Happy Birthday, human genome. On June 26, 2000 a group of scientists at the White House announced that they had a working draft of our genetic blueprints. They hadn’t sequenced all our genes; the Human Genome Project and its private-sector competitor Celera Genomics still had some gaps to fill in. Still, scientists believed this data might hold clues to the causes of certain diseases and could lead to new treatments.
Even before the project’s start, some scientists were skeptical: Was mapping our genome a waste of money and time? Even among public hoopla and presidential speeches, scientists cautioned that applying the results would take time. Now, ten years later, many are asking: What have we learned? Here we round up some opinions about the impact of the project.
The Bad?
Some see fewer medical treatments than advertised. Instead of simple relationships between common variants and specific diseases, sequencing uncovered sheer complexity. Researchers now think that intricate relationships between rare variants may cause many diseases.
The difficulties were made clear in articles by Nicholas Wade and Andrew Pollack in The Times this month. One recent study found that some 100 genetic variants that had been statistically linked to heart disease had no value in predicting who would get the disease among 19,000 women who had been followed for 12 years. The old-fashioned method of taking a family history was a better guide. Meanwhile, the drug industry has yet to find the cornucopia of new drugs once predicted and is bogged down in a surfeit of information about potential targets for their medicines. [The New York Times]
As genetic sequencing goes, what once took years and millions of dollars can now take months and thousands. Still, some worry that the drive to sequence more, faster has led to techniques that make reading results increasingly hard.
The advances in speed … have come at a cost. Only short stretches of DNA can be sequenced at a time, so the pieces have to be joined together by looking for overlaps between them. While early instruments sequenced pieces up to 900 base pairs long, most high-speed machines produce “reads” of less than 100 base pairs. That means the overlaps are much shorter, making it far harder to join the pieces together, so assemblers use existing genomes as a guide — which can lead to mistakes. [New Scientist]
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Charles Darwin may have been right in worrying that the ill health that plagued his family were a result of inbreeding. Darwin didn’t only marry his first cousin, Emma Wedgwood–in fact, the Darwins and the Wedgwoods made a habit of intermarrying (Darwin’s maternal grandparents were also third cousins). Now a new study, which crunched the numbers on first-cousin marriages over four generations of the two dynasties, suggests that his children had an elevated risk of health problems.
The degree of inbreeding among Darwin’s children, while not excessive, was enough to increase the risk of recessive diseases — ones that occur if a harmful version of a gene is inherited from both parents. Three of his 10 children died before age 10 — 2 of bacterial diseases. Childhood mortality from bacterial infections is associated with inbreeding. So, too, is infertility, and three of Darwin’s children who had long marriages left no children [The New York Times].
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In a far-reaching judgment that could have major implications for the biotech industry, a federal judge in Manhattan has struck down patents related to two human genes linked to hereditary breast and ovarian cancers, BRCA1 and BRCA2.
Myriad Genetics held the patents, and women who want to find out if they have a high genetic risk for these cancers have to get a test sold by Myriad, which costs more than $3,000. Plaintiffs in the case had said Myriad’s monopoly on the test, conferred by the gene patents, kept prices high and prevented women from getting a confirmatory test from another laboratory [The New York Times]. In his decision, United States District Court Judge Robert W. Sweet found that the company’s patents were invalid because the genes are “found in nature,” and products of nature can’t be patented. In essence, he agreed with the plaintiffs’ argument that the genetic code contained in each human being’s cells shouldn’t be private property.
Tuesday’s decision, if upheld, could have wide repercussions for the multi-billion dollar biotech industry, which is built on more than 40,000 gene patents. Already, about 20 percent of the human genes have been patented. The decision, however, is not binding on other federal courts and other judges may or may not abide by it. But it does the set the stage for years of litigation over other gene patents. Myriad Genetics plans to appeal the judgment.
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You are what you eat, and perhaps in some ways, what your mother ate. Back in 2003, Cheryl Rosenfeld’s team found that the diet they fed to pregnant mice caused a “striking variation” in the sex ratios of the offspring: High fat favored males, low fat favored females. Now Rosenfeld has a new study in the Proceedings of the National Academy of Sciences that says the mother’s diet can also affect the very way genes are expressed in the placenta.
To figure this out, Rosenfeld’s team studied the placentas attached to fetal mice 12 and a half days after conception, when the mice were midway through gestation but had yet to produce sex hormones like estrogen or testosterone (those can also alter gene expression, which would have confounded the study). They found that gene activity in the placentas differed significantly depending on whether the mom was fed a high- or low-fat diet. The biggest differences were found when comparing the high- and low-fat placentas linked to female fetal mice, suggesting that placentas nourishing females do a better job of responding to diet—and potentially protecting the fetus from harmful ingredients—than do those connected to males [ScienceNOW]. Specifically, of the 700 genes that they saw behave differently between the sexes, 651 were expressed more in females than males. In all, their study saw changes in the expression of nearly 2,000 genes.
