Advancing Personalized Patient Care
Whole Genome Sequencing
Whole genome sequencing (WGS) is a new test that is entering routine clinical practice. The test is designed to determine the entire genetic makeup of an individual by sequencing, or reading, the entire genome. Whole genome sequencing is ushering in the era of personalized medicine.
Whole genome sequencing identifies several million variants in an individual that differ from the reference genome. Most of these variants are benign (having no effect on health), but a small number of variants are pathogenic (related to disease). There are also many rare variants whose relationship to disease are not well understood at this time, which are referred to as variants of uncertain clinical significance. As the field of genomics matures it likely that our knowledge of these variants will improve.
The ability to interpret the significance of a rare change in a gene depends on how well the function of that gene is understood. Currently, some genes are well understood, while others have not been as well studied. At present about a quarter of genes have been connected to human disease. That number continues to rise as scientists connect other genes to disease. (Those new discoveries are why periodic reanalysis of a patient with a ‘negative’ whole genome sequencing result can be valuable.)
In the process of analyzing a genome looking for a disease-causing variant, the laboratory may identify an incidental finding, which is a pathogenic variant that is not connected to the patient’s clinical presentation but may have implications for their health . For example, an analysis of a child with a seizure disorder may uncover a pathogenic variant in BRCA1, a gene associated with hereditary breast and ovarian cancer. Such a finding may be relevant to both the patient undergoing WGS and other members of their family. Before a test is ordered, families can choose what kind of incidental findings they would like to have reported to them. Genetic counseling can be helpful as families make these decisions.
Our test form contains relevant information about the types of secondary or incidental findings that can be reported back to the ordering physician. Patients can choose to have no other incidental findings reported, or select from several other options including untreatable childhood disorders (e.g. Tay-Sachs Disease), treatable adulthood disorders (e.g. hereditary colon cancer), untreatable adulthood disorders (e.g. Alzheimer’s Disease) and disease carrier status (e.g. phenylketonuria).
There is no such thing as a perfect genetic test. Whole genome sequencing is powerful but cannot detect all types of genetic variation that may contribute to or cause disease. For example, trinucleotide repeat disease including fragile X syndrome, Huntington’s disease, a variety of ataxias, and others are not well assessed by whole genome sequencing. A negative result on a genome sequencing test does not rule out the possibility of a genetic condition.
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