Pedigree Analysis

ONE
SDK
December 8, 2014

Learning Objectives
Pattern of Inheritance
Define common terms used in genetic pedigree
What are the goals of pedigree analysis
What a genetic pedigree is
How to read a genetic pedigree
How to draw a human genetic pedigree

Pattern of inheritance
Pattern of inheritance is broken in to two major parts.
Classical mendelian

Autosomal
Dominant
Recessive

Sex(X)Linked
Dominant
Recessive

Non classical----------Mitochondrail

Terms
Trait characteristic of an organism
Gene a heredity unit that codes for a trait.
Allele different gene forms(Alternative forms of genes)
Allelic genes do not necessarily carry the same information.
For example; gene of black and gene of brown color are allelic
genes, because they control one trait (ani mals color).
Nonallelic genes: Genes that control different traits such as genes that
causes hemophilia and color Blindness are X-chromosome linked genes,
they are nonallelic genes.

Homozygous: If alleles on homologous chromosomes are

similar for a single locus (BB or bb), the individual Genotype is
called homozygous

Heterozygous: If the alleles are different for a locus (Bb; one is

dominant & the other is recessive), the individual genotype is
called heterozygous
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Terms
Dominant the gene that is expressed (shown) whenever it is
present.
In this case one of the gene at one loci is defective and this will
disturb(decrease) the action of the other normal gene of the other
chromosome and brought upon abnormal phenotype.

Recessive the gene that is hidden. It is not expressed unless

a homozygous condition exists for the gene.
In this case also one of the gene at one loci is defective but
this will not disturb(decrease) the action of the other
normal gene of the other chromosome rather other gene
will function normally and give a normal phenotype

Terms
In general the
Dominant Gene : Code for Structural protein
such as receptors, defect in one allele is enough
to produce disease
Recessive Gene: Code for Functional proteins
such as Enzymes .defect in one allele is do not
produce disease

Dominance is not always complete

Incomplete dominance
If the offspring express a mixture of the traits of
parents, the genes that control these traits are
incomplete dominant alleles.

Codominance
When two all aellels for single locus are
expressed in hybrid; heterozygous individuals,
they are called co-dominant alleles.

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Linked & Non linked Genes

Linked genes: When two genes are close together on the
same chromosome, they do not assort independently
and are said to be linked. Linked genes have a
recombination frequency that is less than 50%.
Non Linked genes: When two genes located on
different chromosomes assort independently and have a
recombination frequency of 50%.
The closer together two genes are, the more likely they will be inherited
together.
Cross-over frequencies are related to distances between genes.
The higher the frequency, the further the genes are apart
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12

Gene linkage

Cross-over frequencies can be converted into map units.

Ex: A 5% cross-over frequency equals 5 map units.

gene A and gene B cross over 6.0 percent of

the time
gene B and gene C cross over
12.5 percent of the time

gene A and gene C cross over 18.5 percent of the time

Draw a linkage map based on the

following cross over percentages:
A B = 8%
B C = 10%
A C = 2%

8.0

2.0

A
8.0 + 2.0 = 10.0

Terms
Homozygous two identical (same) alleles for a
given trait (TT) also called purebred.
Heterozygous two different (opposite) alleles
for a given trait (Tt), also called hybrid.
Gamete sexual reproductive cell (sperm &
egg).
Fertilization the fusion of two gametes.
Phenotype physical trait of an organism.
Genotype the genes present in the cell.

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Remember
Homozygous = AA or aa = purebred
Heterozygous = Aa = hybrid
Dominant = capital letter (A)
Recessive = lower case letter (a)
Genotype = alleles involved (AA, aa, or Aa)
Phenotype = trait expressed (blue or green)

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Goals of Pedigree Analysis

1. Determine the mode of inheritance:
1.
2.
3.
4.
5.

Dominant
Recessive
Sex-linked
Autosomal
mitochondrial, maternal effect.

2. Determine the probability of an affected

offspring for a given cross.

