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Genome 351, 15 April 2013, Lecture 5
•Meiosis: how the genetic material is partitioned
during the formation of gametes (sperm and
eggs)
•Probability:
-the product rule
-the sum rule
•Independent assortment of nonhomologous
chromosomes during meiosis
Meiosis: the formation of gametes
DNA
Replication
DNA
Recombination
(crossing over)
Meiotic Division 1
• Copied chromosomes (sister
chromatids) stay joined
together at the centromere.
• Homologous chromosomes pair
up and physically join at sites
of recombination
• Proteins pull the two homologs
to opposite poles
Meiotic Division 2
• Proteins pull the two sister
chromatids to opposite poles
• Each gamete gets a copy of
only one homolog (usually a
maternal-paternal hybrid).
Mitosis vs. Meiosis
1m
1p
2 x 1m
2 x 1m
2 x 1p
2 x 1m
2 x 1p
1m
1p
1m
1p
1m
1m
1p
1m
1p
exact copies
2 x 1m/p
2 x 1m/p
2 x 1m/p
1m
1p
DNA
Replication
2 x 1p
DNA
Recombination
2 x 1p/m
2 x 1p/m
2 x 1p/m
1p/m 1m/p
1p
Meiotic Division I
Crossovers hold the homologues together until all
of the chromosomes are attached to the spindle
Meiotic Division I
Crossovers hold the homologues together until all
of the chromosomes are attached to the spindle
The homologues then
separate from one another,
exchanging corresponding
portions as they do so
Meiotic Division II
The two daughter cells from meiotic division I
go directly into meiotic division II
Sister chromatids separate during meiotic division II
Mitosis vs. Meiosis
• One round of DNA
synthesis with one cell
division
• Two genetically identical
daughters
• Sister chromatids
segregate
• Homologs do not line up or
separate
• Homologs do not exchange
corresponding segments (no
crossing over)
• Final products are diploid
(2n)
Probability in
genetics
Probability is important in genetics
Needed for…
- testing hypotheses
- mapping disease genes
- genetic counseling
Pedigree of a family segregating
phenylketonuria (PKU)
What can we infer from the pedigree?
Use of the Product and Sum rules
A couple has a first child who tests positive for
PKU. What can you infer about their genotypes?
What is the
probability that their
next child will have
PKU?
What is the chance
the next child, if he or
she is not affected,
will be a carrier?
Following the
fate of the
PAH gene in
a PAH+/heterozygote
during
meiosis
PAH+
2 copies PAH+
2 copies PAH+
PAH+
PAH+
PAH+
PAH+
PAH+
PAH+
PAHDNA
Replication
2 copies PAHDNA
Recombination
2 copies PAHPAHPAHPAHPAHPAHPAH-
PAH+ PAH+ PAH- PAH-
Following the
fate of the
PAH gene in
a PAH+/heterozygote
during
meiosis
PAH+
2 copies PAH+
2 copies PAH+
PAH+
PAHPAH+
PAHPAH+
PAH-
PAHDNA
Replication
2 copies PAHDNA
Recombination
2 copies PAHPAH+
PAHPAH+
PAHPAH+
PAH-
PAH+ PAH- PAH+ PAH-
Genetic accounting
sperm
What are the
possible genotypes
and phenotypes of
the children of
parents who are both
phenylketonuria
carriers?
eggs
Product rule
PAH+/-
PAH+/-
PAH-/-
Probability of
sperm
Product Rule: The
probability of 2 or more
independent events
occurring simultaneously
What is the
probability that their
next child will have
PKU?
eggs
PAH-/-?
½ PAH+ ½ PAH½ PAH+
PAH+
PAH+
PAH+
PAH-
½ PAH-
PAH+
PAH-
PAHPAH-
Sum rule
PAH+/-
What is the chance the
next child, if he or
she is not affected,
will be a carrier?
eggs
PAH+/-
PAH-/-
½ PAH+ ½ PAH-
sperm
Sum Rule: The
probability of an
event that can occur
in 2 or more ways
= sum of the separate
probabilities
Probability of PAH+/-?
