Fetal Genome Deduced from Parental DNA

Image: Flickr/lunarcaustic

From Nature magazine

Heralding a future in which a child’s genetic blueprint can be safely scanned for traits and defects long before birth, researchers have announced that they have reconstructed the genome of a fetus using a blood sample from its mother and a saliva sample from its father. The work is published in Science Translational Medicine.

The feat is possible because when a woman is pregnant, her blood contains fragments of DNA both from her genome and from that of her unborn child. Generally, around 13% of the DNA in her blood plasma — called ‘cell-free' DNA — comes from the fetus. The first challenge facing those who wish to glean information about the fetus in this way is to figure out how to distinguish fetal from maternal DNA.

Jay Shendure, a geneticist at the University of Washington in Seattle, and his colleagues isolated 5 nanograms of cell-free DNA from a maternal blood sample taken at 18.5 weeks of gestation. They performed 'deep sequencing' on the DNA, which involved sampling fragments roughly 78 times.

The researchers constructed the mother’s genome by sequencing the DNA in her blood cells and then computationally predicted the ratios at which certain blocks of gene variants, or haplotypes should appear as cell-free DNA in her blood. Where the observed ratios diverged from what was predicted, the researchers surmised they were reading some of the genetic material from the fetus.

To work out the paternal contribution, the researchers sequenced the father's genome using DNA from his saliva (blood could also have been used but in this case was not available). Variants of his that didn't turn up in the maternal blood were presumed not to have been inherited by the fetus; those that did were presumed to come from the fetus.

The researchers also developed computational techniques to try to detect de novomutations in the fetus's genome, which arise spontaneously rather than come from a parent.

To test the accuracy of the deduced genome, the researchers sequenced the child’s genome from cells collected from its cord blood after birth. The researchers were able to predict inherited mutations using the parental samples at most but not all variant sites. Where they were able to make predictions, they report 98% accuracy. They also managed to detect 39 of 44 de novo mutations in the fetus, but with false positives. Mindful that fetal screening needs to be done sooner to give parents time to respond, they then tested the technique on a second family with a 8.2 week-old fetus and obtained 95% accuracy.

Difference or defect?
At present, most prenatal diagnosis is done from a sample of either placental tissue or amniotic fluid, both of which must be obtained using invasive methods that can trigger miscarriage. Some tests already sample maternal blood, but they target specific chromosomal disorders such as Down’s syndrome. Wide-ranging, non-invasive screening could reach the clinic within a few years, says Shendure. But he warns that more needs to be done to refine the method and make the results meaningful to patients. “The technical piece is not the only challenge,” he says.

James Evans, a clinical geneticist at the University of North Carolina at Chapel Hill, agrees that the idea is not yet ready for the clinic. “We don’t know how to interpret the vast majority of variations we find in the genome,” he says. He also warns that parents have very little time to make life-or-death decisions. “The stakes are high,” he says. “Many are testing to decide about termination.”

“Catching everything in the basket” may also hasten our intolerance for variation, says Françoise Baylis, a bioethicist at Dalhousie University in Halifax, Canada. “As technology moves on, so does our willingness to think of difference as a defect,” she says.

PAN explained.......

PAN is a 10 digit alpha numeric number, where the first 5 characters are letters, the next 4 numbers and the last one a letter again. These 10 characters can be divided in five parts as can be seen below. The meaning of each number has been explained further.
1. First three characters are alphabetic series running from AAA to ZZZ
2. Fourth character of PAN represents the status of the PAN holder.
• C — Company
• P — Person
• H — HUF(Hindu Undivided Family)
• F — Firm
• A — Association of Persons (AOP)
• T — AOP (Trust)
• B — Body of Individuals (BOI)
• L — Local Authority
• J — Artificial Juridical Person
• G — Government
3. Fifth character represents first character of the PAN holder’s last name/surname.
4. Next four characters are sequential number running from 0001 to 9999.
5. Last character in the PAN is an alphabetic check digit.
Nowadays, the DOI (Date of Issue) of PAN card is mentioned at the right (vertical) hand side of the photo on the PAN card

The once rare brown argus butterfly is on the move........

The once rare brown argus butterfly is on the move, expanding its range and numbers in the U.K.—and it’s all thanks to climate change.Thus far, the world’s climate has warmed roughly 0.8 degree Celsius over the course of the last century or so, thanks to a rise in greenhouse gas concentrations now approaching 400 parts-per-million. With that amount of warming, biologists expect some species ranges to expand and others to contract but, thus far, many wily animals and plants have been confounding scientists’ expectations. In some cases, species that favor a warmer climate have actually retreated (think: lizards or amphibians). Or others have expanded even faster than the climate has warmed (think: tree species moving up a mountain slope).Obviously climate change isn’t the only factor in play. Habitat loss and disease seem to be dooming many varieties of amphibian while plants may be benefiting from human help (carried along on our own fossil fueled travels by car or plane).But for the brown argus butterfly with its trademark orange and white spots near its wingtips, climate seems to play a key role. It has spread northwards nearly 80 kilometers in just the last two decades, according to the U.K. Butterfly Monitoring Scheme. Warm summers have allowed the butterfly to begin using a new type of plants—such as the dove’s foot cranesbill—as a host in the U.K., the way it does in continental Europe. In prior decades, the butterfly had restricted itself to the rockrose.

That appears to be a result of the cooler climate back then. The long-lived and relatively sprawling rockrose plant allows for more stable populations of the butterfly when times are tough because of cool weather. It hosts the caterpillars on the underside of leaves on south-facing (and therefore sun-warmed) hillsides. But when generally balmy summers abound, as recently, the annual cranesbill can help the brown argus butterfly expand its range, according to new research to be published inScience on May 25.Of course, this expansion in the north is counterbalanced by a loss of habitat further south, where conditions are rapidly becoming too hot for the butterfly. “The picture across its whole distributional range in Europe looks somewhat different,” notes ecologist Oliver Schweiger of the Heimholtz Centre for Environmental Research in Halle, Germany, who was not involved in the research. His modeling work suggests that, even assuming the butterfly can fly past any natural features that might otherwise restrict range expansion, “large range retractions in the South cannot be counterbalanced by the expansions in the North.” And even flying animals, like butterflies and birds, can’t seem to keep pace with the poleward march of temperature bands, according to Schweiger’s work.

Nevertheless, this kind of adaptation to a changing climate may offer hope for other species. “Not all species must necessarily suffer from climate change,” Schweiger adds. “Showing that an extension of the utilizable host plants is possible and can help to cope with the consequences of climate change can be considered as good news.” In other words, don’t underestimate a species’ ability to adapt and make the best of it.

Image: Courtesy of Louise Mair

About the Author: David Biello is the associate editor for environment and energy at Scientific American. Follow on Twitter @dbiello.

Article in scientificamerican