Transcript Meiosis: Chapter 10 - University at Buffalo

Make a Life to
Save a Life
by
Peggy Brickman
University of Georgia
1
The Case
Jack and Lisa Nash’s daughter
Molly was born with a rare,
incurable genetic condition
called Fanconi anemia, which
rendered her body unable to
produce enough blood cells…
2
Matching Organs:
HLA
Finding a correct match for tissue
transplantation depends on matching a
specific group of proteins found on the surface
of white blood cells that are used to
distinguish one’s own cells from foreign cells,
called HLA, for human leukocyte antigen.
3
Learning Objectives
1. Recognize how the number and type of
chromosomes differ in a gamete compared to a
somatic (body) cell.
2. Describe how chromosomes are separated in
meiosis and how this differs from mitosis.
3. Apply the knowledge of how chromosomes
separate during meiosis and the rules of
probability to predict the likelihood that
offspring from two parents would inherit a
specific combination of chromosomes and the
genes they contain.
4
Matches for Organ Donation
• HLA proteins encoded by several genes on
chromosome 6.
»Many variants of gene = mutations that
create differences (alleles)
HLA Class I
Gene
A
Alleles
B
C
697 1,109 381
E
F
G
9 21 36
HLA Class II
6
Alleles
1,012
5
HLA Proteins Present Foreign Antigens
foreign cell
Macrophage
Lysosome
digests
proteins
Peptides
displayed by
HLA
proteins
6
HLA: Inherited from Parents
Mrs. Nash is
diploid = two
homologues
of chromosome 6
HLA-A1
HLA-B35
HLA-A2
HLA-B44
7
A1
B35
Review: Mitosis
A2
B44
S phase
• Asexual reproduction.
Sister chromatids Sister chromatids
• Occurs in somatic (body cells)
A1
A1
B35
B35
for growth and division.
• Creates genetically identical cells.
A2
A2
B44
B44
• Not a way to combine traits
mitosis
together in reproduction.
• Need new method: sexual
A1
A2
A1
A2
B35
B44
B35
B44
reproduction.
8
Why do diploid organisms need to have
specialized sex cells?
• Sex cells (gametes) allow traits to be
combined from two organisms.
• Can’t just fuse any two random cells.
A1
B35
A2
B44
2n
(46)
+
2n
(46)
A3
B41
A26
B35
4n = 92
too many
9
Sexual Reproduction
• Meiosis = specialized cell division so you have only
one of each chromosome, called
• Gametes: (n) made only in gonad (testis, ovary)
A2
B44
n
(23)
+
n
(23)
2n = 46
A2
B44
A26
B35
A26
B35
10
Mitosis versus Meiosis
MITOSIS
MEIOSIS
Diploid
somatic
cell
Diploid
gamete
precursor
duplication
division
Diploid
Haploid
division
Meiosis has 2 divisions: Meiosis I and Meiosis II
11
CQ#1: When Mrs. Nash produces eggs,
they would have which combinations of
the HLA-A and HLA-B genes and in what
proportions?
A. 100% B35-A1
B. 50% B35-B44 & 50% A1-A2
C. 50% B35-A1 & 50% B44-A2
D. 100% B44-A2
E. 50% B35-A2, & 50% B44-A1
A1
B35
A2
B44
Mrs. Nash’s
chromosome 6s
12
A2
A1
A2
B35
B44
B35
B44
Sister chromatids
A1
B35
A1
B35
A2
B44
A2
B44
Sister chromatids
Homologues
Pair
A1
B35
Meiosis I
Mitosis
A1
A2
B44
Prophase & Metaphase Differ
13
Chromosome Pairing: Synapsis
• Close proximity favors crossing over
Exchange of parts of non-sister chromatids
Duplicated
Duplicated
Maternal
Paternal
chromosome chromosome
tetrad
• Allows exchange of traits
sister
chromatids
non-sister
chromatids
14
A1
B35
Mitosis
A2
B44
A1
B35
Meiosis I
Sister chromatids
A1
B35
A1
B35
A2
B44
A2
B44
Homologues
Pair
mitosis
A1
B35
A2
B44
A2
B44
Sister chromatids
A1
B35
A2
B44
meiosis I
A1
B35
A2
B44
A1
B35
A1
B35
A2
B44
A2
B44
15
Update: Meiosis I completed
• Homologous chromosomes are separated
into two different cells.
