Week 2 - Mendelian Genetics

Cont.

We could use a Punnett Square

The genotypes of F1
are on the right

This Punnett Square

Shows the possible genotypes of the F2 generation

Sum Law
Sum Law of Probability:
The probability of either one or the other of
two mutually exclusive events is the sum of
their individual probabilities.
P(A or B) = P(A) + P(B)

A real example
You are playing a game with dice

You are almost done with the game.

You win a new car if you roll a 5 or a 6!
What are your chances?

Product Law of Probability

The probability of a joint occurrence of two
independent events equals the product of
their separate probabilities.
Or the probability of two or more events
occurring simultaneously is equal to the
product of their individual probabilities.

Product law of probabilities

The probability of a joint occurrence of two
independent events equals the product of
their separate probabilities.

Roll one die

Roll two dice

Chance of rolling a six is 1/6

What is the chance of rolling 2 sixes?

Chance of rolling two sixes is 1/6 X 1/6 = 1/36

A
A AA

a
Aa

albino

a Aa

aa

normal pigmentation

If two heterozygous parents (Aa) have 2 children,

what is the probability that the both children will have albinism?

Child 2

Child 1
Pigmented

Pigmented

Pigmented

Pigmented

Pigmented

Pigmented

Albino

Albino

child 1
and
child 2
are
independent events

Real-World Example

Sheep
Important for wool
Many different traits in sheep
Hairy (dominant) vs Wooly (recessive)
White (dominant) vs. Black (recessive)
Brown eyes (dom.) vs. Blue eyes (recessive)

Real World Example

Two villages each have true breeding lines
hairy white with brown eyes
HHWWBB

wooly black with blue eyes

hhwwbb
A farmer wants a wooly white brown-eyed sheep,
what are the odds shell get one?
(shell wait for the F2 generation of course)

We could use a Punnett Square

The genotypes of F1
are on the right

This Punnett Square

Shows the possible genotypes of the F2 generation

We could use
the Product Law of Probability
These are and events.
wooly and white and brown-eyed so we can use
the Product Law of Probability
hairy white with brown eyes
HHWWBB

wooly black with blue eyes

hhwwbb
A farmer wants a wooly white brown-eyed sheep, what are
the odds shell get one?

We could use
the Product Law of Probability

wooly white brown-eyed

x x

= 9/64

New Key Point

You rolled a die
You just got a 6!
What are the odds of rolling a 6
on the next roll?

Practice calculating genotypic and

phenotypic ratios
G = green; g = white
P = Powerful; p = weak
C = Creepy; c = nice
Calculate ratios for the following cross:
GgppCc X ggPPCc

Tracking human traits

Same principles apply as with peas
Look at data retrospectively
cant set up controlled crosses
before there were genetic tests, this was
the only way to look at data

Analyze family trees in pedigrees

Patterns of inheritance in
humans: pedigree charts

Figure 3-12

Refer to individuals as e.g. II-2

Pedigree for autosomal

recessive trait
Diamond is unknown gender

Figure 3-13
example: albinism

Albinism - recessive trait

Enzyme that produces melanin is defective
recessive trait: heterozygotes are not affected
still have one functioning copy of enzyme

Albinism can happen

in many different animals

Pedigree for autosomal

dominant trait

Figure 3-13

example: hypercholesterolemia

Recessive and Dominant human

traits - diseases

Normal variation in humans

caused by single genes(?)
Widows peak
S-methyl ester
detection
DD

dd

Other traits include: earwax, earlobe attachment, freckles,

folding hands
http://udel.edu/~mcdonald/mythintro.html

Pedigrees reveal patterns of

inheritance in humans

Is this likely to be a dominant or a recessive trait?

Probability + Pedigrees
Using the rules of probability that we
discussed, can you predict the probability
that a particular child will have a disease?
Product law of probability

Pedigree of a trait

III-5 and III-6 have a child together

What is the probability of that child having the trait?

Dominant or recessive?

What do we know?
II 4 and II 5 have an aa daughter (III 4) so
they must both have a Aa genotype.
III 5 can therefore either be AA (1/3
probability) or Aa (2/3 probability)
III 6 is 100% aa.
so?

2 analysis
Chi-square analysis
a statistical test commonly used to compare
observed data with data we would expect to obtain

taking real-life data and decides if it fits

your genetic theory
Chi-square analysis evaluates the
influence of chance on data

Working with real-life data

2 analysis
Chi-square analysis
Tests the goodness of fit between observed and
expected

tests the null hypothesis

Null Hypothesis
There is no difference between the observed
number of phenotypes and the expected number
of phenotypes.
Looking for the probability that the true average
is the same as the expected average.
If the probability is less than 0.05 then the
observed is statistically different than the
expected.

