Children of older mothers, scientists have long known, are at higher risk for certain genetic disorders such as Down syndrome. But the father’s age is matters, too. As a father’s age increases, research shows, so does his child’s risk of mental illness, schizophrenia and autism in particular. In Scientific American, Nicole Grey explores the link between a father’s age and his child’s health, as well as the tricky questions about what mechanisms are behind the that link: genes, epigenetic changes, environment, or some combination of the three.

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What’s the News: By knocking out a single gene, scientists at the University of Pennsylvania have significantly increased the physical endurance of lab mice, as explained in their recent paper in the Journal of Clinical Investigation. The researchers also found that certain variants of the same gene may be linked to greater endurance in humans.

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What’s the News: While you may be able to hide your age with makeup and plastic surgery, don’t think that your deception is foolproof. Researchers have now developed a technique to ascertain your age to within five years using only your saliva. The new method, published in the journal PLoS One, could someday be used by forensic experts to pinpoint the age of crime suspects.

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What’s the News: Scientists have identified three gene mutations that lead to acute myeloid leukemia, a cancer that afflicts white blood cells, which may lead to better cancer drugs in the future. As Wellcome Trust Sanger Institute hematologist George Vassiliou told the BBC, his team’s study “found critical steps that take place when the cancer develops. Identifying the biological steps … means we can look for new drugs to reverse the process.”

How the Heck:

• The researchers discovered the major mutation by switching on the Npm1 gene in mice: They observed that about one third of the mice went on to develop leukemia.
• They knew some other genes were involved because not all the mice contracted cancer. So next, they randomly mutated mouse genes, and then analyzed the mutations in the ones that developed cancer, identifying two other mutations in the process. The second mutation affected cell growth and division and the third affected the cell’s environment.

What’s the Context:

• Acute myeloid leukemia occurs when the body develops an abnormal amount of undeveloped white blood cells. It’s the most common type of acute leukemia, accounting for more than 6,000 deaths in the U.S. each year.
• The scientists chose to work on this kind of leukemia because “there had been little progress in developing new drugs.”
• 80beats has covered acute myeloid leukemia in the past, including its link to a possible HIV cure, and more on leukemia in general, from whether the cancer can be passed on from mother to child to decoding a cancer patient’s genome.
• In 2005 Discover covered the news of a possible vaccine for leukemia.

Not So Fast: Researchers caution that it could take decades before new cancer-fighting drugs based on this study come on the market. This present study only used mice as subjects.

Reference: George S Vassiliou et al. “Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice.” Nature Genetics. doi:10.1038/ng.796

Image: Wikimedia Commons / Bruce Wetzel

A study of an experimental drug from the company Vertex, called VX-770, successfully reduced lung problems in CF patients, and the company hopes to try for approval of the drug later this year. If all goes well, doctors may soon have their first drug to treat the cause of this devastating disease, instead of just combatting the symptoms.

Cystic fibrosis is a genetic disease that impairs lung and digestive function. In particular, the normally thin layer of mucus in the lungs thickens up and impairs breathing; this happens because patients have a faulty version of a protein that helps clear mucus.

About 1800 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been implicated in the disease. The gene encodes a molecular channel that shuttles chloride ions across cellular membranes, and people with two mutated copies develop mucus-filled lungs susceptible to infection. Few patients live to see their 30s. In 1989, CF became the first disease pinned to a specific gene mutation, without the benefit of knowing the protein first. [Nature]

This newest test was a Phase III trail of Vertex’s drug, which was funded in part by the Cystic Fibrosis Foundation. The treatment goes after one major genetic mutations that causes the disease, called G551.

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As more hospitals have begun using DNA testing to analyze babies with birth defects, doctors have occasionally discovered that a family’s little bundle of joy is also a product of incest. Since this is a new dilemma brought on by the spread of technology, doctors are now debating how to handle these incest surprises.

Geneticist Arthur Beaudet at Baylor College of Medicine addressed the issue yesterday in an article in the medical journal The Lancet. The genetic test, the single nucleotide polymorphism-based array, helps doctors identify missing genes (and can therefore help explain a child’s birth defect or disability)–but it also identifies swaths of identical DNA that a child may have inherited from two closely related parents.

