Download Polygenic inheritance and genes in populations

Continuous and
discontinuous variation
Genes in population
Discontinuous Variation
• The phenotypes we have consider
so far have been due to two
segregating alleles of single genes.
• This means that alternative
phenotypes are clearly different.
• This variation or difference
between phenotypes is known as
discontinuous variation.
Continuous Variation
• Many phenotypes show continuous variation – there are
many intermediate forms and the distribution of the
phenotypes in a population is a bell curve.
• Traits that show continuous variation include: height
and weight in humans, milk production in cows and the
size of flowers.
• Continuous traits are usually polygenic, with alleles of
many different genes contributing to produce the final
phenotype.
• This results in considerable phenotypic variation, and
further variation may also occur due to interactions with
the environment.
Variation in Phenotype
• Variation in phenotype in populations is
influenced by the following factors:
– One gene can have many alleles
– Meiosis involves independent assortment and genetic
recombination of alleles
– Dominance may not be complete
– Several genes can affect the one trait
– One gene can determine more than one trait
– The expression of genes can be affected by other
genes and by the environment
Genes in populations
• Different people in same community have different risks
for disease.
• The reasons for this are a complex mix of genetic,
environmental and social risk factors.
• Epidemiology is the description and analysis of the
pattern of diseases in the population, the causes of
these different patterns, and the use of this information
to improve public health.
• We know that some diseases, both rare and common,
seem to ‘run in families’.
• Genetic epidemiology attempts to determine the size of
genetic influences on disease.
Heterozygote Advantage
• Some extremely serious and often fatal
genetic diseases continue to be present
in the population but why????
• If individuals who are homozygous for
such a disease normally die before
reproducing, we would expect natural
selection to lead to low frequencies for
the disease allele in the population.
• This is not always the case – take the
sickle cell anaemia gene and the cystic
fibrosis gene as examples.
Heterozygote Advantage:
Sickle Cell Anaemia
• High frequency of the mutant allele in people
of African descent
• Homozygotes suffer from life-threatening
anaemia
• The explanation for the unexpected frequency
is that being heterozygous for this allele is
advantageous in areas where malaria is
present.
• The mutant allele results in defective
haemoglobin molecules alter the red blood
cells so that they are less susceptible to
infection by the malarial parasite.
Heterozygote Advantage:
Cystic Fibrosis
• High frequency of the mutant allele in people of
Caucasian background (1 in 28 Caucasians are
heterozygotes)
• Mutant copy of CFTR gene leads to defective channel
proteins being produced in the cell membrane
• The bacteria Salmonella typhi requires the channel
protein in order to get across the intestine wall
• This means that heterozygotes are less susceptible to
typhoid fever
• The gene frequencies currently observed are a result of
previous heterozygote advantage when typhoid fever
was widespread in Europe
What is the gene pool
• The genetic information in an individual is a genotype.
• The genetic information in a population is a gene pool.
• A gene pool is described in terms of the allele
frequencies (proportions) of each gene.
• When genotypes of all members of a population are
known, allele frequencies may be calculated directly
from genotype frequencies.
• When allele frequencies are not known, they may be
estimated starting from the frequency of the
homozygous recessive phenotype.
Calculating Allele Frequencies
• Looking at this picture, the 10 sheep
comprises two black (genotype ww), two
heterozygous white (genotype Ww) and six
homozygous white (genotype WW) sheep.
• Each sheep has two alleles, and so the total
number of alleles of this gene is twice the
number of organisms in the population.
• In this population:
–
–
–
–
total number of alleles = 10 × 2 = 20
number of W alleles = (6 × 2) + 2 = 14
number of w alleles = (2 × 2) + 2 = 6
Frequency of W alleles or freq (W) = 14/20
= 0.7
– Frequency of w alleles or freq (w) = 6/20 =
0.3
• The allele frequencies total 1.0, so we can
write: freq (W) + freq (w) = 1.
Calculating Allele Frequencies
• This means that, if the frequency of one
allele only is given, the frequency of the
second allele can be obtained by
subtracting the given frequency from one:
– freq (W) = 1 − freq (w)
– freq (w) = 1 − freq (W).