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Louise Brown, the first baby conceived through in vitro fertilization, will be turning 32 this year, and most people born through IVF are still younger than 30. While the technique has become commonplace for would-be parents struggling with fertility problems, doctors note that the long-term effects of the procedure still aren’t certain. Now, some scientists are saying they see slight differences in the DNA expression of people born via IVF, and that it’s possible they could be at higher risk for conditions like cancer or diabetes later in life.
Says lead researcher Carmen Sapienza said “By and large these children are just fine, it’s not like they have extra arms or extra heads, but they have a small risk of undesirable outcomes” [The Guardian]. Rather, the team found a very subtle impact. In 75 IVF babies and 100 naturally conceived ones, they examined 700 genes that particularly interested the researchers because they are linked to fat cell development, insulin signaling, and other functions associated with diseases for which people tend to be at higher risk as they age. The scientists checked DNA methylation, a modification to DNA which affects gene expression, and found that 5 to 10 percent of IVF babies had abnormal patterns of methylation.
Sapienza’s team published the study in October in Human Molecular Genetics, but his work is picking up attention after he spoke at the American Association of the Advancement of Science meeting in San Diego.
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DeCode Genetics, a genome sequencing and drug development company, found out the hard way that predicting disease risk simply by reading someone’s genes isn’t so straightforward. On Tuesday, deCode filed for chapter 11 bankruptcy protection in Delaware. The company’s financial problems have also raised some troubling questions about genetic privacy.
DeCode’s mission was to uncover genetic risk factors for common diseases and to develop personal genome scans so individuals could learn their risk. DeCode quickly became the leader in the worldwide race to identify the causes of common disease. The company’s researchers discovered mutations linked to schizophrenia, heart disease, diabetes, prostate cancer and many other illnesses. Its approach was to identify the mutations first in Icelanders and then to confirm them in other populations [The New York Times]. Iceland was seen as an ideal spot for genetic studies, because the population was fairly isolated and the country has excellent medical and genealogical records. However, the company’s early successes did not translate into dollars, in part because the mutations they found only account for a small percentage of the overall incidence of a given disease.
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In very rare cases, the womb is a dangerous place for a developing fetus. Researchers have found that pregnant women can pass on cancer cells to their unborn babies, if those cancer cells carry a particular genetic mutation. The new study resolves a longstanding puzzle, because in theory any cancer cells that manage to cross the placenta into the baby’s bloodstream should be targeted for destruction by the child’s immune system. But there are records of 17 cases of a mother and baby appearing to share the same cancer – usually leukaemia or melanoma [BBC News].
In the study, which will be published in Proceedings of the National Academy of Sciences, researchers used a genetic “fingerprinting” technique to match the cancer cells found in a mother and baby. The case, involving a Japanese mother aged 28 and her daughter, revealed that both patients’ leukaemic cells carried the identical mutated cancer gene BCR-ABL1 even though the infant had not inherited this gene [The Times]. This meant that the child, who was diagnosed with cancer at the age of 11 months, could not have developed leukemia independently.
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For two squirrel monkeys nicknamed Dalton and Sam, life has gotten a lot more colorful. Researchers used gene therapy to correct the color blindness of the two adult monkeys, giving them the ability to distinguish between red and green for the first time. The fascinating accomplishment suggests that scientists may someday be able to cure other kinds of blindness in humans. And because the treated monkeys were “middle aged”, it challenges the assumption that gene therapies cannot work in adults because their brain connections are too set in their ways to change beneficially [New Scientist].
The field of gene therapy, in which a malfunctioning gene in a patient’s body is replaced with a functional one, fell into disarray one decade ago following the death of an 18-year-old in a clinical trial. But since then scientists have regrouped, using animal studies to probe the technique’s safety. Last year, researchers progressed to the point of safety trials in humans for the treatment of one rare eye condition called Leber congenital amaurosis, and were able to dramatically improve the patients’ sight. Those results were stunning, but they were also achieved in children, whose still-growing brains can rewire themselves on the fly in response to new sources of visual stimuli [Wired.com].
In the new study, published in Nature, the researchers used a type of squirrel monkey in which the males lack a visual pigment called L-opsin. Its absence renders the monkeys color-blind, unable to distinguish reds and green. Most of the females, on the other hand, see in full color. So the scientists got to wondering: what would happen if they gave a boy squirrel monkey the same opsin that girls have [Scientific American]. They used a harmless virus to ferry in the gene that makes opsin, injecting the virus behind the monkeys’ retinas.
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Some lucky people don’t groan awake to the alarm clock when they’ve only gotten six hours of sleep–instead they pop out of bed, bright-eyed and invigorated and ready for a new day. Now, researchers investigating the phenomenon of people who don’t need as much sleep as the rest of us have found a rare genetic mutation that accounts for some cases of shortened sleep cycles.
The scientists were searching the samples for variations in several genes thought to be related to the sleep cycle. In what amounts to finding a needle in a haystack, they spotted two DNA samples with abnormal copies of a gene called DEC2, which is known to affect circadian rhythms [The New York Times]. When they looked up the volunteers who had given the two DNA samples, they found a mother and daughter who habitually get about six hours of sleep each night and report no ill effects.
