Genetic Testing for People

Healthy people who have family members with Alzheimer's disease may want to pursue genetic testing to find out if they are at risk. However, genetic testing for Alzheimer's disease is only available under very specific circumstances. Because the one gene for which genetic testing is available tends to cause an early onset form of the disease, genetic testing is only appropriate for people who's family members developed Alzheimer's at an early age. In some cases, genetic testing can also be used to confirm a diagnosis of Alzheimer's disease in people who already show symptoms.

Testing for Predictive Genes

There are three rare genetic syndromes that cause people to develop Alzheimer's disease at an early age, typically before age 60. These syndromes are caused by mutations in single genes called APP, PS1, and PS2. If one of your parents has a mutation in any of these genes, you have a 50 percent chance of inheriting the mutation and developing Alzheimer's yourself. This pattern of inhertance is called autosomal dominant. By examining your family's medical history, a genetic counselor can often assess your risk of carrying one of these mutations, and can determine whether genetic testing is appropriate for you.

Drawbacks. 

If you do have a family history of early onset Alzheimer's disease, genetic testing may still not be able to detect the mutation that's causing your family's disease.Clinical genetic testing is currently only available for one of the three known genes – PS1. Testing for the other two genes is available on a research basis only.

The three genes for which genetic testing is available only account for about half of the families with Alzheimer's – or about five percent of all cases. Therefore, there must be other genes that have not yet been identified.The 

Importance of Testing the Right Family Member

Even if you decide to pursue genetic testing, you may not be the best person in your family to be tested. This is because testing should begin with the family member who is most likely to have a mutation — and that generally means someone who's already been diagnosed with Alzheimer's. The research lab will sequence this person's entire PS1 gene. If they find a mutation, then other family members can be screened for this same mutation. (Screening for a known mutation is generally faster and less expensive than sequencing the entire gene.) If the lab does not find a mutation in a family member with Alzheimer's disease, then your family's Alzheimer's is not caused by a mutation in the PS1 gene and genetic testing will not be helpful in determining your risk.

Not All Cases of Alzheimer's Disease Result From a Mutated Gene

When looking at your family history of Alzheimer's disease, it is important to keep in mind that Alzheimer's can develop in people who have not inherited a mutated PS1, PS2, or APP gene. In families who have identified a mutation in PS1, even family members who did not inherit this mutation are at risk of developing the disease — the same risk as people in the general population. For this reason, you should keep in mind the age of onset for a family member who you choose to have tested. If they didn't develop the disease until late in life, they are probably not the best person to be tested for a mutation. You and your relatives should also be aware that if you test negative for a mutation that runs in your family, it does not mean that you won't develop the disease, only that you aren't at higher risk than the general population.

Testing for Susceptibility Genes.

Mutations in APP, PS1, or PS2 all virtually guarantee that a person will develop Alzheimer's disease. However, there is a fourth gene – called APOE – that is also involved in determining Alzheimer's risk. The APOE gene comes in three forms, called e2, e3, and e4. Having the e4 version puts people at higher risk of Alzheimer's disease, but does not ensure that they will develop the disease. Because testing for e4 cannot predict who will get the disease, many medical ethicists and geneticists have recommended against testing for APOE in healthy people.The rationale for not testing for APOE is that over half the people who carry e4 will not develop Alzheimer's and many people who don't carry e4 will still go on to develop the disease; therefore, genetic testing is not very useful. In fact, genetic testing for this gene is only currently available to help confirm doctor's diagnoses of Alzheimer's, and a doctor is required to sign a form that says the patient has dementia before the test can be performed.

The Future of Testing for Susceptibility Genes.

If you do not qualify for standard genetic testing for the APOE e4 variation, and you still wish to be tested, genetic testing for APOE and the other Alzheimer's genes is sometimes available as part of ongoing research studies. A medical geneticist or genetic counselor may be able to help you find such studies.Furthermore, ethicist have suggested that testing for susceptibility to Alzheimer's would be much more acceptable if there were a way to prevent the disease. Thus, as researchers make strides towards preventing and treating Alzheimer's, genetic testing for APOE e4 (and other genes for Alzheimer's susceptibility that might be discovered in the future) are likely to be more widely available.Issues to Consider

Considering genetic testing for Alzheimer's is complicated by the fact that even if you test positive for a mutation, there is no way to prevent the disease or treat it once it develops. Despite this drawback, some people decide to pursue genetic testing because it helps them plan for the future and relieves anxiety. However, other people find that they simply don't want to know whether they are going to get a disease that they cannot prevent.

