Groundbreaking genetic research now allows scientists to detect potential diseases in unborn babies, revolutionizing prenatal care and offering new hope for expecting parents.
Thanks to incredible breakthroughs in genetic research, scientists can now detect potential diseases before birth. By studying the physical traits of a developing fetus (called fetal phenotypes) and using advanced tools like Next-Generation Sequencing (NGS) and the Human Phenotype Ontology (HPO), scientists are changing the way we detect and understand genetic diseases. But how does this work, and what does it mean for expecting parents?
By Julieta Asenjo
Key Takeaways:
Gene mutations cause many genetic disorders and can now be spotted early through fetal phenotyping.
A fetus's physical traits and growth patterns can hint at underlying genetic conditions.
Tools like Next-Generation Sequencing (NGS) and Human Phenotype Ontology (HPO) are revolutionizing prenatal diagnostics.
Early detection helps families plan better, access support, and prepare for specialized care.
Collaboration between genetics, medicine, and bioinformatics is key to advancing prenatal care.
Understanding Genetic Disorders
Within every living being lies a powerful code written in just four letters: A, T, C, and G. These letters, known as base pairs, form the DNA (deoxyribonucleic acid), the molecule that holds the information needed to build and maintain our bodies. DNA is organized into genes, which provide the blueprint for making proteins, the molecules responsible for nearly every function in our cells.
But what happens if there is a “typo” in our DNA? This is called a genetic mutation, a change in the DNA sequence that can sometimes lead to a genetic disorder. Mutations can happen randomly, or they can be caused by external factors like UV radiation, chemicals, or viruses. While our bodies often fix these mistakes, some mutations stick around and can lead to genetic disorders.
We inherit half of our genes from each parent, which means mutations can also be passed down. These inherited mutations can cause conditions that appear at birth or develop later in life. The severity of genetic disorders can range from life-threatening conditions to milder, everyday challenges. For example, a mutation in a gene that controls cell growth can cause cancer, where cells grow out of control and form tumors. A change in a gene that makes hemoglobin (the protein in red blood cells) can lead to sickle cell anemia, where red blood cells become misshapen and can’t carry oxygen properly. On the milder side, a mutation in the LCT gene, which helps the body digest lactose, can cause lactose intolerance, making it harder to break down dairy products. By studying these genetic mutations and the traits associated with them, scientists can better understand, treat, and potentially prevent many disorders.
What Are Fetal Phenotypes?
A phenotype is simply the physical traits we can observe, like eye color or height. When referring to fetal phenotypes, we’re focusing on the physical traits of a fetus during the prenatal period (the time during pregnancy). These traits can include growth patterns, organ development, and other features that may provide clues about the fetus’s health.
Fetal phenotypes are observed through tools such as ultrasounds, MRI scans, and other imaging technologies. Doctors might look at the size and shape of the fetus’s head or the length of limbs to assess growth and detect abnormalities. However, prenatal imaging has its limits. Some organs, like the skin, are hard to assess before birth, while others, like the lungs, change significantly after delivery, making it tricky to compare observations before and after birth. Despite these challenges, new technologies are helping researchers and doctors better understand fetal development.
The Impact of Next-Generation Sequencing (NGS)
Traditional methods of examining DNA could only analyze one gene at a time, but Next-Generation Sequencing (NGS) allows scientists to analyze all 20,000+ human genes in a single test. Here’s how it works:
Extract DNA: A blood or tissue sample is taken, and DNA is isolated.
Prepare DNA: The DNA is cut into pieces and tagged for analysis.
Sequence DNA: Machines read the sequence of A, T, C, and G in the genes.
Analyze Data (Bioinformatics): Computers compare the DNA to a “normal” reference to spot any disease-causing variants.
This technology is a game-changer for prenatal care because it provides a comprehensive look at the fetus’ genetic health.
A particularly powerful application of NGS is Whole Exome Sequencing (WES). Instead of looking at the entire genome (which is like reading a giant encyclopedia), WES focuses on the exons—the sections of DNA that directly code for proteins. This approach provides a detailed look at the parts of the genome most likely to impact health and development.
One of the most effective forms of WES is trio-based sequencing, where researchers compare DNA from both parents and the fetus to spot inherited genetic variants that might cause diseases. This method is especially effective for diagnosing rare genetic disorders that traditional tests might miss. WES can also be used in single setups (just the fetus) or duo setups (fetus and one parent). Even in these arrangements, it delivers valuable genetic insights, especially when resources are limited. This adaptability makes NGS an incredibly versatile tool in genetic research.
