Mendelian
Genetics, Chapter 14
Mendels work
The Law of Segregation
The Law of Independent Assortment
Rules of
probability
Extensions of
Mendelian Genetics
Mendelian
Inheritance in Humans
Heritable Variation & Patterns of Inheritance
Until the 20th
century, most biologist thought that offspring were a
blend of both parents (blending hypothesis).
Gregor Mendel was the first to
analyze patterns of inheritance in a systematic, scientific way
Heritable Variation & Patterns of Inheritance
Breeding garden peas
during the 1860s his experimental and mathematically rigorous research is a
classic in the history of biology
Mendels Particulate Model of Inheritance
Parents pass on
to their offspring discrete factors that are responsible for inherited traits
Mendels Principles
The discrete
factors (genes) retain their individuality across generations.
An organisms collection of genes is more like a bucket of
marbles than a pail of paint.
Predictions
of the blending model:
Over many
generations, a freely mating population would give rise to a uniform population
of individuals.
Think pail of paint: blue plus yellow would make
green, so all subsequent individuals would be green.
Everyday
observations and breeding experiments do not support this hypothesis.
Predictions
of the particulate model:
Over many
generations, variation would be maintained.
Traits could skip
a generation.
Everyday
observations and breeding experiments support this hypothesis.
Table 14.1
Fig. 14.2
Mendel used different true-breeding varieties
to study what would happen when they were crossed with each other.
He removed the stamen from one parent so that it would not self fertilize and
then brushed on pollen from a second parent.
Offspring of 2
different true-breeding varieties are hybrids
Cross-fertilization is called hybridization or
a cross
Parental plants are called P generation (parental)
Their hybrid offspring are the F1
generation (filial)
When F1 plants self-fertilize or are crossed their
offspring are called F2 generation
In his scientific study Mendel chose seven pea
characteristics that displayed two distinct forms
In his scientific study Mendel chose seven pea
characteristics that displayed two distinct forms
Fig. 14.3
Mendels
Monohybrid Cross
Mate purebreds
Mendel found that F1 plants (monohybrids) were all purple,
not a blend of purple & white
So was the heritable factor in the white flowers lost due to
hybridization?
Mate F1s to each other
Examine offspring (F2 -
grandkids)
Always found approximately
3:1 ratio of both original phenotypes in F2
Ratio calculations:
705/929 = 76% = 3/4
224/929 = 24% = 1/4
Figure 14.5 Mendels law of
segregation
Mendel concluded that:
The heritable factor for white flowers did
not disappear in F1 plants
Mendel developed four hypotheses:
There are
alternate forms of genes (alleles)
For each
inherited characteristic, an organism has two genes, one from each parent.
These genes may be the same alleles or different alleles
A sperm or an egg
only carries one allele for each inherited characteristic
When the alleles of a gene pair are different &
one is fully expressed and the other no effect, the alleles are called Dominant
and Recessive respectively
Principle Of Segregation
This led Mendel to develop
his Principle of Segregation
Pairs of alleles segregate
(separate) during gamete formation; the fusion of gametes at fertilization
creates allele pairs again
This Principle of Segregation applies to all sexually reproducing
organisms
Some
Definitions
A genes is a segment of DNA that codes for a particular trait.
It gives
instructions for the manufacture of a protein or RNA molecule.
A locus is the
physical location of a gene on the chromosome.
A character is
heritable feature that varies between individuals.
i.e. flower color
Each variant for
a character is called a trait.
i.e. purple or white flowers.
Figure 14.4 Alleles,
alternative versions of a gene
Phenotype versus Genotype
An organisms:
Collection of expressed, or physical, traits, is its Phenotype
Genetic make up is its Genotype
For the F2 plants:
The phenotypic ratio is 3:1
The genotypic ratio is 1:2:1
Mendel found that one
parent trait disappeared in the F1 generation only to reappear in a quarter of
the F2 generation
Figure 14.6 Genotype versus
phenotype
Genetics, Alleles & Homologous Chromosomes
Every diploid individual
has two sets of homologous chromosomes: one from each parent
Alleles of a gene reside
at the same locus on homologous chromosomes (Fig 14.3)
Homologous chromosomes may
have either the same alleles or different ones at a given locus
For any gene:
When the alleles are
identical, it is homozygous
When the alleles are different, it is heterozygous
Other Monohybrid Crosses
Know that brown eyes are
dominant to blue eyes
Can start with any type of
parent and predict kids
Predict offspring if
heterozygous brown-eyed parent and blue eyed parent.
Predict offspring of two
blue eyed parents.
Start with kids and figure
out what parents must have been
Two brown-eyed parents
have 2 kids with brown eyes and one with blue; determine all genotypes or
genotype possibilities.
Mum has blue eyes, kid has
brown eyes; what must be true for dad?
