy-Weinberg Law of • independently discovered by Godfrey H.
Hardy (1877-1947) and Wilhelm Weinberg
Genetic Equilibrium (1862-1937).
• allele frequencies remain constant from
generation to generation

• after the first generation of random mating,

genotype frequencies also remain constant

W. Weinberg

Genotypic frequencies after one generation of random mating

Example Males

A hypothetical population consists of 1000 MM MN NN

individuals. The genotypic frequencies for the MN 0.3 0.6 0.1
blood typing of the population are as follows: 0.09 MM
MM 0.09 MM 0.03 MN
0.09 MN
MM MN NN F 0.3
E
0.09 MM
300 600 100 M MN 0.09 MM
0.18 MN
0.03 MN
A 0.6 0.09 MN 0.03 NN
Compute for the allelic frequencies. 0.09 NN
L
E NN 0.03 MN
S 0.03 MN 0.01 NN
0.1 0.03 NN

Genotypic frequencies after 1 generation of random mating:

MM MN NN
0.36 0.48 0.16
Allele frequencies after one generation of random mating:
frequency of allele M (p) = 0.6
frequency of allele N (q) = 0.4

Genotypic frequencies after two generations of random mating

Males Assumptions of Hardy-Weinberg Principle

MM MN NN • diploid organism
0.36 0.48 0.16
• sexual reproduction
MM 0.1296 0.0864 MM 0.0576 • nonoverlapping generations
F 0.36 MM 0.0864 MN MN
E
M • random mating
0.0864 0.0576 MM
A MN 0.0384 MN
MM 0.1152 MN
L 0.48
0.0864 MN 0.0576 NN
0.0384 NN • large population size
E
S • equal allele frequencies in the sexes
NN 0.0576 0.0384 MN 0.0256
0.16 MN 0.0384 NN NN • no migration
Genotypic frequencies after 2 generations of random mating:
MM MN NN • no mutation
0.36 0.48 0.16
Allele frequencies after 2 generations of random mating:
frequency of allele M (p) = 0.6 • no selection
frequency of allele N (q) = 0.4

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Lecture 2: Hardy-Weinberg Equilibrium Population Genetics

Frequency of Mating Types

Genotypic Frequencies in Progeny
Paternal Genotypes

Paternal Gametes AA (p2) Aa (2pq) aa (q2)

A (p) a (q) AA x AA AA x Aa AA x aa
AA (p2)
(p4) (2p3q) (p2q2)

A (p) AA (p2) Aa (pq) Maternal Aa x AA Aa x Aa Aa x aa

Maternal Gametes Genotypes Aa (2pq)
(2p3q) (4p2q2) (2pq3)
a (q) Aa (pq) aa (q2)
aa x AA aa x Aa aa x aa
aa (q2)
(p2q2) (2pq3) (q4)

Frequencies of genotypes AA, Aa, and aa relative to the frequencies of

Frequency of Different Genotypes in Offspring from Each alleles A and a in populations at Hardy-Weinberg equilibrium.
Mating Type

Mating Offspring
Frequency
Type AA Aa aa
AA x AA p4 p4
AA x Aa 4p3q 2p3q 2p3q
AA x aa 2p2q2 2p2q2 Max. heterozygosity
@ p = q = 0.5

Aa x Aa 4p2q2 p 2 q2 2p2q2 p2 q2
Aa x aa 4pq3 2pq3 2pq3
aa x aa q4 q4

AA offspring = p4 + 2p3q + p2q2 = p2(p2 + 2pq + q2) = p2(p+q)2 = p2

Aa offspring = 2p3q + 2p2q2 + 2p2q2 + 2pq3 = 2pq(p2 + 2pq + q2) = 2pq(p+q)2 = 2pq
aa offspring = p2q2 + 2p3q + q4 = q2(p2 + 2pq + q2) = q2(p+q)2 = q2

Effects of Genotype Frequency on the Ratio of

Implications of Hardy-Weinberg Law Heterozygotes to Homozygotes
• a population cannot evolve if it meets the Hardy-
Weinberg assumption

