INTERNATIONAL UNIVERSITY FOR

SCIENCE & TECHNOLOGY

GENETICS lecture course

Dr. A. Rahmo
PhD. Biochemistry and Molecular biology USC

GENETICS COURSE LECTURES

1- INTRODUCTION
2- MONOGENIC INHERITANCE (ONE GENE)
3- MONOGENIC INHERITANCE (TWO GENES)
4- PEDIGREE ANALYSIS
5- BEYOND CLASSICAL (MENDELIAN) GENETICS
6- EXAM
7-POLYGENIC INHERITANCE
8- CYTOGENETICS
9- MOLECULAR GENETICS OF PROCARYOTES
10- MOLECULAR GENETICS OF EUCARYOTES
11- ONCOGENETICS
12- EXAM
13- TESTING & TREATMENT OF GENETIC DISEASES
14- POPULATION GENETICS
15- REVIEW

PEDIGREE ANALYSIS
Classical (Mendelian) Genetics

Pedigrees
symbolic representations of family
relationships and inheritance of a trait

Normal female

Normal male

Pedigrees
symbolic representations of family
relationships and inheritance of a trait

Single bar indicates mating

Normal parents and normal offspring

Single parent means partner is not significant for the analysis

Double bar indicates consanguineous mating

Fraternal twins (not identical)

Pedigrees
symbolic representations of family
relationships and inheritance of a trait

Identical twins

Number of children

Affected

Heterozygote

Female X-linked carrier

Dead

Aborted or stillborn

Effect of consanguinity

The Royal Egyptian family

A Pedigree with Consanguinity

Effect of consanguinity
DD

DD

Dd

Dd

DD

Dd

Dd

DD

Dd

DD

Dd

DD

dd

Consanguinity increases the risk of sharing a common ancestral mutation

Congenital Insensitivity to Pain

(congenital analgesia): is one or more

rare conditions where a person cannot
feel (and has never felt) physical pain

Sclerosteosis

A rare genetic disorder

characterized by syndactyly
(condition where two or more
digits are fused together) and
thickening and overgrowth of
bone. interferance with a
process which plays a key role
in the regulation of bone
formation.

autosomal recessive

Autosomal Traits
Albinism

Autosomal Recessive Inheritance

Brachydactyly

"shortness of the fingers and

toes" (digits)
Autosomal Dominant Inheritance

Achondroplasia

is a bone-growth disorder
responsible for 70% of dwarfism
cases, the limbs are
disproportionally short compared to
the trunk (abdominal area), with
the head larger than normal and
characteristic facial features.

Autosomal Dominant

Chands Syndrome

CHAND is an acronym for Curly HairAnkyloblepharon-Nail Dysplasia

syndrome. This combination of
anomalies belongs to the group of
ectodermal dysplasias and has been
described in less than five patients.

Autosomal recessive

Tay-Sachs Disease

known as infantile TaySachs

disease, it causes a relentless
deterioration of mental and physical
abilities that commences around six
months of age and usually results in
death by the age of four.

Autosomal Recessive;
Lethal before reproduction

Freckles

Freckles are clusters of

concentrated melanin
which are most often
visible on
people with a fair
complexion.

Autosomal Dominant

X-linked Recessive Traits

Always expressed in hemizygous males

Female homozygotes show the trait but female heterozygotes do not

Affected males: Inherited from affected or heterozygous mother

Affected females : affected fathers and affected or heterozygous
mothers

Possible genotypes
X+Y Hemizygous wild type male
XmY Hemizygous mutant male
X+X+ Homozyogus wild female
X+Xm Heterozygous female carrier
XmXm Homozygous mutant female

Ichtyosis

All types of ichthyosis have dry,

thickened, scaly or flaky skin.[1]
In many types the skin is said to
resemble the scales on a fish

X-linked Recessive Inheritance

HEMOPHILIA A

(clotting factor VIII deficiency)

Colorblindness
Colorblindness is a defect of
vision affecting the ability to
distinguish colors, occurring
mostly in males. Color
blindness is caused by a defect
in the retina or in other nerve
portions of the eye. Also known
as dichromatism, this disease
consists of the inability to
differentiate between reds and
greens.

X-linked recessive

X-linked dominant trait

What does the pattern look like?

Affected female
Affected male
Normal male
Normal female

Example with male survival

X-linked dominant, male lethal

What does the pattern look like?

Affected female

Normal male
Normal female

Example with male lethality

X-linked dominant recurrence risks

Mother
X1

X1

X1X1

X1Y

X2

X1X2

Daughters
50% normal
50% affected

X2Y

Sons
50% normal
50% affected

Congenital Generalized Hypertrichosis

describes hair growth on the body in

an amount considered abnormal.
Extensive cases of hypertrichosis have
informally been called werewolf
syndrome.

