A technique called non-invasive fetal sequencing (NIFS), developed by scientists at Harvard University, allows accurate and comprehensive genetic screening of a fetus using only a blood test from the expectant mother.
The researchers looked at nearly 7.9 million fetal variants, and the test had a median sensitivity of 94.0% and precision of 94.9% for detecting these mutations.
The test identified 97.2% of the reportable fetal variants that could be found by invasive testing.
Notably, the NIFS test was more sensitive at detecting de novo and paternal variants at around 97% or higher and less sensitive at detecting inherited maternal variants at around 95%.
If successful it will likely be the first U.S. company to bring an exome scale non-invasive prenatal test like this to the market.
A technique called non-invasive fetal sequencing (NIFS), developed by scientists at Harvard University, allows accurate and comprehensive genetic screening of a fetus using only a blood test from the expectant mother.
At the European Society of Human Genetics conference in Gothenburg this week, the researchers report that the technique allowed them to identify 97% of all the genetic variants normally identified using more invasive testing during pregnancy such as amniocentesis or chorionic villus sampling.
Non-invasive prenatal testing (NIPT) that focuses on cell free DNA in maternal blood has been offered for some time but has only historically tested for a limited set of mutations, mostly conditions with chromosome number abnormalities such as Down syndrome, as these were easiest to detect accurately in the small amount of fetal DNA found in maternal blood.
However, a combination of improvements in sequencing accuracy and coverage and other advances such as developments in machine learning can now help interpret such tests and it is now possible to detect a wide range of genetic variants in the fetus using only maternal blood.
In this study, the team applied NIFS to 565 pregnancies at a median gestational age of 17.5 weeks. Blood samples were sequenced to a high level of coverage (an average of 860x), and ensemble machine learning was used to call heterozygous, hemizygous, and homozygous sequence variants, and copy number variants across the full exome. The NIFS results were validated against matched genome sequencing from invasive procedures in 388 samples.
The researchers looked at nearly 7.9 million fetal variants, and the test had a median sensitivity of 94.0% and precision of 94.9% for detecting these mutations. The test identified 97.2% of the reportable fetal variants that could be found by invasive testing.
Notably, the NIFS test was more sensitive at detecting de novo and paternal variants at around 97% or higher and less sensitive at detecting inherited maternal variants at around 95%.
“The test performed really well in capturing all of the clinically relevant variants found by invasive genome sequencing that would have been missed by all current non-invasive tests,” said presenting scientist Christopher Whelan, PhD, a senior computational scientist working at the Broad Institute of Massachusetts Institute of Technology and Harvard, in a press statement.
“There were also some unexpected discoveries, such as twin pregnancies with abnormal tissue, and evidence that some mothers had received a bone marrow transplant from a male donor that confounded NIPT results. This provided further evidence of the strength of the technique.”
Whelan works in the lab of Michael Talkowski, PhD, the director of the Center for Genomic Medicine at Massachusetts General Hospital, who was also involved in the research. Talkowski is co-founder of the diagnostics company First Genomic Insights, which is developing this test for commercialization. If successful it will likely be the first U.S. company to bring an exome scale non-invasive prenatal test like this to the market.