Chi squared test for

goodness of fit
Statistical test to check your experimental
results against expected ratios
are they significantly different?

2 =

2
(o-e)
________
e

e = expected number in a phenotypic class

o = observed number in a phenotypic class

Chi-Squared Analysis
Monohybrid cross example from Klug

2 =

2
(o-e)
________
= 0.53
e

With this number (0.53),

together with degrees of freedom (df),
go to look-up table

df = # phenotypes - 1
Here its 1

Chi-Square look-up table

Figure 3-11

Chi-Square Analysis
Monohybrid cross example from Klug

Example
You cross two P1 generations of fruit flies,
long wings and dumpy wings. You believe long
is dominant to dumpy. All F1 flies are long
winged. Your F2 generation has the following
traits:
792 long winged
208 dumpy winged
Can you support the hypothesis that this is a
simple case of Mendelian dominance?
2
(o-e)
________
2 =
e

Variations on the standard

Mendelian model
2 alleles
Complete Dominance
Genes are independent
No genotype is lethal

Nomenclature
In Drosophila, an initial letter or a combination of two-three
letters of the name of the mutant is used.
Example: body color
Ebony mutant phenotype is indicated by e.
Normal gray (wild-type) is indicated by e+.
e+/e+: gray homozygote (wild type)
e+/e: gray heterozygote (wild type)
e/e: ebony homozygote (mutant)
OR
+/+: gray homozygote (wild type)
+/e: gray heterozygote (wild type)
e/e: ebony homozygote (mutant)

Nomenclature
If no dominance exists between alleles, italic
uppercase italic letters and superscripts are used
to denote alternative alleles (R1, R2, CW, CR).

Nomenclature
Many diverse systems of genetic nomenclature are used to
identify genes in various organisms.
The symbol used should reflect the function of the gene or
even a disorder caused by the gene.
Yeast cdk represents the cyclin dependent kinase gene whose
product is involved in cell-cycle regulation.
In bacteria, leu- refers to a mutation that interrupts the
biosynthesis of the amino acid leucine, and the
wild-type gene is designated leu+.
The symbol dnaA represents a bacterial gene involved in DNA
synthesis.
In humans, capital letters are used to name genes: BRCA1, the
gene associated with breast cancer.

New Types of Dominance

Mendel saw classic complete dominance
Complete dominance
occurs when the phenotype of the heterozygote is
completely indistinguishable from that of the
dominant homozygote.
e.g. GGWW and GgWw are both yellow-round

But, other types of dominance exist

Incomplete dominance
Crosses with
Snapdragon flowers

Figure 4-1

Hypercholesterolemia: another example

of incomplete dominance
LDL receptor defect
Heterozygotes (+/-)
increased risk of vascular clogging
affected as young adults

Homozygotes (-/-)
have even more risk of vascular disease
affected as children

Co-dominance
Two alleles of a gene can produce
distinct, detectable gene products in
heterozygotes: codominance
MN blood group (different glycoproteins)
LM or LN allele

Co-dominance
Two alleles of a gene can produce
distinct, detectable gene products in
heterozygotes: codominance
In codominance, the influence of both
alleles in a heterozygote is clearly
visible.
Genotype
LM LM
LM LN
LN LN

Phenotype
M
MN
N

Multiple alleles of a gene can

exist in a population
ABO blood type
Gene for isoagglutinogen: I

3 alleles:
IA make A antigen
IB make B antigen
IO make no antigen

Multiple alleles of a gene can

exist in a population
ABO blood type: 3 alleles: IB, IA, IO
What kind of dominance is
this?

Genotype

Antigen

Phenotype

IAIA

IAIO

IBIB

IBIO

IAIB

A,B

AB

Universal recipient

I OI O

Neither

Universal donor

A) incomplete
dominance
B) complete
dominance
C) codominance

Table 4.1

Alterations of Mendelian 3:1 ratio:

Example in agouti mice
Figure 4-3

agouti

Banding pattern
in agouti hair

agouti

All agouti
Agouti breeds true - homozygous

A different mouse strain with

yellow fur color
Figure 4-3

X
yellow

Banding pattern
in yellow hair

1/2
yellow

agouti

: 1/2 agouti
Yellow is a dominant mutation?

Yellow mouse crossed with yellow

mouse gives surprising F1 ratio
Figure 4-3

X
yellow

2/3
yellow

yellow

: 1/3 agouti
What would give rise to a 2:1 ratio??

