Translational Genomic Protocols
Each person has a unique set of genes, passed down from their parents, that determine their physical features — like eye color, hair color and height.
Genomics is the study of a person’s genome, or their complete set of genes. Almost every cell in a person's body contains a complete copy of the genome.
Genomics is an important part of diagnosing and personalizing treatment for children who receive care at Nationwide Children’s. Researchers have found the root causes of many childhood diseases can be found in the genome. By using testing to find out if a patient has a particular genetic variant — a gene that’s changed, added, missing or in the wrong place — their health care team can better understand their risk for a certain disease.
There may be more diseases that have genetic causes doctors have not yet identified. Every day, research leads to new understandings of the genetic causes of conditions and improvements in the technologies that help patients, families and doctors get answers more quickly.
What is Translational Research in the Field of Genomics?
Translational genomics research aims to find new and better ways to understand how changes in genes can help patients and their families find answers. By revealing information about genetic causes of patients’ diseases, what variants may be associated with certain diseases, how to test for them, who should be tested and more, translational genomics research enables providers to diagnose conditions earlier, better predict patient outcomes and personalize treatment for each individual patient.
The Steve and Cindy Rasmussen Institute for Genomic Medicine, in collaboration with clinical departments across Nationwide Children’s, has developed several new translational research programs.
Principal Investigator: Peter White, PhD
Individuals with rare diseases, symptoms or birth defects may undergo genetic testing to help families and clinicians learn about their conditions. But there are times when traditional genetic testing can still leave questions unanswered.
The Rare Disease Research study aims to help uncover the underlying genetic differences that may be behind some of these rare and complex conditions. The main goal of this study is to help families find answers about possible genetic causes of disorders or birth defects while helping clinicians understand what causes patients’ unique symptoms.
By taking a deeper look into a patient’s genetic code using different methods, researchers can learn more about what causes rare diseases. This study may also reveal new information about genes/genetic conditions and new genetic testing methods.
Methods/technologies used:
- Genome sequencing
- Exome sequencing
- RNA sequencing
- PacBio Long Read Sequencing
Learn more:
Principal Investigator: Daniel Koboldt, MS
The Epilepsy Research Study uses the latest genetic testing methods to help identify gene changes that influence brain functioning. Families may learn about the genetic basis of a patient’s epilepsy, brain malformation, overgrowth and/or neurological disorder. Studying the genomics of these conditions may improve understanding of these conditions and help find better treatments.
By studying both blood and brain tissue collected from surgery and comparing gene changes patients have been born with to gene changes found in brain tissue associated with epilepsy and neurological disorders, researchers can help identify the gene changes that may lead to disease.
This study aims to help the research community better understand the genetics of epilepsy and neurological disorders and to help patients and their clinicians understand the role genetics play in patient care and treatment, including testing, diagnosis, and evaluating eligibility for targeted therapeutics and clinical trials.
Technologies used:
- Genome sequencing
- Exome sequencing
- RNA sequencing
Learn more:
Principal Investigator: Bimal Chaudhari, MD, MPH
This study has focused on developing new laboratory technology and software to implement an effective workflow for a rapid genomic profiling program (with results in 14 days or less) at Nationwide Children’s to improve patient diagnosis and treatment. Rapid genome sequencing at Nationwide Children’s allows clinicians in acute and critical care settings to find out the genetic basis of a health condition more quickly, as compared to sending samples to another laboratory for testing. The study will evaluate the potential impact of using this approach.
Technologies used:
- Rapid genome sequencing
- RNA sequencing
- Natural language processing
- Machine learning
Learn more:
Principal Investigator: Catherine Cottrell, PhD
The purpose of this study is to learn more about the genomic basis of cancer, blood diseases and noncancerous malformations/lesions. Studying the genomics of these conditions may help researchers learn more about their causes, learn more about these diseases overall, find better treatments and assess how to use comprehensive genomic profiling in understanding these conditions.