• when a population is in HWE, the genotypic

frequencies are determined by the allelic frequencies
heterozygote frequency never exceeds 0.5
when a recessive allele is rare, most individuals
who carry the allele are heterozygous

• a single generation of random mating produces

the equilibrium frequencies of p2, 2pq, and q2

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Lecture 2: Hardy-Weinberg Equilibrium Population Genetics

Exercises Exercises

1. Given gene A at frequency 0.2 and gene B at 3. Albinism occurs with a frequency of about 1 in
frequency 0.6, find the equilibrium frequencies 20,000 in European populations. Assuming it to
of the gametes AB, Ab, aB, and ab. be due to a single autosomal recessive gene,
and assuming the population to be in HWE,
what proportion of people are carriers?
2. At what allelic frequency does homozygous
recessive genotype (aa) become twice as 4. What should be the gene frequency of a
frequent as the heterozygous genotype (Aa) in recessive mutant in a random-breeding
a Hardy-Weinberg population? population that would result in one-third of
normal individuals being carriers?

Chi-square Test for HWE Exercises

Ho: the data follow HW proportion 1. Jeffrey Mitton and his colleagues found 3
genotypes (R2R2, R2R3, and R3R3) at a locus
Ha: the data do not follow HW proportion
encoding the enzyme peroxidase in
2
observed expected ponderosa pine trees growing in Colorado.
computed
exp ected The observed number of these genotypes
were 135 for R2R2, 44 for R2R3, and 11 for
tabular df , where df (degrees of freedom) = k - 1- m R3R3. Are the ponderosa trees in HWE at the
k is number of genotypes and m no. of independent
allele frequencies estimated from the data
peroxidase locus?

If calculated tabular
reject Ho

The Case of Di- and Multi-Hybrid

• genes are independent

2. A population survey for a microsatellite locus in
a Drosophila population resulted in the
• the probability of any combination of hybrid can be
following numbers of different genotypes:
determined by applying the product rule of probability
A1 A1 A1 A2 A1 A3 A2 A2 A2 A3 A3 A3,
• if another pair of genes C and c are represented by z and
8 38 121 27 252 401
y, respectively, the probability of getting a genotype AAbbCc
Calculate the allelic frequencies for all the would be
alleles and test whether the genotypic
frequencies deviate significantly from Hardy- p2 s2 2 zy 2 p 2 s 2 zy
Weinberg proportions.

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Lecture 2: Hardy-Weinberg Equilibrium Population Genetics

Phenotype and Genotype Frequencies for Two Pairs of

Genes at Genetic Equilibrium Example: If the frequency of gene A is o.4, gene b =
Mendelian Ratios 0.3, gene C = 0.2 and gene D = 0.5 and the genes are
Phenotypes and
Frequencies at
Genotypes Frequencies in different chromosomes, what is the frequency at
Equilibrium genetic equilibrium of the following phenotypes or
AABB p2 r2 p2r 2 genotypes?
AB AaBB 2 pq r 2 2 pqr 2
1 q2 1 s2
AABb p 2 2rs 2 p 2 rs
AaBb 2 pq 2rs 4 pqrs (a) abcd (b) AabbCcdd (c) AaBBccDD
AAbb 2
p s 2 2 2
p s
(d)ABCD (e) AaBbCcDd
Ab 1 q2 s2 Aabb 2 pq s 2 2 pqs 2
aaBB q2
r2
q2r 2
aB q2 1 r 2
aaBb q2 2rs 2q 2 rs

ab q2 s2 q2 s2 q2 s2
aabb

X-Linked Genes
X-Linked Genes
• In females, Hardy-Weinberg frequencies are the same for any
• the relationship between gene frequency and genotype other locus: = p2 + 2pq + q2 = 1
frequency in the homogametic sex is the same as with an
autosomal gene • In males, genotype frequencies are the same as allele
frequencies: =p+q
• heterogametic sex has only two genotypes and each individual
carries only one gene • consider two X-linked alleles, A and a, with frequencies p and
q, and let the genotypic frequencies as follows:

