Detecting fetal chromosomal defects without risk: Noninvasive sequencing is faster, cheaper and safer for mother and fetus

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A team of scientists describe a new benchtop semiconductor sequencing procedure and newly developed bioinformatics software tools that are fast, accurate, portable, less expensive and can be completed without harm to mother or fetus. Current diagnoses often rely upon invasive tests that sample amniotic fluid or placental tissues for fetal DNA that can then be analyzed using a variety of complex and expensive methods. While highly reliable, these invasive tests may cause infections in the pregnant woman and pose as much as a 1 percent risk of miscarriage and fetal loss.

Chromosomal abnormalities that result in birth defects and genetic disorders like Down syndrome remain a significant health burden in the United States and throughout the world, with some current prenatal screening procedures invasive and a potential risk to mother and unborn child.

In a paper published online this week in the Early Edition of PNAS, a team of scientists at the University of California, San Diego School of Medicine and in China describe a new benchtop semiconductor sequencing procedure and newly developed bioinformatics software tools that are fast, accurate, portable, less expensive and can be completed without harm to mother or fetus.

"We believe this approach could become the standard of care for screening of prenatal chromosomal abnormalities," said Kang Zhang, MD, PhD, professor of ophthalmology, founding director of the Institute for Genomic Medicine at UC San Diego and a staff physician at the San Diego VA Healthcare System.

The incidence of chromosomal abnormalities — in numbers or structure — is one in 160 live births in the United States, higher in other countries. In China, for example, the rate is one in 60 live births. The effects of these abnormalities, known as aneuploidies, can be severe, from developmental delays and neurological disorders to infertility and death. The incidence rate rises with maternal age, most notably after age 35.

Current diagnoses of fetal aneuploidies often rely upon invasive tests that sample amniotic fluid or placental tissues for fetal DNA that can then be analyzed using a variety of complex and expensive methods, including full karyotyping in which the entire set of chromosomes is viewed microscopically. While highly reliable, these invasive tests may cause infections in the pregnant woman and pose as much as a 1 percent risk of miscarriage and fetal loss. Results are not available for one to two weeks, extending anxiety for families waiting for information.

Written By: Science Daily
continue to source article at sciencedaily.com

5 COMMENTS

  1. I wanted to comment on this having raised a daughter with Down’s syndrome. I couldn’t it was too emotive and I’m unable to express what I think and feel on this subject in the space of a few hundred words.

  2. The new method relies upon massively parallel sequencing of cell-free fetal DNA using a benchtop semiconductor sequencing platform (SSP) called an Ion Torrent sequencer developed by Life Technologies. Cell-free fetal DNA is genetic material from the fetus that circulates naturally and freely in the mother’s bloodstream. It can be obtained through an ordinary blood draw, with SSP analysis achieved in less than four days.

    I wonder how early in the pregnancy the cell-free fetal DNA can be detected. If this test could be conducted in the early weeks of a pregnancy the results one way or another would have major impact on the decision to commit to the pregnancy or to abandon it.

    I expect the “pro-life” anti-abortion bunch will be out in force against this test and all of the power it places squarely in the hands of women who will take advantage of this new opportunity to control the timing and genetic composition of our own offspring.

    Waiting for the Pope to issue a statement imminently with threats of hellfire and damnation against women who object to old white dudes wearing lace doily dresses and magical hats controlling their fertility. Fundamentalists of all stripes expected to chime in with him as well.

    I expect that along with the list of aneuploidies that can be detected, the sex of the fetus will also be revealed by this test. It seems reasonable to expect an increase in sex selection in that case, especially if this test can be undertaken in the early weeks of the pregnancy.

    Major implications!

    • In reply to #2 by LaurieB:

      Cell-free DNA & RNA can be detected from the 5th post-menstrual week onwards and gets more reliable with advancing age (at least for sex determination). Determining ploidy is relatively easy as are finding paternally-derived problems. It’s separating fetal from maternal sequences that is the challenge. The tech has been commercially available since at least 2011 and the article sounds like a validation of their particular platform (which is good for them but also for the future sales pitch).

