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Genome 351, 15 April 2013, Lecture 5. Today…. 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.

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slide1

Genome 351,15April 2013, Lecture 5

Today…

  • 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
slide2

Meiosis: the formation of gametes

DNA

Replication

  • 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 twohomologs 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).

DNA

Recombination

(crossing over)

slide3

Mitosis vs. Meiosis

1m

1p

1m

1p

DNA

Replication

2x1m

2x1p

DNA

Recombination

2x1p

2x1m

2x 1m/p

2x 1m/p

2x 1p/m

2x 1p/m

2x1m

2x1p

2x 1m/p

2x 1p/m

1m

1m

1p

1p

1m

1p/m

1p

1m

1m

1m/p

1p

1p

exact copies

slide4

Meiotic Division I

Crossovers hold the homologues together until all of the chromosomes are attached to the spindle

slide5

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

slide6

Meiotic Division II

The two daughter cells from meiotic division Igo directly into meiotic division II

Sister chromatids separate during meiotic division II

slide7
One round of DNA synthesis with one cell division

Two genetically identical daughters

Sister chromatidssegregate

Homologs do not line up or separate

Homologs do not exchange corresponding segments (no crossing over)

Final products are diploid (2n)

Mitosis vs. Meiosis

slide9

Probability is important in genetics

Needed for…

  • testing hypotheses
  • mapping disease genes
  • genetic counseling
slide10

Pedigree of a family segregating phenylketonuria (PKU)

What can we infer from the pedigree?

slide11

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?

slide12

Following the fate of the PAH gene in a PAH+/- heterozygote during meiosis

PAH-

PAH+

DNA

Replication

2 copies PAH+

2 copies PAH-

DNA

Recombination

2 copies PAH+

2 copies PAH-

PAH+

PAH-

PAH+

PAH-

PAH+

PAH-

PAH+

PAH-

PAH-

PAH+

PAH-

PAH+

PAH+

PAH+

PAH-

PAH-

slide13

Following the fate of the PAH gene in a PAH+/- heterozygote during meiosis

PAH-

PAH+

DNA

Replication

2 copies PAH+

2 copies PAH-

DNA

Recombination

2 copies PAH+

2 copies PAH-

PAH+

PAH+

PAH-

PAH-

PAH+

PAH+

PAH-

PAH-

PAH+

PAH+

PAH-

PAH-

PAH+

PAH-

PAH+

PAH-

slide14

Genetic accounting

eggs

What are the possible genotypes and phenotypes of the children of parents who are both phenylketonuria carriers?

sperm

slide15

Product rule

PAH+/-

PAH+/-

eggs

What is the probability that their next child will have PKU?

½ PAH+

½ PAH-

PAH-/-

PAH+

PAH-

PAH+

PAH+

½ PAH+

Product Rule: The probability of 2 or more independent events occurring simultaneously

sperm

PAH+

PAH-

PAH-

PAH-

½ PAH-

Probability of PAH-/-?

slide16

Sum rule

What is the chance the next child, if he or she is not affected, will be a carrier?

PAH+/-

PAH+/-

PAH-/-

eggs

Sum Rule: The probability of an event that can occur in 2 or more ways

½ PAH+

½ PAH-

PAH+

PAH-

PAH+

PAH+

½ PAH+

= sum of the separate probabilities

sperm

PAH+

PAH-

PAH-

PAH-

½ PAH-

Probability of PAH+/-?

slide17

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)

slide18

Two events necessary:

II-3 must be Aaand they must have aa child

Using the product and sum rules

a = no pigment

Example: Albinism…

What is the probability that III-1 will be albino?

independent assortment of nonhomologous chromosomes during meiosis
Independent assortment of nonhomologous chromosomes during meiosis

What happens to non-homologous chromosomes during meiosis?

slide20

1m

1p

1p

1m

2m

2p

2m

2p

1p

1p

1p

1m

1m

1m

1m

1p

1p

1p

2p

2p

2p

2m

2m

2m

2m

2p

2p

2p

1m

1m

2m

2m

Independent assortment of nonhomologous chromosomes during meiosis

Two equally probable arrangements:

slide21

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
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
slide23

Some background on ABO blood groups

A red cells

= A antigen

AB red cells

= B antigen

O red cells

B red cells

slide24

The ABO (I) gene

There are 3 different versions (alleles) of the I gene:

adds A sugar to red cell surface

A

I alleles

IA

B

adds B sugar to red cell surface

IB

adds no sugar to red cell surface

i

slide25

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

IAis co-dominant with IB

IA/IB- AB blood type

The I gene lies on chromosome 9q34

slide26

CFTR+

CFTR-

CFTR-

CFTR+

IA

i

IA

i

CFTR+

CFTR-

CFTR-

CFTR+

i

IA

i

IA

CFTR+

CFTR+

CFTR+

CFTR-

CFTR-

CFTR+

CFTR-

CFTR-

i

IA

i

IA

IA

i

i

IA

Independent assortment of genes on nonhomologous chromosomes

Gametes formed from a CFTR+/- IA/i double heterozygote:

slide27

Gametes that arise from a CFTR+/- IA/i double heterozygote:

IA

CFTR+

1/4

IA

CFTR+

i

CFTR-

1/4

i

CFTR-

CFTR-

IA

1/4

CFTR-

IA

i

CFTR+

1/4

i

CFTR+

slide28

CFTR+

IA

CFTR-

i

CFTR-

IA

CFTR+

i

CFTR+

IA

CFTR-

i

CFTR+

i

CFTR-

IA

Possible genotypes and phenotypes from a mating of CFTR+/- IA/i double heterozygotes

What genotypes give CF and A blood type?

Eggs

What genotypes give nonCF and A blood type?

C+/+

IA/IA

C+/+

IA/i

C+/-

IA/i

C+/-

IA/IA

C-/-

i/i

C+/-

IA/i

C+/-

i/i

C-/-

IA/i

What genotypes give nonCF and O blood type?

Sperm

C+/-

IA/i

C+/-

i/i

C+/+

IA/-

C+/+

i/i

What genotype gives CF and O blood type?

C-/-

IA/IA

C+/-

IA/IA

C-/-

IA/i

C+/-

IA/i

slide29

1/4

1/4

1/4

1/4

CFTR+

IA

CFTR-

i

CFTR-

IA

CFTR+

i

C+/+

IA/IA

CFTR+

IA

C+/+

IA/i

C+/-

IA/i

C+/-

IA/IA

1/4

9 N, A

3 N, O

3 CF, A

1 CF, O

CFTR-

i

C-/-

i/i

C+/-

IA/i

C+/-

i/i

C-/-

IA/i

1/4

C+/-

i/i

CFTR+

i

C+/+

i/i

C+/-

IA/i

C+/+

IA/-

1/4

C+/-

IA/i

C-/-

IA/IA

CFTR-

IA

C-/-

IA/i

C+/-

IA/IA

1/4