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CASE
CASE 31
You, From A to T
YO U R P E R S O N A L G E N O M E
As an American Studies
major at Georgetown
University, Claudia
Gilmore had plenty
of experience taking
exams. But at the age
of 21, she faced an
altogether different kind
of test—and no amount
of studying could have
prepared her for the
result.
Answers in the genetic code.
Claudia Gilmore found that her
Gilmore had decided
genome contains a mutation that to be tested for a
can lead to breast cancer.
mutation in a gene
known as BRCA1. Specific
mutations in the BRCA1 and BRCA2 genes are associated
with an increased risk of breast and ovarian cancers.
Gilmore’s grandmother had battled breast cancer and
later passed away from ovarian cancer. Before she died,
she tested positive for the BRCA1 mutation. Her son,
Gilmore’s father, was
Mutations that increase the risk
tested and discovered
of developing a particular disease he had inherited the
are called risk factors.
mutation as well. After
talking with a genetic
counselor to help her understand the implications of the
test, Gilmore gave a sample of her own blood and crossed
her fingers.
“I had a fifty-fifty chance of inheriting the mutation. I
knew there was a great possibility it would be a part of my
future,” she says. “But I was 21, I was healthy. A part of
me also thought this could never really happen to me.”
Unfortunately, it could. Two weeks after her blood was
drawn, she learned that she, too, carried the mutated gene.
Genetic testing is becoming increasingly common—
in some cases, even routine. In 2003, after 13 years of
painstaking work, scientists published the first draft of the
complete human genome. The human genetic code contains
about 3 billion base pairs, or structural units of DNA. In
the years that followed, much attention has been placed on
understanding the genetic differences between individuals.
In reality, there isn’t one single human genome.
Everyone on Earth (with the exception of identical
twins) has his or her own unique genetic sequence. Your
personal genome is the blueprint that codes for your hair
color, the length of your nose, and your susceptibility to
certain diseases. On average, the genomes of two people
are 99.9% identical, meaning that they differ at about 3
million sites.
Oftentimes, those individual differences have no
impact on health. In some cases, however, a particular
genetic signature is associated with disease. Sometimes a
gene mutation makes a given illness inevitable. Certain
mutations in a gene called HTT, for instance, always result
in Huntington’s disease, a degenerative brain condition
that usually appears in middle age.
The link between mutations and disease isn’t always
so clear-cut, however. Most genetic diseases are complex
in origin, and may require multiple genetic mutations,
as well as other nongenetic factors, for the disease to
develop. Mutations that increase the risk of developing a
particular disease are called risk factors.
Certain mutations in the BRCA1 and BRCA2 genes are
known risk factors for breast and ovarian cancers, for
instance. But not everyone with these mutations develops
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BRCA2
gene
What does your genome say about you?
Researchers have identified genes that, when
mutated, contribute to disease, as well as
differences that reveal parts of who you are
and where you come from.
The BRCA1 and BRCA2
genes are associated
with an increased risk
of breast and ovarian
cancer.
Chromosome 13
BRCA1
gene
HTT
gene
A mutation in the HTT
gene on chromosome
3 causes Huntington’s
disease.
The particular pattern
of mutations inherited
on the Y chromosome
can reveal a person’s
ancestry.
Chromosome 17
Chromosome 3
Distinct
pattern
of SNPs
Y chromosome
cancer. According to the National Cancer Institute,
about 60% of women with a harmful BRCA mutation
will develop breast cancer in her lifetime, compared
to about 12% of women in the general population. And
15% to 40% of women with a BRCA mutation will be
diagnosed with ovarian cancer, versus just 1.4% of
women without that genetic signature.
The BRCA mutations are just some of the thousands
of harmful genetic changes that geneticists have
identified so far. Other common mutations have
been shown to elevate one’s risk of developing heart
disease, diabetes, various cancers, and numerous
other common illnesses. Often, these mutations
involve changes to just a single base pair of DNA. These
common single-letter mutations are known as single
nucleotide polymorphisms, or SNPs.