• A convention exists whereby the frequency
of the allele controlling the dominant trait is
denoted by the letter p, and the frequency
of the allele controlling the recessive trait is
denoted by the letter q. So, we can write:
– p+q=1
– p=1−q
– q = 1 − p.
Calculating Allele
Frequencies
• It is only when all genotypes in a population can be identified
with certainty that the allele frequencies in the gene pool can
be calculated directly.
• This occurs when there is a co-dominant relationship between
two alleles.
• In reality we could not directly calculate the allele frequencies
in the sheep population on the previous slide as we cannot tell
the difference between homozygotes and heterozygotes with
a white phenotype.
• When genotypes of all individuals are not known, the allele
frequencies in that population cannot be calculated directly.
However, under certain conditions, allele frequencies can be
estimated using the Hardy-Weinberg equilibrium equation.
Hardy-Weinberg Principle
• Allele frequencies in populations remain constant, generation
after generation, provided a particular set of conditions apply.
• Conditions include:
– The population must be large.
– Members of the population mate at random; random mating
contrasts with non-random or assortative mating in which matings
are restricted to those between organisms of like phenotypes.
– All matings are equally fertile, producing equal numbers of viable
offspring.
– The population is closed, with no migration either into or out of
the population.
• Under these conditions, the allele frequencies in a large closed
population will remain constant from generation to generation.
Such a population is said to be in Hardy–Weinberg
equilibrium (H–W equilibrium).
• The situation will remain like this until an agent of change acts
on the population.
Hardy-Weinberg Equation
•
•
The Hardy-Weinberg equilibrium equation was derived to calculate the
frequency of alleles in a population.
If p is defined as the frequency of the dominant allele and q as the
frequency of the recessive allele for a trait controlled by a pair of
alleles (A and a) the following equation applies:
(p + q)² = 1
or more simply
p² + 2pq + q² = 1
•
In this equation:
– p² is the predicted frequency of homozygous dominant (AA) people in a
population
– 2pq is the predicted frequency of heterozygous (Aa) people
– q² is the predicted frequency of homozygous recessive (aa) ones.
Hardy-Weinberg Equation
• From observations of phenotypes, it is usually only
possible to know the frequency of homozygous
recessive people, or q² in the equation.
• Since p = 1 - q and q is known, it is possible to
calculate p as well.
• Knowing p and q, it is a simple matter to plug these
values into the Hardy-Weinberg equation
(p² + 2pq + q² = 1).
• This then provides the predicted frequencies of all three
genotypes for the selected trait within the population.
Example of Hardy-Weinberg
equation in action
• Albinism is a rare genetically inherited trait that is only
expressed in the phenotype of homozygous recessive
individuals (aa).
• The most characteristic symptom is a marked deficiency in
the skin and hair pigment melanin.
• This condition can occur among any human group as well as
among other animal species.
• The average human frequency of albinism in North America
is only about 1 in 20,000.
• Based on the Hardy-Weinberg calculation on the next slide,
we can determine the following:
– Albinos will be found with a frequency of 0.005%
– Heterozygous carriers for this trait have a predicted frequency
of 1.4% (about 1 in 72)
– Vast majority of humans (98.6%) probably are homozygous
dominant and do not have the albinism allele.
Example of Hardy-Weinberg
equation in action
Hardy-Weinberg equation
(p² + 2pq + q² = 1)
•
•
•
•
Frequency of homozygous recessive individuals (aa) in a population is
q².
The following must be true for albinism:
– q² = 1/20,000 = .00005
– q = .007
p = 1 - qp = 1 - .007p = .993
p² + 2pq + q²
= 1(.993)² + 2 (.993)(.007) + (.007)²
= 1.986 + .014 + .00005
=1
This gives us the frequencies for each of the three genotypes for this
trait in the population:
p² = predicted frequencyof homozygous dominant individuals = .986 = 98.6%
2pq =predicted frequency of heterozygous individuals = .014 = 1.4%
q² =predicted frequency of homozygous recessive individuals = .00005 = .005%