DNA on the Loose: Next-Gen Blood Tests Tap Free-Floating Genetic Material
Tests using floating nucleic acids could diagnose disease, monitor pregnancy and weed out "mad" cows
Scientific American, By Barbara Juncosa, 18 March 2009
Free-floating messages in the bloodstream could soon provide a unique window into the body. Researchers worldwide are racing to decipher circulating genetic material for better ways to diagnose disease, monitor pregnancy, and even improve food safety.
Circulating DNA and RNA-temporary gene copies that act as blueprints for protein production-was first discovered in 1948. Researchers still do not fully understand how the free-floating genetic fragments (chemically referred to as nucleic acids) survive outside the protective barriers of cells, but recent technological advances now allow scientists to comb through these tiny messages for clues about human health.
Traditional genetic screens, such as paternity tests and criminal profiling, utilize the abundant DNA stored in the nuclei of circulating blood cells. Although these tests shed light on a person's genetic inheritance, they do not provide insights on the current health of specific tissues and organs-information that could potentially be gleaned from the free nucleic acids.
Debate about the exact origins of circulating DNA and RNA continues, but dead cells from all areas of the body certainly contribute to the pool with new evidence mounting that living cells also release nucleic acids, perhaps enabling cell-to-cell communication over vast distances in the body, says Asif Butt, senior research fellow at King's College London.
Even healthy patients have circulating DNA and RNA, says Michael Fleischhacker, a molecular biologist at CharitÃ©-UniversitÃ¤tsmedizin Berlin hospital, but individuals with chronic disease such as cancer, inflammatory bowel disease and systemic lupus typically harbor increased levels of these messages in their blood. Simply monitoring the overall concentrations of nucleic acids in circulation, however, does not provide sufficient information about any one condition, prompting scientists to hunt for genetic targets specific to particular diseases.
Cancer researchers, for example, are seeking out patterns of chemical modifications and mutations detectable in the circulating gene fragments that are unique to malignancies. This approach could allow physicians to profile tumors without invasive sampling, says David Hoon, a molecular oncologist at the John Wayne Cancer Center Institute in Santa Monica, Calif.
The long-term goal is to identify genetic guides that can point physicians to a tumor's location as well as patterns that are characteristic of its stage to determine and monitor treatment and disease progression in patients, says Brian Durie, an oncologist at the Cedars-Sinai Medical Center's Samuel Oschin Comprehensive Cancer Institute in Los Angeles.
Fleischhacker cautions, however, that preparing these tests for routine cancer screening is likely to take a few years, because today's sensitive techniques can also detect rare mutations in healthy people that are of no clinical consequence.
Perhaps the most successful application of testing circulating DNA to date has been in the area of prenatal care. In the late 1990s researchers first recognized that fetal DNA could be detected in the mother's blood, albeit at very low levels, opening the door for noninvasive testing during pregnancy.
Traditional methods for examining fetal DNA, such as amniocentesis, require removing a sample of amniotic fluid surrounding the baby, increasing the risk of miscarriage, says Diana Bianchi, professor of pediatrics at Tufts University School of Medicine in Boston. Analysis of the mother's blood, on the other hand, could allow physicians to safely monitor the fetus and mother throughout the pregnancy.
In the U.S. and Europe, blood tests have already been approved for the diagnosis of rhesus D incompatibility-a condition in which a mother produces antibodies against her fetus due to the absence of the blood factor in her own body. Gender screening is also performed in Europe for families at high risk of passing on genetic disorders linked to the X chromosome. Bianchi says blood tests for Down's syndrome could be available in the near future.
Beyond cancer and prenatal testing, circulating nucleic acids could help physicians track a broad range of diseases, including stroke, heart attack and complications from diabetes. Butt's team has already identified several genetic markers important for diagnosing (and potentially predicting)diabetic retinopathy -damage to the eye's retina. Currently, only annual comprehensive eye tests can detect the condition, which is a leading cause of blindness in adults in the U.S., according to the National Eye Institute in Bethesda, Md.
Even the safety of animals stands to get a boost from testing circulating DNA. Researchers last month announced that chronic wasting disease in elk and bovine spongiform encephalopathy ( mad cow disease ) in cattle could be diagnosed up to six months before symptoms show up.
