Do DTC Personal Genome Testing Services Represent a Cultural Divide?
In a succint commentary on the actions of the California Department of Public Health's cease and desist order to 13 direct-to-consumer personal genome testing companies, Thomas Goetz argues that he has a right to this information, especially in a climate where the vast majority of the medical professionals are clueless about these emerging technologies.
He suggests that this issue represents a cultural divide as much as a regulatory one.
The assumption that there must be a layer of "professional help" is exactly what the new age of medicine bodes -- the automation of expertise, the liberation of knowledge and the democratization of the tools to interpret and put to use fundamental information about who we are as people. Not as patients, but as individuals. This is not a dark art, province of the select few, as many physicians would have it. This is data. This is who I am. Frankly, it's insulting and a curtailment of my rights to put a gatekeeper between me and my DNA.
This is *my* data, not a doctor's. Please, send in your regulators when a doctor needs to cut me open, or even draw my blood. Regulation should protect me from bodily harm and injury, not from information that's mine to begin with.
Epigenetics Research Among Utah and Iceland Populations May Explain â€śLate-Onsetâ€? and Other Diseases
June 24, 2008 -- Contrary to conventional wisdom, it appears that while the overall health of our genomes is indeed inherited from our parents, chemical marks on our genomesâ€™ DNA sequences actually change as we age, driving increased risk of disease susceptibility for us and similarly for our close family members.
Summarizing results of an international collaborative research project, Andrew Feinberg, M.D., M.P.H., concluded that â€śweâ€™re beginning to see that changes wrought by these epigenetic marks may help explain why susceptibility to many diseases such as diabetes and cancer increases with age.â€?
Feinberg, a professor of molecular biology and genetics and director of the Epigenetics Center at the Johns Hopkins School of Medicine, added that they may also explain why diseases such as diabetes and cancer, in which we know the environment is important, might arise in part because the environment changes the genes themselves. â€śIn this sense, epigenetics probably stands at the center of modern medicine because unlike our DNA sequences, which are the same in every cell, epigenetic changes can occur as a result of dietary and other environmental exposure,â€? he said.
Reporting results of the new study in this weekâ€™s Journal of the American Medical Association, Feinberg said he and an international team embarked on their study to nail down more evidence that epigenetic changes interact with external factors by focusing on a chemical phenomenon called methylation, one particular type of epigenetic mark in which chemical methyl groups attach themselves to DNA in response to various triggers.
â€śAbnormal methylation levels, either too much, which could turn necessary genes off, or too little, which could turn genes on at the wrong time or in the wrong cell, already have been shown to contribute to cancer and other diseases,â€? said Vilmundur Gudnason, M.D., Ph.D., a professor of cardiovascular genetics at the University of Iceland, who designed the Reykjavik, Iceland, component of the study.
For the new study, researchers first collected DNA samples collected in 1991 and again between 2002 and 2006 from 600 participants already enrolled in the AGES Reykjavik Study. The AGES study is renowned for its value to genetics research because of the historic isolation and reduced number of genetic â€śvariablesâ€? among Icelandâ€™s population, making certain patterns of genetic information easier to identify.
Among the 600, the research team measured the total amount of DNA methylation in each of 111 samples and compared total methylation from DNA collected in 2002 to 2005 to that personâ€™s DNA collected in 1991.
They discovered that in almost one-third of the subjects, methylation changed over that 11-year span, with some gaining DNA methylation and others losing it.
â€śThe key thing this part of the study told us is that levels changed over time, proof of principle that an individualâ€™s epigenetic profile does change with age,â€? said M. Daniele Fallin, Ph.D., an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.
Still a puzzle, though, was why or how, Fallin said, â€śso we wondered whether the tendency to those changes was also inherited, right along with our DNA sequences. That would explain why certain families are more susceptible to certain diseases.â€?
To that end, the team measured total methylation changes in a different set of DNA samples collected from Utah residents of northern and western European descent. These DNA samples were collected over a 16-year span from 126 individuals from two- and three-generation families.
Similar to the Icelandic population, the Utah family members also showed varied methylation changes over time. But they found that family members tended to have the same kind of change: If one individual lost methylation over time, they saw similar loss in other family members.
â€śIt seems,â€? said Fallin, an epidemiologist interested in patterns of disease among populations, â€śthat epigenetic changes could be an important link between environment, aging and genetic risk for disease.â€?
Feinberg said interest in the field of epigenetics is growing because â€śthe more we learn about the genetic contribution to aging, health and disease, the more we understand that the DNA sequences we inherit at conception are not the whole story.
