Transcript Bloodline- A Human Genetics Case

Bloodline:
A Human Genetics Case
By
Peggy Brickman
University of Georgia
This case is based on the CBS show, Ghost Whisperer, Season 4, episode 5, “Bloodline.”
Original Airdate: October 31, 2008
1
Opening Scene
Olivia, a blond teen, is resoundingly beating her male tennis
opponent, Ned. She is new in town and jokes that her partner
went easy on her to make her feel welcome. From nowhere,
a tennis ball cuts across their court. The dark-eyed brunette
who hit it, Diana, stares at them. Olivia seems stunned into
silence. Diana sneers at her and says, “Any day now.” Olivia
hits the ball back to her, almost directly into her face.
“What was that all about? You know Diana Morrison?” Ned
asks.
“I used to, back when I lived in Granville the first time,” Olivia
answers. “Back then we were friends. It was like a million
years ago.”
2
Opening Scene Continues…
As they walk away, we hear Diana’s tennis coach
screaming, “Diana, Diana! Somebody help Diana,
please!”
“Is she OK? What’s happened?” Olivia gasps after
running over. Diana has collapsed to the tennis court,
not breathing.
“She just dropped unexpectedly,” Diana’s coach
responds. “Call 911!”
3
Emergency Room
Diana is taken by ambulance to the emergency room. Olivia
follows by car. At the hospital, Olivia’s brunette mother walks
in. “I went to the courts to pick you up and when you weren’t
there, they said a girl had collapsed, I thought…” she
stammers.
“I’m fine, Mom,” Olivia assures her. “I’m sorry for scaring you.
I should have called. It’s Diana.”
“Diana Morrison?” her mother asks, alarm spreading across
her face.
“Where’s Diana Morrison?” a blond woman who has just come
in demands. “I’m her mother. They told me she was here.”
Olivia and her mother turn to stare at the new arrival.
4
Scene Continues
“Olivia?” Diana’s mother asks. All three women stare at
each other in confusion. “What are you doing here?”
“Mrs. Morrison, I was at the courts with Ned, and Diana
was there, too, taking a lesson I guess.” Olivia explains.
“She just collapsed.”
“Was it heat stroke?” Mrs. Morrison asks. “She barely
ate any breakfast.”
5
Memorial Scene
Night has fallen in downtown Granville. A candle
flickers over flowers and stuffed animals at a
makeshift memorial. Diana’s mother is there
comforting–and being comforted by—several young
friends of her daughter.
Olivia approaches Mrs. Morrison and tries to speak to
her, but Mrs. Morrison rebuffs her.
6
Scene Continues
Olivia explains to her friend Ned, “When we were little
our moms were such good friends, we did everything
together. It was almost like we were sisters. Play dates,
sports, camping, we even have the same birthdays so
our parties were like this whole big deal every year.”
“What happened?” Ned asks.
“It just ended,” Olivia explains. “I remember one night I
woke up and my Mom was in bed with me—she was
rocking me and crying and crying. I asked her what was
wrong, but all she would say was that she loved me.”
7
Scene Ends
“And then after that, everything changed. Diana’s mom
and dad split up. We stopped hanging out with them,
and then we got transferred to Texas, or my Dad did, so
we left,” Olivia shrugs. “My mom told me to forget
about Diana, to make new friends. It was like she was
mad at her, too.”
Olivia looks up and stares across the street. “What’s Dad
doing here?”
Olivia’s father heads toward Mrs. Morrison, offering her
comfort in an embrace.
8
Questions
• What do you think is going on with these
two families?
• The hospital would have simple things like
Diana’s blood type on file. How could you
use blood type to figure out what is going
on?
9
CQ#1: Olivia’s parents, Mrs. Lisa Keller and Mr. Kevin Keller, are
(A-) and (O+). You know about the IA/IB/i alleles for ABO blood type
and the Rh D factor alleles, +/-. Write down all possible genotypes
for Lisa and Kevin Keller and use them to create several Punnett
squares to indicate the possible genotypes for their offspring.
Olivia has O- blood. Using your Punnett Squares and the
phenotypes of the three Kellers, indicate which of the following
is the most likely set of genotypes for Lisa and Kevin Keller.
A.
B.
C.
D.
