What is exome sequencing?

Exome sequencing is a single test that can be used to detect many genetic disorders. Lab personnel, using high-tech machines, analyze blood drawn from you or your child to read the genetic code of about 20,000 genes. They are looking for any changes that could lead to differences in the way the body grows and develops.

Instead of analyzing single genes one by one like some types of genetic testing, exome sequencing technology can analyze many genes all at once.    

Since exome sequencing is complex, an appointment with a genetic counselor and/or geneticist is typically arranged prior to starting the test. 

Why might my child need exome sequencing?

Your child’s doctor may recommend exome sequencing if a physical exam or medical record reveals certain features that could have an underlying genetic cause. Finding out if your child has a genetic condition can sometimes help their doctor determine the best course of treatment and provide information about what to expect going forward.

Understanding the exome and genome [What are we testing?]

Specific segments of our DNA are called genes. Genes serve as the instructions that tell our body to produce proteins that make us grow and develop. The exome is the part of the genome that codes for proteins.  Most genetic conditions are due to changes in the exome. In exome sequencing the lab team pays special attention to the medical exome in particular, this is made of the about 6000 genes that are known to cause genetic conditions. 

How is exome sequencing performed?

To perform medical exome sequencing, we will typically take a sample of your child’s blood. Less frequently, other tissue types (for example, skin cells or cheek swabs) are needed. DNA is extracted from these blood or tissue samples and then analyzed.

We also request blood samples from both biological parents and/or siblings to help with analysis. If biological family members are not available, the testing can still be performed.

Laboratory technicians will use a special method to extract only the portion of the genome that contains genes (the exome). High-tech machines then sequence, or read, the genetic code of the exome. This reading is compared to a standardized reference sequence.

If your child’s genetic code is different from the reference sequence, the changes are highlighted. The data is then reviewed by both laboratory personnel and clinicians to determine if any of these highlighted changes could be the cause for your child’s clinical features.

In addition to comparing your child’s sequence to a reference sequence, lab personnel also compare it to other family members’ sequences. This comparison allows the lab to determine what sequence changes are unique to the child and what sequence changes other family members share. Determining what changes are inherited and what changes are new can be extremely helpful when trying find the one or two changes that may have caused a genetic condition.

Exome sequencing is a highly complex test and requires time for both sequencing and interpreting the information. Most exome results will be available to families within three months.

What kinds of results can I expect?

Exome sequencing can produce one of several results.

• Positive: A change(s) that can account for the patient’s primary clinical features was identified.
• Negative: No alterations to explain the primary indication were identified.
• Inconclusive: The laboratory did not find a definitive answer for the primary features.