The only way to confirm a case of these diseases right now is to examine an animal's brain postmortem, says study leader Christoph Sensen, director of the Sun Center of Excellence for Visual Genomics at the University of Calgary in Alberta. But by comparing the circulating DNA profiles of sick and healthy animals, Sensen's team was able to identify disease-specific genetic patterns for diagnostic use in live animals. Providing a cheap method for testing all livestock in slaughterhouses, Sensen says, will be important for certifying the safety of meat exports and preventing future disease transmission to humans.
Although blood has been the primary focus for work on circulating nucleic acids, some researchers are now looking to test other bodily fluids. Urine is a particularly attractive candidate as it could provide an alternative source for testing circulating DNA and RNA in the developing world where drawing blood can be impractical, notes Timothy Block, co-founder of the Hepatitis B Foundation and a virologist at the Drexel University College of Medicine in Philadelphia.
With such broad applications, King's College's Butt agrees that the future of this technology is bright, but cautions that commercial partners will be key for developing clinical tests in the coming years.
Howard Urnovitz, CEO of Chronix Biomedical, Inc., in San Jose, Calif., is already looking for companies in the diagnostic field to help commercialize his company's bioinformatic approach to computationally mining thousands of sequenced circulating DNA fragments from healthy volunteers and patients for diagnosing and tracking specific diseases, including multiple myeloma (a cancer of disease-fighting plasma cells that is incurable but treatable), breast cancer and multiple sclerosis.
Despite the pressing need for identifying and validating new disease markers, Peter Gahan, a cell biologist at King's College, is optimistic. "Funding was virtually nonexistent five to 10 years ago," Gahan says, but "we are already beginning to get markers that could enter into predictive medicine."
UK National Survey
Scotland's National Newspaper
96% of women are liars, honest
5,000 women polled
Half the women said that if they became pregnant by another man but wanted to stay with their partner, they would lie about the baby's real father.
Forty-two per cent would lie about contraception in order to get pregnant, no matter the wishes of their partner.
Infidelity--It may be in our genes. Our Cheating Hearts
Devotion and betrayal, marriage and divorce: how evolution shaped human love.
South Korean Husband Wins Paternity Fraud Lawsuit
Associated Press, USA
June 1, 2004
South Korean husband successfully sues wife for Paternity Fraud and gets marriage annulled. Wins $42,380 in compensation
Paternity Fraud Philippines
DNA test confirms fraud, annulment granted: judge
The Visayan Daily Star, Bacolod City, Philippines, BY CARLA GOMEZ, February 28, 2009
Bacolod Regional Trial Court Judge Ray Alan Drilon has annulled the marriage of a Negrense couple after a DNA test showed that the child borne by the wife was not the biological offspring of the husband who works abroad.
The family court judge ruled that the marriage of the couple, whose names are being withheld by the DAILY STAR on the request of the court, was null and void.
Due to fraud committed by the wife in getting her overseas worker husband to marry her, properties acquired during their marriage are awarded in favor of the husband, the judge said in his decision, a copy of which was furnished the DAILY STAR yesterday.
The judge also declared that since the overseas worker is not the biological, much less the legitimate father of the child of the woman, the Civil Registrar is ordered to change the surname of the child to the mother's maiden name and remove the name of the plaintiff as father of the child.
The complainant said he was working as an electronics engineer in the United Arab Emirates and on his return to the Philippines in 2001, his girlfriend of 10 years with whom he had sex, showed him a pregnancy test result showing that she was pregnant.
On receiving the news he was overjoyed and offered to marry her. Shortly after he went to Saudi Arabia to work, and his wife gave birth to a baby girl in the same year.
The birth of the child only five months after their marriage puzzled him but his wife told him that the baby was born prematurely, so he believed her, the husband said. Read More ..
Adulterous woman ordered to pay husband £177,000 in 'moral damages'
The Daily Mail, UK
18th February 2009
An adulterous Spanish woman who conceived three children with her lover has been ordered to pay £177,000 in 'moral damages' to her husband.
The cuckolded man had believed that the three children were his until a DNA test eventually proved they were fathered by another man.