• Each new cell has only one of each different
chromosome (n, haploid).
• Still need to separate the sister chromatids
so that the total amount of chromosomes
and DNA is truly half of a normal cell.
16
Meiosis II: Sister chromatids separate
A1
B35
A1
B35
A2
B44
meiosis II
A1
B35
A2
B44
meiosis II
A1
B35
A2
B44
A2
B44
End result: Four haploid cells total
17
CQ#2: When Mr. Nash produces sperm,
the sperm would have which combinations
of the HLA-A and HLA-B genes and in
what proportions?
A. 100% B5-A26
B. 50% B35-A3 & 50% B41-A26
C. 50% B35-B41 & 50% A3-A26
D. 100% B44-A2 B35-A26
E. 50% B35-A26, & 50% B41-A3
A3
B41
A26
B35
Mr. Nash’s
chromosome 6s
18
CQ#3: Which of the following shows one
combination of HLA-A and HLA-B genes
expected in an offspring of Lisa and Jack
Nash?
A. B35, B35, A1, A2
B. B35, B44, A2, A3
C. B44, B35, A2, A26
D. B41, B44, A26, A2
A1
B35
A2
B44
Mrs. Nash
A3
B41
A26
B35
Mr. Nash
19
CQ#4: Is it possible for any child born to
this couple to be identical in both HLA-A
and HLA-B with either parent?
A. Yes
B. No
A1
B35
A2
B44
Mrs. Nash
A3
B41
A26
B35
Mr. Nash
20
CQ#5: Using the proportion of each type of
sperm and egg that you calculated in
questions I and II, what is the likelihood that
Molly’s sibling would inherit the same
combination of HLA genes and thus be a
good organ donor for Molly?
A. No chance
B. 25%
C. 50%
D. 75%
E. 100%
A26
B35
A2
B44
Chromosome 6s
for Molly Nash
21
Clearly Molly’s best chance of finding a bone marrow
match was with a sibling. Unfortunately, Molly was an
only child. The Nashes had always wanted to have more
children, but because Fanconi anemia is an inherited
condition, they knew that if they had another child that
child had a chance of getting the disease just as Molly
had. But neither Jack nor Lisa had the disease because
the mutation is recessive. In order to have Fanconi
anemia like Molly, both copies of the FANCC gene
would have to have this recessive mutation, and they
only had one.
How is that possible?
22
Fanconi Anemia: Chromosome 9
Normal
FANCC
FANCC
Mother
meiosis
Normal
Normal
Father
meiosis
FANCC
FANCC
FANCC
Normal
FANCC
Molly
23
CQ#6: Using what you know about how
meiosis created eggs and sperm, what is
the likelihood that Lisa and Jack Nash
could conceive a sibling for Molly that
would NOT have Fanconi anemia
(presence of at least one normal)?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%
24
Punnett Squares: Show All
Possible Combinations of Gametes
FANCC
Normal
Father
meiosis
FANCC
Normal
FANCC
Normal
normal
FANCC
normal
normal
FANCC
FANCC
normal
FANCC
Normal
Mother
FANCC
25
Pre-Implantation Genetic Screening
• When they discovered that they could
conceive a baby that was free from Fanconi
Anemia, Jack and Lisa Nash underwent in-vitro
fertilization followed by a procedure called
pre-implantation genetic screening to choose
an embryo that would have HLA proteins (B44,
B35, A2, A26) that matched Molly, and to
choose an embryo that would also be free of
Fanconi anemia.
26
Pre-Implantation Genetic Screening
• Ethics: This is the first example of the use of preimplantation genetic screening to select for a baby
solely as a treatment for its sibling.
• List two ethical objections someone might have to
allowing the Nashes to use this technique.
• List two reasons why you think the Nashes should be
allowed to use this technique.
• What kind of regulations if any should be used for
parents hiring doctors to do this procedure? When is
it OK, when not?
