June 7: Scientists have for the first time sequenced the genome of a foetus using only the blood sample of the mother and a saliva sample of the father, promising a new era of non-invasive prenatal screening for thousands of genetic disorders.
The feat, announced on Wednesday by researchers in the US led by Indian-origin scientist Jay Shendure, is based on a technique they had developed to reconstruct the genome of a woman of Gujarati descent.
The accomplishment heralds an era in which parents might find it easier to know the complete DNA blueprint of a child months before it is born.
The team’s method of reconstructing almost the full genome of a foetus from genetic material from the parents may emerge as an alternative to current invasive techniques in which doctors insert a needle into the womb to extract a sample of amniotic fluid that contains fetal genetic material. The invasive procedures carry a small risk of inducing a miscarriage.
“This work opens up the possibility that we’ll be able to scan the whole genome of a foetus for more than 3,000 single-gene disorders through a single, non-invasive test,” said Shendure, an associate professor of genome sciences at the University of Washington, Seattle.
Shendure and his colleagues described their research on Wednesday in the journal Science Translational Medicine.
Standard invasive tests typically look for chromosomal abnormalities — duplicated, deleted, or rearranged chromosomes — and a small set of single gene disorders. The new method could be used to assess many more subtle variations in the foetal genome, down to minute, one-letter changes in the genetic code, said Jacob Kitzman, a co-author and a graduate research fellow at the University of Washington.
“It’s an extraordinary piece of technology, really quite remarkable,” said Peter Benn, professor of genetics and developmental biology at the University of Connecticut in the US, who was not involved in the work. “What I see in this paper is a glance into the future.”
The genome scientists took advantage of new high-speed genome sequencing and some statistical and computational acrobatics to deduce the genome sequence of the foetus with about 98 per cent accuracy.
The University of Washington researchers estimated that it would cost $20,000 (Rs 11.2 lakh) to $50,000 (Rs 28 lakh) to do one foetal genome today.
Shendure and his colleagues took maternal blood at about 18 weeks into pregnancy and a paternal saliva sample from two expectant couples — and authenticated the accuracy of their results through umbilical cord blood collected from the babies at birth.
“A non-invasive procedure of this type would hopefully be available more widely, even to those who lack access to specialised care required to safely carry out the procedure like amniocentesis,” Kitzman told The Telegraph.
Scientists have long known that a pregnant woman’s blood contains cell-free genetic material from the developing foetus. Shendure and his colleagues had only three years ago sequenced the first Indian genome — the genome of a woman of Gujarati descent — introducing a technique of reconstructing the genome.
“That work established the technology that led to this new paper,” said Shendure, who was born in the US to parents from Maharashtra who moved there in 1968. “I go back a lot, have lots of family there,” said Shendure, who had spent a year working at Sassoon Hospital in Pune during 1996-97.
Shendure, a medical scientist with an MD as well as a PhD, said certain genetic mutations have been shown in recent years to be linked to multi-gene disorders such as autism, schizophrenia or epilepsy.
“There is definitely plenty of room for improvement,” Shendure said. But he added: “This is not science fiction any more.”