The husband, who along with the other man cannot be named for legal reasons to protect the children's identities, suspected his second wife may have been unfaithful in 2001.
Infidelity 'is natural'
BBC, U.K., September 25, 1998
Females 'stray to gather the best possible genes for their offspring'
Infidelity may be natural according to studies that show nine out of 10 mammals and birds that mate for life are unfaithful.
Experts found animals that fool around are only following the urges of biology.
New studies using genetic testing techniques show that even the most apparently devoted of partners often go in search of the sexual company of strangers.
Females stray to gather the best possible genes for their offspring, while males are driven to father as many and as often as possible.
"True monogamy actually is rare," said Stephen T Emlen, an expert on evolutionary behaviour at Cornell University.
Who's the Daddy?
Up to three million Britons may be wrong about who their real father is , experts claim. But using DNA paternity tests to discover the truth can cause its own problems.
BBC, U.K., May 16, 2003
Dad's got blue eyes, Baby brown...
When Tessa found out she was pregnant after fertility treatment, she felt a mix of delight and doubt.
This wasn't simply pre-baby nerves - she suspected that her husband might not be the father. For Tessa had started sleeping with a colleague when the stress of the ongoing treatment became too much.
Keen to build a family with her husband, she let him believe the baby was his. But her lover threatened to reveal all if she ended the affair, and Tessa soon fell pregnant again. This time, her lover started to make nuisance calls to her home.
Tessa had no choice but to tell her husband. "I said to him, 'I've had an affair and you may not be the father of my children.' So with that, he went up the stairs, got dressed and left. And that was it," Tessa says in Women Who Live a Lie, a programme for the BBC's Five Live Report.
Would you wear the jacket?
THERE IS A story I used to find hilarious in my high school years about a not too bright man. He was light skinned, his wife was of similar hue, but their first child was born with very dark complexion (darker dan Bello, blacker dan Blakka).
When the man wondered aloud about the baby's complexion his wife assured him that the child was born dark because the child was conceived in darkness (they had sex with the lights off). The man accepted the explanation. Because he loved his wife dearly, he also ignored the fact that the child had other obvious signs of resemblance to the young dark skinned man who did their gardening. To fix the problem, the husband put flood lights, strobe lights, spotlights and forty other lights in the bed room so there would be no more darkness to create dark babies.
"Duped Dads, Men Fight Centuries-Old Paternity Laws"
"Supporters of paternity identification bills point to a 1999 study by the American Association of Blood Banks that found that in 30 percent of 280,000 blood tests performed to determine paternity, the man tested was not the biological father." Read More ..
Download / view pdf file
American Association of Blood Banks
Parentage Testing Program Unit
Annual Report Summary Testing in 2001
Volume of testing 310,490 for the 2001 study
The Supreme Court of Canada -
Cour suprÃªme du Canada
Big win for child identity rights.
Father wins right to be named on birth registration forms. Read More ..
Tricked 'fathers' may get bill's help
Michael Lautar was devastated when he learned his first wife was cheating on him, and then crushed to discover the then 5-year-old girl who called him "Daddy" wasn't really his daughter.
Next came the sucker punch.
Lautar is under court order to pay nearly $800 a month in child support and other expenses, despite the fact his ex-wife has admitted in Allegheny County court papers that Lautar is not the girl's father. The child was born during their marriage. After the couple divorced, the mother married the girl's biological father. The mother, the father and the daughter live together in Moon, according to papers filed in Allegheny County Common Pleas Court.
"I'm stuck in this rip-off, this fraud," said Lautar, 40, of North Strabane. "It's paternity fraud, is what it is. ... And the state is enforcing this fraud." Read More ..
Lack of DNA Paternity testing abuses Dads and Kids
New Zealand Child Support Reform Network.
10 November 2004
Lack of free Family Court Ordered DNA Paternity testing abuses Dads and Kids.
"The Labour Government is abusing fathers and children by failing to legislate for free DNA testing to establish paternity", is how Jim Nicolle, spokesperson for the New Zealand Child Support Reform Network, responds to United Futures call for Family Court Ordered DNA paternity tests. Read More ..