Category Archives: Gene Medicine

February 28, 2017 A South African child is evaluated as part of a Stellenbosch University study. Credit: Stellenbosch University

A child's genetic make-up can play a large, hidden role in the success of efforts to maximize his or her development, South African research suggests.

The study, published February 28 in PLoS Medicine and supported by the Government of Canada through Grand Challenges Canada's Saving Brains program, sheds new light on why some children benefit more than others from interventions and raises complex questions about psychosocial intervention programs in future.

In a study led by Professor Mark Tomlinson of Stellenbosch University, the study followed-up an intervention implemented between 1999 and 2003, in which expectant mothers underwent mentoring to improve attachment with their childrenattachment being a measure of a child's psychological security, and predictive of future wellbeing. In the original study, a control group of roughly equal size was composed of expectant mothers who did not receive mentoring.

The original study concluded that the intervention had a small-to-moderate effect on mother-child attachment, evaluated once the children reached 18 months of age.

The follow-up study, conducted thirteen years after the intervention, re-examined the original attachment results and revealed something surprising: the intervention had in fact worked well for toddlers who had a particular genetic characteristic.

Conducted in collaboration with colleagues from the University of Reading, University College London, and Western University, the study re-enrolled and conducted genetic tests on 279 of the original 449 children.

220 children had both genetic and attachment data, enabling the investigators to test whether the original attachment outcomes were influenced by their genes.

The researchers factored in whether the child had the short or long form of gene SLC6A4the serotonin transporter gene, which is involved in nerve signalling, and which other studies have linked to anxiety, depression and other conditions. Serotonin is popularly thought to contribute to feelings of well-being and happiness.

The attachment of children with the short form of the gene, and whose pregnant mothers were mentored, were almost four times more likely to be securely attached to their mothers at 18 months old (84 percent were secure) than children carrying the short form whose mothers did not receive mentoring (58 percent were secure).

Meanwhile, children with the long gene were apparently unaffected by their mother's training or lack thereof: in both cases, the rate of secure attachment was almost identical (70 and 71 percent).

Subject to further validation, says Professor Tomlinson, the insight has "important implications for scientists designing and evaluating interventions to benefit as many people as possible in South Africa and worldwide."

"Without taking genetics into account, it is possible that other studies have under-estimated the impact of their interventions, as we originally did."

Says lead author Dr. Barak Morgan of the University of Cape Town: "The immediate significance of this research is the revelation that in principle, and probably in many cases in practice too, the effectiveness of interventions has been mis-measuredunder-estimated for genetically susceptible individuals and over-estimated for those who are genetically less susceptible. But even more worrying is the implication that the negative consequences of not receiving an intervention also differ by genotype."

"This is an enormously important insight because, in this case, the subgroup with the short form of the SLC6A4 gene is also the one with the most to lose if not helped."

"Individuals with the long form of the gene, on the other hand, appear less sensitive and derived little benefit from the same intervention, and little detriment from not getting it."

Adds Professor Tomlinson: "In the original study, we did not see such a big impact from this intervention because only those with the short gene improved, and this improvement was 'diluted' by the large number of children with the long gene who did not improve."

The researchers caution that, among other limitations, this study involved a relatively small sample and only measured one gene and one outcome (attachment).

Dr. Morgan stressed: "We are certainly not saying that only some people should receive the interventionthose who are 'susceptible' to improving from it. There is little scientific justification for this. For example, many children with the non-susceptible long genotype of the SLC6A4 gene may carry the susceptible form of another gene which renders them much more likely to benefit from the same intervention but for a different but equally important outcome.

"Going forward, the implications are therefore two-fold. Firstly, measuring genetic differences allows for proper assessment of the effectiveness or lack of effectiveness of an intervention for a particular outcome in different individuals. Secondly, this information can then be used to find out how to intervene effectively for allto guide what might be done to improve outcomes for a non-responsive gene-intervention interaction while continuing to optimise outcomes for the responsive one."

Says Dr. Karlee Silver, Vice President Programs of Grand Challenges Canada: "This work is fundamentally about better understanding the impact of interventions which is an important step forward to creating a world where every child can survive and thrive."

Says Dr. Peter A. Singer, Chief Executive Officer of Grand Challenges Canada: "This is a startling finding that changes the way I think about child development. Why is it important? Because child development is the ladder of social mobility used to climb out of the hole of inequity by millions of children around the world."

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More information: "Serotonin Transporter Gene (SLC6A4) Polymorphism and Susceptibility to a Home-Visiting Maternal-Infant Attachment Intervention Delivered by Community Health Workers in South Africa: Re-analysis of a Randomized Controlled Trial" DOI: 10.1371/journal.pmed.1002237

Journal reference: PLoS Medicine

Provided by: Grand Challenges Canada

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To maximize a child's development, genetics provide important insight - Medical Xpress

Editorial Board | Published 8 hours ago

On Feb. 14, the National Academies of Sciences and the National Academy of Medicine released a report recommending that heritable gene-editing trials in human embryos be permitted to move forward given certain conditions.

