Today…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
DNAReplication
DNARecombination
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).
(crossing over)
Mitosis vs. Meiosis1m 1p
2 x 1m 2 x 1p
1m
1p1m1p
1m
1p1m
1p
2 x 1m 2 x 1p
exact copies
DNAReplication
DNARecombination
1m 1p
2 x 1m 2 x 1p
2 x 1m/p 2 x 1p/m
1m 1p1m/p1p/m
2 x 1m/p 2 x 1p/m
2 x 1m/p 2 x 1p/m
Meiotic Division ICrossovers 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 ICrossovers hold the homologues together until all of the chromosomes are attached to the spindle
The two daughter cells from meiotic division I go directly into meiotic division II
Sister chromatids separate during meiotic division II
Meiotic Division II
• 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)
Mitosis vs. Meiosis
Probability in genetics
Probability is important in genetics
- testing hypotheses
- mapping disease genes
- genetic counseling
Needed for…
Pedigree of a family segregating phenylketonuria (PKU)
What can we infer from the pedigree?
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?
Use of the Product and Sum rules
DNAReplication
DNARecombination
2 copies PAH+ 2 copies PAH-
2 copies PAH+ 2 copies PAH-
PAH+ PAH-
PAH-
PAH-PAH+
PAH+
PAH-
PAH-PAH+
PAH+
PAH-
PAH-PAH+
PAH+
PAH+ PAH+ PAH- PAH-
Following the fate of the PAH gene in a PAH+/- heterozygote during meiosis
DNAReplication
DNARecombination
PAH+
PAH-PAH+
PAH-
2 copies PAH+ 2 copies PAH-
2 copies PAH+ 2 copies PAH-
PAH+ PAH-
PAH+
PAH-
PAH+
PAH-PAH+
PAH-
PAH+
PAH-
PAH+ PAH- PAH+ PAH-
Following the fate of the PAH gene in a PAH+/- heterozygote during meiosis
Genetic accounting
What are the possible genotypes and phenotypes of the children of parents who are both phenylketonuria carriers?
eggs
sper
m
Product rulePAH+/- PAH+/-
PAH-/-
What is the probability that their next child will have PKU?
PAH+
PAH+
eggs
sper
m ½ PAH+
½ PAH-
½ PAH+ ½ PAH-
PAH+
PAH-
PAH+
PAH-PAH-
PAH-Probability of PAH-/-?
Product Rule: The probability of 2 or more independent events occurring simultaneously
Sum rulePAH+/- PAH+/-
PAH-/-
What is the chance the next child, if he or she is not affected, will be a carrier?
PAH+
PAH+
eggs
sper
m ½ PAH+
½ PAH-
½ PAH+ ½ PAH-
PAH+
PAH-
PAH+
PAH-PAH-
PAH-Probability of PAH+/-?
= sum of the separate probabilities
Sum Rule: The probability of an event that can occur in 2 or more ways
Punnett Square
Determine types of gametes from each parentCombine each type of female gamete with each male gamete
Advantages of Punnett SquareOrganized and systematicGives all possible combinations of genotypes automatically
Slow and labor intensive, especially for complex genotypes (e.g., AaBbCc X AabbCc)
Disadvantages of Punnett Square
Execution
Two events necessary:II-3 must be Aa and they must have aa child
Example: Albinism…a = no pigmentWhat is the probability that III-1 will be albino?
Using the product and sum rules
Independent assortment of nonhomologous chromosomes
during meiosisWhat happens to non-homologous chromosomes during meiosis?
1m 1p
2m 2p
1m
2m1p
2p
1m2m
1m2m
1p
2p1p
2p
1p 1m
2m 2p
1p
2m
1p
2m1p
2m
1m2p
1m2p
1m2p
Two equally probable arrangements:
Independent assortment of nonhomologous chromosomes
during meiosis
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 gametes23 pairs of homologous chromosomes gives 223 (8 million) types of gametes
Examples:
Meiosis and independent assortment of nonhomologous chromosomes can create many different 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 antigen= B antigen
A red cells
B red cells
AB red cells
O red cells
The ABO (I) gene
There are 3 different versions (alleles) of the I gene:
IB
i
IA A adds A sugar to red cell surface
B adds B sugar to red cell surface
adds no sugar to red cell surface
I alleles
The ABO gene - dominance relationships
IA is dominant to i
The I gene lies on chromosome 9q34
IA/IA or IA/i - A blood type
IB is dominant to i IB/IB or IB/i - B blood type
IA is co-dominant with IB IA/IB - AB blood type
i is recessive i/i - O blood type
Independent assortment of genes on nonhomologous chromosomes
CFTR+ CFTR-
IA iCFTR+CFTR-
IA i
CFTR+
IACFTR-
iCFTR-
IACFTR+
i
CFTR+
IACFTR+
IACFTR-
iCFTR-
iCFTR-
IACFTR-
IACFTR+
iCFTR+
i
Gametes formed from a CFTR+/- IA/i double heterozygote:
CFTR+ IA
CFTR- i
CFTR- IA
CFTR+ i
CFTR+ IA
CFTR- i
Gametes that arise from a CFTR+/- IA/i double
heterozygote:
CFTR+ i
CFTR- IA
1/4
1/4
1/4
1/4
CFTR+
IA
CFTR+
iCFTR-
IA
CFTR-
i
CFTR+
IACFTR-
iCFTR+
iCFTR-
IAC+/+
IA/IAC+/-
IA/iC+/+
IA/iC+/-
IA/IA
C+/-
IA/iC+/+
IA/-C+/-
IA/IA
C-/-
i/iC+/-
i/iC-/-
IA/i
C+/-
i/iC-/-
IA/iC+/+
i/iC+/-
IA/iC+/-
IA/iC-/-
IA/IA
Eggs
Sper
m
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?
Possible genotypes and phenotypes from a mating of CFTR+/- IA/i double
heterozygotes
CFTR+
IA
CFTR+
i
CFTR-
IA
CFTR-
i
CFTR+
IACFTR-
iCFTR+
iCFTR-
IA
C+/+
IA/IAC+/-
IA/iC+/+
IA/iC+/-
IA/IA
C+/-
IA/i
C+/+
IA/-
C+/-
IA/IA
C-/-
i/i
C+/-
i/i
C-/-
IA/i
C+/-
i/iC-/-
IA/i
C+/+
i/iC+/-
IA/i
C+/-
IA/iC-/-
IA/IA
9 N, A 3 N, O 3 CF, A1 CF, O
1/4
1/4
1/4
1/4
1/4 1/4 1/4 1/4