The Role of Human Phenotype Ontology (HPO)
NGS often generates a lot of data, including many genetic variants whose significance isn’t immediately clear. This is where the Human Phenotype Ontology (HPO) comes in. The HPO acts like a universal dictionary for medical symptoms, assigning each symptom, or phenotype, a unique code. With over 18,000 codes for hereditary diseases, the HPO is a powerhouse of information. For example, a heart defect might be coded as “HP:0001629” for a “ventricular septal defect.” This code acts as a common language, allowing doctors and researchers worldwide to share and compare findings more effectively, improving the accuracy of diagnosing genetic disorders.
By combining genetic data with these HPO codes, scientists can match specific DNA variants to the symptoms they cause. This helps them make sense of complex cases and even discover new connections between genes and diseases. Here is a look at how researchers work on these cases:
Identify Phenotypes: Record the fetus’s phenotypes using HPO codes.
Analyze Genetic Data: Use NGS to find variants that might explain the symptoms.
Reclassify Variants: Review uncertain variants using updated guidelines from the American College of Medical Genetics (ACMG).
Discover New Connections: If symptoms don’t match any known conditions, researchers dig deeper to try to find new links between genes and phenotypes. This is how we discover previously unknown genetic conditions.
Collaborate: Doctors, geneticists, and bioinformaticians work together to connect the dots between genes, symptoms, and medical care.
Why Early Detection Matters
In 2023, the World Health Organization (WHO) reported that congenital disorders (birth defects) cause an estimated 240,000 newborn deaths worldwide each year. Early detection of genetic conditions can help reduce this number. By identifying potential issues before birth, families and healthcare providers can take proactive steps to ensure the best possible outcomes. Fetal phenotyping allows doctors to recognize specific conditions, allowing them to create personalized care plans and offer focused support. This not only improves the fetus’s health outcomes but also gives families time to prepare emotionally and logistically for what lies ahead.
For instance, if a fetus is diagnosed with a medical condition, parents can work with healthcare providers to create a care plan, connect with support groups, and explore treatment options. Early detection also opens the door to emerging therapies, such as gene editing (a technology that can correct genetic errors) or in-utero treatments (treatments given to the fetus while still in the womb). These advancements hold promise for reducing the effects of certain genetic disorders, offering hope for healthier outcomes.
Conclusion and Personal Reflection
The combination of fetal phenotyping and advanced genetic tools is transforming our understanding of human development. With technologies like NGS and HPO, scientists are not only improving the diagnosis of known conditions but also discovering new genetic disorders. This progress is shifting how we view genetic diseases—from fixed outcomes to challenges that can be proactively addressed. This perspective is opening up new possibilities in research and clinical practice, creating more opportunities for intervention and treatment.
As a Master’s student in Biotechnology, I am excited to be working with these very tools for my thesis research. My work involves revisiting genetic data to explore the role of variants that were previously inconclusive or of uncertain significance. By carefully reanalyzing this information, I hope to better understand how these genetic changes might influence fetal development. It is challenging work, but every discovery brings us closer to better diagnostics, treatments, and outcomes for families.
Frequently Asked Questions
What are the ethical concerns around prenatal genetic testing?
Prenatal testing raises questions about handling unexpected results, genetic discrimination, and the emotional impact on families. Balancing the benefits of early diagnosis with these challenges is key to moving the field forward.
Can fetal phenotypes predict how severe a genetic disorder will be?
While phenotypes can hint at the presence of a disorder, predicting severity often requires additional genetic and clinical analysis. Phenotypes alone may not fully capture the range of outcomes.
How accessible are advanced genetic tools like NGS and HPO in prenatal care?
While NGS and HPO are becoming more widely used, access to these tools can vary depending on geographic location, healthcare infrastructure, and cost. Efforts are ongoing to make these technologies more accessible globally.
What happens if a genetic variant is identified but its significance is unknown?
Variants of uncertain significance (VUS) are common in genetic testing. Researchers use databases, functional studies, and family history to reclassify these variants over time, but some may remain unresolved until more data becomes available.
How might emerging technologies like CRISPR or gene editing impact prenatal genetic diagnosis in the future?
Technologies like CRISPR hold the potential to correct genetic mutations before birth, but they are still in experimental stages for prenatal use. Ethical, safety, and regulatory challenges must be addressed before they can be widely applied in clinical settings.
References
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About Julieta Asenjo, B.S., MSc Candidate
I have always been driven by a deep curiosity for science and a love for sharing knowledge in ways that resonate. As a researcher and writer at BioLife Health Research Center, I focus on conducting research, analyzing data, and developing content for healthcare articles and books. My goal is to share insights that improve health outcomes and spark curiosity about the wonders of life sciences. I am constantly inspired by the chance to learn, grow, and be part of research that drives meaningful change! Follow me on Linkedin.