DNA sequencing has fast picked up pace as a means to identify various diseases. Unlike popular belief though, only genetic sequencing doesn’t suffice the needs of gaining an understanding about human diseases. Scientists from Duke University Medical Center have revealed that it is important to accompany these with functional tests that throw light on the biological relevance of the sequencing results.
With tests in hand, researchers can help associate them with a host of diseases, employing the ciliopathies. This suite helps identify the disease that may be causing individuals to show numerous traits.
“Right now the paradigm is to sequence a number of patients and see what may be there in terms of variants,” mentioned Nicholas Katsanis, Ph.D., of Duke Pediatrics and Cell Biology. “The key finding of this study says that this approach is important, but not sufficient. If you really want to be able to penetrate, you must have a robust way to test the functional relevance of mutations you find in patients. For a person at risk of type 2 diabetes, schizophrenia or atherosclerosis, getting their genome sequenced is not enough – you have to functionally interpret the data to get a sense of what might happen to the particular patient.”
“This is the message to people doing medical genomics,” added lead author Erica Davis, Ph.D., Assistant Professor in the Duke Department of Pediatrics, who works in the Duke Center for Human Disease Modeling. “We have to know the extent to which gene variants in question are detrimental – how do they affect individual cells or organs and what is the result on human development or disease? Every patient has his or her own set of genetic variants, and most of these will not be found at sufficient frequency in the general population so that anyone could make a clear medical statement about their case.”
As part of the investigation, Davis in conjunction with a number of ciliopathy labs across the world sequenced the TTC21B gene. The latter is known to be an integral part of the primary cilium. Sequencing enabled the scientists to ascertain two human disorders namely a kidney disease and an asphyxiating thoracic condition on the basis of few of the mutations. However, they couldn’t settle on the implication of most of the DNA variants.
These variants were then tested by Davis in a model of zebrafish to determine TTC21B as the main contributor of disease-related mutations. It was found that it accorded for nearly 5 percent cases of human ciliopathy. According to the research, genetic variations could not only cause ciliopathies but also had the ability to communicate with other disease-leading genes. This in turn could result in a completely different group of patient problems.
Davis suggests that it would require more laboratories conducting analysis of this nature to actually gain a complete know-how of the ciliopathies and other ailments.
This finding features in Nature Genetics online.