Transcript Pedigree - Solon City Schools

Sample pedigree - cystic fibrosis
male
female
affected individuals
Autosomal recessive traits
• Trait is rare in pedigree
• Trait often skips
generations (hidden in
heterozygous carriers)
• Trait affects males and
females equally
Autosomal recessive diseases in humans
Most common ones
• Cystic fibrosis
• Sickle cell anemia
• Phenylketonuria (PKU)
• Tay-Sachs disease
Autosomal dominant pedigrees
• Trait is common in the pedigree
• Trait is found in every generation
• Affected individuals transmit the trait to ~1/2 of
their children (regardless of sex)
• Assume individuals with trait are heterozygous
Autosomal dominant traits
There are few
autosomal dominant
human diseases
(why?), but some
rare traits have this
inheritance pattern
ex. achondroplasia
(a sketelal disorder
causing dwarfism)
X-linked recessive pedigrees
• 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 traits
ex. Hemophilia in European royalty
X-linked recessive traits
ex. Glucose-6-Phosphate Dehydrogenase deficiency
• hemolytic disorder causes jaundice in infants and
(often fatal) sensitivity to fava beans in adults
• the most common enzyme
disorder worldwide, especially
in those of Mediterranean
ancestry
X-linked recessive traits
ex. Glucose-6-Phosphate-Dehydrogenase deficiency
X-linked dominant pedigrees
• Trait is common in pedigree
• Affected fathers pass to ALL of their daughters
• Males and females are equally likely to be affected
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 (bone lesions)
Mitochondrial Genes
• Mitochondria are only
inherited from the
mother.
• If a female has a
mitochondrial trait, all of
her offspring inherit it.
• If a male has a
mitochondrial trait, none
of his offspring inherit
it.
• Note that only 1 allele is
present in each
individual, so dominance
is not an issue.
Pedigree Analysis in real life
Remember:
• dominant traits may be rare in population
• recessive traits may be common in population
• alleles may come into the pedigree from 2 sources
• mutation happens
• often traits are more complex
• affected by environment & other genes
Dominant vs. Recessive
• Is it a dominant pedigree or a recessive
pedigree?
• 1. If two affected people have an unaffected
child, it must be a dominant pedigree: D is the
dominant mutant allele and d is the recessive wild
type allele. Both parents are Dd and the normal
child is dd.
• 2. If two unaffected people have an affected
child, it is a recessive pedigree: R is the dominant
wild type allele and r is the recessive mutant
allele. Both parents are Rr and the affected child
is rr.
• 3. If every affected person has an affected
parent it is a dominant pedigree.
Dominant Autosomal Pedigree
I
2
1
II
1
2
3
4
5
6
III
1
2
3
4
5
6
7
8
9
10
Assigning Genotypes for
Dominant Pedigrees
• 1. All unaffected are dd.
• 2. Affected children of an affected parent and an
unaffected parent must be heterozygous Dd,
because they inherited a d allele from the
unaffected parent.
• 3. The affected parents of an unaffected child
must be heterozygotes Dd, since they both passed
a d allele to their child.
• 4. Outsider rule for dominant autosomal
pedigrees: An affected outsider (a person with no
known parents) is assumed to be heterozygous
(Dd).
• 5. If both parents are heterozygous Dd x Dd,
their affected offspring have a 2/3 chance of
being Dd and a 1/3 chance of being DD.
Recessive Autosomal Pedigree
Assigning Genotypes for
Recessive Pedigrees
• 1. all affected are rr.
• 2. If an affected person (rr) mates with an unaffected
person, any unaffected offspring must be Rr heterozygotes,
because they got a r allele from their affected parent.
• 3. If two unaffected mate and have an affected child, both
parents must be Rr heterozygotes.
• 4. Recessive outsider rule: outsiders are those whose
parents are unknown. In a recessive autosomal pedigree,
unaffected outsiders are assumed to be RR, homozygous
normal.
• 5. Children of RR x Rr have a 1/2 chance of being RR and a
1/2 chance of being Rr. Note that any siblings who have an
rr child must be Rr.
• 6. Unaffected children of Rr x Rr have a 2/3 chance of
being Rr and a 1/3 chance of being RR.
What is the pattern of inheritance?
What are IV-2’s odds of being a carrier?
Sample pedigree - cystic fibrosis
What can we say about
I-1 and I-2?
What can we say about
II-4 and II-5?
What are the odds that
III-5 is a carrier?
What can we say about
gene frequency?
What is the inheritance pattern?
What is the genotype of III-1, III-2, and II-3?
What are the odds that IV-5 would have an affected son?
III-1 has 12 kids with an unaffected wife
8 sons - 1 affected
4 daughters - 2 affected
Does he have reason to be concerned about paternity?
Problem
Your grandfather’s sister had
cystic fibrosis (rare, autosomal
recessive). That’s the only case
in your family.
(A) What’s the chance that you
are a carrier of CF?
A.2/3
B. 1/2 C. 1/4
D. 1/6 E.1/8
Your grandfather’s sister had CF but he, his
parents, and his descendants are unaffected, as
are those who married into the family
A
B
D
C
F
E
G
H
you
A.
B.
C.
D.
E.
2/3
1/2
1/4
1/6
1/8
A
D
B
d
D DD Dd
D
C
F
2/3
E
G
H
you
d Dd dd
IF
D
F
THEN
E
G
H
you
?
A. 1/4
ANSWERS
= Chance that you got any particular allele from
from grandpa
B. 1/6
= correct answer = 1/4 (see A) x 2/3 (chances
that grandpa was a carrier)