Genetics I - Simple patterns

of inheritance

BIOL4002 - Cell biology and genetics

Brooker et al., Biology 5th ed.

Prof. John Runions Week 7 - Chapter 17

Genetics
Scientists now believe that some people may have genes that initiate
reactions inside their bodies that limit the severity of Ebola infection.
Gregor Johann Mendel

1822–1884
Entered monastery and became a priest
Historic studies on pea plants
Paper ignored at the time (Even by Darwin!)
Independently rediscovered years later
Gregor Johann Mendel
Garden Pea, Pisum sativum

Several advantageous properties

Many readily available characters or
traits
Normally self-fertilising
True-breeding lines exhibit the
same traits
Ease of making crosses with large
flowers
Cross-fertilisation or hybridisation
Garden Pea, Pisum
sativum
The ‘traits’ of pea plants studied by Mendel
Mendel’s experiments

Single-factor cross
Experimenter follows the
variants of only 1 trait
P generation
True-breeding parents
F1 generation
Offspring of P cross
F2 generation
F1 self-fertilises
Mendel’s experiments
Mendel’s experiments - 3 important ideas

1. Dominant and recessive traits 2. Genes and alleles

• Dominant is displayed trait • Particulate mechanism of inheritance
• Recessive trait masked by • His “unit factors” are genes
dominant trait • Every individual has 2 genes for a trait
• Gene has two variant forms or alleles
Mendel’s experiments - 3 important ideas

3. Segregation of alleles
• Approximately 3:1 ratio
• Two copies of a gene carried by a
plant segregate (separate) from
each other, so that each sperm
or egg carries only one allele
• Mendel’s Law of Segregation
• 2 copies of a gene segregate
from each other during the
transmission from parent to
offspring
Genotype and phenotype

Genotype
Genetic composition of
individual
SS or ss – homozygous
Ss – heterozygous
Phenotype
Characteristics that are the
result of gene expression
SS and Ss are tall
ss is dwarf
Predicting genotype and phenotype rations - Punnett square

Step 1. Write down the Step 3. Create an empty Punnett square.

genotypes of both parents Male gametes
Male parent: Tt
Female parent: Tt
♂ T t

♀
Step 2. Write down the T
possible gametes that each

Female gametes
parent can make
Male gametes: T or t
Female gametes: T or t
t
 Punnett square
Step 4. Fill in possible genotypes Step 5. Determine relative proportions of
genotypes and phenotypes
Male gametes

♂ T t

Genotype ratio
♀ TT:Tt:tt
T TT Tt 1:2:1
Female gametes

Phenotype ratio
Tall:Dwarf
t
tT tt
3:1
Testcross
A dwarf pea plant must be tt
A tall pea plant could be either TT or Tt
(this is the ‘unknown’ genotype,
therefore)
Cross the unknown individual to a
homozygous recessive individual
If some offspring are dwarf, unknown
individual must have been Tt
If all offspring are tall, the unknown
individual was TT
Two-factor cross

Follow inheritance of 2 different traits

Possible patterns that Mendel might have observed:
2 genes linked so that variants found together in parents are always inherited
as a unit
2 genes are independent and randomly distributed
Two-factor cross
If genes are linked If genes assort Result when Mendel did this
independently

A 9:3:3:1 phenotype ratio

This indicates that the genes for

seed colour and seed roundness
assort independently
Independent assortment

Dihybrid offspring- offspring are

hybrids with respect to both traits
Mendel’s data for F2 hybrids was
consistent only with independent
assortment
Law of Independent Assortment
Alleles of different genes assort
independently of each other during
gamete formation
Chromosome theory of
inheritance

1. Chromosomes contain the genetic

material, which is transmitted from parent
to offspring and from cell to cell. Genes are
found in (as part of) the chromosomes.
2. Chromosomes are replicated and passed
from parent to offspring. They are also
passed from cell to cell during the
multicellular development of an organism.
Each type of chromosome retains its
individuality during cell division and
gamete formation.
Chromosome theory of
inheritance (con’t)

