Whole genome sequencing improves diagnosis in babies

Whole genome sequencing (WGS) is twice as effective as targeted gene sequencing in diagnosing a range of genetic conditions in newborns and infants.

In 2020, around one in every 45 babies born in England had a congenital abnormality, which includes structural and genetic disorders. Importantly, increasing amounts of research suggests that DNA sequencing may help to diagnose genetic disorders and improve health outcomes. The GEMINI study, led by a research team at Tufts Medical Centre, Boston, compared the accuracy of two different methods of DNA sequencing to identify genetic abnormalities.

The researchers were led by Dr Jonathan Davis, chief of newborn medicine at Tufts Medical Centre. 'Successfully diagnosing an infant's genetic disorder as early as possible helps ensure they receive the best medical care', said Dr Davis, highlighting the importance of early diagnosis.

The recent study included 400 newborns and infants below the age of one year who were hospitalised and suspected of having an undiagnosed genetic disorder. Researchers took small samples of blood from each of the newborns and infants in the study. The blood samples were tested using WGS and targeted genome sequencing. WGS can identify changes in 20,000 genes, whereas targeted gene sequencing can find changes in more than 1700 genes currently associated with genetic disorders.

Published in the Journal of the American Medical Association, the study found that WGS identified a genetic condition in 49 percent of the newborns and infants in the study. These results show that WGS is more effective than targeted gene sequencing, which only identified a genetic disorder in 27 percent of the newborns and infants.

The study identified 134 genetic changes not previously observed. However, the study also found that there were disparities in how different laboratories interpret the results of genetic sequencing. This meant there was disagreement in 43 percent of cases over whether a gene abnormality was the cause of the suspected genetic condition.

Although WGS is more effective at diagnosing genetic conditions, the study also found that it took around two days longer to receive the results compared with targeted gene sequencing. The additional time needed for WGS is an important consideration when an earlier diagnosis can improve health outcomes for the newborns and infants. Moreover, there are some ethical concerns around WGS, which could accidentally identify health risks for later in life that the parents may not have wanted to know.

Dr Davis said, 'this study shows that WGS, while still imperfect, remains the gold standard for accurate diagnosis of genetic disorders in newborns and infants.'