The report is a scientific green light for humanity to start using new technology to address an intransigent subset of disease. Its also, albeit in a much more limited sense, a go-ahead for us to intentionally alter our own genetic book. Thats a story we should care about.

Our genes play an essential role in determining our health as well as almost everything else about who we are. They contain the DNA code that guides the development and daily function of our bodies. This code is passed down and reassorted from generation to generation.

Unfortunately, genes dont always encode what we would like them to encode. Genetic variants directly affecting only one gene product, as in cystic fibrosis, are enough to cause crippling illness and early death. Single-gene inheritable diseases like these affect 5 to 7 percent of the population.

Gene-editing, especially since the development of the CRISPR-Cas9 system in the last few years, holds the promise to cure such diseases. In some cases, this will not involve changing heritable genetic material.

For genetic diseases that affect multiple different systems in the body, though, the most effective treatments may involve altering the genetic make-up of all cells (which would mean affecting the genes that are passed on in reproduction as well as those in normal body cells).

The limited applications of germ-line editing the editing of genes that will be passed to the next generation recommended by the NAS promise clear benefit in treating awful diseases. Once the era of germ-line gene-editing begins in earnest, though, its easy to imagine a rise in the availability of heritable gene-editing for other purposes. People may seek to have their embryos genetic material altered not only to prevent genetic disease, but also in the hopes of increasing the athleticism, intelligence or beauty of their future children.

While making changes to personal appearance or fitness is widely accepted (we dont worry too much about the flaunting of the natural order when people dye their hair or exercise), editing heritable genetic material brings up a whole slew of questions about autonomy and social impact: Is making changes to embryos without their consent OK? What about if such changes will endure as part of the human gene pool?

Just as concerning are questions of access to gene-editing. Such access will almost certainly not be universal, and a gap one more stark even than our socioeconomic or racial divides might split our future society into those who have been gene-edited and those who have not been.

Andrew Niccols 1997 sci-fi film, "Gattaca," envisions such a development. Does such a gap bother us? And, if so, can we avoid it while still reaping the benefits of gene-editing?

We dont know the answers to many of the questions that accompany the coming world of gene-editing. However, we do know that now is the time to begin seeking them as a society. The contents of our genetic compendium and of history hang in the balance.

More here:
Opinion: Gene-editing is here. How should it be used? - The Daily Tar Heel

In 2012, Madurai-based Avinash Shetty, then 30, was busy making arrangements for his wedding. But festivities were not the only thing on his familys mind. With serious health scares on both sides, his fiance and he were aware they had the odds stacked against them in the genetic department. My mother-in-law had succumbed to leukaemia and my mother was suffering from lung carcinoma and diabetes. Plus, I was (and still am) a smoker, says Shetty. My mother, a nurse, insisted that my future bride and I get genetic testing done, he says. Blood and tissue samples were sent for testing. Fortunately, there was nothing amiss. The couple married and now have two daughters.

The 46 chromosomes or genetic material that we inherit from our parents are responsible for more than just shaping our physical characteristics. They can give us insight into the kind of diseases we could be exposed to. With a single blood test, doctors are now able to analyse our risk to disease at the DNA level and tell in advance the kind of illness you might possibly develop, says Mumbai-based Priyanka Raina, genetic counsellor at Positive Bioscience, a clinical genomics company, and consultant at Saifee Hospital.

The study of a persons DNA to identify various mutations is called genetic testing. Genomic medicine is the broad disciplinebasically medical care attuned to the bodys unique genetic make-up. So, when you get tested for disease based on your genetic coding, it is called genetic testing. The medical care that results is genomic medicine.

Advances in genomic medicine are the results of ground-breaking research. We expect it to transform the very fabric of healthcare, says Samarth Jain, founder and chief executive officer of Positive Bioscience, which offers genetic testing and evaluation of ones risk for disease.

Perhaps the most famous example of genetic diagnosis is Angelina Jolies preventive breast surgeries in 2013. A simple blood test showed the actor carried the BRCA1 gene, which meant she had an 87% risk of contracting breast cancer and a 50% risk of ovarian cancer. She knew she had a strong family risk for both diseases, since her mother and aunts had succumbed to them. Jolie removed her breasts, uterus and fallopian tubes in successive operations.

Shortly afterwards, there were reports of a steady rise in demand for pre-emptive surgeries by women. Doctors still advise caution, however; they say pre-emptive surgery necessitates a thorough assessment of risk factors, age and family history.

