BIO152 Human Pedigree
Lecture 15
November 6
Outline:
Human pedigree or family tree
(Text: Freeman Ch 13.7)
Family trees instead of experimental crosses
Recognizing patterns:
Autosomal recessive
Autosomal dominant
X-linked recessive
Constructing pedigrees
Calculating probabilities
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Inheritance patterns in humans
• We can’t do test crosses, reciprocal
crosses, etc.
• Instead we must piece together
information based on family history
Reading a pedigree
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www.uic.edu/classes/bms/bms655/gfx/symbols.gif
General rules for pedigrees
1. Males are always represented by square symbols
2. Females with circular symbols.
3. A line drawn between a square and a circle represents a
mating of that male and female.
4. Two lines drawn between a square and a circle indicate
a consanguineous mating, the two individuals are
related, usually second cousins or closer relatives.
5. When possible, the square should be placed on the left
and the circle on the right of the mating line.
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Pedigree rules continued
1. Generations are connected by a vertical line extending
down from the mating line to the next generation.
1. Children of a mating are connected to a horizontal line,
called the sibship line, by short vertical lines.
2. The children of a sibship are always listed in order of
birth, the oldest being on the left.
3. Normal individuals are represented by an open square or
circle, depending upon the gender, and affected
individuals by a solid square or circle.
4. Each generation is numbered to the left of the sibship
line with Roman Numerals. Individuals in each
generation are numbered sequentially, beginning on the
left, with Arabic Numerals.
Autosomal recessive:
appears in both males and females.
both parents must carry the allele responsible. If allele is rare,
affected, individuals may not appear in every generation.
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Autosomal dominant:
both sexes with trait
usually every generation
Sample pedigrees
5
four hallmarks of autosomal
dominant inheritance
1. Except for new mutations, which are rare in nature and extremely
rare on examination pedigrees, and the complexities of incomplete
penetrance to be discussed later, every affected individual has an
affected biological parent. There is no skipping of generations.
2. Males and females have an equally likely chance of inheriting
the mutant allele and being affected. The recurrence risk of
each child of an affected parent is 1/2.
3. Normal siblings of affected individuals do not transmit the trait
to their offspring.
4. The defective product of the gene is usually a structural
protein, not an enzyme. Structural proteins are usually defective
when one of the allelic products is nonfunctional; enzymes usually
require both allelic products to be nonfunctional to produce a mutant
phenotype.
• What is the probability of inheriting an
autosomal dominant trait?
Construct a Punnett Square
6
• father is heterozygous for
an autosomal dominant
gene, with allele D, the
mutant dominant allele,
and allele d, the
recessive normal allele.
He can produce two
types of gametes, D and
d.
• mother is homozygous
normal, having both d
alleles.
X-linked recessive pattern
Boys are primarily
affected
www.biologia.arizona.edu/...
/gifs/Pedigree.gif
7
http://www.ucl.ac.uk/~ucbhjow/medicine/FHD/pedigree_exe
rcise/index.html
• No cases of father to son inheritance-why?
• http://www.mansfield.ohio-state.edu/~sabedon/074ped.gif
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X-linked recessive
How to read a pedigree
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What is this pattern?
Construct a pedigree
Alice and Bob have a two year old son, Charles, who is showing mental
retardation, short stature, micropenis, and cryptorchidism.
Alice has two living, unaffected, brothers but her eldest brother died at
age 9 and a second brother died aged 10 months. Both had similar
problems to Charles.
Alice's father, David, who was symptomless, has a sister, Ethel, who
has an unaffected boy and girl, and a brother, Fred, who also has
two unaffected children.
Alice's mother, Gertrude, has two living sisters and had a brother who
had died in childhood and who, she remembers, had been mentally
retarded.
Bob has two brothers, Henry and Ignatius, who are still unmarried. His
parents, John and Kate, had tragic lives, both were adopted and
never knew their biological parents and both died as the result of a
road accident.
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Draw the information one step at a time in a
logical manner.
Step 1
• Begin with Alice, Bob and Charles.
• Here are three possible drawings of this
nuclear family—which one is correct?
If dominant what is the chance that III6 will have
affected children?
If recessive who are obligate carriers
(heterozygous)
Who are at risk of being carriers?
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Compare the probability of X-linked
to autosomal recessive inheritance
So what is the frequency of carrier females in the
population?
One person in 10,000 suffers from this condition.
i.e. one male in 5,000. The males carry a sample
of the X chromosomes in the population. If 1
male in 5,000 is affected then 1 X chromosome
in 5,000 is affected, i.e. the gene frequency is 1
in 5,000 or 0.0002. The frequency of carrier
females is given by Hardy-Weinberg (2pq)
it must be 2 × 0.9998 × 0.0002 = 0.0004
Compare this with the likelihood of
observing this pedigree under the model of
autosomal recessive inheritance which
was 0.000008. X linked inheritance is thus
0.0004/0.000008 (= 50) times more likely
than autosomal inheritance.
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