When Two Parents Aren’t Enough

April 5, 2013

By Medical Discovery News

Ask expectant parents what kind of child they want, and one word almost always comes up: healthy. So, the possibility that a new baby may carry a genetic disorder can be understandably devastating. But a recent research from the Oregon Health Sciences Center may offer a unique approach to actually preventing certain types of genetic diseases – the three-parent child. 

When they invented this approach, researchers were thinking of the 4,000 children born each year with genetic defects in their mitochondrial DNA. These children consequentially develop one or more of 50 known mitochondrial diseases, many with devastating symptoms like stroke, epilepsy, dementia, blindness, deafness, and kidney or heart failure. Mitochondria are the power plants of the cell, producing the energy needed for a cell to function. Each mitochondrion has its own DNA independent and outside of a person’s DNA, which is housed in the cell’s nucleus. Diseases affecting mitochondria are difficult to treat, so this new way of actually preventing them is a welcome, while controversial, discovery.

First, eggs are obtained from the mother and a female donor. The nucleus from the egg of the natural mother is removed, separating her chromosomal genetic information from her mitochondria, which would have been passed on with the mutation to the child. This nucleus is then transferred to the donor egg, from which the nucleus and genetic information has been removed and discarded. The result is an egg with the nucleus and genes of the natural mother and the functioning mitochondria of the donor.

Then the egg is fertilized with the natural father’s sperm (which does not contribute any mitochondria to an egg), producing a fertilized egg with the DNA of the natural mother and father and the healthy mitochondrial DNA of the donor.  However, the contribution of the donor egg’s mitochondrial DNA is not much – the mitochondrial genome accounts for only 1 percent of the total DNA present in a human cell. So, the embryo will have genetic information from three people. The future child would share the genetic characteristics of the mother and father but have the mitochondrial genetic makeup of the egg donor.

In recent studies, scientists removed the nuclei and the DNA within from 65 human eggs and replaced them with donated nuclei. After fertilization, just under half of the eggs grew to a 100-cell stage called a blastocyst, the precursor to an embryo. This is the same rate seen for unaltered fertilized eggs. While the blastocysts were not implanted into wombs, they could have eventually developed into three-parent children. The change to their mitochondrial DNA could be permanent, and they could pass on the functional mitochondria to future generations. 

While this is huge progress for treating genetic disease, it also raises some significant ethical questions, such as whether the discovery could eventually be used to create “designer” babies, whose DNA has been manipulated to meet parents’ wishes. This technique holds great potential as an advance in genetic therapy, but its ensuing controversy means scientists should take steps to prevent abuses. 

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Your Baby, Bit By Bit

By Medical Discovery News

Oct. 6, 2012

Your Baby, Bit by Bit

Now, women wait longer to have their first child than ever before. National health statistics report the number of women having children after age 40 has quadrupled since 1980. As a result, when they are ready, women often worry their baby will carry a genetic defect. Today a variety of genetic tests are available, mostly by screening the mother’s blood for specific fetal proteins and hormones. But many of the test results can’t be confirmed until a doctor performs Chorionic villus sampling (CVS) or an amniocentesis. Both are invasive and carry a relatively high (1 percent) risk of miscarriage.

For over a decade scientists predicted a noninvasive, risk-free technique was close because fragments of fetal DNA are present in the mother’s blood. Henry Lo of the Chinese University of Hong Kong, who made the initial discovery, also wrote in a paper two years ago that there’s enough fetal DNA fragments to not just screen for genetic diseases, but to construct the fetus’s entire genome.

Recently researchers from the University of Washington proved this theory by developing a method to assemble these DNA fragments and successfully sequenced the genome of an 18.5- week-old fetus. Later, when the baby was born and traditional sequencing was done, a comparison of the two showed the researchers had been 98 percent accurate, a major breakthrough in fetal genetic testing.

A major challenge for researchers was differentiating fetal DNA fragments from the mother’s DNA, which took three steps. The first was obtaining the father’s saliva to yield his genome sequence. From the mother’s blood, the maternal genome was decoded, down to reading the DNA sequence in each of her 23 pairs of chromosomes.

Then researchers isolated all the DNA fragments floating in the plasma portion of the mother’s blood, of which 10 percent belongs to the fetus. Having sequenced the genomes of both parents, researchers could then pick out DNA that varied from the parental DNA sequence and reassemble them to form the fetal genome.

The method worked on a fetus in the second trimester, and researchers believe as they fine tune the technique it may be possible to start as early as six weeks after conception.

A major limitation now is the cost of fetal genomic sequencing – $50,000 per child. But scientists predict, with the price of genomic sequencing continuing to drop, the test will eventually become available in doctor’s offices.

Though parents could choose to have the entire fetal genome sequenced, it still won’t predict or rule out all genetic diseases because scientists have identified just a fraction of all the genes responsible for birth defects. To complicate matters, some abnormalities are not gene related, and certain genetic mutations only predispose a baby to disease.

Geneticists will continue to identify disease-causing genes, but eventually they will also discover genes behind traits such as intelligence and athletic ability. The use of that information will become an ethical dilemma.

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