Lethal alleles represent

essential genes
Figure 4-3

Ay allele is dominant for

yellow fur
Ay allele is recessive for
lethality

Altering Mendelian ratios

Epistasis: interaction between

different genes
This can lead to modifications from
expected ratios, e.g. 9:3:3:1

Agouti mouse crossed with black

mouse is monohybrid cross
X

AA
agouti

aa
black
a

A Aa Aa

All progeny
are agouti

A Aa Aa

Aa
agouti

Epistasis: interaction between

different genes
Separate gene B, determines whether mice are albino

bb mice are albino, regardless of other genes

What happens when we do a dihybrid

cross of agouti and albino?

Epistasis: interaction between

different genes
X

AABB
agouti

aabb
albino

X
AaBb
agouti

F1
AaBb
agouti

F2

Epistasis: interaction between

different genes
X
Key
A- : agouti
aa: black
bb: albino

F1

AaBb
agouti

AaBb
agouti

F2
Ratio

Genotype

Phenotype

9/16

A-B-

agouti

3/16

A-bb

albino

3/16

aaB-

black

1/16

aabb

albino

Final phenotypic ratio

9/16 agouti
4/16 albino
3/16 black

9:4:3

Modifications to Mendelian ratios

caused by epistasis

Epistasis changes genotype - phenotype connection

Figure 4-7 in Klug

Epistasis: another example

Remember ABO blood types:
Gene I has 3 alleles: IA, IB, IO

Epistasis: another example

Remember ABO blood types:
Genotype

Antigen

Phenotype

I AI A

IAIO

I BI B

IB IO

I AI B

A,B

AB

IOIO

Neither

Confusing pedigree: woman with

O blood type
Bombay phenotype for blood type
Figure 4-2
=
=

How could this happen?

Another gene
plays a role:
Epistasis

Epistasis explains Bombay

phenotype
FUT1 gene required to make A or
B
H: wild-type version of FUT1 gene
h: mutant version of FUT1 gene
precursor

FUT1

hh

A or B antigen

O phenotype

Epistasis explains Bombay

phenotype
FUT1 gene required to make A or B
Figure 4-2

Genotypically: B
Phenotypically: O

Epistasis explains Bombay

phenotype
FUT1 gene (H) required to make A or B

Figure 4-5

Epistasis explains Bombay

phenotype
FUT1 gene (H) required to make A or B

3:6:3:4
ratio

Figure 4-5

Question: If a mother has type A blood and

her son has type O blood, what are the
possible blood types of her sons father?

A) Type O only
B) Types A or O
C) Types B or O
D) Types A, B, or O
E) Any blood type

Question: If a mother has type A blood and

her son has type O blood, what are the
possible blood types of her sons father?

Answer(s):
If not considering epistatic effects of other genes:
D. Types A, B, or O
Explanation:
The father must carry the IO allele, so he could be IOIO (type O), IAIO
(type A), or IBIO (type B).

If considering epistatic effects of FUT1 (H):

E. Any blood type
Explanation:
If both mother and father are carriers of the h allele and the son is hh,
then the father could have any I blood type, because hh is epistatic to
the effects of I (isoagglutinogen)

Epistasis & pleiotropy are

opposites in a way
Gene 1

Epistasis

Gene 2
Gene 3

Trait

Gene 4
Trait 1

Pleiotropy

Gene

Trait 2
Trait 3
Trait 4

Pleiotropy example:
Werner syndrome
Recessive allele: defect in DNA helicase
causes premature aging

Pleiotropic
Effects

- graying and hair loss as teens

- short stature
- thin extremities
- cataracts in their 20s
- a change of voice
- osteoporosis, bone deformities
- wrinkled, dry skin
- diabetes
- atherosclerosis
- ankle ulcers
- malignancies

What is two individuals share the

same trait, but its caused by
different mutations?
When would this occur and how do
you test for it?

Complementation analysis
Allows one to determine if two mutants are
defective in the same gene
Screen for mutant phenotypes
Find 2 different mutants with same phenotype
mutant a and mutant b
Are a and b defective in the same gene?

Example: screen for flies without wings

Complementation analysis
comparing wingless mutants
P
Wingless
mutant a

X
Wingless
mutant b

F1
Wild-type:
has wings

What is the result of this test?

A) fail to complement; same gene
B) complement; same gene
C) fail to complement; different genes
D) complement; different genes

Complementation tests
If mutations are in the same gene, the
mutants fail to complement
If mutations are in different genes, the
mutants complement