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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When Drugs Don’t Work

By Medial Discovery News

July 14, 2012

 

 

Without the liver, many important medications would simply pass through the human body and not produce any effect. The liver is able to metabolize and break down drugs or chemically alter them so that they become active.

But people with certain genetic variations either process drugs more quickly or lack the ability to metabolize specific drugs. Patients who are unaware they possess such a genetic trait could face potentially fatal complications if their lives depend on the very drug their livers can’t process.

This problem comes up in patients who get cardiac stents. Since the 1990s, hundreds of thousands, if not millions, of Americans have had stents put in. It is a metal mesh tube that is inserted into a blocked artery, especially in heart attack victims, to keep the artery open. A drawback is that within months, the artery can close back up as scar tissue grows. To solve this problem, a new stent came on the market in 2008 that slowly releases medication to prevent tissue growth. Yet the enormously popular stent carries a big risk: clot formation. The body tends to respond to the bare metal as a foreign object and cover it with platelets, increasing the risk of a fatal heart attack or stroke.

To prevent this, patients are given blood thinners, such as Plavix (clopidogrel), for at least a year.  Studies have shown the drug greatly decreases a person’s risks for developing clots. However, a rather large percentage of people carry a genetic variation that does not metabolize Plavix, which means the drug won’t work.

Forty to 50 percent of people with Asian ancestry, 30 percent with African ancestry, and 25 percent with European ancestry can carry this genetic variation. Doctors usually do not know until a patient with a stent begins forming blood clots, and genetic testing for the variation takes days. Now a Canadian company, Spartan Biosciences, has developed a bedside gene test capable of detecting this gene variant.

This gene encodes a liver enzyme belonging to a family of enzymes called P450 that is important in processing drugs. Of the eight known variants of this gene, seven encode inactive versions of the enzyme. The new machine can screen patients for these variants in about an hour.

Tests done at hospitals show personnel are capable of using the machine with little training and results are quick. Spartan Biosciences is waiting for regulatory approval of its machine in Europe and America and hopes to have it in hospitals soon. The company will give away the machine but charge about $200 per test.

The company is also exploring other applications for their technology, including determining drug resistance patterns of a bacterial superbug, methicillin-resistant Staphylococcus aureus (MRSA), and hereditary resistance to standard Hepatitis C treatments. This is likely only the beginning of bedside genetic testing. Ultimately, entire human genomes could be sequenced and analyzed next to the patient, helping doctors practice  personalized medicine.

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