Lisa
Kevin
IA / i, -/IA / IA, -/IA / i, -/IA / IA, -/-
i / i, +/+
i / i, +/i / i, +/i / i, +/+
10
CQ#2: Looking at the Kellers and Morrisons, is it possible
that Kevin Keller had an affair with Cynthia Morrison and is
Diana Morrison’s biological father?
Lisa Keller
A-
A.
B.
C.
Kevin Keller
O+
Cynthia Morrison
B+
Mr. Morrison
O-
Olivia Keller
Diana Morrison
OA+
Yes, Cynthia and Kevin could have a child like Diana with Rh
positive blood.
No, Cynthia and Kevin could not have a child who has type A
blood.
No, Cynthia and Kevin could not have a child who was Rh
positive.
Before we go to the next slide, what other problem do you see?
11
Several Days Later: Mercy Hospital
A nurse is reminiscing with a colleague:
“The day that Diana Morrison was born, there’d been this huge
accident on the interstate. We were understaffed, overwhelmed.
The bracelets must have come off in the bath. The charge nurse
seemed confused. I asked if everything was OK. She ordered me
to go to room 214 and get Mrs. Keller up and walking – now. I
was fresh out of nursing school. I was trying to learn without
asking too many questions. What could I do? I didn’t have any
proof that the girls were switched. It was just a feeling. But, I did
remember those girls’ names. I saw the mothers bonding, talking
in the hallways, cradling their babies. When I saw Diana again 16
years later, I recognized her name when the paramedics brought
her in.”
12
Several Days Later: Mercy Hospital
The nurse continues, “The circumstances of her
death due to that blood clot – the thought of it made
me wonder all over again. So, I pulled the girls’
medical records. That’s what confirmed it. You know,
I’ve been trying to contact the families ever since.
I’m determined to reach them because the blood clot
that killed Diana sounds like it could be a genetic
condition. It could affect someone else in her
biological family. They have to be told.”
13
Inherited Blood Disorders
Hemophilia is a group of hereditary genetic disorders
that lead to deficiencies of factors used to stop
bleeding when a blood vessel is broken. Hemophiliacs
don’t bleed more intensely than a normal person, just
longer. Even a minor injury can result in blood loss
lasting days, weeks, or not ever healing completely.
– Hemophilia A (90%, of cases, about 1/10,000 births), clotting
factor VIII (gene on chromosome X) is absent.
– Hemophilia B, factor IX (on chromosome X) is deficient.
– Hemophilia C, factor XI (on chromosome 4) is deficient.
14
Hemophilia C: Autosomal recessive
child
Carrier children
child
15
Autosomal Recessive:
Punnett Square
Using H and h for the dominant and recessive alleles for
hemophilia C, fill in this Punnett Square using the parents
on the previous slide and their predicted offspring.
16
Autosomal Recessive
Write three rules to keep in mind when
counseling someone about the likelihood of
inheriting an autosomal recessive condition:
1. About the parents’ genotypes.
2. About the parents’ phenotypes.
3. About the probability of the offspring showing
the trait.
17
CQ#3: Lisa Keller and her parents and sister have
normal blood clotting, but she has a brother with
hemophilia C (autosomal recessive). What is the
probability that she is a carrier?
A.
B.
C.
D.
E.
25%
50%
67%
100%
More information is required.
18
Pedigree Symbols
Way to visually represent human family
relationships and infer inheritance patterns.
1 2
3 4
Male
Female
marriage/mating
offspring in order of birth
deceased individuals
individuals showing trait
carriers
19
Pedigree
For the following blank pedigree, darken in an
offspring to show the inheritance pattern
predicted from your rules for an autosomal
recessive trait. Indicate carriers.
20
21
Autosomal Recessive:
Punnett Square
Using Y, HX for the dominant allele for hemophilia A
(normal) and hX for the recessive allele for hemophilia A
(hemophilia), fill in this Punnett Square using the parents
on the previous slide and their predicted offspring.
22
X-linked Recessive
Write three rules to keep in mind when
counseling someone about the likelihood of
inheriting an X-linked recessive condition:
1. About the parents’ genotypes.
2. About the parents’ phenotypes.
3. About the probability of the offspring showing the
trait.
23
CQ#4: If instead of having Hemophilia C
(autosomal recessive), Lisa Keller’s brother had
Hemophilia A (X-linked recessive), what would be
the probability that she was a carrier?
A.
B.
C.
D.
E.
25%
50%
67%
100%
More information is required to answer
this question.
