Genetic sequencing can be expensive, and sometimes it can give us some information about our health or families. Other times, claims that genetic sequencing can improve health might be greeted with deserved skepticism. But when is genetic sequencing necessary? Scientists have assessed two groups of patients to learn more about when genetic sequencing should be applieed to diagnose a disorder that clinicians have not been able to identify. The findings have been reported in the New England Journal of Medicine.
There are many disorders that can be directly attributed to a mutation in the genome, such as cystic fibrosis. This is often when a serious but not fatal mutation arises in a gene that encodes for a protein. There are also far more complex diseases that can be affected by variations in many different genes, and these diseases can be much harder to diagnose or prevent by simply analyzing the human genome. Cardiovascular disease is one example of a complex disorder that could be impacted by tens or possibly hundreds of genes, and all the small changes within those genes that an individual may carry -- variations that could be influencing one another in different ways; these complex diseases can be hard to understand with current genetic tools and data.
But for a disease that is caused by a known, protein-coding gene, exome sequencing can be applied. In this process, portions of the human genome that code for protein are sequenced, and this is only about one to two percent of the human genome.
However, exome sequencing does not provide an answer for two-thirds of patients, even when they have a disease that seems to be due to genetics, noted Professor Rami Abou Jamra of Leipzig University. "For patients and their families, a clear diagnosis means a great deal: not only does it confirm that the disease is not their own fault, it also paves the way for public recognition and where possible, personalized treatment."
In this work, the researchers assessed one group of 744 families, and another group of 350 families in which a child was suspected to have a genetic disease, but exome sequencing did not reveal a diagnosis.
DNA from these groups was then analyzed with a technique called short-read sequencing in which the whole genome is diced up into small bits that are sequenced, then pieced back together with computational tools.
Exome sequencing can reveal mutations that are due to losses of tiny bits of DNA, abnormal lengthening of sequences, or mutations that are not in the coding region of the genome, explained Jamra.
This effort revealed a diagnosis for another eight percent of families, each of which got an answer after a medical odyssey. That number may seem small but it is "significant," said Abou Jabra.
"Our data suggests that genome sequencing should be used more quickly, especially when exome sequencing has not provided clarity," the researcher added.
This work can also reveal novel mutations that are associated with different disorders, and expand our diagnostic capabilities in new ways.
The researchers aren't done looking for answers, either. "We will read more genomes, and we will do it all with an even more revealing technique called long-read sequencing," said Abou Jamra. "We want to decode all genetic diseases."
Sources: Leipzig University, New England Journal of Medicine