Studies in Huntington's disease – which is similar to Alzheimers in that it is autosomal dominant and currently has no prevention or treatment – gives some insight into how people make decisions about genetic testing for these types of diseases. These studies have found that only about 15 to 20 percent of those at risk actually seek out and go through with getting a genetic test.

Meeting with a genetic counselor can help you understand both whether you are eligible for genetic testing and what risks and benefits there are to testing. In addition to meeting with a genetic counselor, it can be helpful to discuss the decision with family members, religious advisors, and possibly other people who have faced the same decision, such as through a support group. Even if you choose not to have a genetic test for Alzheimer's, you can make legal and financial plans to protect your family's future. The Alzheimer's Association has information to help you with those steps. It is also important to remember that deciding not to be tested is not a permanent decision; you can change your mind at any time as more researchers uncover methods for treatment and prevention.

Which genetic tests make the grade decent?

Tests for diseases with a proven link to single genes. Unlike SNPs tests, which look at gene variations that may put you at higher risk for diseases, some tests screen for specific gene mutations that have been scientifically proven to either definitively cause a disease or greatly increase your chance of developing one. Some disorders that can be screened for this way include breast cancer, colon cancer, Huntington's (a neurological disorder), and hemochromatosis (when the body stores too much iron). When people concerned about these diseases are trying to protect their privacy, some opt to use at-home versions of tests so the results won't be part of medical records. Companies that offer this type of testing include DNA Direct, Kimball Genetics, and Myriad Genetics.

Consider with caution SNPs tests from companies that use a laboratory certified by CLIA, which sets standards for US clinical laboratories. This accreditation ensures that the company uses laboratories that adhere to standards and guidelines for clinical testing. Companies using CLIA-certified labs include DNA Direct, deCODEme, and Navigenics.

Companies that offer genetic counseling. Some genetic tests deal with statistical risk that can be tough to understand and needs to be considered with your family history, so be sure a knowledgeable health professional interprets your test to avoid needless anxiety and any rash medical decisions. Some companies include free online or telephone sessions with certified genetic counselors and send detailed reports to help explain what test results really mean.

Avoid "Nutrigenomic" tests that promise to identify your risk of certain diseases and then sell you expensive vitamin regimes that are supposedly based on your genetic profile and help you prevent disease. The General Accounting Office, the investigative arm of Congress, looked at a number of these companies and found that some of these recommended supplements cost $1,200 a year and were actually similar to supplements found in stores for $35. In some cases, the vitamins exceeded recommended daily allowances, making them potentially harmful, and regardless of the different DNA sample, the "personalized"supplements sent were all the same. GAO investigators couldn't verify any of the scientific claims made by manufacturers of these tests.

Tests from companies without strict privacy policies. Despite last year's passage of the Genetic Information Nondiscrimination Act, which prohibits your insurance company and employer from using your genetic information against you, no laws yet exist to limit what genetic testing companies can and cannot do with a person's genetic information or DNA sample. Be sure that a company securely stores your DNA sample and will not sell it to be used in a research study without your permission. If the company doesn't provide this information on its Web site, ask for it directly. "Using your information without your consent is unethical," says Caroline Lieber, director of the graduate program in human genetics at Sarah Lawrence College.

Tests that don't provide documented scientific evidence validating their claims. You should be fully informed about what a test can and cannot say about your health. Companies should make scientific references available on their Web sites to document the data used for the tests. If they don't offer it, ask for it.

Even if you have one of the 18 genes linked to diabetes, it's not as if it's hardwired into your DNA that you'll get the disease on your 40th birthday--or even at all 

Breakthrough: Should you customize your drugs to your DNA?