Genome-sequencing technology has improved
significantly over the last decade, making it easier
and less expensive to scan an individual’s DNA for
potentially harmful SNPs. A number of companies now
offer genetic tests directly to the public. Unlike tests
such as the BRCA blood test that Gilmore was given,
these direct-to-consumer (DTC) tests are offered to
customers without any involvement from a medical
professional, at a cost of a few hundred dollars.
Some of these tests aren’t related to health at
all. Your personal genome contains many unique
features—from the shape of your fingernails to the
shade of your skin—that don’t impact your health,
but make you the person you are. Some DTC testing
services aim to tell customers about their heritage,
by screening genes to identify mutations that are
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more common in certain geographical regions or among
members of certain ethnic groups. One such company
offers genetic tests to African-Americans to determine
from what part of the African continent their ancestors
originated.
Other popular DTC tests inspect DNA samples for
SNPs associated with certain diseases and physical
traits—everything from Parkinson’s disease and
age-related macular degeneration to earwax type and
propensity for baldness.
Advocates of the tests say the technology puts the
power of genetic information in the hands of consumers.
Critics, on the other hand, argue that the information
provided by DTC tests isn’t always very meaningful.
Some SNPs might raise the risk of an already-rare disease
by just 2% or 3%, for example. In many cases, the precise
link between mutation and disease is still being sorted
out. Also, without input from a genetic counselor or
medical professional, consumers may not know how
to interpret the information revealed by the tests. The
American Medical Association has recommended that
a doctor always be involved when any genetic testing is
performed.
Moreover, knowing your genetic risk factors isn’t the
whole story. When it comes to your health and wellbeing, the environment also plays a significant role.
Someone might override a genetic predisposition for
skin cancer by using sunscreen faithfully everyday. On
?
the other hand, a person might have a relatively low
genetic risk for type 2 diabetes, but still boost the odds of
developing the disease by eating a poor diet and getting
little physical exercise.
Claudia Gilmore is especially careful to exercise
regularly and eat a healthy diet. Still, she can only control
her environment to a degree. She knew that, given her
genetic status, her risk of breast cancer remained high.
She made the extraordinary decision to eliminate that risk
by undergoing a mastectomy at the age of 23. It wasn’t
an easy decision, she says, but she feels privileged to have
been able to take proactive steps to protect her health.
“I’ll be a ‘previvor’ instead of a survivor,” she says.
For now, it’s still too costly to sequence every
individual’s entire genome. But each year, many more
genetic tests hit the market. Already, doctors are
beginning to design medical treatments based on a
patient’s personal genome. People with a certain genetic
profile, for example, are less likely than others to benefit
from statins, medications prescribed to lower cholesterol.
Doctors are also choosing which cancer drugs to prescribe
based on the unique genetic signatures of patients and
their tumors.
We’ve only just entered the era of personal genomics.
While there’s much left to decipher, it’s clear that each
of our individual genomes contains a wealth of biological
knowledge. And, as Gilmore says, “I’ve always been taught
that knowledge is power.”
CASE 3 QUESTIONS
Answers to Case 3 questions can be found in Chapters 12-20.
1. What new technologies will be required to sequence your personal genome? See page 12-16.
2. Why sequence your personal genome? See page 13-4.
3. What can your personal genome tell you about your genetic risk factors? See page 14-4.
4. How can genetic risk factors be detected? See page 15-9.
5. How do genetic tests identify disease risk factors? See page 16-17.
6. How can the Y chromosome be used to trace ancestry? See page 17-14.
7. How can mitochondrial DNA be used to trace ancestry? See page 17-16.
8. Can personalized medicine lead to effective treatments of common diseases? See page 18-12.
9. How do lifestyle choices affect expression of your personal genome? See page 19-10.
10. Can cells with your personal genome be reprogrammed for new therapies? See page 20-5.
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