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Basic Symbols

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More Symbols

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What is a Genetic Pedigree?

a diagrammight
of family
that uses
symbols
APedigree
doctor orisgeneticist
draw relationships
a family pedigree
if some
one to
represent
people
andoflines
to represent
genetic relationships
had
a family
history
a particular
disease.
A genetic
pedigree is they
an easy
waysee
tohow
trackthe
your
family
With
this information
could
disease
is traits.
inherited
calculate
probability
of also
passing
on theinformation
disease to future
and
It looks
like the
a family
tree, but
contains
about the
mode .of inheritance (dominant, recessive, etc.) of genetic
children
diseases.

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Generations
This is an example of a family tree showing 3 generations of family

I members.

The roman numerals (in red) on the left indicate the generation each person
belongs to.

II Each individual in a generation is then numbered (in green).

2

Notice it restarts at 1 every new generation.

Older siblings are on the left and younger siblings are on the right in
descending order.

III
Using this system, the individual at the bottom of this pedigree is III:1.
1

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Symbols
Each of the individuals indicated by a circle is a woman and
each of the squares represents a male family member.
Individual III:1 is a male.
Occasionally, the sex of an individual may not be known.
Common reasons for this would be, miscarriages or early death,
babies given up for adoption, a child that has not been born yet.
These individuals can be noted by using a diamond symbol ( )
instead of a square or circle.
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Marriage Lines
I
1

II
2

III
1

The lines highlighted in red

indicate individuals that have had
children together. Even though
we call them marriage lines it
does not matter if they are
married, were married, or were
never married.
It is important to realize that time
has no meaning on a genetic
pedigree, therefore we do not
usually indicate if someone has
died or been divorced.

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Children Lines
I
1

II
2

III
1

The lines highlighted in red are

children lines
The marriage line that they are
connected to from above indicates
who gave them their genetic traits
rather than who raised them.
If a couple has more than one
child together then we split the
child line as the green highlighted
line shows. More siblings would
simply require a longer line with
more lines coming down from it.
Thus II:2 and II:3 are children of I:1
and I:2, but II:1 married into the
family and has different parents. We
also know that II:2 is older than his
sister (read left to right). However,
we dont know anything about the
relative age of II:1 even though she
is on the left since she married into
the family.
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Remarriages Half Siblings

I
1

II
1

This is an example of how to

show a parent who has had
children with more than one
person. It does NOT mean that
they are married to more than
one person at the same time.
Remember, time has no meaning
in a pedigree.
In this example, II:1 and II:2 are
half brother and sister. They
share the same mother, but
different fathers.
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Adoptions
I
1

II
1

The red line (dashed) children lines to denote a

child that is not related biologically (adopted).
In this example, the couple adopted a son.
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 Twins are another fairly

common occurrence. However,
there are two kinds and from a
genetic standpoint it is very
important to know the
difference.

Twins

I
1

II

In the case of identical twins, the

two siblings have the same DNA.
To show this we split the sibling
line at an angle. The red
highlighted line is an example of
this.
In the case of fraternal twins,
although born at the same time, the
siblings are no more related than
any other siblings. Thus, they are
drawn the same as any siblings.
The green highlighted lines show
this.
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Penetrance
Penetrance - the frequency of expression of an
allele when it is present in the genotype of the
organism.
If 9/10 of individuals carrying an allele express
the trait, the trait is said to be 90% penetrant.
Or 10% reduce penetrance.

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Variable Expressivity
Expressivity is the variation in allelic expression
when the allele is penetrant.
Not all phenotypes that are expressed are manifested
to the same degree.
For polydactyly, an extra digit may occur on one or
more appendages, and the digit can be full size or just
a stub.
Therefore, when the P allele is present it expresses
variable expressivity.
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Pleomorphisim
Gnees acuses disese in more than one sysytem.
Such as Marfan Syndrome It involve
Occular abnormality
CVS problems and
Skeletal abnormalities.