â€śIf it were the whole story,â€? he added, â€śthen such things as susceptibility would not vary so much or change over time. We know that changes to the genome must occur but that nature protected that genome from easy alteration. Methylation is natureâ€™s work-around.â€?
Authors on the paper are Hans Bjornsson, Martin Sigurdsson, Rafael Irizarry, Hengmi Cui, Wenqiang Yu, Michael Rongione, Fallin and Feinberg, all of Hopkins; Thor Aspelund, Gudny Eiriksdottir and Vilmundur Gudnason of Hjartavernd, Reykjavik, Iceland; Tomas Ekstrom of Karolinska Institute, Stockholm, Sweden; Tamara Harris and Lenore Launer of the National Institute on Aging, Bethesda, Md; Mark Leppert of University of Utah, Salt Lake City; and Carmen Sapienza of Temple University Medical School, Philadelphia, Pa.
When people know the results of genetic tests confirming they have inherited an increased risk of developing melanoma, they follow skin cancer screening recommendations more proactively--much like those who have already been diagnosed with the potentially deadly disease, according to results of a study completed at the University of Utah's Huntsman Cancer Institute and published in the June issue of Cancer Epidemiology, Biomarkers & Prevention.
Tests for mutations in the CDKN2A gene can reveal a reason that melanomas "run" in families. The study evaluated the intent to follow, and the actual practice of, skin cancer early detection methods by members of families that carry CDKN2A gene mutations. Study participants were drawn from a group of Utahns who participated in the original "CDKN2A gene hunt" 10 to 12 years ago. They already knew that their family history might put them at increased risk for melanoma, and they had previously received melanoma prevention and screening education.
The results showed that people who tested positive for the CDKN2A mutation followed melanoma screening recommendations more carefully than before, even if they had not had a melanoma. In addition, knowing the test results did not lead family members without the mutation to decrease their screening measures.
"Before these studies, it was unclear whether reporting the results to family members who have been tested was valuable or potentially harmful to patients," said co-principal investigator Sancy Leachman, MD, PhD, director of the Tom C. Mathews Jr. Familial Melanoma Research Clinic (FMRC) and associate professor in the Department of Dermatology at the University of Utah School of Medicine. Leachman specializes in melanoma genetics.
Lisa Aspinwall, PhD, associate professor in the University of Utah Department of Psychology, is co-principal investigator on the studies. "We wanted to know whether learning their results helps people comply better with melanoma screening recommendations. We also wanted to know if people who find out that they are negative for the mutation decrease their efforts as a result of knowing their genetic status."
"People with a family history of melanoma who do not carry the mutation are still at almost twice the risk of developing melanoma as people in the general population," Leachman said.
Melanoma is the most serious type of skin cancer. The National Cancer Institute estimates that more than 62,000 people will be diagnosed with the disease in 2008, and more than 8,000 will die of it. Cancer experts estimate that about ten percent of melanomas are associated with familial or inherited syndromes.
Samantha Leaf, Erin Dola, and Wendy Kohlmann are co-authors of the published paper. The work was supported by a Funding Incentive Seed Grant from the University of Utah's Office of the Vice President for Research, Huntsman Cancer Foundation, the Tom C. Mathews Jr. Familial Melanoma Research Clinic endowment, the Pedigree and Population Resource of Huntsman Cancer Institute, and a Templeton Positive Psychology Prize, awarded to Aspinwall by the John Templeton Foundation and the American Psychological Association. Huntsman Cancer Institute core facilities are supported by a Cancer Center Support Grant from the National Cancer Institute.
DNA study begins to unlock etiology of diverse traits in dogs
Physical and behavioral traits in dogs are amongst the most variable within a single species. The amazing versatility and variability within Canis familiaris is astounding--even more so since all of these observable differences were achieved by selective breeding by humans. The underlying factors that contribute to this variation has not been understood, but a new report in the current issue of Genetics reports data that begins to explain these familiar phenomena.
Dogs originally derived from the wolf more than 15,000 years ago -- a blink of the eye in evolutionary terms. Selective breeding produced dogs with physical and behavioral traits that were well suited to the needs or desires of their human owners, such as herding or hunting ability, coat color and body and skull shape and size. This resulted in the massive variance seen among the more than 350 distinct breeds that make up today's dog population. Until now, the genetic drivers of this diversity have intrigued scientists who have been trying to explain how and why the difference in physical and behavioral traits in dogs changed so rapidly from its wolf origins.