½ PAH+
PAH+
PAH+
½ PAH-
PAH+
PAH-
PAH+
PAHPAHPAH-
Punnett Square
Execution
Determine types of gametes from each parent
Combine each type of female gamete with each male gamete
Advantages of Punnett Square
Organized and systematic
Gives all possible combinations of genotypes automatically
Disadvantages of Punnett Square
Slow and labor intensive, especially for complex
genotypes (e.g., AaBbCc X AabbCc)
Using the product and sum rules
Example: Albinism…
a = no pigment
What is the probability that III-1 will be albino?
Two events necessary:
II-3 must be Aa and they
must have aa child
Independent assortment of nonhomologous
chromosomes during meiosis
What happens to non-homologous chromosomes during
meiosis?
Independent assortment of nonhomologous
chromosomes during meiosis
Two equally probable arrangements:
1m
2m
1m
2m
1m 1 m
2m 2m
1p
1p
2p
1m
2m
1p
2p
1p 1p
2p 2p
2p
1m
2p
1p
2m
1p 1p
2m 2m
1m
2p
1m
2p
Meiosis and independent assortment of
nonhomologous chromosomes can create
many different types of gametes
Examples:
1 pair of homologous chromosomes gives 2 types of
gametes (21 = 2)
2 pairs of homologous chromosomes gives 4 types of
gametes (22 = 4)
n pairs of homologous chromosomes gives 2n types of
gametes
23 pairs of homologous chromosomes gives 223 (8
million) types of gametes
An example of independent assortment
• Following the fate of genes on
different (nonhomologous)
chromosomes
– Cystic fibrosis on chromosome 7
– A gene that influences ABO blood types
on chromosome 9
Some background on ABO blood groups
A red cells
= A antigen
= B antigen
B red cells
AB red cells
O red cells
The ABO (I) gene
There are 3 different versions (alleles)
of the I gene:
I alleles
IA
A
adds A sugar to red cell surface
IB
B
adds B sugar to red cell surface
i
adds no sugar to red cell surface
The ABO gene - dominance relationships
IA is dominant to i
IA/IA or IA/i - A blood type
IB is dominant to i
IB/IB or IB/i - B blood type
i is recessive
i/i - O blood type
IA is co-dominant with IB
IA/IB - AB blood type
The I gene lies on chromosome 9q34
Independent assortment of genes on
nonhomologous chromosomes
Gametes formed from a CFTR+/- IA/i double heterozygote:
CFTR+
CFTR- CFTR-
IA
CFTR+
IA
i
CFTRi
CFTR+
IA
i
CFTR-
IA
CFTR+
i
CFTR+ CFTR+ CFTR-CFTR-CFTR-CFTR- CFTR+ CFTR+
i
IA
i
IA
IA
i
i
IA
Gametes that arise from a CFTR+/IA/i double heterozygote:
CFTR+ IA
CFTR+
IA
1/4
CFTR- i
CFTR- i
1/4
CFTR- IA
CFTR- IA
1/4
CFTR+ i
CFTR+ i
1/4
Possible genotypes and phenotypes from a
mating of CFTR+/- IA/i double heterozygotes
Eggs
Sperm
CFTR+
IA
CFTR- CFTR+
i
i
CFTRIA
CFTR+ C+/+
IA
IA/IA
C+/IA/i
C+/+
IA/i
IA/IA
CFTRi
C+/IA/i
C-/i/i
C+/i/i
C-/IA/i
CFTR+ C+/+
i
IA/-
C+/i/i
C+/+
i/i
C+/IA/i
CFTR- C+/IA IA/IA
C-/IA/i
C+/IA/i
C-/IA/IA
C+/-
What genotypes
give CF and A
blood type?
What genotypes
give nonCF and
A blood type?
What
genotypes give
nonCF and O
blood type?
What
genotype gives
CF and O
blood type?
1/4
1/4
1/4
1/4
CFTR+
IA
CFTRi
CFTR+
i
CFTRIA
C+/IA/i
C+/+
IA/i
C+/IA/IA
+/+
+
C
CFTR
1/4
IA/IA
IA
CFTR
1/4
i
C+/IA/i
C-/i/i
C+/i/i
C-/IA/i
+
CFTR
1/4
i
C+/+
IA/-
C+/i/i
C+/+
i/i
C+/IA/i
CFTR
1/4
IA
C+/IA/IA
C-/IA/i
C+/IA/i
C-/IA/IA
9 N, A
3 N, O
3 CF, A
1 CF, O