Here's a shocker: Due to differences in DNA, up to 60% of the most common drugs are associated with adverse reactions. This includes medication used to treat common conditions like hypertension, heart failure, depression, high cholesterol, and asthma.

Hence the hope being pinned on "pharmacogenetics," a field of medicine that promises to improve health care by allowing doctors to customize medical treatment to suit a person's unique genetic signature. Though experts predict that it could be decades before personalized medicine becomes the norm, research is moving ahead: Last fall, for instance, researchers at Duke University reported that people with a specific genetic variant saw less reduction in LDL, or "bad" cholesterol, when taking statins.

But for some drugs, the future is now. A genetic test recently approved by the FDA should help doctors determine the optimal dose of warfarin (sold as Coumadin), a blood thinner used by 1 million Americans. Determining the right dose is crucial: Too much may result in an increased risk of excessive bleeding, while too little may cause a potentially fatal blood clot. By one estimate, using DNA analysis to prescribe warfarin would prevent about 17,000 strokes and 85,000 serious bleeding incidents.

A small but growing number of doctors and hospitals are also using genetic testing to tailor treatment for these medicines:

• Tamoxifen DNA testing identifies the 8% of women with genetic variants that keep them from metabolizing the breast cancer drug, rendering it ineffective.
  
• Painkillers like codeine Up to 8% of whites and 2% of Asians and African Americans are poor metabolizers of these drugs and won't get relief from them; for the 1% of "ultrarapid metabolizers," risks include respiratory problems.
  
• Antidepressants and antipsychotics Some of these drugs are metabolized by the CYP2D6 and CYP2C19 genes. In 2005, the FDA approved a test that looks for these gene variations, and now companies sell consumer versions. But experts advise against using the at-home tests without having your doctor interpret the results, notes Julie Johnson, PharmD, professor of pharmacy and medicine at the University of Florida. The reason: These genes are involved in the metabolization of 25% of all prescription drugs, including several where they're very important. If you misinterpret the results of an at-home test (and mistakenly think you don't have the gene), you might avoid taking one or more drugs you really need.

Test results: helpful or confusing?

Proponents of mail-order genetic testing claim it has just the opposite effect and instead helps people gain new insights that sometimes dramatically boost their health. David Agus, MD, an oncologist and cancer researcher at the University of Southern California, started Navigenics with the hope that people would get tested, discuss results with their physicians, and use the information to seek an earlier diagnosis or delay the onset--or prevent--certain conditions altogether. That's precisely what happened in the case of Mari Baker, the company's CEO. When her results revealed a 5-times-greater risk of celiac disease, follow-up testing ordered by her physician confirmed she has the digestive disease, which is caused by an intolerance to gluten, a protein in wheat, rye, and barley. The diagnosis explained the GI problems Baker, 44, suffered over the years. She immediately changed her diet and stocked her kitchen with gluten-free pasta, bread, and beer. "Feeling a little bit better every day for the next 20 years is pretty important," she says.

Unfortunately, test results aren't always so clear-cut and accurate. Mike Spear, the communications director for a genomic research nonprofit in Alberta, took tests from deCODEme and 23andMe and received some conflicting findings. For instance, the deCODEme test showed a higher-than-average risk for MS, but the 23andMe test said his risk was no higher than that of the average person. The test from deCODEme also had a big check mark next to "male pattern baldness," while the 23andMe test said he was on par with the rest of the population. (Spear, who's 55, still has plenty of hair.) Most surprisingly, both tests told Spear that his risk of asthma was no different from the average person's--even though he already suffers from the disease. His impression: "I'd be careful about basing your life around genetic test results."

Although new genetic research emerges every day, scientists haven't discovered all the genetic variants--or all the SNPs--for common diseases. Green, 54, took two genetic tests, one from 23andMe and the other from Navigenics, and both told him that he had an average risk of cardiac disease. Yet he had undergone triple bypass heart surgery the previous year. As a runner who is not overweight, doesn't smoke, and has low cholesterol, Green suspects there's a genetic cause for his tendency toward blocked arteries--and he chalks up the discrepancy in his test results to the fact that more research is needed to fully understand the genetic causes of cardiac disease.