Frequencies at Hardy-Weinberg Equilibrium

XA (p) Xa (q) Y Gender Females Males
XA (p) XA XA XA Xa XAY
(p2) (pq) (p) Genotype XA XA XA Xa Xa Xa XA Y XaY

Xa (q) Xa XA Xa Xa XaY
(pq) (q2) (q) Frequency p2 2pq q2 p q

X-Linked Genes X-Linked Genes

• two-thirds of the sex-linked genes in the population are carried • if alleles are X-linked and sexes differ in allelic frequency,
by the homogametic sex and one-third by the heterogametic Hardy-Weinberg equilibrium is approached over several
sex generations

• the frequency of A in the whole population is • allelic frequencies oscillate each generation until the allelic
frequencies of males and females are equal
p 2 p 1 p
3 f 3 m • recessive X-linked traits are more common among males
• the frequencies in the progeny generation are

p 'm pf p'f 1 pm pf
2

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Lecture 2: Hardy-Weinberg Equilibrium Population Genetics

Frequencies of Different Kinds of Offspring Resulting from Various Marriages

Involving X-linked Genes
Types of Types of Offspring
Marriages Frequencies Females Males
Females X of Marriages
AA Aa aa A a
Males
AA x A p2 x p = p3 p3 p3

AA x a p2 x q = p2q p2q p2q

Aa x A 2pq x p = p2q p2q p2q p2q

2p2q
Aa x a 2pq x q = pq2 pq2 pq2 pq2
2pq2
aa x A q2 x p = pq2 pq2 pq2

aa x a q2 xq= q3 q3 q3
Approach to equilibrium under random mating for a sex-linked gene, showing the
gene frequency among females, among males, and in the two sexes combined.
The population starts with females all of one sort (qf = 1), and males all of the
TOTAL p2 2pq q2 p q
other sort (qm = 0).

Calculating Gene Frequencies

3. Sex-Influenced Traits
A. Autosomal Loci with Two Alleles
Example: In the human population, an index finger shorter than the ring
1. Codominant Autosomal Alleles finger is thought to be governed by a sex-influenced gene that appears to
be dominant in males and recessive in females. A sample of the males in
Example. The following numbers of the human M-N blood groups were this population was found to contain 120 short and 210 long index fingers.
recorded in a sample of American Whites: Calculate the expected frequencies of long and short index fingers in
M = 1,787 MN = 3,039 N = 1,303 females of this population.

(a) What are the genotype frequencies in this sample? (b) What are the
gene frequencies? (c) With the gene frequencies observed, what are the B. Autosomal Loci with Multiple Alleles
genotype frequencies expected from the Hardy-Weinberg law?
Example. A sample of a human population was blood-grouped and found
2. Dominant and Recessive Autosomal Alleles to contain 23 group AB, 441 group O, 371 group B, and 65 group A.
Calculate the allelic frequencies of IA, IB, and i.
Example: About 30 % of people do not recognize the bitter taste of
phenyl-thiocarbamate (PTC). Inability to taste it is due to a single
autosomal recessive gene. What is the frequency of the nontasting
gene, assuming the population to be in Hardy-Weinberg equilibrium?

C. Sex-Linked Loci

1. Codominant Alleles
Example: In domestic cats, black melanin pigment is deposited in the hair
by a sex-linked gene, its alternative allele produces yellow hair. CBCB
females or CB males are black. CYCY females or CYY males are yellow,
CBCY females are tortoiseshell (blotches of yellow and black). A population
of cats in London was found to consist of the following phenotypes:

Black Yellow Tortoiseshell Totals

Males 311 42 0 353
Females 277 7 54 338
Determine the allelic frequencies.

2. Dominant and Recessive Alleles

Example: Color blindness in humans is an X-linked recessive trait.
Approximately 10 % of the men in a particular population are color-blind.
(a) If mating is random for the color-blind locus, what is the frequency of
the color blind allele in this population? (b) What proportion of the women
in this population are expected to be color-blind? (c) What proportion of the
women in the population are expected to be heterozygous carriers of the
color-blind allele?

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