Classical Genetics
References:
Principles of Genetics, Snustad & Simmons,
John Wiley & Sons, 2010
Campbell Biology Australian & New Zealand
Version, Jane B. Reece, Noel Meyers, Lisa A.
Urry, Michael L. Cain, Steven A. Wasserman, Peter V.
Minorsky, Robert B. Jackson, Bernard N. Cooke
Pearson Higher Education AU, 1 Dec 2014
[Link]
a.) To manage endangered
species
Inbreeding due to reduction of
available breeding individuals
caused the appearance of
kinked tails and atrial septal
defects in Florida panther
[Link]
[Link]
[Link]
b) Resolve taxonomic uncertainties
The African savanna elephant (Loxodonta africana) has
evolved to be about twice as big as the forest elephant
(Loxodonta cyclotis).
[Link]
[Link]
The Sumatran Orangutan is the rarer of
the two species of orangutans (Bornean
Orangutan)
3) Forensics
4) Genetic improvement of
livestock
[Link]
5) Medical applications
Mice provide effective models for
diseases and conditions such as
atherosclerosis, hypertension,
diabetes, osteoporosis, glaucoma,
neurological and neuromuscular
disorders, and cancer, as well as
many rare diseases.
[Link]
Advantages of the mouse as a model
organism
Genetic manipulation of the mouse
genome
Identification of causative mutations in
the mouse genome
Characterization of genetic background
effects
Value of inbred strains and strain
panels
Classical Genetics
Chapter Outline
Classical Genetics
Mendelian Genetics
Neomendelian Genetics
Mendelian Genetics
The Principle of Dominance: In
a heterozygote, dominant allele
conceals the presence of another.
The Principle of Segregation: In
a heterozygote, two different
alleles segregate from each other
during the formation of gametes.
*Allele-alternative form of a gene (one *Dominant -Traits that appear to
member of a pair) that is located at a mask (or hide) other traits.
specific position on a specific *Recessive -Traits that can be
chromosome. hidden in one generation and then
appear in the next.
*Trait-A distinguishing
characteristic.
In cattle, hornless (called "polled,"
represented by P) is dominant over
horned (p)
P dominant allele,
p recessive allele.
PP – Homozygous
dominant
pp – Homozygous
recessive
Pp – Heterozygous
Homo – same
Hetero - different [Link]
Why peas?
They grew quickly, Mendel could see the results of his
experiment sooner & he had more control over them – he
could choose self pollination or cross pollination &
could physically do it.
[Link]
Mehz7tCxjSE
Pea Flowers
Copyright@2009 Pearson Education Inc.
cross between F1 offspring (first-generation
offspring) of two individuals that differ in
two traits of particular interest.
Dihybrid Crosses
Seed colour &
seed shape
P parent
F filial
The Principle of
Segregation – In a
heterozygote, two
different alleles
segregate from
each other during
the formation of
gametes
*Phenotype -
The observable Punnett
physical or square
biochemical
characteristics of
an organism, as
determined by
both genetic
makeup and
environmental
influences.
Comparison of Observed and
Expected Results in the F2
*chance effects of random fertilization
Mendel’s Principles
The Principle of Independent
Assortment: The alleles of different
genes segregate, or as we sometimes
say, assort, independently of each
other.
The traits in the offspring of this crosses did
not always match the combinations of traits in
the parental organisms.
Key Points
Mendel studied the inheritance of seven
different traits in garden peas, each trait
being controlled by a different gene.
Mendel’s research led him to formulate
three principles of inheritance:
1) The alleles of a gene are either dominant or
recessive.
2) Different alleles of a gene segregate from each
other during the formation of gametes.
3) The alleles of different genes assort
independently.
Applications of Mendel’s
Principles
Mendel’s principles can be used to
predict the outcomes of crosses
between different strains of organisms.
Three methods to predict outcomes
– The Punnett Square Method
– The Forked-Line Method
– The Probability Method
The Punnett Square Method
P p
Pp X Pp
P PP Pp
p Pp pp
[Link]
hz7tCxjSEMendel's Peas
The Punnett Square Method
Copyright@2009 Pearson Education Inc.
The Forked-Line Method
for an Intercross
Intercross: A mating between two individuals both heterozygous at a
specified locus or loci.
The Forked-Line Method
for a Testcross
Testcross: A cross between an individual exhibiting the dominant phenotype of
a trait and an individual that is homozygous recessive for that trait in order to
determine the genotype of the dominant individual.