Another reason to think twice about these tests: The industry is a virtual free-for-all. No single government agency watches the labs performing the tests to ensure that the science behind the tests is even real. Currently, the FDA reviews most other home-use medical tests for safety and effectiveness, but at-home genetic tests don't fall under the agency's territory. Pending legislation would require makers of direct-to-consumer genetic tests to prove that their tests are accurate and properly performed. But right now, "the public's best approach is buyer beware," says Kathy Hudson, PhD, founder and director of the Genetics and Public Policy Center at Johns Hopkins.

Despite these warnings, experts predict that people will be very tempted by the chance to peek into the genetic crystal ball. If you're one of them, heed Katz's reminder: "DNA isn't destiny." And be aware that when it comes to the lifestyle choices that are the greatest predictors of health, your future is in your hands.

Genetic Testing Goes Mainstream

People clearly approve of DNA testing. In a recent Prevention.com poll, 87% of respondents said they'd want to know which genetic diseases they're at high risk of developing. Moreover, 54% said they'd be likely to have a genetic test even if there was no known treatment or way to prevent the disease.

Plenty of companies are eager to meet this demand, selling at-home tests that range in cost from hundreds to thousands of dollars. Some offer tests that have long been available through doctors and genetic counselors--for instance, those that check for BRCA 1 or 2, the genes linked to a small percentage of inherited cases of breast cancer. Newer versions look at your SNPs (pronounced snips, short for "single nucleotide polymorphisms"), the slight variations within DNA that can account for differences in appearance and how we develop genetic diseases. The companies don't predict that you're going to get, say, cancer or macular degeneration. Rather, you get back a report showing the risk you run, compared with the average person. One of the newest entrants into the at-home arena, Navigenics, recently launched its $2,500 HealthCompass test, which looks for markers associated with 23 common conditions--including diabetes, prostate cancer, and Alzheimer's disease--that are "actionable," or able to be prevented or detected early. For an additional $250 per year, subscribers receive personalized updates when relevant genetic research--for instance, the discovery of new SNPs--changes their health outlook.

Health-conscious consumers are clearly enamored with these high-tech tests--they're expected to spend an estimated $6 billion to have their DNA decoded over the next 5 years. But while the business of do-it-yourself DNA testing is booming, experts say this new frontier of medicine isn't ready for prime time. They worry that the field is insufficiently regulated, not all of the tests are reliable, and the information garnered is incomplete and possibly misleading. "Some tests lack adequate scientific evidence to support their use, and the lack of regulation means there's no way for consumers to separate the good from the bad," says Gail Javitt, law and public policy director for the Genetics and Public Policy Center at Johns Hopkins University.

The Risks of Peering into Your Medical Future

Despite an explosion in the discovery of SNPs, most experts say it's too early to make strong links between these tiny genetic variants and the development of genetic diseases. That's because the role played by a single mutation is believed to be modest. Rather, it's the interaction between multiple SNPs and factors like diet, exercise, and weight that predispose you to disease--indeed, studies show that lifestyle accounts for about 70% of our susceptibility to health problems such as diabetes, heart disease, and some types of cancer. As a result, "these tests can't accurately predict the risk of developing these complex diseases at the moment," says David Hunter, MD, ScD, professor of epidemiology and nutrition at the Harvard School of Public Health. Likewise, some tests that claim to gauge your risk of diseases such as depression examine single genes that explain only a small part of the predisposition to those illnesses.

Critics also note that DNA testing results can be tough to interpret, making it difficult to know when and if you should take action. A Navigenics test told Robert C. Green, MD, PhD, MPH, a professor of neurology, genetics, and epidemiology at Boston University Schools of Medicine and Public Health, that he had a 20% above-average risk of developing multiple sclerosis. But the average risk is 0.3%, and his was just 0.5%. These are both very low risks (3 out of every 1,000 versus 5 out of every 1,000, respectively), yet the results were highlighted in orange, indicating an elevated risk. Green, a geneticist, understood his real risk, but the average person might not, causing needless worry.

