Genetic testing can be beneficial across the entire life span, beginning even before conception. Many people choose to have carrier screening done before they become pregnant or during pregnancy to learn whether they carry a genetic mutation for hereditary diseases such as cystic fibrosis or spinal muscular atrophy. If both parents are carriers of the same genetic disease, there’s a 25% chance that their children will have the disorder. Newborn screening is now standard for certain genetic, endocrine, and metabolic disorders, as well as for hearing loss and serious congenital heart defects.
Then, throughout our lives, predictive and pre-symptomatic testing can be used to determine whether we are predisposed to certain hereditary conditions – like cardiovascular disease, diabetes, or cancer, as well as genetic abnormalities – and to diagnose adult-onset genetic conditions like heart disease or diabetes.
Joyce So, MD, PhD, UCSF’s Epstein Professor of Human Genetics, points out that the availability and types of genetic testing have changed significantly over the lifetimes of today’s adults. “Even if they were seen as a child for something that was thought to be genetic,” she says, “if they didn’t have a diagnosis and they came back now for genetic evaluation, there’s a much higher likelihood that we would find a diagnosis because the testing has changed so much over the last 15 to 20 years.”
Norton explains that “genetic counseling is really an opportunity for patients to find out more about genetic testing before deciding whether or not to have it done.” The purpose of genetic counseling is multifold, Tong says. One is gathering information about the patient’s personal and family history, determining the likelihood of a hereditary predisposition or hereditary risk of disease, and looking at the guidelines to determine whether genetic testing is appropriate.
“The counseling side of [genetic testing] in the pretest setting is talking with the patient about what the testing entails, what you learn, what you don’t learn, what the risks and benefits are, and helping the patient come to a decision whether or not they want to do the genetic testing – making an informed decision about it,” Tong says. He adds that there are no medical risks to genetic testing. But testing could reveal information the person wasn’t seeking, there could be family implications, or the person might not be psychologically prepared for the information learned from the testing. This is why the third part of the process, interpreting and explaining the results to the patient, is so critical.
The Genetic Information Nondiscrimination Act (GINA) prohibits health insurers from using genetic information to set rates or offer or withhold policies and prohibits employers from using it in employment decisions. But GINA’s protections don’t apply to long-term care insurance, life insurance, or disability insurance, nor do they apply to the military, which is allowed to use genetic information in employment decisions.
Nadav Ahituv, PhD, director of the UCSF Institute for Human Genetics, says an ethical dilemma can arise when genetic testing yields what’s known as a variant of unknown significance (VUS). These are variants that are quite rare and have not yet been connected to a health condition. “So those are very hard to interpret, and [counselors] really try to make sure that if they provide results, they’re reliable,” Ahituv says.
“As medical professionals, we must ensure that genetic testing is conducted ethically, equitably, and with sensitivity to the historical context that may affect trust among minority groups,” Rajkovic says. “Our goal is to make genetic testing accessible and fair for all individuals, irrespective of their ethnicity or race, and to actively address and work to overcome the barriers created by past misuses of genetic science.”
We are living in the midst of a genetic revolution, but it’s still in its infancy, and it has its limitations. Ensuring equitable access to genetic testing remains a challenge. And currently, there is much more genomic information about people of European ancestry than of any other demographic group. In order for more people to benefit from the revolution, it’s essential for research studies to include more individuals of non-European ancestry.
Additionally, no one test can detect every genetic condition, nor is every test definitive. A negative result could mean that the wrong test was done, that there is not yet a test for that specific condition, or that there simply isn’t a genetic cause for the person’s illness.
It’s also important to remember that genetics is only one part of the health equation. “Genetics is not simple and does not in itself determine our health. Our health is a confluence of genetics, environment, education, socioeconomic status, and other variables,” Rajkovic says.
Still, countless people have benefited from genetic testing – and there will no doubt be many more in the future. After all, says Rajkovic, we understand only 1.5% of the genome that codes for proteins and even less about the noncoding part of the genome.
One area that is quickly gaining traction is epigenetics – the study of how behavior and environment can cause changes in the way our genes work. “Epigenetics is increasingly used to classify tumors and predict the course of cancer syndromes,” Rajkovic explains, adding that because epigenetic signatures are so specific to tissue and tumor type, companies are exploring ways to use them to screen individuals for cancer.
“Similar to how a Pap smear is used to detect precancerous or cancerous cells, there is a growing effort to use epigenetic markers to identify early signs of cancer elsewhere in the body. This could enable early detection and treatment, potentially improving outcomes for patients,” Rajkovic says.
Studies also are looking at the impact of sequencing the genomes of every newborn, thus creating a genetic passport that can be used during their lifetime. Rajkovic says the likelihood of such a practice increases as costs decrease and as the benefits of early intervention become clearer. However, he emphasizes that significant research is still needed to establish the clinical value of such an approach, particularly its ability to reduce suffering and bring about positive health outcomes. “To validate the effectiveness and benefits of creating genetic passports for newborns, a large-scale study will be necessary. We expect considerable developments in this area within the next decade. Success in this endeavor will likely require government support,” Rajkovic says.
“This could revolutionize preventive health care, allowing for early detection and intervention for countless conditions. It can also lead to the development of whole new classes of therapeutics to prevent disease manifestations,” he adds.
The ABCs of DNA: A Genetic Glossary
DNA
DNA is the molecular structure in every living thing containing that organism’s genetic code; it’s a long strand of nucleotides twisted into a double helix shape. Medical genetic testing doesn’t require visualizing DNA with microscopy but instead uses laboratory techniques and bioinformatics to analyze nucleotide sequences in specific, targeted regions on the strand.
Gene
A gene is a discrete segment of DNA that carries the information needed to make a specific protein. Each protein, in turn, directs a particular bodily function. Abnormal (or mutated) genes cause genetic conditions. Genetic testing is done when a specific gene or set of genes is suspected to be the culprit behind a disease.
Chromosome
Human genes are organized into 23 pairs of thread-like structures called chromosomes; we inherit one set of chromosomes from each parent. Some genetic conditions, such as Down syndrome, result when there are too many or too few chromosomes due to errors during cell division. In other cases, such as cystic fibrosis and sickle cell anemia, a mutation in a single gene on a specific chromosome can cause the disease.
Cell
A cell is the most basic unit of life. The process of genetic testing requires DNA to be extracted from the patient’s cells. First, a chemical reaction breaks down the cell membranes. Then the DNA is separated from the other cellular components through a series of purification procedures.
Genome
An organism’s genome is its complete set of DNA. Variations in our genome influence our risk of developing genetic diseases, as well as our responses to medications. Whole-genome sequencing involves analysis of an individual’s entire genome and can be done when the cause of a disease or disorder is unclear.