A new technique can map the genome of an unborn baby from bits of its own DNA found floating in the mother’s blood, offering a way to detect inherited conditions without using invasive methods that may cause miscarriages.
The technology was used for the first time to identify the full set of genes in a fetus conceived by two parents who each carried mutations causing beta thalassemia, an inherited blood disorder. Researchers in Hong Kong obtained a blood sample from the mother and father, analyzed each parent’s genes, isolated the fetal genome from the mother’s blood and concluded the fetus had inherited the father’s and not the mother’s mutation.
Mapping the entire genome of a fetus using this method would take three weeks and costs about $200,000, said Dennis Lo, the Hong Kong professor who developed the technique. He is refining it to analyze only those portions of the genome that are suspected of harboring mutations for any particular family. This will reduce the cost, Lo said.
“For any particular family you want to screen, there are only a handful of genes that are clinically important,” Lo, who is the Li Ka Shing professor of medicine at Chinese University of Hong Kong, said yesterday in a telephone interview.
Prenatal screening now is conducted by techniques called amniocentesis and chorionic villus sampling to find birth defects and genetic mutations. Both methods involve inserting a needle, either into the amniotic sac surrounding a fetus or into the placenta to remove fluid that carries fetal DNA. The techniques carry about a 1 percent risk of inducing a miscarriage, Lo said.
“Many pregnant women going for such invasive prenatal diagnosis are very worried,” Lo said. “A key objective of our research is to develop a noninvasive platform for prenatal diagnosis which does not carry this risk.
Today’s report, published in the journal Science Translational Medicine, caps more than a decade of work by Lo. In 1997, he discovered that unborn fetuses release genetic material into the blood of their mothers. About 10 percent of the DNA floating in a pregnant woman’s bloodstream comes from the fetus, not the mother.
Until now, there has been no practical way to figure out which bits of DNA come from mom and which come from fetus, Lo said. He developed the technique using maps of the mother’s and father’s genes as guidelines and enlisting computational methods to determine whether bits of floating DNA carry the signature of the father or the mother. If the DNA bits are unique to the father, they must therefore belong to the fetus. He has developed software that accomplishes this analysis.
“It’s more technologically challenging than most gene sequencing,” Lo said. “Imagine millions of jigsaw puzzle pieces and then put in 10 times as many pieces from another jigsaw and you try to assemble the first one.”
Sequenom Inc. of San Diego and the government of Hong Kong provided funding for the study.
Before the technique can be used clinically, the cost must be cut significantly and a host of ethical issues will need to be addressed, Lo said. These include questions about who would have access to the expensive technology, whether information gathered might encourage abortions and whether it’s ethical to collect such detailed personal information for someone who hasn’t yet been born and doesn’t have a say in the decision.
“I think we need a lot of discussion between ethicists and scientists,” Lo said.
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