And consider the flip side: that someone who tests negative for a gene or is told she's at low risk for developing a dreaded disease becomes less motivated to lead a healthy lifestyle. David Katz, MD, MPH, director of the Prevention Research Center at Yale University School of Medicine, points to a study on premenopausal women given a range of tests to determine their risks of developing heart disease. Half saw scans of their coronary arteries, which were surprisingly healthy. But despite other risks revealed from triglyceride and blood glucose levels, the group that saw its healthy scans did less to follow recommendations to prevent heart disease. "We don't want a single test talking people out of taking care of themselves, and this study suggests that can happen," says Katz.

Do-It-Yourself DNA Testing

At-home genetic tests are all the rage. But can they really calculate your risk of developing life-threatening diseases? Before buying one, read this Prevention special report.

Anna Peterson is only 27, but she's already watched her mother and her aunt develop breast cancer. She also saw her grandmother's eyesight fail from macular degeneration. So Peterson, a graduate student in Ottawa, Ontario, took her health care into her own hands and did what millions of others of all ages are doing: She opted for at-home DNA testing for genetic diseases.

When the results from the $985 test from deCODEme arrived in her e-mail, Peterson felt relief learning that she didn't have an elevated genetic risk for macular degeneration. Yet the test did show a slightly elevated risk for the more common forms of breast cancer. The results, Peterson says, empowered her to make healthier choices. Together with her physician, she'll use that information to advocate for earlier screening for breast cancer--and possibly start getting mammograms at age 30. "Prevention starts with knowing the odds," says Peterson. "I now have the opportunity to make lifestyle changes in my 20s, rather than in my 60s."

Welcome to the brave new world of genetic analysis. Once the exclusive domain of doctors and genetic counselors, DNA testing is now a do-it-yourself proposition, with several dozen companies marketing tests directly to consumers, claiming that they will allow you to understand your genetic profile. The process is surprisingly simple: Buy a test online, swab the inside of your cheek or spit into a test tube to collect a DNA testing sample, and then mail it to the company. In return, you'll receive personalized medical information that purportedly allows you to combat genetic diseases by making informed choices about your health. Bolstering that promise is new research that shows you can actually turn off genes that promote certain diseases by improving your diet and better managing stress.

DNA test can help detect

(CNN) - DNA is already being used in criminal and paternity tests. But, now genetic testing offers doctors a new way to look for problems of the heart.

For years, Donna Mitchell has tried to lower her cholesterol levels through diet and exercise. Now, she is hoping a cutting-edge genetic test will give her a better picture of her risk for developing heart disease. "I want to live, I like living, I have grandchildren I want to see grow up," said Mitchell. "So, it was a no-brainer for me."

Doctors can test for millions of genetic variations for a number of diseases through a simple cheek swab and blood test. They are looking for inherited traits passed on from relatives. 

Mitchell's father died of a heart attack. While some experts say this type of testing needs more development, Mitchell saw potential benefits and so did her doctor. "If you have heart disease and you have one of these heart disease genes then the likelihood that is contributing to your problem is very high," said Dr. Robert Superko, of St. Joseph's Hospital in Atlanta. "And, if it gives you a therapeutic direction, a diet or drug to take then it becomes valuable." Mitchell's testing revealed that she would benefit from taking a cholesterol lowering statin. So in addition to sticking with a healthy diet and daily exercise, she has a new prescription for change. Mitchell tested negative for the so-called heart attack gene.

Gene Tests and Gene-Diet Interaction

You've personalized your ring tones, your screensaver on your laptop, and your stationary. You will soon be able to add your diet to that list of customizable items. However, the process won't be quite as quick or simple as a 10-second download, but the promised benefits should be well worth the extra effort.

Genes and health

You probably have at least a basic understanding of genes, those sequences of DNA that control every structure and process in your body. While the basic set of genes that control one characteristic (say eye color) are organized the same for everyone, little differences in the DNA sequence give one person brown eyes and another blue. Likewise, the genes that control how you utilize a certain vitamin, or metabolize cholesterol level, can vary from one person to the next. Now many of these differences can be measured by simple genetic tests, and the results can be turned into personalized diet and nutrition recommendations.