The integration of clinical care and research is a central priority of the hospital’s latest strategic plan. This study aims to unify the clinical and research aspects of comprehensive genomic profiling. The process of genomic testing and the impact of associated findings on patient care is evaluated.
Results obtained using a novel research assay will be confirmed, when possible, using an approved assay. Results are returned to the patient/clinician and diagnostic findings are reported in the patient’s medical record. Learn more about the Steve and Cindy Rasmussen Institute for Genomic Medicine Clinical Laboratory.
Patients may learn information that can help their clinical team better diagnose or treat their blood disorder, cancer or noncancerous malformation/lesion.
Technologies used:
- Germline/comparator exome sequencing
- RNA sequencing
- Methylation array
- Fusion analysis
Learn more:
Principal Investigator: Rolf Stottmann, PhD
Studying the genetic variants (changes in genes) that naturally occur in humans can help scientists understand the genetic causes of conditions at birth (congenital) affecting the structure and function of the developing brain and face. The Craniofacial Research Study uses genetic testing to help uncover the underlying genetic causes of congenital craniofacial (tissues of the central nervous system and facial structures) differences, such as syndromic cleft palate/cleft lip and structural brain malformations.
By studying the genetics of patients and families with these conditions, this study aims to provide clinicians and families with information about the reason for these structural differences and risk of recurrence.
This study is designed to identify genetic origins of these malformations and has a strong basic research component, employing the tools of molecular embryology and genome editing (CRISPR/CAS9) to create novel cellular and animal models. These experimental platforms allow researchers to directly test the hypotheses derived from the sequencing, study the underlying molecular mechanism(s) and potentially use these cellular and animal models to test therapeutic interventions.
Technologies used:
- Genome sequencing
- Exome sequencing
- RNA sequencing
- CRISPR/CAS9
- Cellular models
- Animal models
Principal Investigator: Richard Wilson, PhD
Traditional genetic approaches have had minimal success in identifying genetic risk factors for psychiatric and behavioral health disorders and conditions. These can include mood disorders, autism spectrum disorder, bipolar disorder, schizophrenia, major depression and suicidality. There are many questions about how genetic changes may contribute to behavioral health disorders.
This family-based study examines how gene changes may cause or contribute to a patient’s behavioral health disorder. Researchers use next generation genomic sequencing, interviews and other analyses of genomic data in patients and their families. This may provide insight into genetic factors that may be one of the contributing factors to these diseases. Identifying these genetic/genomic risk factors would allow for better counseling and personalized risk assessment in families with a history of behavioral health disorders. Insights from this study also have the potential to inform treatment and management of these disorders, specifically related to psychiatric medications and the relationships between specific genes and the most effective therapies.
If a genetic cause or contributing factor for the behavioral health disorder is found, patients may be able to learn how the disorder is being passed down through the family or who else is at risk.
Technologies used:
- Genome sequencing
- RNA sequencing
More Information
DNA: The molecules inside cells that carry genetic information and pass it from one generation to the next.
Etiology: The cause or origin of disease.
Exome Sequencing: A laboratory method used to learn the exact order of the building blocks that contain information for making proteins that make up the pieces of a person’s DNA. These pieces, exons, are thought to make up about 1% of a person’s genome (complete set of DNA). Whole exome sequencing (WES) is used to find mutations (changes) in genes that may cause diseases, such as cancer.
Genome: The complete set of DNA (genetic material) in an organism. In humans, almost every cell in the body contains a complete copy of the genome. The genome contains all the information needed for a person to develop and grow. Studying the genome may help researchers understand how different diseases, such as cancer, form and respond to treatment. This may lead to new ways to diagnose, treat, and these diseases.
Genomic Profiling: A laboratory method used to learn about all the genes in a person or in a specific cell type and the way those genes interact with each other and with the environment. Genomic profiling may be used to find out why some people get certain diseases while others do not or why people react in different ways to the same drug. It may also be used to help develop new ways to diagnose, treat and prevent diseases such as cancer. Also called genomic characterization.
