Spinal Muscular Atrophy Carriers Can be Detected Through Next Generation Sequencing Method

Researchers have developed a novel method for detecting carriers of spinal muscular atrophy (SMA) using next generation sequencing screening. The new technique can easily be incorporated into current next generation sequencing screening panels, analyzing hundreds of genes involved in severe childhood diseases.

While a rare disease, SMA is still the most common genetic cause of infant death. One in 60 adults carry a mutant gene, which leads to the risk of having children affected by SMA if they are unfortunate enough to partner with another carrier. The American College of Medical Genetics and Genomics has recommended SMA carrier testing to identify couples at risk of having an SMA affected child. However, current carrier screening has been dependent on techniques that — albeit accurate — are not easily incorporated into screening panels assessing multiple diseases.

The new study, entitled “Validation of a high resolution NGS method for detecting spinal muscular atrophy carriers among phase 3 participants in the 1000 Genomes Project,” and published in BMC Medical Genetics, analyzed samples from 56 healthy volunteers along with known carriers of SMA. The team also analyzed 2051 previously published genome sequences from what is known as the “1000 Genomes Project.”

Comparing the results to the older, accurate, qPCR technique, the team observed complete correspondence between the two techniques. Authors of the study, Jessica L. Larson, and colleagues from GenePeeks in collaboration with Princeton University claim the new method also offers an extra advantage. Using an advanced computational model, they could measure carrier probability on a continuous scale, making more specific predictions about SMA risk for future children. The technology is, however, less sensitive for next generation sequencing samples of lower quality, and — as is the case with present methods — cannot identify individuals with two SMA1 copies on one chromosome but none at the other.

These kinds of difficulties are typical of SMA screening. Humans usually have two almost identical copies of the survival of motor neuron (SMN) gene — the faulty gene responsible for SMA. SMN1 is a functional gene while SMN2 gives rise to very low levels of protein. The genes are sometimes duplicated, so that an individual may have 2-4 (or more) copies of the SMA2 gene, giving rise to the different clinical manifestations of SMA. An individual can hence end up with a variety of combinations of SMA1 and SMA2 copies on the two chromosomes.

The authors of the study argue that this issue could be overcome by extending the technique to encompass known DNA mutations in the vicinity of SMA1 as markers, a solution presented in an earlier study of such SMA carriers.

GenePeeks is a US-based company developing commercially available genetic screening test for recessive childhood disorders, offering genetically safe egg and sperm donor services.