Pedigree Analysis and

Genetic Counseling
 Learning objectives:
✔ Describe genetic counseling
✔ Discuss the importance and process of genetic counseling
✔ Differentiate genetic testing types
✔ Describe pedigree
✔ Explain the importance of pedigree
✔ Interpret pedigree chart
Topics
• Genetic Counselor and his Works
• Genetic Testing
- Pre-natal Test , Newborn Screening , Children Test
- Adult Test
• Pedigree Analysis
 Genetic
Counseling
Genetic Counselors
• In 1947, “Genetic counseling” was coined by Sheldon Reed, a geneticist who
advises physician on how to explain heredity to patients with single-gene diseases
• In 1971, the first batch of trained genetic counselors were trained; nowadays,
should have a Master’s degree
• help patients and their families:
1. understand the inheritance pattern of a specific medical condition
2. interpret genetic testing results and
3. evaluate risk
• lead the patient to take genetic testing if necessary
• have medical, scientific and communication skills because genetic counseling
addresses medical, psychological, sociological and ethical issues
• work directly with patients and part of a health care team that work in a medical
center
Reasons for patient to see Genetic counselor:
1. Family history of cancer
2. Family history of multifactorial disease
3. Family history of abnormal chromosomes
4. Elevated risk of single-gene disease
Genetic counseling involves the following:
1. Family history assessment
2. Pedigree construction and identifying family member/s who is/are
at risk
3. Genetic Testing (includes Karyotyping) and discussion of results and
treatments
Genetic counseling
Family history
assessment

Genetic Pedigree
Testing construction
Genetic Testing Techniques
Genetic Testing Techniques
Genetic Testing Technique
• Genetic analysis
method to
determine disease
family history
 Pedigree Analysis
• Genetic counselor deduce dominance and distinguish autosomal from
X-linked inheritance
• He traces the history of some variant phenotype back through the
history of the family and draws up a family tree (pedigree) using the
standard symbols
• The clues in the pedigree have to be interpreted differently
depending on whether one of the contrasting phenotypes is a rare
disorder or whether both phenotypes of a pair are common morphs
of a polymorphism

https://www.ncbi.nlm.nih.gov/books/NBK21257/
Pedigree Chart

-family tree,” drawn with standard genetic

symbols, showing inheritance patterns for
specific phenotypic characters
https://www.ncbi.nlm.nih.gov/books/NBK21257/
 Analyzing pedigrees can reveal
(1) whether a trait is dominant or recessive,
(2) the type of chromosome, autosomal or sex, a trait is linked to,
(3) genotypes of family members, and
(4) probabilities of phenotypes in future generations. For families
with a history of autosomal or sex-linked diseases, this
information can be crucial to family planning.
Pedigree Chart
▪Squares represent males and
circles represent females.
▪Shaded squares or circles
signify the presence of a trait
of interest.
▪Rows are generations,
labeled with Roman
numerals.
▪The oldest generation
comprises the top row, with
each subsequent generation
on separate rows.

Symbols used in human pedigree analysis.(After W. F. Bodmer and L. L. Cavalli-Sforza,Genetics,

https://www.ncbi.nlm.nih.gov/books/NBK21257/ Evolution, and Man.Copyright © 1976 by W. H. Freeman and Company.)
Pedigree Chart
▪ Within each generation, or row, family
members may be labeled numerically
from left to right and referred to by
their generation and position.
▪ horizontal line connecting two parents
is called a marriage line, although
marriage is not necessarily involved.
▪ A vertical line of descent extending
downward from a marriage line
connects to a horizontal sibling line.
Individuals connected to the line of
descent via the sibling line are
offspring.
▪ Individuals that are not directly
connected to the sibling line entered
the family via marriage lines, and are
not biological offspring of the
preceding generation.

