RNA analysis in maternal blood could provide insight into fetal development
Scientists develop a test that could potentially be used to monitor fetal development by measuring circulating RNA in maternal blood.
A research group based at Stanford University (CA, USA) used a combination of high-throughput methods such as microarrays and next-generation sequencing to analyze free circulating RNA in the blood of a cohort of human subjects. The team found that they could monitor health and development of specific tissues by analyzing RNA molecules encoding tissue-specific proteins.
The researchers were able to analyze the combined cell-free RNA transcriptomes of pregnant women over the three trimesters of pregnancy and after delivery. In addition to maternal RNAs, they were able to measure circulating RNA originating from fetal tissues in the maternal blood sample. In fact, the team was able to monitor development of the fetal brain and liver, as well as the placenta, during the three trimesters of pregnancy by analyzing blood samples from the pregnant women over time. Another encouraging result is that they detected elevated levels of neuronal-specific RNA messages in patients with Alzheimer’s disease compared with the healthy participants.
In addition to monitoring mRNA levels, the researchers also detected other types of RNA -such as long, noncoding RNA and circular RNAs, which could offer further insight into health and disease.
“We think of this technique as a kind of ‘molecular stethoscope’, and it’s broadly useful for any tissue you care to analyze. There are many potential practical applications for this work. We could potentially use it to look for things going wrong in pregnancy, like pre-eclampsia or signs of preterm birth. And we hope to use it to track general health issues in various organs,” said Stephen Quake (Stanford University), senior author of the study.
It is known that free-floating DNA and RNA in the blood are released by cells that are under stress or are undergoing apoptosis. Even though this might represent normal cellular turnover it could also be an indication of an underlying disease. The increased sensitivity of current bioanalytical methods has made it possible to detect minute levels of these analytes.
“We’ve moved beyond just detecting gene sequences to really analyzing and understanding patterns of gene activity,” said Quake. “Knowing the DNA sequence of a gene in the blood has been shown to be useful in a few specific cases, like cancer, pregnancy and organ transplantation. Analyzing the RNA enables a much broader perspective of what’s going on in the body at any particular time.”
The team hopes that this technique could potentially be used in diagnostics by providing early detection of distress signals from diseased organs, even before any clinical symptoms are apparent.
Source: Koh W, Pan W, Gawad C et al. Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. PNAS DOI: 10.1073/pnas.1405528111 (2014) (Epub ahead of print).
