Pedigree Analysis

Learning Guide 3.1

Pedigree chart
  a genetic representation of a family tree
showing the inheritance of a particular trait
over several generations
 displays the relationships between family
What is a members and indicates which individuals
pedigree express or silently carry the trait in question
chart?  useful when trying to know the nature of a
newly discovered disease, or when an
individual with a family history of a disease
wants to know the chance of passing the
disease on to their children
  squares to represent males
 circles to represent females
 matings are indicated as a line
joining a male and a female
 descendants are listed below
the (abovementioned) line

Standardized
set of symbols
  affected individuals are shaded
 unaffected are unshaded
 carriers (typically, female
heterozygotes) are half shaded

Standardized
set of symbols
  consider the five (5) major
inheritance patterns namely:
 1. autosomal dominant (AD)
Inferring the  2. autosomal recessive (AR)
Mode of  3. X-linked dominant (XD)
Inheritance  4. X-linked recessive (XR)
 5. Y-linked (Y)
  Huntington’s Disease
 progressive brain
disorder caused by a
single defective gene
on chromosome 4
 nerve cells of an
1. Autosomal affected individual
quickly degenerate
Dominant which leads to
symptoms that include
dementia, memory
loss, decreased mental
capacity, and muscle
rigidity
 defect is "dominant”
 1. Only one copy of a disease allele is needed
for an individual to express the phenotype or
symptoms of the disease (assuming complete
penetrance).
 2. The disease or the trait tends to appear in
every generation of the pedigree and that
affected fathers and mothers transmit the
phenotype to both sons and daughters. It
does not skip a generation (unless there is
incomplete penetrance).
 3. If one parent is heterozygous for the
disease and therefore is affected, each child
has 50% chance of inheriting the disease. It is
also likely for an affected individual to have a
family without any affected children.
 4. All affected individuals will have at
least one parent who is affected (unless
a new mutation has occurred).
 5. The proportion of affected males
should be equal to the proportion of
affected females across a population.
There is no alternation of sexes - we
see father to son, father to daughter,
mother to son, and mother to
daughter.
Autosomal
Recessive
 1.Two copies of a disease allele are required for an
individual to be susceptible to expressing the phenotype.
 2. Two unaffected parents can produce affected offspring,
that is, if they are heterozygous for the trait or disease.
 3. With each pregnancy of carrier parents, the following
are the probabilities:
 a. There is a one in four (25%) chance the offspring will get two
copies of the disease allele and will therefore have the
phenotype.
 b. There is a one in two (50%) chance the offspring will get one
copy of the disease allele and will be a carrier.
 c. There is a one in four (25%) chance the offspring will not get a
copy of the disease allele and will not express the phenotype or
be a carrier.
 4. The proportion of affected males should be equal to the
proportion of affected females in a given population.
  1. Study the pedigree shown below. How is the pattern of inheritance described?
A B

Sample
problems

ANSWER: A is autosomal recessive, B is autosomal dominant

  2. Brown eyes are a dominant eye-color and blue eyes are
recessive. A brown-eyed man whose father had blue eyes, and
whose mother had brown eyes, marries a blue-eyed woman
whose parents are also brown-eyed. They have a son who is blue-
eyed and a daughter with brown eyes. Draw a pedigree showing
all four grandparents, the two parents, and the son. Indicate each
individual’s possible genotypes.
Sample
problems
  only one copy of a disease
allele on the X chromosome
is needed for an individual
to be susceptible to an X-
linked dominant disease
 hypophosphatemic rickets,
X-linked oral-facial-digital syndrome
type I, and Fragile X
Dominant syndrome
  1. Even though males may be severely affected
(because they only have one copy of genes
found on the X chromosome), both males and
X-linked females can be affected.
Dominant  2. When a female is affected, each pregnancy
will have a 50% probability for the offspring to
inherit the disease allele.
 3. When a male is affected, none of his sons will
be affected but all his daughters will be
affected.
X-linked
recessive
 1. Two copies of a disease allele on the X chromosome
are required for an individual with two X chromosomes
(a female) to be affected.
 2. Since males are hemizygous for X-linked genes (they
only have one X chromosome), any male with one copy
of an X-linked recessive disease allele is affected. They
will transmit the disease allele to their daughters but
not to their sons.
 3. For a carrier female, with each pregnancy there is a
50% probability that her daughters will be carriers and
a 50% chance that her sons will inherit the disease.
 4. If a woman is affected, all her sons will be affected,
and all her daughters will be unaffected carriers
 trait is carried on the Y
chromosome (and will only have
Y-linked the allele for the gene) and is
transmitted from father to son
only.
  1. Below is a pedigree of a rare human disease. Inheritance of the
disease by individual II-6 rules out what type of inheritance?

Sample
problems

 ANSWER: X-linked recessive

  1. Once you have identified the mode of
inheritance of a disease or trait, the genotype
of individuals in a pedigree can be made, based
on their phenotypes and where they appear in
the family tree.
Calculating  2. Given these genotypes, it is possible to
Probabilities calculate the probability of a particular
genotype being inherited in subsequent
generations.
 3. Probabilities in pedigrees are calculated
using knowledge of Mendelian inheritance and
the same basic methods used in other fields.
  Assuming that the pedigree below follows the autosomal
recessive mode of inheritance, what is the probability that
individual 14 is affected?

Example
How to solve
it?
  1. Assign possible genotypes.

How to solve
it?
  1. Assign possible genotypes.

How to solve
it?
  2. Apply the product and sum rules of probability.

How to solve
it?

 Thus, the overall probability that both individuals #12 and #13
are heterozygous, and that a particular offspring of theirs will
be homozygous for the disease alleles is 1/3 x 1/3 x 1/4 = 1/36.
  1. When analyzing a pedigree, look for the
recessive phenotype and start from there.
If only males are affected, consider sex-
linkage.
 2. Individual not showing the trait cannot
Key points to have any alleles of a dominant trait
remember! because just a single allele causes an
individual to be affected.
 3. Any individual not showing the
phenotype can be a carrier of a recessive
trait (have 1 allele) because of 2 alleles
affected individuals would appear.
  4. Though, not all pedigrees provide necessary
information to differentiate XD and AD. One
conclusive indication that a trait is inherited as
AD, and NOT XD, is that an affected father
passes the disease or trait to a son; this is not
possible with XD, because males inherit their X
chromosome from their mothers.
Key points to  5. What distinguishes AR from AD or XD is that
remember! unaffected individuals can have affected
offspring.
 6. In XR inheritance, males are affected more
often than females in a population. This is in
contrast to AR and AD, where both sexes tend to
be affected equally, and XD, in which females are
affected more often.