Author Interviews, Genetic Research, Ophthalmology / 05.04.2018 Interview with: Wen-Tao Deng, Ph.D. Department of Ophthalmology, College of Medicine| University of Florida, Gainesville, FL What is the background for this study? What are the main findings? Response: Blue cone monochromay (BCM) is a devastating vision disorder characterized by loss function of both L- and M-cones due to mutations in the L- and M-opin gene cluster on the X chromosome. BCM patients display severely reduced visual acuity, loss of color-vision, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. In our studies, we showed that an M-opsin knockout mouse model resembles human BCM, and expression of either human M- or L-opsin individually or combined through adeno-associated viral vector promotes regrowth of cone outer segments and rescues M-cone function in the treated M-opsin dorsal retin (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 03.04.2018 Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH  4322  What is the background for this study?  What are the main findings? Response: The background is that we had recently shown that some colorectal cancer patients who underwent traditional screening for Lynch syndrome were eventually found to have double somatic (two acquired) mutations in the MMR genes and they did not have Lynch syndrome at all. This was discovered after their tumor had already had MSI and/or IHC screening test, followed by MLH1 methylation and/or BRAF testing, followed by germline DNA testing on a blood sample from the patient for MMR gene mutations, then finally by sequencing their tumor. This gave us the idea to reverse the sequence and start with tumor sequencing since it might streamline testing, save time, and prevent several other tests. In addition, we knew that all stage IV colorectal cancer are already supposed to have tumor sequencing of the KRAS, NRAS, and BRAF genes and MSI testing for treatment purposes. Our hypothesis was that an upfront tumor sequencing test could replace all these separate tests with similar sensitivity and specificity. (more…)
Author Interviews, Genetic Research, Nature, OBGYNE, UCLA / 22.03.2018 Interview with: Marlena Fejzo, PhD Aassociate researche David Geffen School of Medicine UCLA. What is the background for this study? Response: Most women experience some nausea and vomiting of pregnancy, and the worst 2% are diagnosed with Hyperemesis Gravidarum which is associated with poor maternal and fetal outcomes. I had HG in 2 pregnancies. In my second pregnancy my HG was so severe that I could not move without vomiting and did not keep any food or water down for 10 weeks. I was put on a feeding tube, but ultimately lost the baby in the second trimester. I am a medical scientist by training so I looked into what was known about HG. At the time, very little was known, so I decided to study it. I partnered with the Hyperemesis Education and Research Foundation (HER) and we did a survey on family history of .Hyperemesis Gravidarum that provided evidence to support a role for genes. I collected saliva samples from HG patients and their unaffected acquaintances to do a DNA study. Then I partnered with the personal genetics company, 23andMe to do a genome scan and validation study, which identified 2 genes, GDF15 and IGFBP7, linked to HG. (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research, Genetic Research / 26.02.2018 Interview with: Maureen E. Murphy, Ph.D. Program Leader and Professor Molecular and Cellular Oncogenesis and Subhasree Basu PhD Postdoctoral researcher The Wistar Institute Philadelphia, PA 19104 What is the background for this study? What are the main findings? Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis. In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  (more…)
Author Interviews, Breast Cancer, Genetic Research / 19.02.2018 Interview with: Amanda Toland, PhD, Cancer biology and genetics researcher of The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute What is the background for this study? What are the main findings? Response: The Breast Information Core (or BIC) is a database that catalogs BRCA1 and BRCA2 sequenced variants.  The BIC is hosted by the National Human Genome Research Institute at NIH and has a steering committee that oversees the BIC and has members from Europe, the middle East, Australia and the US.  In BIC SC discussions, we learned that there are differences in how BRCA1/2 clinical is testing between countries. To characterize this variation, we performed an international survey of 86 genetic testing labs from around the world. Our main findings are that there were many variations between testing laboratories.  These include: technologies differed for finding “large” genetic sequence variants, what parts of the genes were assessed, how genetic variants were classified as disease associated or not being associated with diseases, if genetic sequencing information was shared in public databases and testing volume. (more…)
Author Interviews, Dengue, Genetic Research, PLoS / 16.02.2018 Interview with: Luisa Pereira PhD Institute for Research and Innovation in Health University of Porto What is the background for this study? What are the main findings? Response: By using admixture mapping along the genome in Thai cohorts, we were able to identify new candidate genes conferring protection/susceptibility to dengue fever. A very interesting result was that the set of genes differed with the dengue phenotype: genes coding proteins that may link to the virus, conditioning its entrance in the host cells and mobility therein were associated with the less severe phenotype; genes related with blood vessels permeability were associated with the dengue shock syndrome.  (more…)
Author Interviews, Genetic Research, OBGYNE / 08.02.2018

“Pregnancy 1” by operalynn is licensed under CC BY Interview with: Professor Jane Halliday, PhD Group Leader, Public Health Genetics Genetics Murdoch Childrens Research Institute The Royal Children’s Hospital Parkville, Victoria  AUS What is the background for this study? Response: The aim of the study was to examine the choice that pregnant women make about the amount of genetic information they want from their pregnancy. Women who underwent prenatal testing via chorionic villus sampling (CVS) or amniocentesis were recruited from across seven sites in Victoria. Provision of this choice is not routinely offered but we thought it was important to look at this issue carefully, in a real-time setting, because, over the last five years, advances in technology have transformed how genetic abnormalities can be detected during a pregnancy.  Rather than examining genetic material (chromosomes) down the microscope, it is now possible to use a technique called ‘microarray’ which can do the analysis with 100 times greater depth than can be achieved using a microscope. The plus side is that the microarray technique can detect a far greater number of potentially important genetic differences; but a down side is that it can also detect many changes for which the impact on the health of the baby is unknown or uncertain. Examples of genetic differences that carry certainty are major chromosome abnormalities such as the trisomies e.g. Down Syndrome, and deletions associated with severe intellectual disability in 100% of cases, e.g. 1p.36 deletion. Uncertain findings are the various small deletions and duplications that are known to only have an adverse outcome in 10-20% of people with them. All participants were provided with a decision aid which described in detail the choice available in regards to the genetic information. The options were ‘targeted’, where only the information that would affect health of the baby was provided, or ‘extended’, where all information, even the uncertain aspects, was provided. Participants were asked to read the decision aid, complete a ten minute survey along with indicating their choice of genetic information. (more…)
Author Interviews, Biomarkers, BMJ, Genetic Research, Prostate Cancer, UCSD / 29.01.2018 Interview with: “DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD Radiation Oncology Center for Multimodal Imaging & Genetics UC San Diego What is the background for this study? Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.