Using a Test Cross to Determine an Unknown
Genotype
A test cross is a mating between an individual of unknown genotype and
a homozygous recessive
The phenotype (appearance) of the offspring reveals the genotype
Mendel used test crosses to determine whether he had true-breeding
varieties of plants
Figure 14.7 A testcross
Test Cross
Used ONLY when have
dominant phenotype & dont know genotype
Cross with recessive
phenotype (since know genotype)
3 offspring
Mendel's Principle of Independent Assortment
What would result from a mating of parental varieties differing in two
characteristics a dihybrid cross?
Mendel crossed homozygous plants having round yellow seeds (genotype
RRYY) with plants having wrinkled green seeds (rryy),
producing:
F1: all yellow and spherical
(establishes dominance of both traits)
Were the two characteristics transmitted as a
package or independently of each other?
If the genes were inherited together:
The F1 hybrids would produce the same two kinds (genotypes)
that they received from their parents
The F2 generation would show a 3:1 phenotype ratio
If the two seed characteristics segregated independently:
F1 generation would produce 4 gamete genotypes RY, Ry, rY, ry
in equal quantities
Nine different genotypes producing four different phenotypes in a ratio
of 9:3:3:1 (two simultaneous monohybrid crosses)
Figure 14.8 Testing two
hypotheses for segregation in a dihybrid cross
Mendel's Principle of Independent Assortment
Mendel tried his seven pea
characteristics in various dihybrid combinations and always observed a 9:3:3:1
ratio (or two simultaneous 3:1 ratios) of phenotypes in the F2
generation
These results supported
hypothesis (b) that:
each pair
of alleles segregates independently of the other pairs during gamete formation
Figure 14.9 Segregation of
alleles and fertilization as chance events
Mendelian
inheritance reflects rules of probability.
A heterozygote,
Pp has a probability of ½ for passing down each allele into a gamete.
According to the rule
of multiplication, the probability of two Pp parents producing a pp gamete
is ½ x ½ = Ό.
The rule of
multiplication can be applied to dihybrid crosses. What is the probability of two YyRr parents producing a yyrr offspring?
Ό x Ό = 16.
The Rule
of Addition
What is the
probability that two heterozygous parents produce a heterozygous offspring?
First:
Probability of
dominant allele from sperm is ½.
Probability of a
recessive allele from the egg is ½.
½ x ½ = Ό.
Second
Probability of
dominant allele from sperm is ½.
Probability of a
recessive allele from the egg is ½.
½ x ½ = Ό.
Third
Both of these
events are possible, so the probabilities for each are added:
Ό + Ό = ½.
More on
Dominance
An allele can be completely
dominant, so that the phenotype of a homozygous dominant individual is
indistinguishable from that of a heterozygous individual.
An allele can be incompletely
dominant, so that the phenotype of a heterozygous individual is
intermediate between than that of a homozygous dominant individual and a
homozygous recessive individual.
An allele can be codominant,
in which two allele have affect the phenotype in
separate, distinguishable ways and both influence the phenotype equally. Note this is not an intermediate phenotype.
Figure 14.9 Incomplete
dominance in snapdragon color
Multiple
Alleles and Codominance
The ABO blood
group is an example of multiple alleles of a single gene.
There are three
alleles of this gene, IA, IB or i.
The IA
allele codes for the A red blood cell surface marker.
The IB
allele codes for the B red blood cell surface marker.
The
i
allele does not code for a functional
protein.
The IA
and IB alleles are codominant, because in individuals with the
genotype, both A and B surface markers are produced.
There are four
possible genotypes. A persons blood group may be A, B, AB or O.
Figure 14.10 Multiple
alleles for the ABO blood groups
Table 14.2
Pleiotropy
The ability of a
gene to affect an organism in may ways is called
pleiotropy.
This is because
there are many intricate molecular mechanisms within a cell, and many genes
influence more than one characteristic in an organism.
Epistasis
A
gene at one locus influence the
phenotypic expression of a gene at another locus.
Usually an
epistatic gene is one of the first enzymes within a metabolic pathway. If the first enzyme is non-functional, then
the pathway is shut down, even of the following enzymes are functional.
An
example of epistasis
In mice, the
color locus has a gene that codes for an enzyme at the beginning of a pigment
making pathway.
There are two
alleles, C which allows the coat to be colored, and c which produces a
non-functional enzyme.
The black/brown
locus codes for an enzyme further down in the pigment making pathway.
The dominant B allele give a
black coat color.
A BB or Bb mouse
is black.
The recessive b allele codes for a version of the
enzyme that is less robust.
A bb mouse is brown.
A cc mouse is
white, regardless of the genotype at the brown/black locus.