X-linked Dominant Inheritance

Incontinentia pigmenti

Linear blisters on leg

Linear erosions on soles

Linear blisters in newborn girls

Crops followed by scarring
Small teeth
Eye abnormalities
Patchy hair loss
Only girls are affected
Males are typically not affected

X-linked dominant
(male lethal condition)

Potentially confusing in
X-linked pedigree analysis

Male lethal X-linked conditions

New mutations may be hard to recognize as X-linked
Sex-limited conditions may look X-linked
With carrier mother and affected father can see male
to male inheritance

Y-linked Traits

Genes on the Y chromosome

Very rare
Transmitted male to male
No affected females
Currently, identified Y-linked traits
involve infertility and are not
transmitted
Example: Y chromosome infertility

Codominant Alleles

Punnett squares

Offspring from Parents with

Blood Type A and Blood Type B

ABO blood typing:

co-dominant alleles

A/-

-/-

B/-

A/-

AB

AB

A/-

B/-

BB

B/-

BB

BB

EXERCISES
What type of inheritance is present in this Pedigree?

Inconclusive

EXERCISES
Genetic Predictions
Ellens brother Michael has sickle cell anemia, an
autosomal recessive disease.
- What is the probability that Ellens child has a
sickle cell anemia allele?
Ellen and Michaels parents must be
heterozygous

S
Probability Ellen is a carrier = 2/3
Probability child inherits sickle cell allele =
Probability child carries sickle cell allele from Ellen
= 2/3 x 1/2 = 1/3

SS

Ss

Ss

ss

Ellen is not affected and

cannot be ss

EXERCISES

Question #1

Write the genotypes in every possible place.

If individuals 1 and 2 marry, what is the probability that
their first child will be sick?

EXERCISES

Question #2
PKU is a human hereditary disease resulting from inability of the body
to process the chemical phenylalanine (contained in protein that we
eat).
It is caused by a recessive allele with simple Mendelian inheritance.
Some couple wants to have children. The man has a sister with PKU
and the woman has a brother with PKU. There are no other known
cases in their families.
What is the probability that their first child will have PKU ?

EXERCISES
Question #2-Solution Highlights

P/p

P/p

P/p

P/p

p/p

P/-

P/-

p/p

P the normal allele

p the mutant allele
Answer: 1/9

EXERCISES

Question #3
The disease is rare.

a. What is the most likely mode of inheritance ?

b. What would be the outcomes of the cousin marriages
1 x 9, 1 x 4, 2 x 3, and 2 x 8 ?

10

EXERCISES
Question #3-Solution Highlights
a.

Observations:

b.

After the disease is introduced into the family in generation #2, it

appears in every generation  dominant!
Fathers do not transmit the phenotype to their sons 
X-linked!

The outcomes:

1 x 9: 1 must be A/a
9 must be A/a
1 x 4: 1 must be A/a
4 must be a/a
2 x 3: 2 must be a/a
3 must be A/a
2 x 8: 2 must be a/a
8 must be a/a

Same
All normal

EXERCISES
What is the probability that a clinically unaffected sibling of a child
with an autosomal recessive disease is a carrier for that disorder ?

EXERCISES
What is the probability that the consultand III-3 is a
carrier of Duchenne muscular dystrophy ?

1
2
3
4
5

1/2
1/4
1/8
1/9
1/18

EXERCISES

EXERCISES

EXERCISES

EXERCISES

EXERCISES
Solutions to the exercises

REVIEW OF PROBABILITY RULES

Definition of Probability
The probability of an event equals the number of times it
happens divided by the number of opportunities.
These numbers can be determined by experiment or by
knowledge of the system.
For instance, rolling a die (singular of dice). The chance of
rolling a 2 is 1/6, because there is a 2 on one face and a total of
6 faces. So, assuming the die is balanced, a 2 will come up 1
time in 6.
It is also possible to determine probability by experiment: if the
die were unbalanced (loaded = cheating), you could roll it
hundreds or thousands of times to get the actual probability of
getting a 2. For a fair die, the experimentally determined
number should be quite close to 1/6, especially with many rolls.

The AND Rule of Probability

The probability of 2 independent events both happening is the

product of their individual probabilities.
Called the AND rule because this event happens AND that event
happens.
For example, what is the probability of rolling a 2 on one die and a 2
on a second die? For each event, the probability is 1/6, so the
probability of both happening is 1/6 x 1/6 = 1/36.
Note that the events have to be independent: they cant affect each
others probability of occurring. An example of non-independence:
you have a hat with a red ball and a green ball in it. The probability
of drawing out the red ball is 1/2, same as the chance of drawing a
green ball. However, once you draw the red ball out, the chance of
getting another red ball is 0 and the chance of a green ball is 1.

The OR Rule of Probability

The probability that either one of 2 different events will
occur is the sum of their separate probabilities.
For example, the chance of rolling either a 2 or a 3 on a die is
1/6 + 1/6 = 1/3.

The NOT Rule of Probability

The chance of an event not happening is 1 minus the chance of it
happening.
For example, the chance of not getting a 2 on a die is 1 - 1/6 =
5/6.
This rule can be very useful. Sometimes complicated problems
are greatly simplified by examining them backwards.

Combining the Rules

More complicated situations involve combining the AND and OR
rules.
It is very important to keep track of the individuals involved and
not allow them to be confused. This is the source of most
peoples problems with probability.
What is the chance of rolling 2 dice and getting a 2 and a 5?
The trick is, there are 2 ways to accomplish this: a 2 on die A
and a 5 on die B, or a 5 on die A and a 2 on die B. Each
possibility has a 1/36 chance of occurring, and you want either
one or the other of the 2 events, so the final probabilty is 1/36 +
1/36 = 2/36 = 1/18.