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The question of how salamanders regenerate their legs when amputated is an ancient one that dates back to the days of Aristotle. Now scientists have come one step closer to solving the mystery. Contrary to what researchers previously believed, when a salamander’s legs are removed the cells near the amputation site revert to adult stem cells, but do not become pluripotent, or capable of developing into any body part. That explains why a salamander who loses a tail doesn’t regrow a leg in its place.
In the study, published in Nature, scientists explain that when a salamander’s limb is amputated, the muscle, bone, and skin cells at the amputation site change into a clump of adult stem cells called a blastema. Before this experiment, researchers had hypothesized that these undifferentiated blastema cells — which all look identical — are pluripotent and thus able to form many different cells types. But it was not clear how the original cells from adult tissue were reprogrammed, or how the blastema cells went on to form the correct tissue types [Nature News].
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For six years, psychiatrists thought they had found a genetic clue as to what makes some people more prone to depression when they’re hit with an emotional blow: a single gene. A 2003 study created a sensation among scientists and the public because it offered the first specific, plausible explanation of why some people bounce back after a stressful life event while others plunge into lasting despair [The New York Times]. But now a broader analysis of 14 studies has found no link between the gene and the risk of depression, and researchers argue that the 2003 findings were prematurely heralded as a breakthrough. “I think what happened is that people who’d been working in this field for so long were desperate to have any solid finding” [The New York Times], says Kathleen R. Merikangas, one of the authors of the new study.
The so-called “depression gene” that researchers focused on in the 2003 study helps regulate levels of serotonin, a brain chemical that plays a major role in depression and is a key target of antidepressant drugs. Researchers … found from a long-term study of 847 people in New Zealand that those with a short version, or allele, of the serotonin transporter gene were more likely to become depressed by adverse life events than were those with only long alleles [ScienceNOW Daily News].
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Scientists have taken another step in cellular reprogramming that points the way towards the use of a patient’s own cells to treat genetic diseases. In a proof of concept study, researchers took skin cells from patients with a rare condition, Fanconi anemia, which causes skeletal problems and bone-marrow failure, and raises sufferers’ risk of cancer [Technology Review]. In the skin cells, the researchers fixed the genetic defects that caused the disease, and then reprogrammed the cells to act like stem cells capable of growing into any type of tissue.
The corrected stem cells could be grown into blood precursor cells for therapy. As these would carry a patient’s own DNA, except for the mutation responsible for the illness, they could be transplanted without risk of rejection by the body’s immune system [Times Online]. However, the patched up cells were not used to treat patients in this study, because it isn’t yet clear whether such cells are safe. Comments molecular geneticist Chris Mathew: “In future it may become possible to transfer the corrected stem cells back into the patient, but much work remains to be done before this can be transferred from the lab bench to the bedside” [The Scientist].
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A major new lawsuit is challenging the notion that human genes can be patented just like the latest mousetrap built by a basement inventor. The case focuses on two genes, BRCA1 and BRCA2, that are linked to a higher risk of breast and ovarian cancer, and which were patented by the company Myriad Genetics more than 10 years ago. Now, the ACLU has organized a lawsuit backed by organizations representing more than 100,000 doctors and geneticists, and will argue that the information contained in each person’s DNA should not be private property.
The plantiffs also include individual cancer patients like Genae Girard, who was diagnosed with breast cancer, and took Myriad’s genetic test to see if her genes also put her at increased risk for ovarian cancer, which might require the removal of her ovaries. The test came back positive, so she wanted a second opinion from another test. But there can be no second opinion [The New York Times]. Since Myriad owns the patent to both the two genes and the test that looks for them, no other company can develop a competing test.
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Researchers have found good evidence that the troubling sleep disorder narcolepsy is an autoimmune disease, in which the body’s own immune system attacks healthy brain cells. A new study published in Nature Genetics links narcolepsy to mutations of two genes involved in critical roles in protecting the body from disease. These two variations, they say, are likely conspirators against [cells that produce] hypocretin, a hormone that promotes wakefulness, and that narcoleptics have been found to lack [HealthDay News].
Narcolepsy is a disruptive disorder that can trigger “sleep attacks” without any warning during any normal activity. In addition, some people can experience “cataplexy”, where strong emotions such as anger, surprise, or laughter can trigger an instant loss of muscle strength, which, in some cases, can cause collapse [BBC News]. There is currently no cure for narcolepsy, although the symptoms can be largely controlled with a mix of stimulants and sleep-suppressing medications.
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Researchers have taken significant steps towards determining the mysterious causes of autism, with the discovery that two-thirds of autistic people have a genetic variant that influences how neurons connect with each other. An additional study found a link between autism and small “mistakes” in another DNA segment involved with cell communication. Both reports add weight to the idea that autism is related to problems with the way brain cells connect [Los Angeles Times].
The two studies were made possible by improved technology that allowed researchers to compare the genomes of thousands of autistic people to those of thousands of people without the disorder, looking for genetic differences between the two groups. Previous studies that have identified several genes that are implicated in autism, but … they are extremely rare and account for a very small proportion of autism [New Scientist]. The two studies, both published online by Nature, won’t lead immediately to new treatments, but they open up important new avenues of research.
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