Genome Sequencing: A laboratory method that is used to learn the exact order of all of the building blocks (nucleotides) that make up a person’s genome (complete set of DNA). Whole genome sequencing (WGS) is used to find changes that may cause diseases such as cancer.
Germline: The cells that form eggs in females and sperm in males. Germline cells contain the genetic information that is passed down from one generation to the next.
Germline Variant: A gene change in a body’s reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring. Germline variants (or mutations) are passed on from parents to offspring.
Methylation: A chemical reaction in which a small molecule called a methyl group is added to other molecules. Methylation of proteins or nucleic acids may affect how they act in the body.
Phenotype: The physical, biochemical and behavioral traits that can be observed in a person. Some examples of a person’s phenotype are height, eye color, hair color, blood type, and the presence of certain diseases. A phenotype is based on a person’s genes and some environmental factors, such as diet, exercise and smoking.
RNA: One of two types of nucleic acid made by cells. RNA contains information that has been copied from DNA (the other type of nucleic acid). Cells make several different forms of RNA. Each form has a specific job in the cell. Many forms of RNA have functions related to making proteins. RNA can be made in the laboratory and used in research studies.
RNA Sequencing: A laboratory method used to learn the exact sequence (order) of the building blocks that make up all RNA molecules in a cell. In a cell, RNA is copied from pieces of DNA and contains information to make proteins and perform other important functions. RNA sequencing is used to learn more about which genes are expressed (turned on) in different types of cells and when and how these genes are expressed. This may help researchers understand the cause of certain diseases such as cancer.
Somatic Variant: An alteration in DNA that occurs after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases.
Find these definitions and more in the National Cancer Institute (NCI) dictionary and other National Institutes of Health (NIH) dictionaries: https://www.cancer.gov/publications/dictionaries/cancer-terms
Blog Post: Genes, Genetics and Genomics: Understanding What Makes You Who You Are
Genes are short sections of DNA that pass information down from parents to their children, including information about physical traits like eye and hair color and information that can cause diseases. Each person has a unique set of tens of thousands of genes, called a genome.
Blog Post: Rare Disease: Finding Answers for Patients with Mysterious Conditions
Every cell in the body with a nucleus contains a copy of the genome, which gives each part of the body instructions about how to function. When something causes a change in these instructions — genes that are added, missing or in the wrong place — this can also cause disease. Rare genetic conditions can be caused by a single change in one of the 3 billion pieces of DNA that make up the tens of thousands of genes in a person’s genome.
Video: What is DNA and Gene Sequencing?
Studying DNA may reveal the causes of certain genetic abnormalities or diseases, which can help with diagnosing and treating them.
Video: Personalized Medicine: The Science Behind Genomics
Using cutting-edge DNA sequencing technology, researchers in the Steve and Cindy Rasmussen Institute for Genomic Medicine can sequence all genes in a patient’s genome simultaneously and rapidly identify any genetic changes that would be associated with their disease in under two days, for as many as 50 patient samples at a time, giving families long awaited answers and clinicians a diagnosis that allows them to better treat and care for these kids.
Blog Post: The ABCs of DNA Sequencing: Reading Your Genetic Code
To sequence DNA, DNA is extracted from a patient sample and all of its base pairs, “letters,” are read in an instrument called a sequencer. The sequence is compared to databases of other people’s sequence and of known sequence variations that may affect health. However, in the average person’s genome, which contains over 3 billion DNA base pairs, there will be 10 million differences from these compared genomes. Many of these differences are simply what make individual humans unique and aren’t know to be associated with any disease risk. The impact other differences is completely unknown. It’s up to researchers to figure out which differences matter. Researchers at Nationwide Children’s are developing new methods and building new software to compare sequences using all available information and model the impact of individual changes in a cell. This technology helps advance understandings of disease processes and may ultimately lead to better screening and treatments.
Video: When Doctors Don’t Know What’s Wrong
Join the IGM Team
The team at the Institute for Genomic Medicine is growing. Click the link below to view current job listings and to learn more about careers at Nationwide Children's Hospital.