Nutrigenetics

This new science, called nutrigenetics, studies how genes and diet interact. The key word here is "interact." As Rosalynn Gill-Garrison of Sciona, a company that develops genetic tests, points out: "Genes don't determine your fate." Rather these tests give you the information to make optimal choices for your health. A genetic test for bone health, for example, might indicate that you should consume more calcium and vitamin D, rather than saying that your bones are doomed to dissolve.

Currently several companies are developing consumer-friendly tests for known gene-diet interactions. You can be tested for genetic variations that affect bone health, B-vitaminmetabolism, inflammation status, and utilization of certain antioxidants. The tests are typically done on a swab taken from inside your cheek. The sample is sent to a specialized lab, which analyzes DNA from the cells on the swab. You receive a report on which gene variations you have. A qualified health professional can explain the test results, and make specific diet andsupplement recommendations to optimize your health.

What about genetic testing for weight loss?

The $64,000 question is this: When will a genetic test help me to lose weight? Unfortunately, this test does not yet exist. In fact, it is unlikely that just one test will ever answer that question. Registered dietitians Ruth DeBusk and Yael Joffe, co-authors of "It's Not Just Your Genes,"write that genes may someday tell us which weight-loss diet is best, why one person burns more calories than another, and (even better) how to use gene technology to promote weight loss. But they caution that hundreds of genes could impact weight. Deciding which of those hundreds are worth studying will be a daunting task.

The future of personalized diets

Diet and nutrition advice in the future will be increasingly personalized. As genetic researchers identify more gene-diet interactions, dozens of personalized recommendations for diet will be possible. Hopefully, before too long, weight control will also be part of that mix of genetic tests. In the meantime, the first generation of nutrigenetic tests is available for several important diet-gene interactions. One-size-fits-all diet advice will be a thing of the past.

By Donna Feldman, MS, RD

Diet Advice From DNA

Internet marketers claim that a genetic test can give you a personalized diet. Are they advertising cutting-edge science or a high-tech horoscope?By Laura Hercher   When President Bill Clinton stood in the East Room of the White House on June 26, 2000, and hailed the completion of the Human Genome Project, calling its results “the most important, most wondrous map ever produced by humankind,” he was not looking to inaugurate an era of high-tech snake oil sales. Yet less than a decade later Web-based purveyors of genetic tests and dietary supplements are hawking nutritional genetics, or nutrigenetics, with claims that it can look at an individual’s genetic information to figure out what that person should eat to promote stronger bones, shinier hair and other trappings of good health. So far, though, hyperbole has outpaced promise. This nascent field provides a cautionary tale of how commerce often races ahead of science: the commercialization of gene detection technology has occurred before scientists have developed an adequate understanding of how particular genes contribute to health and disease.Information derived from sequencing the DNA code in every human chromosome is gradually enabling scientists to create tests and treatments that have the potential to prevent, diagnose, ameliorate and perhaps even cure disease. It is also paving the way for “personalized medicine,” which is based on the recognition that genetic differences among individuals can explain why one person’s body reacts differently than another’s to food, drugs, sun, exercise, allergens or other stimuli. In an ideal world, a genetic test would reveal which medication or other therapy would work best and produce the fewest side effects in a given individual. And investigators are now beginning to create such tests. One milestone occurred this past summer, when the Food and Drug Administration approved the first genetic test to help a patient gauge the best dosage for a blood-thinning drug called warfarin. The test is certain to be followed by scores of others that attempt to better match drug to patient.

La cocaina “disconnette” il cervello

Le persone dipendenti mostrano una ridotta attività delle aree legate al controllo del comportamento e delle emozioni, e della loro interconnessione.