3. The nucleus of a diploid cell contains two sets of chromosomes, which are found in
homologous pairs. One member of each pair is inherited from the mother and the
other from the father. The maternal and paternal sets of homologous chromosomes
are functionally equivalent; each set carries a full complement of genes.
4. At meiosis, one member of each chromosome pair segregates into one daughter
nucleus and its homologue segregates into the other daughter nucleus. Each of the
resulting haploid cells contains only one set of chromosomes. During the formation of
haploid cells, the members of different chromosome pairs segregate independently of
each other.
5. Gametes are haploid cells that combine to form a diploid cell during fertilisation, with
each gamete transmitting one set of chromosomes to the offspring. In most animals
and plants, one set comes from the mother and the other set comes from the father.
Chromosomes and
segregation

Mendel’s law of segregation

can be explained by the
pairing and segregation of
homologous chromosomes
during meiosis
Locus – physical location of a
gene on a chromosome
Mendelian inheritance

Inheritance pattern of genes that

segregate and assort independently
Simple Mendelian inheritance – one
trait is completely dominant over
the other
 X
Simple Mendelian inheritance

Wild-type allele
Prevalent allele in a population
Encodes a protein made in the proper amount
and functioning normally
Mutant alleles
Altered by mutation
Are rarer than wildtype in natural populations
Usually harmful and selected against but may
be beneficial and, thus, provide genetic
Not a mutant in the genetic sense
variation that evolution is based on
that we are discussing
Simple Mendelian inheritance

In simple dominance, the

recessive allele does not affect
the phenotype of the
heterozygote
A single copy of the dominant
allele is sufficient to mask the
recessive allele
Pea flowers - purple pigment, P
One P allele makes enough
functional protein to provide a
normal phenotype
Simple Mendelian inheritance

Recessive allele does not affect phenotype of heterozygote

Single copy of the dominant allele makes enough functional protein to
provide a normal phenotype, masking recessive allele
Sometimes heterozygote may even upregulate the lone functional allele to
provide high enough expression
Genes and alleles

Wait a minute!! - a gene

can exist as 2 or more
different alleles???
Genes and alleles - Meiosis (more detail during Week 10)
Chromosomes and
independent assortment

Law of independent
assortment can also be
explained by the
behavior of
chromosomes during
meiosis
Note that these two
Random alignment of sets of haploid cells
chromosome pairs during contain different allelic
meiosis I leads to the combinations of genes
independent assortment
of alleles found on
different chromosomes
Chromosomes and
independent assortment

From the previous slide,

You can end up with this
set of gametes
(Ry, Ry, rY, rY)

or...

this set of gametes

(RY, RY, ry, ry)
Human disease
Single-gene mutations cause many inherited diseases and
have pleiotropic effects
i.e. more than one trait might
be affected

Several examples of human genetic diseases in which recessive alleles fail to produce a
specific active protein
Over 7,000 human disorders caused by mutations in a single gene
Majority are recessive but some are dominant
Pleiotropy- mutation in a single gene has multiple effects
Human disease - Cystic Fibrosis (CF) example

Normal CF allele codes for protein that regulates

chloride ion balance
Mutation diminishes function of transporter
Thick mucus in lungs due to water imbalance
due to ion balance
People with CF have very salty sweat because
salt cannot be recycled back into body
Males with CF are infertile because Cl-
transporter needed for proper development of
vas deferens in embryo
A recessive trait
Human disease - expression patterns
Disease genes can be recessive or dominant, autosomal or sex-linked

Many of the alleles causing human genetic disease are recessive, like Cystic Fibrosis
But some are dominant, like Huntington disease
• Huntington disease has an autosomal dominant inheritance pattern
• Gene is on one of 22 pairs of autosomes (i.e. a chromosome that isn’t a sex
chromosome)
• Only one copy of the mutant allele is needed for a person to be affected, i.e.
the heterozygote is affected unlike in the CF recessive example
Disease genes can also be found on the sex chromosomes
 This affected individual can be either
Human disease - expression patterns homozygous or heterozygous for the
mutant gene. Which is it in this
Pedigree for a dominate trait particular case?