24
Pedigree
For the following blank pedigree, darken in an
offspring to show the inheritance pattern
predicted from your rules for an X-linked
recessive trait. Indicate carriers, also.
25
CQ#5: Remember that Lisa’s brother had
hemophilia, but her sister and parents did not.
It turns out that her mother’s sister died very
young, apparently of a massive hemorrhage.
Which of the following is an accurate pedigree
of Lisa Keller’s ( ) family?
A.
B.
C.
26
CQ#6: Lisa Keller can opt for genetic testing to
determine if she is a carrier for hemophilia, but
it is expensive, so she wants to use her family
pedigree to inform her choice. Given this
pedigree, which type of hemophilia can she rule
out?
A. X-linked recessive
Hemophilia A
B. Autosomal recessive
Hemophilia C
C. Neither, not enough
information was given.
Which family member most influenced your decision?
27
Inherited Blood Disorders
• Hemophilia causes a lack of blood clotting, but Diana
died from overactive blood clotting.
• Factor V Leiden is the most common hereditary
hypercoagulability disorder amongst Eurasians: About
5% of Caucasians in North America are affected by this
condition, which is inherited as an autosomal dominant
mutation of a gene on chromosome 1. It is an overproduction of a variant of clotting Factor V that cannot
be easily degraded. It can cause deep vein thrombosis,
pain, life-threatening strokes, and heart attacks.
28
child
Unaffected children
child
29
Autosomal Dominant:
Punnett Square
Using V and v for the dominant and recessive alleles for
Factor V Leiden, fill in this Punnett Square using the
parents on the previous slide and their predicted offspring.
30
Autosomal Dominant
Write three rules to keep in mind when counseling
someone about the likelihood of inheriting an
autosomal dominant condition:
1. About the parents’ genotypes.
2. About the parents’ phenotypes.
3. About the probability of the offspring showing the
trait.
31
Factor V Leiden Tests
• The blood types and testimony of the nurses have pretty well
confirmed that Diana is really the Keller’s daughter. Once made
aware of the potential for carrying Factor V Leiden, Kevin and
Lisa Keller both look into their family backgrounds.
• Factor V Leiden can exhibit incomplete dominance. It is
possible that either parent could carry the dominant allele and
have not exhibited symptoms, so they may wish to be tested.
They wish to look at their family pedigrees to narrow down
who is most likely carrying the allele.
• The problem is that heart attacks and strokes are the most
common form of death in the US, so these symptoms may not
be due to Factor V Leiden.
• There are also other effects of clotting disorder phenotypes
such as miscarriages (blood clots can form during pregnancy in
the veins of the plancenta), pulmonary embolisms, or painful,
32
swollen, sometimes engorged veins.
Keller Family Pedigree
Kevin Keller’s aunt’s husband and cousin have died of
heart attacks, but his mother, sister, and brother are
fine. Lisa Keller’s aunt had multiple miscarriages, her
mother suffered from deep vein thrombosis, and her
grandfather died of a heart attack. Create a pedigree
diagramming these relationships to use to answer the
clicker question on the next slide.
33
CQ#7: Who do you think is more
likely to carry the factor V Leiden
mutation and why?
A.Kevin Keller
B. Lisa Keller
C. Both
34
Pedigree of the Keller Family
Diana
Kevin Keller
Lisa Keller
35
Additional Information
• Online Mendelian Inheritance in Man
has excellent descriptions of the human
genetic disorders mentioned in this
case:
http://www.ncbi.nlm.nih.gov/sites/entrez
?db=OMIM
• Information about thrombophilia can be
found at: http://www.fvleiden.org/
36
Image Credits
Images appearing in this presentation were made by the author, Peggy
Brickman, except the following which were obtained from WikiMedia and
licensed under the Creative Commons Attribution-Share Alike 3.0 Unported
license.
Slide #15: graphic of autosomal recessive inheritance patterns.
Author: Armin Kübelbeck
http://commons.wikimedia.org/wiki/File:Autorecessive_en_01.png
•
Slide #21: picture shows the inheritance of a recessive allele on an Xchromosome.
Author: Armin Kübelbeck, modified to English by Peggy Brickman
http://commons.wikimedia.org/wiki/File:X-chromosomal-rezessiveVater.png
•
Slide #29: picture shows the inheritance of a dominant allele on an
autosome.
Author: Armin Kübelbeck
http://commons.wikimedia.org/wiki/File:Autodominant_en_01.png