An international team of researchers, which included scientists at the National Human Genome Research Institute, the University of Utah, Sundowners Kennels in Gilroy, California and Mars' Waltham Center for Pet Nutrition in the United Kingdom, studied simple genetic markers known as Single Nucleotide Polymorphisms, or SNPs, to find places in the dog genome that correlate with breed traits. Because many traits are "stereotyped" -- or fixed within breeds -- researchers can zero in on these "hot spots" to see what specific genes are in the area that might contribute to differences in traits.
The Genetic Information Nondiscrimination Act (GINA): Implications for policy and practice
After 13 years of effort by literally a cast of thousands, GINA was passed overwhelmingly by both Houses of Congress and signed into law by President Bush this spring. So, now that this policy in place, what does it do and doesn't do regarding protecting individuals from potential genetic discrimination?
Although a landmark piece of legislation that provides much needed protection for healthy people with a genetic predisposition for disease, there are still gaps in protection. It is important for practitioners and researchers to understand GINA's strengths and weaknesses so that they can counsel their patients and research subjects with accurate and complete information about the risks and benefits of genomic medicine and/or participating in genomic research.
Below the fold is a bulleted summary from this article of what GINA addresses for practical purposes.
Prohibits group and individual health insurers from using a person's genetic information in determining eligibility or premiums
Prohibits an insurer from requesting or requiring that a person undergo a genetic test
Prohibits employers from using a person's genetic information in making employment decisions such as hiring, firing, job assignments, or any other terms of employment
Prohibits employers from requesting, requiring, or purchasing genetic information about persons or their family members
Will be enforced by the Department of Health and Human Services, the Department of Labor, and the Department of Treasury, along with the Equal Opportunity Employment Commission; remedies for violations include corrective action and monetary penalties
What GINA does not do
Does not prevent health care providers from recommending genetic tests to their patients
Does not mandate coverage for any particular test or treatment
Does not prohibit medical underwriting based on current health status
Does not cover life, disability, or long-term-care insurance
Does not apply to members of the military
"Genetic information" includes information about:
A person's genetic tests
Genetic tests of a person's family members (up to and including fourth-degree relatives)
Any manifestation of a disease or disorder in a family member
Participation of a person or family member in research that includes genetic testing, counseling, or education
"Genetic tests" refers to tests that assess genotypes, mutations, or chromosomal changes
Examples of protected tests are:
Tests for BRCA1/BRCA2 (breast cancer) or HNPCC (colon cancer) mutations
Classifications of genetic properties of an existing tumor to help determine therapy
Tests for Huntington's disease mutations
Carrier screening for disorders such as cystic fibrosis, sickle cell anemia, spinal muscular atrophy, and the fragile X syndrome
Routine tests such as complete blood counts, cholesterol tests, and liver-function tests are not protected under GINA
Lifestyle can alter gene activity, lead to insulin resistance
Environmental factors are at least as important as genetic sequence in contributing to states of health and disease. Another interesting report on how chronic exposures to diet and activity (or lack thereof) contributes to insulin resistance via changes in gene regulation and expression comes out of a study of energy metabolism in identical twins discordant for obesity.
BETHESDA, Md. (June 18, 2008) A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy.
The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.
The study was carried out by Linda Mustelin and Kirsi PietilĂ¤inen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi SovijĂ¤rvi and PĂ¤ivi PiirilĂ¤ of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-JĂ¤rvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.
Environment can influence genes
Recent studies have suggested that defects in expression of genes involved in the bodyâ€™s conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.
Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.
The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.
Among the discordant pairs, the study found the obese twin had significantly lower:
* Insulin sensitivity, indicating the body has a harder time using glucose to produce energy.
* Fitness levels, as measured by maximum oxygen uptake and maximum work capacity.
* Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation). Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.
Heredity may still play role
â€śThese data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects,â€? the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.
â€śAlthough we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism,â€? lead author Linda Mustelin noted.
The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.
California Sends Warning Letter to Consumer Genetic Testing Firms
A wide array of consumer genetic testing products are available via the internet. New York was the first state to regulate its citizens' access to these products. It looks like California is poised to follow suit. Is this good for public health? Does it unnecessarily limit consumer choice and control? Or protect consumers from bogus and useless tests? And what are the best ways to balance consumer protection with the need for innovation? There is a wide spectrum of opinion about these issues. What do you think?
NEW YORK (GenomeWeb News) â€“ The State of California is trying to keep consumer genetic testing companies from offering their services to the stateâ€™s residents and last week sent letters to thirteen firms saying they are violating state law, California Department of Health spokesperson Lea Brooks told GenomeWeb Daily News today.
The state will not disclose the names of the firms to which it has sent letters, or which laws their services violate, until the companies in question verify with the state that they have received the warnings, Brooks said.