In the few months that Baylor has been performing these detailed genetic tests, there have been fewer than 10 cases of consanguinity — the phenomenon of inheriting the same gene variations from two closely related people, said Dr. Arthur L. Beaudet, chairman of Baylor’s department of molecular and human genetics. However, wider use of such testing in children with disabilities is expected to identify additional cases of incestuous parentage. [ABC News]

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What would you do if calcium deposits were building up in your blood vessels and making it hard to walk, and your doctors said they couldn’t help because they had no idea what disease you had, or how to treat it? Before 2008 you wouldn’t have had many options, but thanks to the National Institute of Health (NIH) you now have at least one: visit the Undiagnosed Diseases Program–where medical researchers just cracked their very first case.

Located in Bethesda, Maryland, this program takes on the medical cases that stump other hospitals. The program has received over 1700 referrals since it started, and has accepted only 330 of them. The results of their first case were published this week in The New England Journal of Medicine, but it all started with dumbfounded doctors and some confusing x-rays:

In 2009, the program received a referral from a Kentucky doctor for two sisters, Paula Allen and Louise Benge, who suffered from joint pain and showed calcium buildup in their arteries in x-rays…. The images “astounded us,” [program director William] Gahl said. The team obtained DNA samples from the sisters and other family members (three of Allen and Benge’s siblings had the same recessive disease) and scanned the DNA for markers called single nucleotide polymorphisms that the researchers used to narrow the location of the disease gene. By also examining this genetic region in two other families with similar disorders, the researchers were able to pinpoint a mutation in a specific gene, NT5E, which is involved in breaking down calcification in the arteries. [ScienceInsider]

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In a remarkable medical feat, researchers used a blood sample from a pregnant woman to work out the entire genome of her unborn fetus. The technique, published in the journal Science Translational Medicine, could provide a safer and less invasive way to check a fetus for fatal genetic mutations.

Currently, determining a fetus’s genome requires either amniocentesis, in which a needle is inserted through the mother’s abdomen into the amniotic sac, or chorionic villus sampling, in which a piece of placenta is removed. But both techniques carry a small risk to the baby, and are reserved for cases when there is an increased risk of genetic defects.

“The major advantage of the technique in this paper is that there’s no risk of miscarriage,” said Dr. Diana W. Bianchi, a reproductive geneticist at Tufts University who called the work a “technological tour de force.” Amniocentesis and CVS testing carry about a 1% risk of miscarriage, she said. [LA Times]

The new technique sequences the fetal genome from fragments present in the mother’s blood. In the late 1990s researchers discovered that fragments of fetal DNA are present in maternal plasma, presumably because the DNA gets broken down and crosses over the placental barrier.

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Researchers have identified 30 genes that play a role in the onset of menstruation in girls. Some of these puberty genes have previously been linked to body weight and fat metabolism, strengthening the connection between the obesity epidemic and the early onset of puberty in industrialized nations.

For the study, published in Nature Genetics, researchers analyzed 32 genome-wide association studies that included more than 87,000 women from the United States, Europe and Australia, and then replicated the results in a further 14,000 women. Of the 30 genes that they found play a role in the timing of women’s first periods, four genes are linked to body mass index, three play a role in metabolism, and three are involved in hormone regulation.

Study co-author, Dr Enda Byrne of the Queensland Institute of Medical Research says the results from this study show that many of the genes that increase risk for weight gain and obesity in adulthood, also influence the onset of puberty. “This supports the idea that the body launches into puberty once it reaches a certain level of nutrient stores and therefore children who are overweight are more likely to undergo early puberty,” says Byrne. [Australian Broadcasting Corporation]

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Next time you’re at the pub with friends, take it easy on the lightweights—the ones who are getting a little silly after just a couple of drinks. That might be a blessing in disguise, according to a new study, because the 10 to 20 percent of people whose genetics make them especially sensitive to booze might also be at greatly reduced risk to develop alcoholism.