A family pedigree for

Huntington disease, an
autosomal dominant trait.
Individuals are either
homozygous or
heterozygous for the
disease but are affected in
either case unlike what
happened in the CF
example
Sex Chromosomes and X-linked Inheritance Patterns

Sex chromosomes are found in many (but not

all) species with two sexes
Several mechanisms for sex determination

X-Y system – males XY and females XX

X-O system – females XX and males X or XO
Z-W system – males ZZ and females ZW
Different mechanisms of sex determination

Not all chromosomal mechanisms involve sex chromosomes

Bees are haplo-diploid – male is haploid and female is diploid

Other mechanisms also exist

Sex is controlled by environment (temperature) in some reptiles and fish

Plants
Some have a single type of plant making male and female gametophytes
Others have sexually distinct plants making male or female gametophytes only
X-linked traits

In humans, the X chromosome is larger and carries more genes than

the Y chromosome
Some genes are found on the X but not on the Y and are are said to
be X- linked genes
Sex-linked genes are found on one sex chromosome but not the other

Males are hemizygous for X-linked genes

example: Hemophilia A
X-linked traits - Hemophilia A example This is a simplified table from the one that is shown in your textbook
(Pg. 361)

Male gametes have a single normal

Hemophilia A is caused by a recessive X- X or Y chromosome
linked gene. ♂︎ X Y
The disease allele encodes a defective
♀︎

Female gametes have a single normal X or an

abnormal X chromosome which carries a
version of a blood clotting protein.
XX XY

mutant hemophilia allele (Xh)

Here, the female parent was a carrier, i.e. she X
had the disease allele but it was masked Unaffected Unaffected
because it is recessive to the normal allele female male
which she also carries.
The hemophiliac male offspring has no
second X-chromosome with a normal allele
X Xh Xh Y
to mask the recessive allele. Xh
Carrier Male with
female hemophilia
Morgan’s experiments showed a correlation between a
genetic trait and the inheritance of a sex chromosome
in fruit flies (Drosophila)
Thomas H. Morgan, 1866-1945, first
geneticist to receive Nobel Prize
Found a mutant male fly with white eyes
rather than the normal red eyes
Testcross results suggested a connection
between alleles for eye colour and sex
This X-linked gene for eye colour was the
first gene to be located on a specific
chromosome
Morgan’s experiments
Here, the gene for eye colour is
designated ‘X’ where:

Xw+ - is wildtype and is a

dominant gene that causes red
pigment to form in the eyes

Xw - is a mutant that does not

produce pigment so that eyes
appear white

Y - implies that the males do not

have another copy of the gene
because they have only one X
chromosome

In principle, XwXw females can

arise by crossing a white-eyed
male with a carrier female but
this is very rare.
Morgan’s experiments - continued

Data are consistent with the

idea that the eye-color
alleles in Drosophila are
located on the X
chromosome
The lower than expected
number of white-eyed flies
can be explained by a
decreased survival rate
Variations in inheritance patterns and their molecular
basis

Simple Mendelian inheritance

Alleles are dominant or recessive
Phenotype ratios follow Mendel’s laws
More complex forms of inheritance occur:
Incomplete dominance
Codominance
Epistasis
Continuous variation
Understanding gene function at the molecular level explains these
differences in inheritance patterns
Variations in inheritance patterns and their molecular
basis

People suggest that Mendel got lucky with the traits and the species he
studied. This is true in that the traits he studied in pea plants are all controlled
by single genes (2 alleles) that have a simple (Mendelian) dominance /
recessivness relationship.
In reality, for situations in which a trait is controlled by one gene with 2 alleles,
there are different possibilities for phenotypes in the offspring. Let's use the
hypothetical example of a plant that has red (R) or white (r) flowers:
Variations in inheritance patterns and their molecular
basis

