We developed a non-invasive prenatal test for identifying fetuses that will develop sickle cell disease (SCD) or beta-thalassemia (B-Thal), both of which result from inheriting two mutated copies of the hemoglobin beta (HBB) gene. Our method is used when both parents are known to be carriers for either of these diseases, and involves “next generation sequencing” of short DNA fragments found in the blood plasma of pregnant mothers at risk for carrying a child that might develop SCD or B-Thal, and “long range sequencing” of DNA isolated from the blood of both parents to determine the full DNA sequence of the HBB gene.

We used a bioinformatic method to increase the proportion of fetal DNA fragments (the fetal fraction or FF), relative to maternal DNA fragments. In some cases, this increased FF alone allows us to accurately predict if the fetus will develop SCD or B-Thal. However, combined use of the increased FF and the full sequence of the HBB genes of the parents allowed us to correctly predict wether or not the fetus will develop SCD or B-Thal in cases where use of the increased FF alone was incorrect.