While pre-emptive surgery isnt the norm in India yet, there is a growing awareness about genetic diagnosis, especially in the area of cancer prediction and treatment, says Vikas Goswami, senior oncologist at the Fortis Hospital in Noida, near Delhi. But in many cases, even as were able to assess our risk to cancer, we wont always have the medicine to treat it. And that is a very real vulnerability.

To be able to diagnose whether we may be at risk of the disease is only part of the story. We need to be able to answer questions such as what the nature of this disease would be, what drugs would be effective, can we predict whether the cancer would spread or recur. We hope that genetic research can provide answers to these in the days ahead, says Dr Goswami.

In addition to cancer, genomic testing has opened up our world to many other diseases that could possibly be diagnosed or predicted, such as cardiovascular diseases, diabetes, autism spectrum diseases and neurological disorders, says Radhika Vaishnav, a Vadodara-based genetic scientist and executive editor of the International Journal Of Molecular ImmunoOncology. Being able to treat previously untreatable conditions is becoming a reality today, she adds. However, though far more accessible (with costs half of what they were in 2011), genetic testing is still in its infancy in India. This is because genomic medicine relies on Big Data (comparing the genetic data of millions of people) for its accuracy in the prediction of disease. There are concerns that there is not enough Indian population-specific data to compare and accurately predict disease risk.

Prenatal care

Since the 1970s, blood tests have been conducted routinely during pregnancy in India to rule out genetic diseases such as Downs Syndrome. Today, were able to catch rare genetic disorders earlier, says Seema Thakur, senior consultant, genetics and foetal diagnosis, at the Indraprastha Apollo Hospitals in New Delhi. Diseases like thalassemia (an inherited blood disorder requiring frequent blood transfusion), dwarfism and Gauchers (an inherited disorder in which the bodys ability to store fats is compromised, accumulating it in the bodys tissues, cells and organs) are now being identified early.

Great strides have also been made in the treatment of muscular dystrophy (MD), a genetic disorder which causes progressive muscular degeneration and weakness. Of the nine kinds of muscular dystrophy, Duchenne Muscular Dystrophy (DMD) the most common oneis treatable after prenatal genetic testing. DMD can begin as early as the age of 3. By the time a child reaches his/her teens, their muscles progressively waste away and they will find themselves in a wheelchair. By the age of 21, the disease can prove fatal, says Berty Ashley, senior research associate at the Dystrophy Annihilation Research Trust, a non-profit in Bengaluru. DMD occurs because a certain gene in our bodies (incidentally the largest gene we have) called the dystrophin gene is not copied in its entirety when it is passed on to the child in the womb. The gene is made of 79 exons, structures that fit like a jigsaw puzzle. When the gene is transferred to the child, exon 51 is missing or deleted, says Ashley.

In September, the US food and drug administration approved the use of new medication (dystrophy eteplirsen) for this. Taking this drug during pregnancy will introduce the missing genetic strand in the child. It wont cure the disease but it could effectively hamper its progression, says Ashley. A child will still have weak limbs, but s/he will be spared a life in a wheelchair or premature death.

Dr Thakur, however, believes that genetic testing without sustained counselling both before and afterwards could lead to greater stress for patients.

Genetic testing is extremely expensive (ranging from Rs12,000 to Rs1.5 lakh) and not all (diagnostic) labs offer standardized results. If you are faced with an incurable disease, there is little you can do. It could cause great anxiety, she says.

It is disturbing that people are requesting tests on their own because emotionally, they may not be equipped to handle the results. Adequate counselling and follow-up on treatment/medication are important, Dr Thakur explains, adding, There is no doubt that our knowledge of genetic diagnosis will bring with it greater responsibility.

Where to go

Places that provide prenatal diagnostic services and genetic diagnosis

The Indian Council of Medical Research in Mumbai provides prenatal diagnostic services (www.icmr.nic.in)

The genetics unit, department of paediatrics, All India Institute of Medical Sciences, New Delhi (a World Health Organization collaborating centre) offers genetic diagnosis, prenatal diagnosis and counselling (www.aiims.edu)

Genetic blood tests and counselling are offered at hospitals across the country such as Apollo (Madurai, Chennai), Saifee (Mumbai), Kokilaben Dhirubhai Ambani Hospital, Breach Candy (Mumbai) and MedantaThe Medicity (Gurugram).

First Published: Mon, Feb 27 2017. 05 44 PM IST

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Taking the gene test - Livemint

February 27, 2017 Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia

A new nasal test may allow patients suspected of having lung cancer to undergo a simple swab of their nose to determine if they have the disease.

Researchers at Boston University School of Medicine (BUSM) have found that a genomic biomarker in the nasal passage can accurately determine the likelihood of a lung lesion being malignant.