With the move to begin regulating consumer genomics companies in the state, California follows New York State, which less than two months ago warned 23 companies that they must have permits to offer their services to New Yorkers.
New Yorkâ€™s warning letter was a shot across the bow not only to new companies, such as Navigenics and 23andMe, that last year entered into the fledgling field of consumer genomics, but also to technology suppliers Affymetrix and Illumina, which make the tools the testing companies use.
Whether California is focusing on consumer genomic testing companies or if it has broadened its authority to include technology suppliers will not be known until the authorities release the names of the companies it is contacting. California authorities also have not said whether information has been referred to the stateâ€™s Attorney General for further action.
One offense that genetic testing companies could commit would be to sell their products to California citizens over the internet without the request or counsel of a doctor, California Department of Public Health official Karen Nickel told Forbes.com last week. Another problem, Nickel said, could be that the companiesâ€™ tests have not been validated for accuracy or for clinical utility, which is required under California law.
Concerns over marketing genomic data to consumers and assertions about the ability of tests to predict disease risk were sharply rendered in January by Muin Khoury, director of the National Office of Public Health Genomics at the US Centers for Disease Control and Prevention.
After publishing a critical op-ed in the New England Journal of Medicine with two other authors, Khoury told GWDN that consumer genomics as it is today should be considered â€śrecreational genomics,â€? and that the field was premature and consumers were not ready to receive the â€śalphabet soupâ€? of genomic information they were buying.
To Khoury and his fellow NEJM writers, the problem of how to show the clinical usefulness of these genomics offerings would prove to be the most critical.
â€śThe bottom line here is that people are beginning to be concerned that there may be more harm than benefit,â€? Khoury said.
Fascinating report on the origins of some of the building blocks for nucleic acids. Dr Zita Martins, of the Department of Earth Science and Engineering at Imperial College London and colleagues report finding the nucleobases xanthine and uracil in meteor fragments. The nucleobases contain an isotope of carbon that is not present on earth, ruling out earthly origins for their findings. Could it really be that the antecedents of life here on earth were extraterrestrial?
Lead author Dr Zita Martins, of the Department of Earth Science and Engineering at Imperial College London, says that the research may provide another piece of evidence explaining the evolution of early life. She says:
â€śWe believe early life may have adopted nucleobases from meteoritic fragments for use in genetic coding which enabled them to pass on their successful features to subsequent generations.â€?
Between 3.8 to 4.5 billion years ago large numbers of rocks similar to the Murchison meteorite rained down on Earth at the time when primitive life was forming. The heavy bombardment would have dropped large amounts of meteorite material to the surface on planets like Earth and Mars.
Co-author Professor Mark Sephton, also of Imperialâ€™s Department of Earth Science and Engineering, believes this research is an important step in understanding how early life might have evolved. He added:
â€śBecause meteorites represent left over materials from the formation of the solar system, the key components for life -- including nucleobases -- could be widespread in the cosmos. As more and more of lifeâ€™s raw materials are discovered in objects from space, the possibility of life springing forth wherever the right chemistry is present becomes more likely.â€?
Family history of disease is one of simplest and predictive genetic screening tests available in clinical and public health practice. In spite of the long-known and well-established association between many common conditions and family history, it remains under-utilized in practice.
Dr. Kathleen D. Griffith and colleagues authored a paper to be published in the July 15, 2008 issue of Cancer that suggests that African Americans with a family history of colorectal cancer get screened less than other groups with a family history of colorectal cancer. This finding suggests that there may be a need to identify the underlying reasons for this finding in order to address this gap in service provision.
A new study indicates that African Americans with a family history of colorectal cancer are less likely to be screened than African Americans at average risk for the disease.
There is also some evidence to indicate that African Americans with a family history are less likely to be screened than their white counterparts. The study is published in the July 15, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. African Americans have the highest colorectal cancer (CRC) incidence and death rates of all racial groups in the United States. The reason for this is thought to be multifactorial but remains poorly understood. Overall, African Americans have low rates of colorectal cancer screening compared to most other racial groups. Early detection is especially important for those with family histories of CRC who are at higher risk of developing the disease. Factors associated with CRC screening are not well understood for African Americans, both those with and without family histories of CRC.
To investigate the factors associated with risk-appropriate CRC screening, Kathleen Griffith, Ph.D., CRNP, of the Johns Hopkins University School of Nursing and colleagues at the University of Maryland Baltimore analyzed data from the 2002 Maryland Cancer Survey, a telephone survey of more than 5,000 Maryland residents, performed under the Maryland Cigarette Restitution Fund Program to identify predictors of screening among African Americans.
