Case Study Bloodline

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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

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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

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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!”

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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.”

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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.”

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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.

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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.”

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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.

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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?

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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.

Lisa Kevin

A. IA _{/ i, -/-} _{i / i, +/+}

B. IA _{/ I}A_{, -/-} _{i / i,}

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+/-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 Kevin Keller Cynthia Morrison Mr. Morrison

A- O+ B+

O-Olivia Keller Diana Morrison

O- A+

A. Yes, Cynthia and Kevin could have a child like Diana with Rh positive blood.

B. No, Cynthia and Kevin could not have a child who has type A blood.

C. No, Cynthia and Kevin could not have a child who was Rh positive.

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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.”

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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.”

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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.

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15

child

Hemophilia C: Autosomal recessive

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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.

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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.

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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. 25%

B. 50%

C. 67%

D. 100%

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Pedigree Symbols

Way to visually represent human family

relationships and infer inheritance patterns.

Male

Female

marriage/mating

offspring in order of birth

deceased individuals

individuals showing trait

carriers

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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.

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Autosomal Recessive:

Punnett Square

Using Y, H_X _{for the dominant allele for hemophilia A}

(normal) and h_X _{for the recessive allele for hemophilia A}

(hemophilia), fill in this Punnett Square using the parents on the previous slide and their predicted offspring.

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X-linked Recessive

Write three rules to keep in mind when

counseling someone about the likelihood of inheriting an X-linked recessive condition:

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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. 25%

B. 50%

C. 67%

D. 100%

E. More information is required to answer

this question.

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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.

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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?

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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.

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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

over-production 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.

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Unaffected children

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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

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Autosomal Dominant

Write three rules to keep in mind when counseling someone about the likelihood of inheriting an

autosomal dominant condition:

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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,

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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.

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A.Kevin Keller

B.Lisa Keller

C. Both

CQ#7: Who do you think is more

likely to carry the factor V Leiden

mutation and why?

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Pedigree of the Keller Family

Diana

Lisa Keller Kevin Keller

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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/

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Image Credits

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 X-chromosome.

Author: Armin Kübelbeck, modified to English by Peggy Brickman http://commons.wikimedia.org/wiki/File:X-chromosomal-rezessive-Vater.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 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.