Figure 14.11 An example of
epistasis
Polygenic
Inheritance
Many traits, such
as human height or skin color can be classified along a continuum.
These are called quantitative
characters.
This continuous
inheritance usually indicated polygenic inheritance, and additive effect of two
or more genes.
Skin color is
determined by at least three genes which show incomplete dominance.
Height is determine by many more genes.
Intelligence,
another continuous trait is determined by many many more genes.
Figure 14.12 A simplified
model for polygenic inheritance of skin color
Multifactorial
Characters
Phenotype can
depend on the environment as well as on genes.
Nutrition, sun tanning of skin, stimulating
environment promotes intelligence.
So a genotype
gives a potential range of phenotypes, called a norm of reaction.
Can be very narrow, ex. ABO blood
group.
Can be very broad, ex. Count of red and white blood
cells.
Altitude,
physical activity, presence of infection
Figure 14.13 The effect of
environment of phenotype
Family Pedigrees
In genetics dominance does not mean a phenotype is normal or more
common than a recessive phenotype
Dominance means that a heterozygote displays the dominant phenotype
Recessive traits are often more common in a population than dominant
ones. (freckles)
We know how particular human traits are inherited by collecting
information on a family history and creating a family tree or pedigree
Figure 14.14 Pedigree
analysis
Human Disorders controlled by a Single Gene
There are over a thousand known human genetic disorders that can be
inherited as dominant or recessive traits controlled by a single gene locus
Recessive Disorders
Most human genetic disorders
are recessive
Using Mendels principles
we can predict the fraction of affected offspring likely to result from a
marriage of two carriers
Pedigree analyses &
prediction applies to any genetic trait controlled by a single gene locus
A family with an inherited form of deafness
Deafness did not
appear in the first generation
Only 2 of the 7
children in the 3rd generation had the condition
Common
Recessive Disorders
Cystic Fibrosis:
Strikes
1/2,500 white of European descent.
1/25
(4%) of white carry the disease.
The normal allele
for the gene codes for a chloride ion channel transporter.
Lack of this gene
causes chloride ions to build up the extracellular fluid, and the production of
a thick mucus.
Blocks
respiratory passages (poor breathing and frequent infections), ducts from
pancreas to the small intestine (poor digestion), seminal tubes (male
sterility)
Common
Recessive Disorders
Tay-Sachs Disease:
Strikes
1/3,600 Ashkenazic Jews.
The normal allele
for the gene codes for an enzyme that breaks down lipids in the brain.
Lack of this gene
causes degeneration of the brain and nervous system
Results
in seizures, blindness, poor mental and motor function, death within a few
years of birth.
Common
Recessive Disorders
Sickle Cell
Disease:
Strikes
1/400 African Americans.
Caused
by the substitution of a single amino acid in the hemoglobin gene.
Causes
red blood cells to sickle when blood oxygen levels fall due to altitude,
exercise, etc.
Heterozygotes are
protected against malaria and some individuals experience some of the symptoms
of those homozygous for the sickle cell allele.
Dominant Disorders
Many dominant disorders
are non lethal, such as extra fingers and toes, or with webbing
An example of a more
serious disorder is Achondroplasia, a form of dwarfism,
which affects about 1 in 25,000 people
Only heterozygotes
have the disorder. Homozygotes for the dominant cause
death in the embryo
Given that 99.99% of the
population have the recessive alleles it shows that a dominant allele is not
necessarily more plentiful in a population
Dominant Disorders
Lethal dominant alleles
are a lot less common than lethal recessives
Afflicted individuals
often die before they reproduce
More common lethal
recessive mutations are perpetuated across generations by the reproduction of
recessive carriers
Lethal dominants that do
not cause death to late on in development can perpetuate through reproduction
Huntingdons Disease, a progressive
degeneration of the nervous system. Death follows 10-20 years after onset of
symptoms
Figure 14.16 Large families
provide excellent case studies of human genetics
Fetal Testing
Many genetic disorders can be detected before birth
Methods used to gain samples for testing are:
Amniocentesis
Chorionic villus sampling
Fetoscopy
Ultrasound imaging
Chorionic Villus Sampling involves taking a small
piece of fetal tissue from the placenta
These cells multiply
rapidly and give back karyotyping data in a matter of
hours
Compared to amniocentesis,
CVS is faster & can be performed earlier (8th-10th
week)
CVS is not suitable for
tests requiring amniotic fluid and is not as widely available
Fetal Testing cont./
Fetoscopy involves a needle-thin
tube containing a viewing scope being inserted into the uterus
The risk of complications,
such as maternal bleeding, miscarriage or premature bleeding resulting from
these techniques varies:
Fetoscopy (10%)
Amniocentesis (1%)
CVS (2%)
These tests are reserved
for pregnancy in which the possibility of a genetic disorder may exist
The End