Probability
The probability of an event is the frequency of
that event in the sample space.
For a coin toss:
– The probability of heads is 1/2.
– The probability of tails is 1/2.
For two heterozygotes (Gg) producing an offspring:
– The probability of GG is 1/4.
– The probability of Gg is 1/2.
– The probability of gg is 1/4.
Probability
The sample space is
the collection of all
events.
What is the probability
two events, A and B,
will occur together?
What is the probability
that at least one of the
two events, A or B, will
occur at all?
The Multiplicative Rule
If the events A and B are independent, the
probability that they will occur together,
denoted P(A and B), is P(A) P(B).
Example: probability of drawing the ace of
hearts, P(A and H)
P(A) = 4/52 P(H) = 1/4
P(A) P(H) = 4/52 1/4 = 1/52
The Additive Rule
If the events A and B are independent, the
probability that at least one of them
occurs, denoted P(A or B), is given by
P(A) + P(B) [P(A) P(B)].
Example: Probability of drawing an ace OR a
heart, P(A or H)
P(A) = 4/52 P(H) = 1/4
P(A or H) = (4/52) (1/4) (4/52 1/4) = 16/52
The Additive Rule
If the two events do not overlap in the sample
space, they are said to be mutually exclusive.
In this case, P(A) P(B) = 0, and the Additive
Rule reduces to
P(A or B) =P(A) P(B)
Example: probability of drawing an ace or a
king, P(A or K)
P(A) = 4/52 P(K) = 4/52
P(A or K) = 4/52 4/52 = 8/52
The Probability Rule
for an Intercross
Key Points
The outcome of a cross can be
predicted by the systematic
enumeration of genotypes using a
Punnett square.
When more than two genes are
involved, the forked-line or probability
method is used to predict the outcome
of a cross.
Testing Genetic Hypotheses
Hypothesis: a well-formulated
scientific idea (The expected proportions can be
predicted and calculated before the experiment starts)
Data collected from observations or
from experimentation enable scientists
to test hypotheses. (An experiment can be
designed to determine whether the data confirms or rejects the
hypothesis)
Genetics: Are the results of a cross
consistent with a hypothesis?
The Chi-Square Test
Observed Expected
2
2
Expected
Predict Expected numbers based on
hypothesis.
Calculate the 2 statistic.
Determine the degrees of freedom. (n-1, n is the
number of phenotype observed)
Compare the 2 statistic to the critical value
Example:
Mendel’s Dihybrid Cross
Example: A Dihybrid Cross
with Campions (Hugo deVries)
Distribution of a 2 Statistic
Comparison to the Critical Value
Mendel’s Dihybrid Cross:
2 = 0.51
Degrees of Freedom = 4 1 = 3
Critical Value = 7.815
Fail to Reject the Hypothesis
DeVries’ Dihybrid Cross:
2 = 22.91
Degrees of Freedom = 4 1 = 3
Critical Value = 7.815
Reject the Hypothesis
Key Points
The chi-square statistic is calculated as 2 =
(observed number expected number)2 /
expected number, with the sum computed
over all categories comprising the data.
Each chi-square statistic is associated with
an index, the degrees of freedom, which is
equal to the number of data categories minus
one.
Pedigree Conventions
Pedigrees are
diagrams that show
the relationships
among the
members of a
family.
Inheritance of a Dominant Trait
Every individual who carries
the dominant allele
manifests the trait.
Every affected individual is
expected to have at least
one affected parent.
If a dominant trait is
associated with reduced
viability or fertility, most
people who show the trait
are heterozygous, and half
their children should inherit
the condition.
Inheritance of a Recessive Trait
Recessive traits may
occur in individuals
whose parents are not
affected.
Rare recessive traits
are most likely to
appear in a pedigree
when spouses are
related to each other.
Key Points
Pedigrees are used to identify dominant
and recessive traits in human families.
The analysis of pedigrees allows
genetic counselors to assess the risk
that an individual will inherit a particular
trait.
NeoMendelian Genetics
Chapter Outline
Allelic Variation and Gene Function
Gene Action: From Genotype to
Phenotype
Inbreeding: Another Look at Pedigrees
Allelic Variation
and Gene Function
The diverse kinds of alleles of
genes affect phenotypes in
different ways.
Mendel’s Work
Each trait that Mendel studied was
controlled by a single gene with two
alleles.