The findings, which appear online in the Journal of the National Cancer Institute, will allow physicians to confidently identify patients who are at low probability for having lung cancer, thus sparing them from costly and risky procedures.

The diagnostic evaluation of lung cancer among high-risk current and former smokers with lesions found on chest imaging (computed tomography or CT) represents a growing clinical challenge given the current clinical recommendations for routine CT screening of high-risk smokers. While there are guidelines for the management of pulmonary nodules, unnecessary, invasive follow-up procedures (including surgical lung biopsy) are frequently performed on patients who are ultimately diagnosed with benign disease.

"Our group previously derived and validated a bronchial epithelial gene-expression biomarker to detect lung cancer in current and former smokers. This innovation, available since 2015 as the Percepta Bronchial Genomic Classifier, is measurably improving lung cancer diagnosis," said corresponding author Avrum Spira, MD, MSc, professor of medicine, pathology and bioinformatics at BUSM. "Given that bronchial and nasal epithelial gene expressions are similarly altered by cigarette smoke exposure, we sought to determine in this study if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium."

After examining nasal epithelial brushings from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer, the researchers determined that the nasal airway epithelial field of lung cancer-associated injury in smokers extends to the nose and has the potential of being a non-invasive biomarker for lung cancer detection.

"There is a clear and growing need to develop additional diagnostic approaches for evaluating pulmonary lesions to determine which patients should undergo CT surveillance or invasive biopsy. The ability to test for molecular changes in this 'field of injury' allows us to rule out the disease earlier without invasive procedures," added Spira, who is also director of the BU-BMC Cancer Center and a pulmonologist at Boston Medical Center (BMC).

"Our findings clearly demonstrate the existence of a cancer-associated airway field of injury that also can be measured in nasal epithelium," added Marc Lenburg, PhD, professor of medicine at BUSM and co-senior author. "We find that nasal gene expression contains information about the presence of cancer that is independent of standard clinical risk factors, suggesting that nasal epithelial gene expression might aid in lung cancer detection. Moreover, the nasal samples can be collected non-invasively with little instrumentation or advanced training."

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Study finds biomarker for lung cancer detection in the nasal passages of smokers - Medical Xpress

Researchers provide further evidence of how gene mutations in a certain brain region might fuel behaviors associated with obsessive-compulsive disorder. The findings could pave the way for new treatments for the condition.

Obsessive-compulsive disorder is a condition characterized by uncontrollable thoughts, obsessions, and compulsions.

Obsessions include repetitive thoughts or mental images that trigger anxiety, while compulsions refer to the urge to repeat certain behaviors in response to obsessions. Common examples of compulsions include excessive hand-washing, arranging items in a particular way, and compulsive counting.

OCD is estimated to affect around 1 percent of adults in the United States. Of these adults, 50 percent have severe OCD, which can significantly interfere with daily life.

While the precise causes of OCD are unclear, previous studies have suggested that the disorder may be caused by specific gene mutations.

In the new study, researchers from Northwestern University in Chicago, IL, have pinpointed gene mutations in the corticostriatal region of the brain that led to OCD-like behaviors in mice.

Lead author Anis Contractor, associate professor of physiology at Feinberg School of Medicine, and colleagues recently reported their findings in the journal Cell Reports.

In humans and mice, the corticostriatal brain region is responsible for regulating repetitive behavior. "People with OCD are known to have abnormalities in function of corticostriatal circuits," notes Contractor.

By analyzing this brain region in mice, Contractor and colleagues identified a number of synaptic receptors - called kainate receptors (KARs) - that play a key role in the development of the corticostriatal region.

The researchers then set out to investigate whether disrupting KAR genes in mice - thereby eliminating KARs - might induce repetitive behavior in the rodents. They found this was the case.

Mice whose KAR genes were erased displayed a number of OCD-like behaviors, such as over-grooming and repeatedly digging in their bedding.

The team says these findings provide further evidence that KAR genes play a role in OCD in humans, and a possible biological mechanism.

"A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans.

I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans."

Anis Contractor

The team suggests that in the future, KAR genes could be a target for the development of new drugs to treat OCD.

Learn how exposure therapy might help treat people with OCD.

See more here:
Gene mutations in brain linked to OCD-like behavior - Medical News ... - Medical News Today

Science Daily

Neanderthal DNA contributes to human gene expression Science Daily "Even 50,000 years after the last human-Neanderthal mating, we can still see measurable impacts on gene expression," says geneticist and study co-author Joshua Akey of the University of Washington School of Medicine. "And those variations in gene ... Neanderthal DNA Influences Your Biology A Lot More Than You RealizeIFLScience Neanderthal DNA influences our height, schizophrenia risk: StudyThe Hans India all 52 news articles »

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Neanderthal DNA contributes to human gene expression - Science Daily