Incomplete dominance
Pink flowers of Four-o’clock plant (Mirabilis
jalapa)
50% of normal protein not enough to give red
color
Note that allele names are designated
differently than in Mendelian situation. ‘C’
stands for Colour
Homozygous Red - CRCR
Homozygous White - CWCW
Heterozygote Pink - CRCW
Variations in inheritance patterns and their molecular
basis

Codominance
3 or more allele variants in a population
Phenotype depends on which 2 alleles are inherited
ABO blood types in humans
Type AB is codominant, expressing both alleles equally
Variations in inheritance patterns and their molecular
basis

Mendelian (Simple) dominance - R is

Parents Offspring
always dominant over r. If R is present
flowers will be red, e.g. RR or Rr - red.
Only if R is absent will flowers be white, x
e.g. rr - white.
RR rr RR Rr rr
(the different notation below implies that neither
allele is dominant over the other)

Incomplete dominance - Both alleles x

contribute equally to the phenotype so
the heterozygote is a blend. CRCR - red, C RC R CWCW C RC R C RC W CWCW
CWCW - white, but CRCW - pink.
Codominance - Both alleles contribute to x
different regions of the phenotype so that
the heterozygote is 'patchy'. CRCR - red, C RC R CWCW C RC R C RC W CWCW
CWCW - white, but CRCW - red patches and
white patches.
Variations in inheritance patterns and their
molecular basis
Epistasis
At least one
Alleles of one gene mask the expression of the dominant allele
of each of ‘C’
alleles of another gene and ‘P’ is
required for
purple coloured
Often arise because 2 or more different proteins flowers

are involved in a single cellular function

2 varieties of white-flowered peas crossed

 F with all purple-flowered plants – Unexpected!
1

 F 9:7 purple- to white-flowered

2

2 genes involved in flower color

Variations in inheritance patterns and their molecular basis
Continuous variation
Discrete traits
Clearly defined phenotypic
variants
Purple or white flowers, red or
white eyes
Quantitative (continuous) traits
Majority of traits
Show continuous variation over a
range of phenotypes
Height, skin color, number of
apples on a tree In this example of a quantitative trait, there are 6 genes responsible for skin colour in
humans. The balance of allele types determines skin pigmentation which can vary based on
Polygenic- several or many genes environmental factors, e.g. the amount of sunshine you are exposed to.
contribute to the outcome
Environment also plays a role
Role of the environment on phenotype
Continuous variation
Genetically identical
plants grow to different
heights in different
temperatures.
This occurs because
many genes interact to
determine the growth
response to
temperature.
Variations in inheritance patterns and their molecular basis
Genetics and probability
Why are phenotype numbers in populations not always exactly as predicted?
Probability (P) – the chance that an event will have a particular outcome

Number of times that an event occurs

Probability (P) = = 1/2
Total number of possible outcomes

But probability isn’t certainty! If you

e.g. for a single coin toss, the chance of getting tossed the coin 100 times you would be
heads is unlikely to get 50 heads and 50 tails. It’s
the same with genetics and this is why
expected and observed phenotype
1 heads
Probability (P) = = 1/2 numbers often differ.
(1 heads + 1 tails)
Genetics and probability
Self-fertilisation of a pea plant heterozygous for the height gene (Tt)

A Punnett square predicts that 1/4 of the offspring will be dwarf

Mendel measured 1064 pea plants

We would expect that 798 would be tall and 266
dwarf based on the Punnett square
He actually found 787 tall and 277 dwarf
Exactly the sort of outcome you would expect
because of the random pairing of gametes that occurs
Genetics and probability
Sample size
Prediction accuracy depends on number of events observed – the sample size
Random sampling error – the deviation between observed and expected outcomes
Larger samples have smaller sampling errors
Humans have small families so observed data may be very different from expected
outcome