Genes may have more than 2 alleles.
Different alleles may affect the
phenotype in different ways.
Incomplete Dominance
The phenotype of
the heterozygote is
midway between
the phenotypes of
the two
homozygotes.
One allele is
partially, or
incompletely,
dominant over the
other.
Codominance
The heterozygote
expresses the
phenotypes of both
homozygotes.
Neither allele is
dominant.
Multiple Alleles of a Single Gene
The most common
alleles in nature is
the wild-type allele.
All other alleles are
mutants.
Allelic Series
An allelic series
describes the
dominance hierarchy
of multiple alleles.
A null allele is
nonfunctional.
A hypomorphic allele
has partial function.
Null allele : An allele whose effect is either
an absence of normal gene product at
the molecular level or an absence of
normal function at the phenotypic level.
Hypomorphic allele: An allele that reduces the expression
of its target protein without eliminating it entirely.
Testing Mutations for Allelism
• Not alleles of the same genes
Allelism: Any of several forms of a gene, usually
arising through mutation, that are responsible for
hereditary variation
Variation Among the
Effects of Mutations
Visible mutations
A mutation that affects the morphology or physical
appearance of an organism.
Sterile mutations
Sterile mutations prevent the production of fertilized
eggs by individuals homozygous for the mutation.
Lethal mutations
The mutations lead to the death of the individual.
Genes Function to Produce
Polypeptides
Dominant and Recessive Mutations
Amorphic allele : Null allele, absence of genetic information, caused by
deletion of a gene causing it to be functionless.
Dominant-negative allele : A mutation whose gene product adversely affects
the normal, wild-type gene product, within the same cell, usually by
combining with it.
a+ : wild-type, a: apomorphic/null, ah: hypomorphic,
aD: dominant-negative
Key Points
Genes often have multiple alleles.
Mutant alleles may be dominant, recessive,
incompletely dominant, or codominant.
If a hybrid that inherited a recessive mutation
from each of its parents has a mutant phenotype,
then the recessive mutations are alleles of the
same gene; if the hybrid has a wild-type
phenotype, then the recessive mutations are
alleles of different genes.
Key Points
Most genes encode polypeptides.
In homozygous condition, recessive mutations
often abolish or diminish polypeptide activity.
Some dominant mutations produce a polypeptide
that interferes with the activity of the polypeptide
produced by the wild-type allele of a gene.
Gene Action:
From Genotype to Phenotype
Phenotypes depend on both
environmental and genetic
factors.
Influence of the Environment
Genes function in a biological and
physical environment.
Examples
– Drosophila shibire mutation (temperature)
Shibire mutation is the cause of temperature-sensitive
paralysis. 'Shibire' means 'paralyzed' in Japanese.
– Phenylketonuria (diet)
Phenylketonuria (PKU) is a genetic condition that is passed to
a baby by the parents, caused by a genetic mutation in the
human phenylalanine hydroxylase (PAH) gene, results in the
body not producing a functioning PAH enzyme - body cannot
process phenylalanine in some foods.
– Pattern baldness (gender)
Male pattern baldness, or androgenetic alopecia (AGA), affects
around 80% of men at some point in their lives- a mutation in a
testosterone receptor.
Incomplete Penetrance
Example: Polydactyly
Individuals do not
express a normal trait
even though they
have the appropriate
genotype.
"Incomplete" penetrance means the
genetic trait is expressed in only part
of the population.
Variable Expressivity
Example: the Lobe Eye Mutation
A trait is not
manifested
uniformly among
individuals that
show it.
In Drosophila, the lobe eye mutation shows variable
expressivity.
Gene Interactions
Example: Chicken Comb Shape
Different
combinations of
alleles from two genes
result in different
phenotypes.
In this example,
R-P- produces walnut
R-pp produces rose
rrP- produces pea
rrpp produces single
Guess which one is the pea type?
The F1 differed from
both parents and two
new phenotypes not
seen in the parents
appeared in the F2
(walnut & single)
More than one
gene could be
responsible for the
expression of a
single phenotype
Epistasis
In epistasis, an allele of one gene overrides
the effect of other genes on the phenotype.
In Drosophila,
– The cinnabar mutation produces bright red eyes.
– The white mutation produces white eyes.
– When both mutations are present in the same fly,
the eyes are white.
– The white mutation is epistatic to the cinnabar
mutation.