Symbols used in human pedigree analysis.(After W. F. Bodmer and L. L. Cavalli-Sforza,Genetics,

https://www.ncbi.nlm.nih.gov/books/NBK21257/ Evolution, and Man.Copyright © 1976 by W. H. Freeman and Company.)
 Modes of inheritance and their properties
Inheritance pattern Description Examples
Autosomal Dominant One mutated allele causes the disease Each Marfan syndrome; Achondroplasia; Huntington
affected person usually has one affected parent disease; Myotonic dystrophy
Appears in every generation of an affected family
(Vertical)

Autosomal Recessive Two mutated alleles needed to cause the disease Beta thalassemia; Cystic fibrosis; Homocystinuria
Parents are usually unaffected heterozygotes Not
typically seen in every generation (Horizontal).

X-linked Dominant Females are more frequently affected than males Rett syndrome; Hypophosphatemia
no male-to-male transmission

X-linked Recessive Males are more frequently affected than females Hemophilia; Duchenne Muscular Dystrophy
Both parents of an affected daughter must be
carriers Fathers cannot pass X-linked traits to their
sons

Mitochondrial Only females can pass on mitochondrial conditions LHON: Leber's hereditary optic neuropathy
to their children (maternal inheritance) Both males
and females can be affected Can appear in every
generation of a family
 Algorithm

• Does offspring with disease have a parent with disease? (Y/N)

• if YES
• dominant (does not skip generations)
• is there male-to-male transmission of disease? (Y/N)
• if YES
• autosomal dominant
• if NO
• do daughters of affected male have disease? (Y/N)
• if YES
• X-linked dominant
• if NO
• mitochondrial
• if NO
• recessive (can skip generations)
• predominantly males with disease? (Y/N)
• if YES
• X-linked recessive
• if NO
• autosomal recessive
What is the pattern of inheritance?
What is the inheritance
pattern? How do you know?
What is the inheritance pattern?
How many children did I-1 and I-2 have?
Pedigree Analysis in Real Life

Keep in mind that pedigrees don’t always give

the pattern of inheritance. Many factors (like the
environment or multiple genes) might be
involved!
 Pedigree Shows Trait and Disease Inheritance
Autosomal Recessive Trait
• Traits caused by genes on autosomes and requiring two allele
copies to influence a phenotype are autosomal recessive.
• Several disorders are autosomal recessive, including cystic
fibrosis, Tay-Sachs disease, and maple syrup urine disease.
• Most people with these diseases have heterozygous parents
who do not have the condition but carry a causal allele.

https://www.ncbi.nlm.nih.gov/books/NBK21257/
 Pedigree Shows Trait and Disease Inheritance
Autosomal Recessive Trait
• Most people with these diseases have heterozygous parents
who do not have the condition but carry a causal allele.
• These carriers can unknowingly impart the disease to their
children, which partially explains why autosomal recessive
diseases are more common than their dominant counterparts.
• Comparing generations on a pedigree can reveal whether an
autosomal trait is dominant or recessive. Neither parent has the
trait, but one child inherits it. Thus, it must be recessive

https://www.ncbi.nlm.nih.gov/books/NBK21257/
Phenylketonuria (PKU)
• A human metabolic
disease caused by a
mutation in a gene
encoding a
phenylalanine-proces
sing enzyme, which
leads to mental
retardation if not
treated; inherited as
an autosomal
recessive phenotype.
 Pedigree Shows Trait and Disease Inheritance
Autosomal Dominant Trait
• These are requiring only one copy of the determining allele to
influence phenotype
• Freckles and polydactylism (extra fingers or toes) are examples
• Autosomal dominant diseases, such as Huntington’s disease,
afflict ~50% of offspring with one affected parent.
• Many of these diseases do not cause symptoms until later in
life and or after reproductive age.
• Children can inherit these diseases from unknowingly affected
parents, highlighting the importance of analyzing family history.