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INCOMPLETE PENETRANCE
Incomplete penetrance should never be confused with variable expressivity.
In diseases with variable expressivity the patient always expresses some of
the symptoms of the disease and varies from very mildly affected to very
severely affected.
In autosomal dominant diseases with incomplete penetrance, the person
either expresses the disease phenotype or he/she doesn't.
Incomplete penetrance and variable expressivity are phenomena associated
only with dominant inheritance, never with recessive inheritance.

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The pedigree illustrates incomplete penetrance in a

known autosomal dominant disease.

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Evidence For Autosomal Dominant Inheritance:

The disease is passed from the father (II-3) to the son (III-5), this never
happens
with
X-linked
traits.

The disease occurs in three consecutive generations, this never happens

with
recessive
traits.

Males and females are affected, with roughly the same probability.
However, II-1 does not express the disease.
He must have inherited the mutant allele because he passed it on to two
children, III-1 and III-3.
II-1 is a classical example of incomplete penetrance, he has the allele for
the disease but he does not express it.

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The Punnet Square

Simple method of depicting the possible genotypes one could
get from various matings.
It is used in predicting the genotypic ratios in the offspring.
Suppose a father is heterozygous for an autosomal dominant
gene Dd.
D = the mutant dominant allele &
d = the recessive normal allele.

Suppose his wife is homozygous normal, having both d alleles

dd.
The Punnett Square will be as follows

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1. The Punnet Square

1. This disease is inherited as a autosomal dominant disease
In Ahmad family Disease (A) is inherited as a
1. Autosomal dominant means that any person with a dominant
autosomal
allele will dominant
be affected. disease.
2.
male marries
a homozygous male
recessivemarries
female. a
AInheterozygous
this family,
a heterozygous
1. Heterozygousrecessive
male Aa (heterozygous
homozygous
female. means one of each
allele)
Draw a Punnett square of the possible
2. Homozygous recessive female aa (homozygous means two of
offspring.
the same allele, here two of recessive alleles)
3. Draw
a Punnett
the possiblethey
offspring
What
issquare
the of chance
will have an
1. Set up the Punnett square with the genotypes of the above two parents.
unaffected
child?
2. What is the chance they will have an unaffected child?

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Father

Aa

aa

Aa

aa

Mother

Aa are affected because they have a dominant gene

So 2 of 4 (2/4 = ), there is a 50% chance that any
child would have the disease and 50% will be normal.

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2. The Punnet Square

This disease is Explanation
inherited as a autosomal
This
diseasedisease.
is inherited as a autosomal recessive disease
recessive
Autosomal recessive means that any person with a two
A
heterozygous male marries a heterozygous
recessive allele will be affected.
female.
A heterozygous male marries a heterozygous recessive
female.
Draw a Punnett square of the possible
offspring.
What
Heterozygous
maleis the chance
Aa they will have
(heterozygous
means one
of each allele)
an
unaffected
child?
Heterozygous recessive female
Aa
Draw a Punnett square of the possible offspring
What is the chance they will have an unaffected child?
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Father

Mother
A

AA

Aa

Aa

aa

What is the chance they will have an unaffected child?

aa are affected because they have two recessive gene
So 1 of 4 (1/4) AA Completely normal
So 1 of 4 (1/4) aa homozygous Completely abnormal
So 2 of 4 (1/4) Aa heterozygous carrier
There is a 25% chance that any child would have the disease.
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Steps in Pedigree Analysis

1. Analyze whether the pedigree belongs to a
dominant or recessive group.
1. Dominant
a) Affected person must have affected parents
b) Every generation will be affected

2. Recessive
a) Parents will be not affected
b) There will be skip generations

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Steps in Pedigree Analysis

1. Autosomal . Both boys and girls will be involved.

Dominant

Disease must be in multiple generation.

Disease person must have an affected parents.
Male & female are equally affected

Recessive

Disease have skip generation.

Disease person must not have an affected parents.
Because autosomes are involved , Male & female are equally affected

2. X-linked

Dominant

Affected male will transmit the character to all daughters but not to sons
Affected female will transmit the character to Half sons and Half daughters.