In the journal Alcoholism: Clinical and Experimental Research, Kirk Wilhelmsen and colleagues identified a particular gene associated with the easily intoxicated. The gene in question encodes an enzyme called CYP2E1, responsible for metabolizing not just alcohol in the brain, but also other substances like acetaminophen (Tylenol).

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In January, we discussed a biotech first–a transformation from skin cell to brain cell, without reverting to a more mutable stem cell in between. Today a paper in the journal Cell describes a similar direct transformation in mice, from a type of structural cell called a fibroblast to heart cells. If one day scientists can entice human cells to make a similar “direct conversion,” the researchers believe this metamorphosis may prove one way to fix heart damage that’s irreparable under the current state of medicine.

The study’s authors at the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco, once attempted to use stem cells for heart repair with little success, Nature News reports. Though the stem cells quickly turned into the beating variety, called cardiomyocytes, they remained feeble, never transforming into the strongly beating muscle cells of a healthy heart.

“I don’t know that this [direct conversion] will entirely replace stem cells,” says Deepak Srivastava [lead author on the study]… “But it will offer another strategy that might remove some of the concerns of using stem cells.” [Nature News]

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One might think that identical-twin bacteria—clones of each other—would grow up and live very similarly. But a study published today in Science that examined individual bacterial cells in detail found that genetically identical E. Coli cells actually seem to express their genes quite differently, simply because of the random accidents of how their molecular machinery happens to operate.

“The paper is quite rich,” said Sanjay Tyagi, a molecular biologist at New Jersey Medical School who was not involved in the research [but published a perspectives piece on it]. “People think that if an organism has a particular genotype, it determines its phenotype [observable characteristics]–that there’s a one-to-one relationship,” said Tyagi. “But as it turns out, [differences in gene expression] can arise just from chance.” [The Scientist]

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We can predict your chances of living exceptionally long, with 77 percent accuracy, by looking at 150 tiny genetic variants. That’s what researchers claimed in a Science paper that we described last week. Those predictive powers have left some feeling a little uneasy–and not just about what futures are buried in their genomes. Where the paper‘s authors saw correlations, some experts are now seeing errors from DNA testing chips.

No DNA chip is perfect; it can get things wrong as it sorts through hundreds of thousands of genetic variants. In fact, certain chips might even make the same error repeatedly. That could cause problems, because what looks like a genetic variant common to a group of people could instead just be an echoed flaw in one chip’s testing capabilities.

Newsweek, which broke this story, reports that the Boston University researchers who led the study did, in fact, use different chips, but not enough different chips to rule out this potential error. They used two different types of DNA chips to test the centenarian group (about 1,000 people whose ages ranged from 95 to 119): a 370 chip that examines 370,000 genetic variants and a 610-Quad that examines 610,000 variants. The control group (of about 1,200 younger people) was tested with those two chips and a few others, thus possibly hiding any shared errors.

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UPDATE: Some experts are questioning the validity of this study, and are suggesting that technical errors skewed the results. Full coverage here.

If you want to know how to get old, it’s best to ask the experts. That’s what Paola Sebastiani, a researcher at Boston University School of Public Health, did;  She decided to look at the genes of 1,055 people, many who had already seen their 100th birthday.

As described in a paper published in Science today, Sebastiani’s team found that they could predict a person’s  “exceptional longevity” with 77 percent accuracy.

The researchers looked at small variants called single-nucleotide polymorphisms (or SNPs) on the centenarians’ genomes;  Sebastiani found she could use 150 SNPs to predict who would live to such exceptional ages.

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Investigators are now swabbing dog cheeks. A dog DNA database–similar to the one the FBI keeps for criminals–may help to deter dog-fighting.

Dog-fighting is a federal crime and a felony offense in every U.S. state, but it’s difficult to detect and stop. Officers rarely catch fighters in the act, and the industry, as a multimillion-dollar business, makes money not only from gambling on the violent and often fatal matches, but also from breeding and selling champion dogs.

The New York Times reports that some dogs sell for as high as $50,000 dollars. The American Society for the Prevention of Cruelty to Animals estimates that there could be tens of thousands of people involved in dog fighting in the United States.

So where does the genetics come in?

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