The researchers analyses revealed that for African Americans, regardless of family history, a health care providers recommendation for colorectal cancer screening was strongly correlated with a higher likelihood of screening. Furthermore, individuals who were more physically active were also more likely to have been screened for colorectal cancer. Surprisingly, though, having a family history of colorectal cancer did not predict a higher likelihood of screening. In fact, the researchers found that African Americans with a family history were less likely to have received risk-appropriate screening than those without a family history. Family history of colorectal cancer is often associated with increased rates of screening in whites.
The authors say it is difficult to explain why a perception of increased risk, which is significantly higher in African Americans with a family history of CRC than in those without, did not translate into screening. Their findings suggest that other unknown or unmeasured factors may play a role is screening decisions. Additional studies to determine what those factors might be could lead to culturally tailored interventions designed to increase screening rates, which in turn could ultimately improve early detection and reduce colorectal cancer deaths in African Americans. This study suggests that African Americans would benefit from a primary care approach that evaluates their risk factors for colorectal cancer, and provides corresponding recommendations for appropriate screening tests, the authors write.
Regular colorectal cancer screening is one of the most powerful weapons in preventing colorectal cancer. It can, in many cases, prevent colorectal cancer altogether. Experts estimate adherence to national screening guidelines could prevent up to eight in ten deaths from the disease. The American Cancer Society recommends that people at average risk begin screening for colorectal cancer at age 50. Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, as well as the third leading cause of cancer-related death among both men and women in the United States.
Mom's high fat diet during pregnancy may be key to child's weight issues
We are learning more and more about the intricate interactions between environmental factors and genes that affect gene regulation and expression without affecting the genetic sequence (epigenetics). As this story continues to unfold, the underlying etiologies of the biological processes that contribute to states of health and disease are being elucidated. In this month's issue of the Journal of Molecular Endocrinology, Kjersti Aagaard-Tillery and colleagues report on the role of dietary fat intake during pregnancy in primates and the metabolic phenotype of the offspring.
HOUSTON -- (June 11, 2008) -- The notion that you are what you eat may go back even farther â€“ to your mother, said a Baylor College of Medicine researcher in a report that appears in the current issue of the Journal of Molecular Endocrinology.
"We want to understand the mechanisms behind the current epidemic of childhood obesity," said Dr. Kjersti M. Aagaard-Tillery, assistant professor of obstetrics and gynecology at BCM. "What efforts can we take in pregnancy to affect this problem? Is it that the mom is obese or is exposure to a high fat diet the problem?" A consortium of researchers from BCM, the University of Utah Health Sciences in Salt Lake and the Oregon National Primate Research Center teamed up to study what happens to the offspring of non-human primate mothers fed a diet consisting of 35 percent fat. When compared to those who ate a 13 percent fat diet, the offspring of these animals had non-alcoholic fatty liver disease (comparable to that found in obese human youngsters). In fact, their triglycerides (one form of fat measured in blood) were three times higher than those of the normal offspring.
In some cases, the mothers on the high fat diet did not become obese themselves but their offspring suffered the same ill effects as those of moms who did become obese.
At a molecular level, Aagaard and her collaborators found modifications in the DNA backbone â€“ the histones â€“ of the offspring of the mothers who ate a high fat diet. This is called an epigenetic change, which means that while it does not affect the DNA code per se, it still affects the way that the genes are regulated and the degree to which they are expressed (the so-called "histone code").
"We found that there were genes that were differentially regulated in the livers of the offspring whose mothers had a high fat diet, and that these changes ere associated with histone alterations," she said. "The genes affected were not always those associated with obesity."
She is now trying to find out why these gene changes exist and how they might affect the animals later in life. She is interested in looking at whether they are the direct result of permanent modifications in the histones in both the liver and brain, and whether they further relate to specific changes in the chemical modifications (or methylation) of the regulatory regions of genes.
Others who took part in this work include Kevin Grove and Jacalyn Bishop of the Oregon Health Science University, Oregon National Primate Research Center and Xingrao Ke, Qi Fu, Robert McKnight, and Robert H. Lane of the University of Utah Health Sciences in Salt Lake.
Funding for this work came from the 2007 National Institutes of Health Director's New Innovators Award to Aagaard, the National Institute of Digestive and Diabetes and Kidney Diseases and the National Institute of Child Health and Human Development.
The full report is available at http://jme.endocrinology-journals.org/cgi/reprint/JME-08-0025v1. The abstract is at http://jme.endocrinology-journals.org/cgi/content/abstract/JME-08-0025v1.