Nelle persone che fanno uso di cocaina si riduce l'attività delle aree del cervello deputate al controllo del comportamento e delle emozioni e la loro interconnessione. E questo influisce sulla capacità di sopprimere il desiderio della droga. Lo suggerisce unostudio del Brookhaven National Laboratory del Dipartimento di Energia statunitense, pubblicato su Pnas: in particolare diminuisce l'attività della corteccia cingolata anteriore.I ricercatori, coordinati dalla psicologa Rita Goldstein, hanno sottoposto 17 consumatori di cocaina e 17 persone che non fanno uso di droghe (campione controllo) a un test. Nella prima fase, i partecipanti hanno imparato ad associare alcune parole (riferite al consumo di stupefacenti, come crack e dipendenza, o termini neutrali) a quattro colori. Poi, ad entrambi i gruppi è stato chiesto di schiacciare il pulsante colorato che corrispondeva a nuove parole, comunque inerenti agli stessi concetti. I partecipanti ricevevano una ricompensa per la velocità con cui schiacciavano il pulsante, fino 50 centesimi di dollaro per ogni risposta corretta, per un massimo di 75 dollari.La risonanza magnetica funzionale - che evidenzia le aree cerebrali che consumano più ossigeno durante lo svolgimento di un compito - ha mostrato ai ricercatori le principali differenze tra i due gruppi. La parte della corteccia cingolata anteriore che di solito si accende quando esercitiamo il self control è molto meno attiva nei consumatori di cocaina, soprattutto quando i partecipanti non ricevono la ricompensa in denaro, o hanno a che fare con i termini neutrali, o hanno fatto ricorso frequentemente alla droga nei 30 giorni precedenti al test.Allo stesso modo diminuisce l'attività di un'altra zona della corteccia cingolata anteriore legata all’inibizione delle emozioni. In più, le due aree, normalmente interconnesse, “comunicano” molto meno tra di loro negli individui dipendenti. Queste differenze nell'attività e nell'interconnessione non comportano un peggior risultato o un minor interesse verso il compito da svolgere. “Nelle persone dipendenti, quando si presenta la necessità di sopprimere il desiderio della droga, l’attività nella corteccia cingolata anteriore tende a diminuire. È possibile che in questo modo il cervello cerchi di reprimere il ricordo del consumo o il pensiero della prossima dose, permettendo così alle persone di focalizzarsi sul compito da eseguire”, ha ipotizzato Goldstein.Secondo i ricercatori, i trattamenti mirati al rafforzamento dell’attività di queste regioni e della loro interconnessione potrebbero aiutare le persone “addicted” a migliorare l'auto-controllo durante il desiderio (craving) o l’astinenza. (p.f.)

Knome offers sequencing of all of your protein-coding genes for $24,500

Personal genomics is a rapidly evolving game, with a clear end goal in sight: offering consumers an accurate, affordable and complete genome sequence, and providing them with tools to dig out the useful nuggets of information contained therein. That goal remains out of reach, and while DNA sequencing technology continues to mature companies in the personal genomics space are offering products at various points on the trade-off curve between information content and cost.

At the low-information/low-cost end, companies such as 23andMe and deCODEme offer cheap (sub-$1000) genome scans looking at between 500,000 and a million sites of common variation throughout the genome. These provide insight into a small fraction of your genome, but include the variants we know the most about (due to the recent explosion of genome-wide association studies, which look for common genetic variants associated with complex disease risk).

Meanwhile, at the other end of the spectrum we have the boutique service offered byKnome - sequencing of the entire human genome, or at least the 85-90% of it that can be reached with current short-read technologies, for the princely sum of close to $100,000. It's difficult to justify this cost given the interpretable information currently obtainable from a genome sequence, but a full genome sequence does offer the possibility of getting insight into rare, severe disease-causing variants lurking in your genome that are largely invisible to genome scans.

Now Knome has launched a new product that provides a substantial chunk of the information value of a whole genome sequence at a quarter of the cost, by focusing exclusively on the 2-3% of the genome that codes for proteins: unlike low-priced SNP-based genotyping, which captures genetic changes known as common variants by taking a sample of less than 0.05% of the genome, comprehensive gene sequencing captures the entire coding region of an individual's genes, collectively known as the exome, enabling the detection of rare variants - mutations that many scientists believe account for the majority of the genetic burden of disease.

That last claim is pretty optimistic - it's now clear from genome-wide association studies that the majority of the common variants associated with common diseases are actually found outside protein-coding regions. However, it's also true that more rare, severe disease-causing mutations do tend to cluster within and around protein-coding regions. 