https://www.ncbi.nlm.nih.gov/books/NBK21257/
Huntington's disease
• an autosomal dominant genetic disorder that affects the central
nervous system of human beings.
• This disease typically shows up when a person reaches their mid
30's or 40's, with no earlier signs or symptoms.
• The nerve cells of an affected individual quickly degenerate in certain
parts of the brain, which leads to symptoms that include dementia,
loss of memory, and severely decreased mental capacity, muscle
rigidity, and loss of bodily function and muscle coordination.
• Huntington's usually shortens an affected persons lifespan, with the
average person dying 15-20 years after onset of the disease, making
the life expectancy around 50-60 years of age.
Pedigree with Huntington’s Disease
X-linked recessive pedigree
• Trait is rare in pedigree.
• Trait skips generations.
• Affected fathers DO
NOT pass to their sons.
• Males are more often
affected than females .
X-linked recessive
• Genders affected
• males must receive defective gene from carrier mother
• carrier mother's sons have 50% of having disease

• affected males give copy to all of their daughters

• Generations affected
• skips generations
• male-to-male transmission not allowed

• diseases passes through carrier daughters

• Pathology
• defects in enzymatic genes
• similar to AR diseases

• Presentation timing
• usually after puberty

• Other notes
• only one defective copy necessary for disease in males
• because males are hemizygous for X chromosome

• two defective copies necessary for disease in females

• can be affected with just one defective copy if normal X chromosome is inactivated to Barr body
Hemophilia in European royalty
X-linked recessive traits
•Red-green color blindness
•Hemophilia
•X-linked ichthyosis
X-linked dominant pedigrees

• Trait is common in pedigree.

• Affected fathers pass to ALL of their daughters, but not
their sons
• Does not skip generations
X-linked dominant
• Genders affected
• male and female at equal frequency
• Generations affected
• does not skip generations
• only possibility is reduced penetrance
• females of affected fathers are always affected
• male-to-male transmission not seen
• male or females of affected mothers can be affected
• Pathology
• defects in structural genes
• Presentation timing
• usually after puberty
X-linked dominant diseases
• X-linked dominant diseases are extremely unusual
• Often, they are lethal (before birth) in males and
only seen in females
ex. incontinentia pigmenti (skin lesions)
ex. X-linked rickets (bones soften/deform)
Y-linked inheritance
• Inheritance of genes on the Y chromosome
• Since only males normally have a Y chromosome, Y-linked genes can
only be transmitted from father to son
• Y-linked inheritance is also called holandric inheritance
Y-linked inheritance
A number of genes were are known to be Y-linked including:

• ASMTY (which stands for acetylserotonin methyltransferase),

• TSPY (testis-specific protein),

• IL3RAY (interleukin-3 receptor),

• SRY (sex-determining region),

• TDF (testis determining factor),

• ZFY (zinc finger protein), PRKY (protein kinase, Y-linked),

• AMGL (amelogenin),

• CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha subunit on the Y chromosome),

• ANT3Y (adenine nucleotide translocator-3 on the Y),

• AZF2 (azoospermia factor 2),

• BPY2 (basic protein on the Y chromosome),

• AZF1 (azoospermia factor 1),

• DAZ (deleted in azoospermia),

• RBM1 (RNA binding motif protein, Y chromosome, family 1, member A1),

• RBM2 (RNA binding motif protein 2) and

Mitochondrial
• Genders affected
• male and females at equal frequency
• Generations affected
• does not skip generations
• only transmitted from affected female
• gives to all offspring
• due to the fact that the sperm do not contribute mitochondria to the zygote
• Pathology
• defects in electron transport/oxidative phosphorylation process
• presents as neuropathies/myopathies
• neurons and muscle cells require high amounts of energy and depend on mitochondria

• Presentation timing
• usually after puberty
• Other notes
• variable expression due to heteroplasmy
• a small percentage of mitochondria within a cell are affected leading to variable severity
https://www.jove.com/science-education/10775/pedigree-analysis