Pleiotropy
A gene that affects many
phenotypes is pleiotropic.
Mutations in the
phenylketonuria gene cause
mental impairment, light hair
color, and the presence of
metabolites in blood and
urine.
Mutations in the Drosophila
singed gene affect bristle
shape and egg production.
Key Points
Gene action is affected by biological and
physical factors in the environment.
Two or more genes may influence a trait.
A mutant allele is epistatic to a mutant
allele of another gene if it has an
overriding effect on the phenotype.
A gene is pleiotropic if it influences many
different phenotypes.
Inbreeding:
Another Look at Pedigrees
Geneticists use a simple statistic,
the inbreeding coefficient, to
analyze the effects of matings
between relatives.
Consanguinous Matings and
Recessive Traits
Albinism - The result of
the biological inheritance
of genetically recessive
alleles passed from both
parents of an individual
Consanguinous mating: The mating of closely related individuals,
such as brothers, sisters, or cousins. (may produce albinism).
Inbreeding Depression
Inbreeding depression is the reduced fitness in a
population as a result of breeding of related
individuals.
Inbred lines (individuals of a particular species
which are nearly identical to each other in
genotype due to long inbreeding) of experimental
species are often less vigorous than hybrid
lines.
Inbred lines of self-fertilized plants are
homozygous for alleles that were present in
the founding line.
Heterosis
When two different inbred lines are
crossed, the hybrids are heterozygous for
many genes.
These heterozygotes display heterosis, or
hybrid vigor (The tendency of a cross-bred
individual to show qualities superior to those of both
parents).
Genetic Analysis of Inbreeding
Individuals A and B are half-
siblings.
Their offspring, I, is inbred, and
inherited one copy of her
genes from A and one copy
from B.
These copies may be identical
by descent if they are
identical copies inherited
from individual C.
C is the common ancestor of
I.
The Inbreeding Coefficient
The Inbreeding Coefficient, F, is the
probability that the two gene copies in
an individual are identical by descent
from a common ancestor.
Calculation of the Inbreeding Coefficient
1) Identify the common ancestor(s) of an inbred
individual.
2) Count the number of individuals (n) in each
inbreeding loop.
3) Calculate the quantity (1/2)n for each
inbreeding loop and sum the results.
Calculating F for a Full-Sibling Mating
1) Identify the common
ancestor(s).
U and V are both common
ancestors, so there are
Insert Unmarked two inbreeding loops.
Figure 2) Count the number of
individuals in each
Figure number inbreeding loop.
Chapter 4 p. 725 Loop 1: U, R, S; n=3
top right Loop 2: V, R, S; n=3
3) Calculate (1/2)n for each
loop and sum the results.
Loop 1: (1/2)3 = 1/8
Loop 2: (1/2)3 = 1/8
F = 1/8 + 1/8 = 1/4
Calculating F (inbreeding coefficient)
for a Half-Sibling Mating
1) Identify the common
ancestor(s).
C is the common
ancestor, so there is one
inbreeding loop.
Insert Unmarked
2) Count the number of
Figure individuals in each
Figure number inbreeding loop.
The Loop includes C, A,
Chapter 4 p. 725 top and B; n=3
left 3) Calculate (1/2)n for each
loop and sum the results.
There is only one loop in
this case
(1/2)3 = 1/8, so F = 1/8
Calculating F when the
Common Ancestor is Inbred
Multiply (1/2)n by the
Insert term [1 + FCA]
Unmarked
Figure FT = (1/2)3 [1 + (1/2)3]
Labeled
= 1/8 (1 + 1/8)
Figure
number p. = 9/64
726 top right = probability that the two
(in-text art) gene copies in T are
identical by descent
from a common
ancestor.
Measuring Genetic Relationships
Calculate the fraction of genes that two
relatives share.
Calculate the inbreeding coefficient F for
the offspring of a mating between the two
relatives
The coefficient of relationship = F 2
For full siblings, F = 1/4, so the coefficient of
relationship is 1/2
This means that full siblings share 1/2 of
their genes.
Key Points
Inbreeding increases the frequency of
homozygotes and decreases the
frequency of heterozygotes.
The effects of inbreeding are proportional to
the inbreeding coefficient, which is the
probability that two gene copies in an
individual are identical by descent from a
common ancestor.
The coefficient of relationship is the
fraction of genes that two individuals
share by virtue of common ancestry.