In NCGENES, There Are Three Types of
Incidental Information
1. Information That Is Medically
Actionable:
In rare cases, incidental information is “medically
actionable”.
What Is Whole Exome
Sequencing?
WES may find genetic variants that cause a serious disease
that is unrelated to your diagnosis. In very rare cases,
knowing this information can lead you and your doctor to
take clear steps to prevent or successfully treat the disease.
We call the information learned from these genetic variants
“medically actionable” because there are definite ways
to use it to help protect your health.
In NCGENES, we will look for variants in a group of
genes that give medically actionable information.
If your WES finds variants in this group, and after
they are confirmed in the UNC Hospitals’ Molecular
Genetics Laboratory, you will be told this medically
actionable incidental information.
2. Incidental Information That Is Not
Medically Actionable:
In some cases, WES may find genetic variants that could
give you information about an unrelated health concern,
but this information does not lead you and your doctor
to take specific steps to prevent it. We call the information
learned from these variants “non-medically actionable”
because there are no definite ways to use it to help protect
your health.
Some adults NCGENES will be asked to decide
whether or not they would like to learn any types of
non-medically actionable incidental information that
may be available from WES.
3. Information That Has No Known
Medical Value:
NC enes
The great majority of variants have no known medical value
so these will not be interpreted or reported to people in
NCGENES.
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9 19 - 5 37-37 9 5 n c g e n e s . o r g
NC enes
North Carolina Clinical Genomic Evaluation
by Next-generation Exome Sequencing
NCGENES
North Carolina Clinical Genomic Evaluation
by Next-generation Exome Sequencing
What Is Whole Exome Sequencing (WES)?
WES is a new genetic test that can find genetic causes of some health
problems. The test studies the exome, which contains the genetic
information used by our cells to make the different proteins in our
body. Proteins, along with our environment, affect how our bodies
work.
We have about 20,000 to 25,000 genes. Genes are long stretches
of DNA. All genes have the same four DNA bases: “A”, “C”, “T”,
and “G”. The order of these four DNA bases in a gene is called the
“sequence”. There can be thousands to millions of DNA bases in a
single gene sequence.
Each gene has a unique DNA sequence. The DNA sequences tell the
cell which protein to make and how to make it.
WES finds the sequence of the DNA bases in
many genes at the same time.
The DNA sequence of a gene is not exactly the same in everyone. WES
reads the sequences of many genes at the same time and finds
many thousands of differences, called “variants”.
Some variants that WES finds may give you information about your
health, but most will not. Most often we don’t know whether or not
a variant will have an effect on health. And, WES will not find all the
variants that could possibly affect your health.
What is a Gene Sequence?
The DNA bases (A, C, T, and G) act like “words” in a sentence. Just like
the order of the words in a sentence is very important, so is the order or
sequence of the DNA bases.
Most people have this version of “Gene 1”:
“A dog ran after the cat” has a
different meaning from “A cat ran
behind the dog”.
A few people have a different version (“version B”) of that gene:
Each gene has a unique DNA
sequence that tells the cell which
protein to make and how.
Let’s say that a person’s “Gene 1”
has this sequence:
A, C, T, G, C, T, A, T, G, G, C, G, C, T, A, G, G, A, G, G, T, T, A, A, A...
This sequence tells the cell to make “Protein 1”
In contrast, the sequence of “Gene 2” in the same person could look
like this:
A, C, T, G, T, A, T, T, T, G, T, C, T, C, A, A, G, C, C, C, T, T, T, C, A...
A, C, G, G, C, T, G, T, G, G, C, G, C, T, A, G, G, A, G, G, T, T, A, A, A, A...
The DNA sequences of both versions will be used to make the same
protein but each person will make a slightly different version. For
example, both sequences could have the instructions to make the
protein that helps digest milk. However, let’s say that people who have
version B digest milk faster than those with the more common version.
Those people with version B have a gene variant that affects their
ability to digest milk.
Most versions of a gene cause
only slight changes (or none at all)
to the meaning of the instructions.
But some gene variants cause such
a big change in the meaning of
the instructions that it harms the
ability of the protein to do its job.
These kinds of genetic variants
can cause health problems.
This sequence tells the cell to make “Protein 2”
These two different proteins will have different jobs in the body.
For example, Protein 1 may work by helping to digest milk while
Protein 2 may work by helping the heart beat at the right rate.
What are Gene Variants?
The DNA sequence of a single gene is not exactly the same in
everyone. Different people can have slightly different sequences of
the same gene.
For example, the following are two, slightly different sequences
of the same gene.
ncge n e s .o rg
A, C, C, G, C, T, A, T, G, G, C, G, C, T, A, G, G, A, G, G, T, T, A, A, A, A...
WES Finds Many Different Types of Gene Variants
The main reason that you had WES was to see if it could find genetic
variants that explain the health problem or the diagnosis that led you to
join NCGENES. A group of genes that are related to your diagnosis will be
studied in-depth. Everyone will learn if WES found gene variants to
explain his or her diagnosis.
In addition, WES can find many other variants that are not related to your
diagnosis but that may affect your health in other ways. That’s because
WES finds the DNA sequences of many genes at the same time. Most of
these genes are not related to your diagnosis. The information that you can
learn from these kinds of unrelated genetic variants is called “incidental
information.” information.”
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