What is whole-exome sequencing (WES)?
Exome sequencing is part of a cutting-edge approach called “personalized medicine.” Personalized medicine prescribes treatment specifically for the baby’s genetic makeup.
With unexpected fetal abnormalities occurring in 2-5% of pregnancies, a clinical exome sequencing test allows clinicians to find and understand disease genes. With this knowledge, we can promote parental counseling and informed decision-making and assist in pregnancy management.
Whole exome sequencing (WES) has expanded high-risk OB’s ability to further clarify abnormalities seen in traditional ultrasound results. With a WES test, we can now offer prospective parents a clearer picture of their baby’s genetic abnormalities and discuss the best course of action.
This genotyping information allows parents to make informed choices about a potential problem early in their pregnancy. Whole-exome sequencing early in the pregnancy allows for more-informed decision-making. If the parents choose not to continue a pregnancy, it is safer than doing so later in the pregnancy.
High-risk mothers in the Los Angeles area seek out the compassionate counsel of Dr. Steve Rad, a double-board certified Obstetrician-Gynecologist with sub-specialty training in Maternal-Fetal Medicine (MFM).
How does whole-exome sequencing work?
To best understand the concept of the whole exome sequence, it is important to grasp the notion of the term genome. A genome represents a person’s (or in this case a baby’s) complete set of genetic instructions.
The two methods used to find genetic abnormalities are whole-exome sequencing and whole-genome sequencing — both known as next-generation sequencing (NGS).
WES is a novel method that allows the doctor to analyze all of the protein-coding regions (exons) of a genome. A DNA sequence has about 3 billion structural units, but only 1% of these code for proteins.
These specific regions are called exomes (instead of genomes). Exomes determine traits such as eye color and blood type. Discrepancies in protein-coding regions show the prevalence of common and rare disease-causing disorders.
Unlike some tests that examine a single gene at a time, exome sequencing analyzes all the protein-coding sequence data at once. The goal of WES is to identify fetal genetic disease quickly.
After extracting a sample of placental tissue, the geneticist looks for mutations caused by unusual genome sequencing. Dr. Rad then collaborates with the geneticist on the data analysis, interprets the results, and relays them to the patient.
How accurate is exome sequencing?
Though the results are not guarantees of a particular genetic disease, exome sequencing can define potential birth defects. This information becomes quite important for prospective parents if a marker for a life-changing event is found.
At that time, the parents can begin planning for specialized treatment early in the baby’s life. A genetic counselor can also be consulted for more clarity on your results.
More about birth defects
Our human genome is amazingly intricate, and as a baby grows, complicated genetic instructions develop in its body. If one of those instructions goes awry, it can lead to serious defects or a number of human diseases.
Using modern sequencing technology, healthcare providers can calculate potential clinical presentations of genetic disorders.
Finding birth defects in the womb is extremely important and allows for health concerns to be addressed immediately after birth. Though some birth defects are untreatable, even with the advances in pediatric care, other children may benefit from new surgical techniques and medicines found from exome sequencing.
…genotyping information allows parents to make informed choices about a potential problem early in their pregnancy.
Who is a good candidate for whole-exome sequencing?
Patients who have a family history of disease or are searching for a diagnosis to explain symptoms may be able to avoid unnecessary, more invasive diagnostic tests by undergoing exome sequencing.
Some patients also choose to have family members undergo WES testing to create a more complete picture of their child’s risk factors.
What can a WES test tell us?
Exome sequencing can detect a variety of genetically-linked conditions. Such as:
Exome sequence testing risks
Though the whole-exome sequencing test opens results that had been unavailable until recently, it is not without some risks. However, the side effects of WES testing are not physical, but psychological.
Bringing the potential for future disease into focus can have its pitfalls. Because doctors can delve deeper into exploring the exome, they may discover “secondary” findings. This means they may find genetic abnormalities that were not originally suspected or variants that may predispose the baby to other conditions — such as autism.
Parents undergoing exome sequencing may choose to opt out of secondary results.
I work closely with my patients and their family to help them understand and cope with their genetic testing results. If further information is needed, I can also refer you to genetic counseling.
More about Dr. Rad and the Los Angeles Fetal and Maternal Care Center
The OB/GYN team at Los Angeles Fetal and Maternal Care Center is highly trained in high-risk pregnancies. In addition to displaying superior medical knowledge, the physicians and staff at the office all display compassion and understanding when guiding patients down their complicated birthing path.
Dr. Rad’s team at Los Angeles Fetal and Maternal Care understands that exome sequencing can be especially helpful for older, pregnant women, as the results can help them to decide how to proceed with their plans.
Dr. Rad has undergone rigorous training with high honors at renowned institutions, including the Department of Obstetrics and Gynecology at David Geffen School of Medicine at the University of California, Los Angeles, USC, Cedars-Sinai Medical Center, and UCSF Medical Center, as well as centers internationally in London, Austria, Israel, and Africa.
Call us at (844) 473-6100 or schedule your consultation online. We are currently accepting new patients.
We are conveniently located for patients throughout Southern California and the Los Angeles area at locations in or near Beverly Hills, Santa Monica, West Los Angeles, West Hollywood, Culver City, Hollywood, Venice, Marina del Rey, Malibu, Manhattan Beach, Newport Beach, Irvine, and Downtown Los Angeles. We also offer in-home prenatal care and a fly-in program for out-of-town and international patients. Dr. Rad even travels to patients who need him throughout the U.S. and around the world.
If you can’t make it to Dr. Rad, he also offers virtual consultations worldwide.
Lee, H., J. L. Deignan, N. Dorrani, S. P. Strom, et al. 2014. “Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders.” Journal of American Medical Association 312 (18): 1880–87. doi: 10.1001/jama.2014.14604. PMID: 25326637
UCLA Health. UCLA Clinical Genomics Center. https://pathology.ucla.edu/genomics.