27
Select a Baby: HLA Match, Normal
A1
B35
FANCC
A2
A3
A26
B44
B41
B35
FANCC
Normal
Mother
A2
A26
B44
Normal
Father
B35
FANCC
FANCC
Molly
28
CQ#7: Using your knowledge of how
A1
chromosomes segregate during
B35
meiosis, what percent of Mrs.
Nash’s eggs would carry a normal FANCC
chromosome 9 and a chromosome
6 with the A-2, B-44 alleles?
A2
B44
Normal
A. No chance
B. 25%
C. 50%
D. 75%
E. 100%
29
Alignment at Metaphase I
Random:
A1
B35
FANCC
A2
A1
B44
B35
Normal
Normal
Meiosis I
Meiosis II
A2
B44
FANCC
Meiosis I
Meiosis II
A1
A2
A2
A1
A1
A2
A2
A1
B35
B35
B44
B44
B35
B35
B44
B44
30
CQ#8: If the same percentage of Mr. Nash’s
sperm carry the correct chromosome 9
(normal) and 6 (A26, B35), what is the
probability that a single embryo would be a
perfect HLA match for Molly and not
develop Fanconi anemia?
A. 1/2
B. 1/4
C. 3/16
D. 1/8
E. 1/16
A1
B35
FANCC
A2
A3
A26
B44
B41
B35
Normal
FANCC
Normal
Father
31
A2
B44
A1
B35
A2
A26
A26
A3
B41
B35
B35
B41
A3
A2
B41
B44
FANCC
A26
A2
B35 B44
FANCCFANCC
A26
A2
A3
A2
B35
B44
B41
B44
NormalFANCC
FANCC FANCC
Normal
A3
A1
A26
A1
A26 A1
A3
A1
B41
B35
B35
B35
B35 B35
B41
B35
FANCC
Normal
Normal
NormalFANCC
A3
A2
A26
B41
B44
B35
B44
FANCC
A1
A3
NormalNormal
A2
B44
Normal
A26
A2
A3
B35 B44
NormalFANCC
Normal
B41
Normal Normal
Normal
A2
B44
Normal
A3
A1
A26 A1
A26
A1
A3
A1
B41
B35
B35 B35
B35
B35
B41
B35
B35
FANCC
FANCCFANCC
Normal FANCC
FANCC FANCC
32
Normal
Update on the Nashes
After four in vitro fertilization attempts,
Lisa Nash gave birth to a baby boy,
Adam, on August 29, 2000. Adam’s
placenta was gathered immediately and
all the cord blood saved. Molly started
chemotherapy to destroy her bone
marrow and received a transfusion of
the cord blood cells a month later.
Today Molly, Adam, and new little sister
Delaine are all doing well. The
transplant cured Molly’s bone marrow
failure, but she still suffers from Fanconi
anemia and visits the doctors 35-40 times a year to screen for solidtumor cancers. A common cold could have dire consequences for
her, but her bone marrow is functioning normally.
33
Slide Credits
Slide 1 and Slide 33
Description: Illustration of embryo in flask.
Author: czardases
Source: Fotolia, http://www.fotolia.com, ID: 7576662
Clearance: ©czardases, licensed royalty free.
Slide 2
Description: Cluttering of red blood cells.
Author: Bram Janssens
Source: Dreamstime, http://www.dreamstime.com, ID: 6767785
Clearance: ©Bram Janssens, licensed royalty free.
Slide 3
Description: Illustration of MHC class I and class II.
Author: David S. Goodsell and the RCSB PDB
Source: Major Histocompatibility Complex, Molecule of the Month, February 2005, http://www.pdb.org
Clearance: Molecule of the Month illustrations are copyrighted but available for educational purposes,
provided attribution is given to David S. Goodsell and the RCSB PDB.
Slide 5 —Bottom left
Description: Drawing depicting HLA genes on chromosome 6.
Author: Philip Deitiker
Source: Wikimedia Commons, http://commons.wikimedia.org/wiki/Image:HLA.jpg
Clearance: Released into the public domain by the author.
Slide 9 and Slide 10
Description: Figure of male and female.
Author: Derived from a public domain NASA image.
Source: WikiMedia, http://commons.wikimedia.org/wiki/File:Human.svg
Clearance: Public domain.
All remaining images appearing in this presentation were created by the
author of this case study, Peggy Brickman.