Case Study: Predicting Breast Cancer and Huntington’s disease
with Pedigrees
ACTIVITY 1: THE BRCA-1 GENE
Recently, the location of a gene responsible for one type of breast cancer has been identified to be the lower
right leg of chromosome 15, thanks to a three-year study led by Dr. Mary Claire King at the University of
California-Berkeley.
Breast cancer afflicts 2% of women in the U.S., yet it's the leading cause of death. Why? Metastasis! Before
growing big enough to be obvious, the cancer spreads into the lymph nodes, and from there, anywhere in the
body. By the time it's detected, the cancer has located in numerous organs.
Some forms of breast cancer runs in families. The odds soar from 2% risk nationally to 50% if it is in the
family. To identify one's risk, a marker can be pinpointed in DNA analysis, but a family pedigree can
determine the need for such a test.
Your Job... Be Dr. King for a day!
Here's a dialogue with a patient named Elisabeth, who had a preventive mastectomy at age 28 because of the
frequency of breast cancer in her family. (Remember, Dr. King had no inkling as to the hereditary pattern of
the BR gene. Here's a tip too, she didn't know it at the outset, but I'll tell you: males can carry the gene
and not be affected)
Here are your notes of Elisabeth’s answers to your questions.
 "It's my two-year old daughter I'm worried about. Will she get this?"
 "I married to Steven, who has no family history of breast cancer"
 "I have three sisters, and two already have breast cancer."
 "Our dad is Frank, who had six sisters (my aunts) one 0f them never showed any signs of breast
cancer, though one got ovarian cancer, and three got breast cancer. The other one died in a car
accident at age 20."
 "Franks' parents (my grandparents) are free of breast cancer, but that's as far back as I can go with
information."
 "Franks's sister Rhonda (one of my aunts who had it), married a guy with no family history of it.
They had three kids (my cousins), two girls and a boy. One of the girls recently got diagnosed with
breast cancer."
TRACKING THE GENE...
First, generate a pedigree as much as possible from the discussion with Elisabeth. From the pedigree,
can you determine if the inherited gene is Sex linked? Dominant? or recessive?
Then, discuss in a small group, then compile a report which explains the diseases' mode of
transmission. Include such explanations as Elisabeth's daughter's likelihood of inheriting the BR
gene. Consider such moral issues as testing for the DNA marker, insurance regulations regarding
knowledge of the carriers of such markers, and anything else which comes to mind about BRCA-1.
ACTIVITY 2: WEXLER'S SEARCH FOR THE HUNTINGTON'S GENE
In 1872, the American physician George Huntington wrote about an illness that he called "an heirloom from
generations away back in the dim past." He was not the first to describe the disorder, which has been
traced back to the Middle Ages at least. One of its earliest names was chorea,* which, as in
"choreography," is the Greek word for dance. The term chorea describes how people affected with the
disorder writhe, twist, and turn in a constant, uncontrollable dance-like motion. Later, other descriptive
names evolved. "Hereditary chorea" emphasizes how the disease is passed from parent to child. "Chronic
progressive chorea" stresses how symptoms of the disease worsen over time. Today, physicians
commonly use the simple term Huntington's disease (HD) to describe this highly complex disorder that
causes untold suffering for thousands of families.
More than 15,000 Americans have HD. At least 150,000 others have a 50 percent risk of developing the
disease and thousands more of their relatives live with the possibility that they, too, might develop HD.
Until recently, scientists understood very little about HD and could only watch as the disease continued to
pass from generation to generation. Families saw the disease destroy their loved ones' ability to feel, think,
and move. In the last several years, scientists working with support from the National Institute of
Neurological Disorders and Stroke (NINDS) have made several breakthroughs in the area of HD research.
With these advances, our understanding of the disease continues to improve
Congress has just issued you the funding to study Huntington's disease- a disorder afflicting more than
50,000 Americans. Very little was known about the inheritance of Huntington's, but Dr. Nancy Wexler
(who's mother died of it) knew about the incredibly high rate of the disease around a place called Lake
Maracaibo, Venezuela. Here, you'll be a part of a team sent to Lake Maracaibo to study a large family
(of more than 5,000 member!), and report your findings!
In your research, you determine the following:
The genetic defect responsible for HD is a small sequence of DNA on chromosome 4 in which several
base pairs are repeated many, many times. The normal gene has three DNA bases, composed of the
sequence CAG. In people with HD, the sequence abnormally repeats itself dozens of times. Over time—
and with each successive generation—the number of CAG repeats may expand further.
The family spans five generations. It is your job (as it was hers) to pedigree the family and
determine what's going on here, and help future generations predict their chances of having this
disease or passing it on to their children.
Below is the Urgent FAX addressed to you that has arrived from Lake Maracaibo...
Urgent fax for:
Mrs. Lambert’s Expert Student, Dr. _________________________
Sparkman 9 University, Harvest, AL
From: Huntington's research team, Lake Maracaibo
Dear Dr. _____________________:
What follows are the results of our interviews with 38 members of the Gonzales family as you have
requested. See what you can make of it. We need you to provide us your solution in pedigree form, with
the poor family members who have Huntingtons Disease to be partly shaded if a carrier and fully shaded if
they have the disease. Draw your pedigree starting from the first generation to the fifth. Don’t forget to
write your genotypic predictions of each allele HH, Hh, or hh under each symbol. Thanks for your expert
opinion! We need this data back as soon as possible!!
Sincerely.
The team
Generation V:Luis, son of Zelda and Ramon.
AFFLICTED
Generation IV:
Ramon, son of Ricardo and Lydia. AFFLICTED
Zelda, married to Ramon. HEALTHY
Felipe, brother of Ramon. AFFLICTED
Juan, son of Miguel and Letty. AFFLICTED
Cira, daughter of Miguel and Letty. HEALTHY
Roberto, son of Miguel and Letty. HEALTHY
Nora, daughter of Jesus and Margarita, AFFLICTED
Alejandro, son of Pedro and Beatriz. AFFLICTED
Delia, daughter of Dano and Andrea. AFFLICTED
Tio, son of Dano and Andrea. AFFLICTED
Maria, daughter of David and Guadelupe. AFFLICTED
Nariza, daughter of David and Guadelupe. AFFLICTED
Generation III:
Lydia, daughter of Carlos and Imelda. AFFLICTED
Ricardo, married to Lydia. HEALTHY
Helga, daughter of Carlos and Imelda. HEALTHY
Letty, daughter of Carlos and Imelda. AFFLICTED
Miguel, married to Letty. HEALTHY
Margarita, daughter of Carlos and Imelda. AFFLICTED
Jesus, married to Margarita. HEALTHY
Beatriz, daughter of Carlos and Imelda. AFFLICTED
Pedro, married to Beatriz. HEALTHY
Juanita, daughter Javier and Bonita. AFFLICTED
Benito, son of Javier and Bonita. HEALTHY
Dano, son of Chito and Chelita. AFFLICTED
Andrea, wife of Dano. HEALTHY
David, son of Chito and Chelita. AFFLICTED
Guadelupe, wife of David. HEALTHY
Horatio, son of Chito and Chelita. HEALTHY
Lucio, son of Chito and Chelita. HEALTHY
Generation II:
Imelda, daugher of Rigo and Esmerelda. AFFLICTED
Carlos, married to Imelda. HEALTHY
Javier, son of Rigo and Esmerelda. AFFLICTED
Bonita, married to Javier. HEALTHY
Chito, son of Rigo and Esmerelda. AFFLICTED
Chelita, married to Chito. HEALTHY
Generation I:
Rigo. AFFLICTED
Esmerelda. HEALTHY