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
2
6
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 Tay–Sachs
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
Y
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
Ellen’s brother Michael has sickle cell anemia, an
autosomal recessive disease.
- What is the probability that Ellen’s child has a
sickle cell anemia allele?
Ellen and Michael’s parents must be
heterozygous
S
•Probability Ellen is a carrier = 2/3
•Probability child inherits sickle cell allele = ½
•Probability child carries sickle cell allele from Ellen
= 2/3 x 1/2 = 1/3
s
S
SS
Ss
s
Ss
ss
Ellen is not affected and
cannot be ss
EXERCISES
1
Question #1
2
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 ?
٣٤
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.
1
2
3
4
5
6
7
8
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 ?
9
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
٣٧
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 can’t affect each
other’s 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
people’s 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.