Perhaps more importantly, there is a sound pragmatic reason for focusing on this fraction of the genome: it's simply much easier to interpret a mutation in a protein-coding region than outside it. Right now, our dismal ability to predict the functional impact of variants in non-coding regions means that sequencing the majority of the genome falling outside protein-coding genes actually adds very little in terms of health prediction. For the moment, combining a cheap genome scan (to pick up genome-wide patterns of common variation) with exome sequencing (to detect any rare, clearly pathogenic mutations) would give you pretty much everything you'd be likely to get from a whole genome sequence.

Knome plans to offer the service for $24,500 for individuals, or $19,500 per person for couples and families. That's still well and truly in the boutique price range - but you should see this as yet another waypoint on the road towards affordable, complete genome sequencing.

Simple genetic test determines transplant drug tolerance

A simple genetic test can determine a kidney transplant patient's tolerance for a potent anti-rejection medication, according to an upcoming study in the Journal of the American Society Nephrology (JASN). The test could allow doctors to individualize each patient's dose, optimizing the drug's benefits and minimizing its side effects.

Cyclosporine A is an important immunosuppressant therapy for individuals who receive kidney transplants - without it, many patients would experience organ rejection and would not survive. Unfortunately, cyclosporine A can cause serious side effects such as elevated blood pressure, increased risk of infections and cancers, and kidney function deterioration. The frequency and severity of cyclosporine A-related side effects vary among patients, even at comparable cyclosporin A levels in the blood. Determining which patients are more sensitive than others is a challenge for physicians who prescribe the medication.

Giuseppe Remuzzi, MD, FRCP, and Piero Ruggenenti, MD (Mario Negri Institute for Pharmacological Research, Italy), and their colleagues, hypothesized that genetics may influence patients' susceptibilities to cyclosporine A's side effects. In particular, they suspected that variations in a gene called ABCB1, which creates a protein that transports drugs out of cells, may play a role. In individuals who have certain genetic changes in the ABCB1 gene, the transporting protein is sluggish so that when a drug is present, it lingers within cells and tissues. This can amplify the drug's effects.

After studying the genetics of 147 kidney transplant recipients, the researchers found that patients with these genetic changes in the ABCB1 gene were more likely to experience side effects after receiving cyclosporine A than patients without the variants. These effects included delayed functioning of the transplanted kidney, increased need for anti-hypertensive medications, and the development of diabetes, infections, and cancers.

"The identification of particular genetic variants performed before transplantation, while patients are on the waiting list, could provide useful information to tailor cyclosporine A dose as early as possible after transplantation, with the ultimate goal to decrease toxicity, improve efficacy, and increase long-term graft survival," said Dr. Remuzzi.The authors report no financial disclosures.

The article, entitled "ABCB1 Genotypes Predict Cyclosporine-Related Adverse Events and Kidney Allograft Outcome," will appear online at http://jasn.asnjournals.org/ on May 21, 2009, doi 10.1681/ASN.2008080819.

http://www.asn-online.org/

Alzheimer più probabile per i depressi.

Secondo uno studio olandese e uno americano, chi ha sofferto di depressione ha due volte e mezzo più probabilità degli altri di contrarre il morbo.

Tuttavia, i ricercatori olandesi, hanno precisato che sono necessarie altre ricerche per comprendere appieno il legame tra la malattia D Alzheimer e la depressione: “Non sappiamo ancora se la depressione contribuisce allo sviluppo dell’Alzheimer – hanno confessato – o se un altro fattore sconosciuto causi sia la depressione che la demenza senile.” Dal canto loro, gli scienziati americani sottolineano comunque che la depressione è un fattore di rischio per l’Alzheimer ma non un sintomo precoce del morbo.
In altre parole, non tutti i depressi si ammaleranno. Insomma, ancorché non definitivi, i risultati aiuteranno comunque a capire di più i meccanismi del morbo e creare nuove prospettive di ricerca.

Articolo pubblicato sul quotidiano “City” in data 9 Aprile 2008.