Transcript Sex linked inheritance, sex linkage in Drosophila and man, XO, XY

Pedigree Analysis
Lecture 8
Dr. Attya Bhatti
Pedigree

A pictorial
representation
of
a family
history, essentially a family tree that
outlines the inheritance of one or more
characteristics.
Introduction:




A “family tree,” drawn with standard genetic symbols, showing
inheritance patterns for specific phenotypic characters is called
pedigree.
Analysis of inheritance pattern of phenotypic characters in a
pedigree is called pedigree analysis.
Propositus/Proband: A member of a family who first comes to the
attention of a geneticist.
The investigator then traces the history of the phenotype in the
propositus back through the history of the family and draws a family
tree, or pedigree.
Goals of Pedigree Analysis

1.
Determine the mode of inheritance:
recessive,
partial
dominance,
sex-linked,
dominant,
autosomal,
mitochondrial, maternal effect.

2. Determine the probability of an affected offspring for
a given cross.
Basic Symbols
Generations labelled roman numerals I, II, ...
Individuals labelled arabic numerals 1, 2, ...
Pedigree Analysis

Males in a pedigree are represented by squares, females by circles. A
horizontal line drawn between two symbols representing a man and a
woman indicates a mating; children are connected to their parents by
vertical lines extending below the parents.
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Persons who exhibit the trait of interest are represented by filled
circles and squares.
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Unaffected persons are represented by open circles and squares.

Each generation in a pedigree is identified by a Roman numeral; within
each generation, family members are assigned Arabic numerals, and
children in each family are listed in birth order from left to right.
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Deceased family members are indicated by a slash through the circle
or square.
Autosomal recessive disorders
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The affected phenotype of an autosomal
recessive disorder is determined by a recessive
allele, and the corresponding unaffected
phenotype is determined by a dominant allele.
For example, the human disease phenylketonuria
is inherited in a simple Mendelian manner as a
recessive phenotype.
Autosomal recessive disorders

The two key points are that
(1)
generally the disease appears in the progeny of
unaffected parents
and
(2)
the affected progeny include both males and
females. When we know that both male and
female progeny are affected, we can assume
that we are dealing with simple Mendelian
inheritance, not sex-linked inheritance.
Autosomal recessive disorders
Fig: Pedigree of a rare recessive phenotype determined by a recessive allele.
Autosomal dominant disorders
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Here the normal allele is recessive, and the
abnormal allele is dominant.
A good example of a rare dominant phenotype
with
Mendelian
inheritance
is
pseudoachondroplasia, a type of dwarfism.
Autosomal dominant disorders

1.
Key points are,
The main clues for identifying a dominant
disorder with Mendelian inheritance are that
the phenotype tends to appear in every
generation of the pedigree
and
2.
That affected fathers and mothers transmit
the phenotype to both sons and daughters.
Autosomal dominant disorders
Fig: Pedigree of a dominant phenotype determined by a
dominant allele.
X-linked recessive disorders

Phenotypes with X-linked recessive inheritance
typically show the following patterns in pedigrees:
1.Many more males than females show the phenotype
under study. This is because a female showing the
phenotype can result only from a mating in which
both the mother and the father bear the allele
(for example, X A X a ×X a Y), whereas a male with
the phenotype can be produced when only the
mother carries the allele. If the recessive allele is
very rare, almost all persons showing the
phenotype are male.
X-linked recessive disorders
2. None of the offspring of an affected male are
affected, but all his daughters are “carriers,”
bearing the recessive allele masked in the
heterozygous condition. Half of the sons of these
carrier daughters are affected.
3. None of the sons of an affected male show the
phenotype under study, nor will they pass the
condition to their offspring. The reason behind
this lack of male-to-male transmission is that a
son obtains his Y chromosome from his father, so
he cannot normally inherit the father’s X
chromosome too.
X-linked recessive disorders
Fig: Pedigree showing that X-linked recessive alleles
expressed in males are then carried unexpressed by
their daughters in the next generation, to be expressed
again in their sons. Note that III-3 and III-4 cannot be
distinguished phenotypically.
X-linked dominant disorders.

These
disorders
characteristics:
have
the
following
1.Affected males pass the condition to all their
daughters but to none of their sons.
2.Affected heterozygous females married to
unaffected males pass the condition to half their
sons and daughters.

One example is hypophosphatemia, a type of
vitamin D-resistant rickets.
X-linked dominant disorders.
Fig: Pedigree showing that all the daughters of a
male expressing an X-linked dominant phenotype
will show the phenotype.
X-linked dominant disorders.
Fig: Pedigree showing that females affected by an
X-linked
dominant
condition
are
usually
heterozygous and pass the condition to half their
sons and daughters