Recessive

No male to male transfer

Affected male will be more than female
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41

1. Autosomal Dominant Inheritance

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Autosomal Dominant
Appears in both sexes with equal frequency
Both sexes transmit the trait to their offspring
Does not skip generations
Affected offspring must have an affected parent
unless they posses a new mutation
When one parent is affected (het.) and the other
parent is unaffected, approx. 1/2 of the offspring will
be affected
Unaffected parents do not transmit the trait
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Autosomal Dominant Traits

A
dominant
condition
is
transmitted in unbroken descent
from each generation to the next.
A typical pedigree might look like
this:

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45

46

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Autosomal Dominant Traits

Huntington's disease
Marfan syndrome
Neurofibromatosis
Retinoblastoma
Familial hypercholestrolemia (LDL receptor defect Type IIa)
Adult polycystic kidney disease
Hereditory spherocytosis
Hypertrophic Obstructive Cardiomyopathy (HOCM)

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Autosomal Dominant Traits

Huntington disease is a progressive nerve degeneration, usually beginning about
middle age, that results in severe physical and mental disability and ultimately in
death
Every affected person has an affected parent
~1/2 the offspring of an affected individual are affected

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2. Autosomal Recessive Traits

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Autosomal Recessive
Appears in both sexes with equal frequency
Trait tend to skip generations
Affected offspring are usually born to unaffected
parents
When both parents are hetrozygout, approx. 1/4 of the
progeny will be affected
Appears more frequently among the children of
consanguine marriages.
The punnet square will be like this
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Autosomal Recessive

A recessive trait will only show

up when homozygous.
Most people are heterozygous
carriers

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Autosomal Recessive Traits

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Autosomal Recessive Traits

Abetalipoproteinemia.
Acute fatty liver of pregnancy
Alkaptonuria.
Congenital hepatic fibrosis.
Cystic Fibrosis.
Cystinosis, Cystinuria.
Dubin-Johnson syndrome.
Fanconi Anemia.

Leukocyte Adhesion Defect.

Nieman Pick Disease.
Rotor syndrome.
Situs Inversus.
Sickle cell Disease and
Trait.
Thalasemia.
Wilson's Disease.
Xeroderma pigmentosa
Friedrech's Ataxia.
Glycogen storage diseases.
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Autosomal Recessive Traits

Albinism = absence of pigment in the skin, hair, and iris of the eyes
Most affected persons have parents who are not themselves affected; the
parents are heterozygous for the recessive allele and are called carriers
Approximately 1/4 of the children of carriers are affected

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CYSTIC FIBROSIS
Cystic fibrosis (CF) is a genetic condition that affects many organs in the
body: especially the lungs, pancreas and sweat glands.
A build-up of thick, sticky mucus in these organs leads to respiratory
problems, incomplete digestion and increased salt loss from the sweat
glands.
CF most commonly affects people who are of Northern European or UK
descent, is also fairly frequent in people whose ancestry is Southern
European and Middle Eastern.
In CF the CFTR gene(salt-transport gene) that contains the information for
the production of the protein that transports salt in and out of the cells is
absent that result in thick secretions loaded with salt.
The CFTR gene is located on chromosome 7, an autosome
This thick secretions block air passages, pancreatic and intestinal ducts will
impair the function of these organs, Indigestion wt loss and increased loss of
Salts.
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Presentation of Disease

Mucous in the airways cannot be easily cleared from the lungs.

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Tay-Sachs
Tay-Sachs is a recessive lethal disease in which
there is neurological deterioration early in life.
This disease is rare in the population overall but
is found at relatively high frequency in
Ashkenazi Jews from Central Europe.

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Tay-Sachs
An apparently normal woman whose maternal uncle had
the disease is trying to determine the probability that she
and her husband(who is also normal) could have an
affected child.
Her father does not come from a high-risk population.
Her husbands sister died of the disease at an early age.
Draw the pedigree of the individuals described. Include
the genotypes where possible.
T = normal allele;
t = Tay-Sachs allele
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Tay-Sachs

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Thank You

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