Research Matters: Genetics and Genomics Research – Why It Matters
This week, CCHD focuses on genetics and genomics research and discusses why these studies are important for understanding the underlying genetic causes of CHD. At some point during a hospital visit, you may have been asked to enroll your child in a genetic study. To help parents and caregivers make a more informed decision about whether or not to participate in a genetic study, CCHD provides an overview of some of the genetic concepts and terms that you will read and hear about when discussing this type of study with a coordinator.
Genetics and Genomics Research – Why It Matters
As parents of a child with congenital heart disease (CHD), we are often left wondering why our child was born with this condition. Even though heart defects are the most common birth defect, shockingly little is actually known about what causes CHD. Although many hospitals and laboratories around the world are tackling the problem of CHD, it turns out that one of the most valuable resources in the fight against CHD is our DNA. DNA is the genetic material that contains all of the instructions for how we develop and grow and what we eventually become. The entirety of one’s DNA is called a genome and everyone’s genome is unique. In most cases, the genome holds important clues about the cause of your child’s CHD.
Why is our DNA so important for CHD research?
Although many factors not related to genetics can increase the risk of heart defects, it is likely that genetics plays a major role in most cases of CHD. The instructions for building a heart are contained in our genes. A gene is a segment of DNA that serves as a blueprint for building a specific protein. Every protein has a specific function and the proper development and function of the heart relies on thousands of different proteins. Therefore, a harmful mutation in a gene that is essential for heart development could be a potential cause of CHD.
How did my child get a mutation?
A mutation is any kind of change in DNA and mutations can be inherited or occur spontaneously in a developing unborn child. In fact, new mutations, which are called de novo mutations, happen in every generation. Although most of these mutations are harmless, some mutations can cause disease. It is the identification of these mutations that will be critically important for understanding why certain children are born with CHD.
How are these mutations identified?
There are several studies that have begun to look at the impact of genetics on CHD. One of the largest is the Congenital Heart Disease Genetic Network Study (CHD GENES). In this NIH-funded study, a small sample of blood is collected from you and your child in order to isolate DNA and determine its sequence. DNA is made up of four building blocks called nucleotides and sequencing is the process by which the exact order of nucleotides that make up the DNA is determined. In whole genome sequencing, the sequence of one’s entire DNA is determined. In whole exome sequencing, only the segments of DNA that code for proteins are sequenced. Sequencing allows for the detection of mutations that could be potentially harmful for your child.
Why is it important that all of us participate in genomics research?
Although CHD is the most common birth defect, it is important to remember that the most complex types of CHD are rare. A mutation in any one of hundreds of genes could potentially cause CHD. Furthermore, two children with the same heart defect could have mutations in different genes. So even if a mutation is found in your child, it is not easy to assign that mutation as the cause of disease. However, if a gene that is mutated in your child is also mutated in many other children with CHD, then it becomes more and more likely that the mutation is responsible for the disease. As the number of people in the study increases, it becomes easier to identify the genes involved in CHD. This type of study is called a genome-wide association study (GWAS) and these studies become more powerful when more people participate.
Why is it important that both parents participate in genomics research?
In many cases, children with a heart defect are born to parents without a family history of CHD. Oftentimes, a de novo mutation is responsible for the disease. This is one reason why many research studies encourage the participation of both parents. By comparing the DNA sequence of the child with the DNA sequences of both parents, it becomes easier to spot new mutations in the child since neither parent will carry the mutation.
What happens if a mutation is identified in my child?
It is important to understand that the identification of a mutation will not lead to an immediate cure. However, it could have many potential implications for the long-term health and development of your child as well as future generations of children born with CHD. For example, many genes that are important for heart development are also important for the development of other organs in the body like the brain and kidney. This might explain why so many children with CHD experience neurodevelopmental delay as well as other non-heart-related health issues. Knowing which gene is affected in your child can help diagnose other problems and allow for earlier intervention. Furthermore, many children with CHD have progressive conditions and understanding the genetics of their disease will be absolutely critical for the discovery of drugs that can stem the tide of the disease. Finally, parents who receive an earlier CHD diagnosis will be well informed and more prepared to care for their child. It is important to remember that science and medicine are advancing at a rapid pace. There is hope for children with CHD and understanding the genes that are important for heart development and function will be the key to conquering this disease.
How can we participate?
Participation in any research study is entirely voluntary. Privacy issues are usually the main concern of parents, but, in most cases, many steps are taken to ensure the privacy of the parents and your child. This and any other issue can be discussed with the clinical coordinator before you enroll in a study. To participate specifically in the CHD GENES study mentioned above, a list of participating centers can be found here.
Michael Kim is a scientist and a father of two little girls. His oldest daughter Sydney was born with total anomalous pulmonary venous return (TAPVR) in 2011. He received his B.A. in Biochemistry from the University of California, Berkeley and his Ph.D. in Cell and Structural Biology from the University of Illinois, Urbana-Champaign. He and his family currently live in Miami, FL.