Bi2030 / Lecture #3 / Slide 1 Bi2030 / Lecture #3 / Slide 2

Bi2030 / Lecture #3 / Slide 3

Natural populations are reservoirs of great genetic variability:
For example, all humans contain the same numbers and kinds of genes, but no two
individuals look alike (except twins).
The human population must contain multiple alleles of many, many genes to explain
this natural variability.
Hardy & Weinberg showed that the human population could be treated as a gene pool,
a reservoir of gametes that combine at random, to produce progeny whose phenotypes
and proportions can be predicted if the frequencies of different alleles in the population
are known. If the allele frequencies are not known, but the population is in Hardy-
Weinberg equilibrium, then the gene frequencies can be calculated from the
populations phenotypic frequencies.

Bi2030 / Lecture #3 / Slide 4
All Hardy-Weinberg arithmetic involves relative gene and phenotype FREQUENCIES
expressed as fractions (i.e, the frequencies of all the alternative alleles of a particular
gene in the population must sum to 1). These fractions are also probabilities, i.e., the
chances of finding a particular allele in a gamete or an individual with a particular
phenotype.

A note on genotype notation: A/A (or A/a or a/A or a/a) indicates the two copies of a
particular gene in a diploid individual. The slash separating the two alleles indicates
that they reside on homologous chromosomes it is NOT a division sign for an
arithmetic operation!
Bi2030 / Lecture #3 / Slide 5
Note that the fractional frequencies (or probabilities) of the three possible phenotypes
must sum to 1.
Bi2030 / Lecture #3 / Slide 6
Bi2030 / Lecture #3 / Slide 7
(a) Let q = the frequency of the recessive cf allele. Assuming HW equilibrium, then
q
2
= 0.0003 and q = (0.0003)
1/2
= 0.017. Then p, the frequency of the wild-type
allele, = (1 - q) = 0.983.
(b) We know that the woman is heterozygous, so she has a 50% chance of passing
the cf allele to any of her offspring. The chance that her unaffected mate is also
a heterozygous carrier (assuming no family history of CF) is [2pq / (p
2
+ 2pq)] =
0.033 / (1 - 0.0003) ! 3.3%. The chance that this couple will have an affected
child is therefore (0.5)(0.033)(0.5) ! 0.8%.
(c) No! We cannot be certain that a population is at HW equilibrium unless we
empirically measure (not calculate) ALL relevant genotype frequencies.
Fortunately, in the case of cystic fibrosis, there's now a genetic screen for
carriers, so families at risk can get objective estimates of the risk factors. (With a
screening test, it would also be possible, in principle, to determine whether cystic
fibrosis is at HW equilibrium.)
Bi2030 / Lecture #3 / in-class slide
Bi2030 / Lecture #3 / Slide 9
The MN blood group antigens are specified by CODOMINANT alleles (each makes a
product that contributes to the organisms phenotype). In this case, the M and N alleles
make antigenically different proteins that are displayed on the surface of red blood
cells. Heterozygotes produce both antigens, so they display a combined phenotype.
Because there is no complete dominance in this system, the organisms MN phenotype
reflects his/her genotype, which allows for simple tests of whether or not a population is
at Hardy-Weinberg equilibrium, as summarized in the next slide.

Bi2030 / Lecture #3 / Slide 10
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Bi2030 / Lecture #3 / Slide 13
The ABO blood group antigens are specified by a gene with three different alleles. The
I
A
and I
B
alleles both make distinctive antigens on the red cell surface and so they are
codominant to each other. The i allele makes no antigen and so is recessive to both
the I
A
and I
B
alleles.

Note that, unlike the simpler MN system, it is not possible to calculate gene frequencies
in the ABO system directly from the ABO blood group frequencies. The data in the
table must have been generated by assuming that each population was at Hardy-
Weinberg equilibrium, then using the various phenotype frequencies and the HW
formula to calculate allele frequencies.
(See the next slide for details of extending the HW analysis to a three-allele system.)
Bi2030 / Lecture #3 / Slide 14
Bi2030 / Lecture #3 / Slide 15
If a population is NOT at HW equilibrium, it can reach equilibrium in one generation of
random mating (assuming that the population is large enough to avoid sampling errors
in individual matings). The matrix shows the proportion of matings involving each of the
three genotypes in the population. For example, if 0.4 of the individuals have EE
genotype and matings are at random, then (0.4)(0.4) or (0.16) of the matings should be
between two EE individuals. (This is directly analogous to how gene combinations are
calculated in HW.) Those matings will yield all EE offspring, so 0.16 of the EE offspring
in the next generation will come from EE x EE matings. To check this calculation,
simply count the dark gray squares at the junction of the EE parents. Similarly, EE x Ee
matings will contribute to EE individuals in the next generation. Although there are two
ways to get such a mating (father EE and mother Ee or father Ee and mother EE), only
0.5 of the gametes from Ee will carry the E allele, so the EE x Ee matings will contribute
(2)(0.5)(0.4)(0.2) = 0.08 of the EE individuals to the next generation. Finally, Ee x Ee
matings can generate EE individuals, but only (0.25) of the matings will yield EE
offspring, so this contribution is (0.25)(0.2)(0.2) = 0.01. Thus, the total EE individuals
after one generation of random mating will be 0.16 + 0.08 + 0.01 = 0.25. Similar
calculations will yield the other phenotype frequencies. The three resulting phenotypes
are shown as different gray shades in the matrix. Count the squares of each type to
check your calculation.
Bi2030 / Lecture #3 / Slide 16
Matings in populations may not be random with respect to all phenotypic traits. For
example, humans choose mates of a similar skin color more often than chance.
Assortative mating patterns cause deviations from the idealized HW phenotype
frequencies: preferential matings between like phenotypes (positive assortative mating)
tends to reduce the proportion of heterozygotes in a population and increase the
proportions of homozygotes; preferential matings between unlike phenotypes (negative
assortative mating) tends to increase heterozygosity and decrease homozygosity.
Note that nonrandom mating alters both genotype and phenotype frequencies, but does
NOT change the allele frequencies in the population.
Bi2030 / Lecture #3 / Slide 17
Inbreeding definitely reflects a nonrandom pattern of mating, although in this case the
factors influencing mate selection are probably based more on proximity and social
custom than on phenotypic appearance. Again, genotype and phenotype frequencies
are changed, but allele frequencies are not (unless there is selection for or against
certain phenotypes in the population).
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