Using just a blood sample from a pregnant woman and saliva from the father-to-be, researchers can reconstruct the whole genome sequence of a unborn baby.
These findings open up the possibility of prenatally evaluating a baby for many genetic disorders… without invasive screening procedures that require inserting needles and tubes into the womb or placenta.
Right now, some diagnoses are done using fetal cells from fluid in the womb (amniocentesis) or placental tissue (chorionic villus sampling). These can cause miscarriages in 1% of all cases.
In 2010, scientists developed a way to scan the unborn baby’s genome using just a small sample of the mother’s blood. This technique utilizes the fetal DNA floating (cell-free) in the mother’s plasma (the liquid where blood cells are suspended). The baby’s DNA makes up 10% of the total mix.
BUT, it’s tricky to distinguish fetal DNA from the mother’s DNA – and doing so takes 3 weeks and costs about $200,000 per case.
- They sequenced DNA from the plasma of a woman 18.5 weeks pregnant.
- Comparing that DNA with genome sequences obtained from the father’s saliva and the mother’s blood allowed them to identify fetal DNA sequences that they could computationally piece together into the baby’s genome.
- Comparison with the baby's genome sequence determined after birth – from its umbilical cord blood – showed the prediction was more than 98% accurate.
- They repeated the procedure with a younger fetus of 8.2 weeks. That sequence was 92% accurate.
The method assesses many and more subtle variations in the fetus' genome. “The improved resolution is like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page," Kitzman says in a press release.
Already there are several commercial companies that sift through the fetal DNA in plasma to look for an extra copy of chromosome 21 that indicates Down syndrome, US News and World Report explains.
But there are over 3,000 single gene (or Mendelian) disorders, which collectively affect about 1% of all new births. These include Tay-Sachs, Marfan syndrome, cystic fibrosis, retinoblastoma, hemophilia, Huntington's disease, and Kabuki syndrome. Most of these are caused by small, difficult to find genetic mutations.
Improving the technique to make it a clinical reality will only take a couple of years, according to Shendure, who estimates that his study cost between $20,000 and $50,000 per child.
Perhaps the near future will involve the routine sequencing of the genomes of fetuses during the first trimester. But Shendure cautions on the medical usefulness of all those data: "There will be many mutations whose impact we just don't know."
The findings were published in Science Translational Medicine today.
Image: Shendure Lab