      I’d like to know why you think there’ll be an increase in sex selection though. I shouldn’t think anyone’d opt to selectively abort based on it being ‘easier’?

      • In reply to #3 by Docjitters:

        Thanks for this info. 5 weeks is even earlier than I would have guessed.

        It’s separating fetal from maternal sequences that is the challenge.

        Indeed! I’ve just finished reading the book Neanderthal Man by Svante Paabo, and I’m in awe of the entire effort to sequence the DNA of Neanderthals and the daunting problem of sample contamination that they had to deal with. The situation is much worse than I had imagined. Based on the experimental design contortions that he had to go through with his team just to be sure of obtaining valid results, I’d like to know more about the controls employed by the types of DNA analysis described in the article.

        I had an amnio in my third pregnancy, 20 years ago, and I can’t help but wonder who’s DNA actually was in that petri dish. :D

        The tech has been commercially available since at least 2011

        So this is old news then? Hmm.

        I’d like to know why you think there’ll be an increase in sex selection though. I shouldn’t think anyone’d opt to selectively abort based on it being ‘easier’?

        Easier. The use of this word gave me pause. Would selective abortion would be easier? In my dictionary, the word “easier” is defined as: achieved without great effort; presenting few difficulties.

        So given that, I will say that if this DNA analysis can be done as early in the pregnancy as you said it can, then the decision on whether to proceed with the pregnancy or not would presumably be made earlier than it has been when results are derived by amnio.

        As far as the medical procedure of abortion goes, is this easier? I don’t know. You probably know the answer to that one already.

        Psychologically, the earlier the better must be true. As the weeks go on, attachment increases. The beginnings of a hard, bulging abdomen and later when the movement of the fetus can be felt and then the image of the fetus on ultrasound all add up to a psychological bond with one’s child who will imminently be snuggling in one’s arms. It’s a strong effect and I remember carrying the ultrasound image of my son’s face around in my purse and gazing at it many times every day before his birth.

        Granted that I can’t speak for all women who are faced with the wrenching decision of whether or not to proceed with a pregnancy where the DNA analysis indicates abnormality, but since I was in fact in the position of waiting for two weeks for those results to come to me about my own pregnancy once in the past, I will say without hesitation that if I had in fact decided that I didn’t want that pregnancy to run it’s course then I wish the whole situation had taken place much earlier than it did at that time.

        If we accept that humans will meddle with the sex of their own fetus if given the opportunity to do so in a way that they understand as being of minor risk, then I believe that they will happily do so. We are aware of how this is well underway in certain locations already. If the meddling can be accomplished in the earliest weeks of an undesirable pregnancy then I will bet my bottom dollar that the number of sex selection abortions will increase because the entire process would be more efficient, safe, ethically defensible (less harm) and psychologically less traumatic than the medical procedure that we currently have in place.

        It’s interesting to speculate as to what effect sex selection will have on our society. Richard has written a paper a while back on this topic and it made me think about the process more deeply than I had done previously. He prompted me to think about sex selection in a way that draws on everything I’ve learned about evo bio-psych-anthropology and I’ll include feminism as well. It’s challenging and complicated.

        • In reply to #4 by LaurieB:

          In reply to #3 by Docjitters:

          Forgive me, some of my info was unclear in my last paragraph. Free fetal nucleic acids were reported in 1997. At least in the UK we’ve been using cffDNA for fetal blood grouping since 2000. The commercial aspect referred to some American data Article behind pay wall.

          For you amniocentesis, it would have been your child’s intact cells, collected directly from the amniotic fluid. The full karyotype requires a cell culture before counting and directly examining chromosomes, hence the 2-week wait. You can find intact fetal cells in maternal blood but they are very few and far between. Interestingly, they have been shown to stay in the maternal circulation in excess of 25 years whereas ffDNA disappears within days of delivery.

          I accept your point about earlier potentially being easier from a bonding point of view. The Royal College of Obs & Gynae released a Scientific Impact Paper recently which talks about the current state of play in the UK. Whilst ffDNA testing is non-risky to the fetus, it counsels doctors not to let prospective mothers forget the implications of testing in the first place…

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