  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment. These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.
Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. (more…)
Author Interviews, Education, Genetic Research / 26.01.2018

“Reading is fun!” by Isaac Wedin is licensed under CC BY Interview with: Bruno Sauce, PhD and Louis D. Matzel, PhD Department of Psychology, Program in Behavioral and Systems Neuroscience Rutgers University New Jersey, USA What is the background for this study? Response: Scientists have known for decades that intelligence has a high heritability, which means that much of the individual differences in IQ we see in people are due to genetic differences. Heritability is a value that ranges from 0.0 (meaning no genetic component) to 1.0 (meaning that the trait is completely heritable). For example, the heritability of breast cancer is estimated at 0.27; the heritability of body mass index is 0.59; and the heritability of major depression is 0.40. In comparison, the heritability of IQ is estimated to be as high as 0.8 – quite a high value! More recently, however, there have been studies showing that intelligence has a high malleability: the studies cover cognitive gains consequent to adoption/immigration, changes in IQ’s heritability across life span and socioeconomic status, gains in IQ over time from societal and scientific progress, the slowdown of age-related cognitive decline, the gains in intelligence from early education, differences in average IQ between countries due to wealth and development, and gains in intelligence that seem to happen from working memory training. Intelligence being both highly heritable and highly malleable is seemingly paradoxical, and this paradox has been the source of continuous controversy among scientists. Why does it matter? Because IQ predicts many important outcomes in life, such as academic grades, income, social mobility, happiness, marital stability and satisfaction, general health, longevity, reduced risk of accidents, and reduced risk of drug addiction (among many other outcomes). A clear understanding of the genetic and environmental causes of variation in intelligence is critical for future research, and its potential implications (and applications) for society are immense. (more…)
Author Interviews, Cognitive Issues, Genetic Research, JAMA, Medical Imaging, Mental Health Research / 25.01.2018 Interview with: “The Fourth Sex: Adolescent Extremes” by Victor Soto is licensed under CC BY 2.0Dag Alnaes, PhD Norwegian Centre for Mental Disorders Research KG Jebsen Centre for Psychosis Research Division of Mental Health and Addiction, Oslo University Hospital Oslo, Norway What is the background for this study? What are the main findings? Response: The transition from childhood to adulthood is characterized by swift and dramatic changes, both in our environment and in our brains. This period of life also coincides with the onset of many mental disorders. To gain a better understanding of why, the clinical neurosciences must attempt to disentangle the complex and dynamic interactions between genes and the environment and how they shape our brains. The ultimate goal is to be able to predict which individuals are at risk before clinical symptoms appear. Advanced brain imaging has been proposed to represent one promising approach for such early detection, but there is currently no robust imaging marker that allows us to identify individuals at risk with any clinically relevant degree of certainty. Our study shows that self-reported early signs of mental illness are associated with specific patterns of brain fiber pathways in young people, even if they may not fulfill criteria for a formal diagnosis or are currently in need of treatment.  (more…)
Author Interviews, Genetic Research, Neurology / 25.01.2018 Interview with: Ona Bloom PhD “Duluth Boat Show - Sea Lamprey Booth” by USFWSmidwest is licensed under CC BY 2.0Associate Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research Associate Professor, Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell What is the background for this study? What are the main findings? Response: Scientists have known for years that an ancient species of fish called the lamprey has a remarkable ability to rebuild their spinal cord after it’s been severed. After the lamprey spinal cord is cut, they recover from paralysis to fully swimming again in about twelve weeks, without taking any medicines or other treatments. We are studying the lamprey because we want to know the recipe of molecular ingredients that supports successful recovery after spinal cord injury. The genome of this animal was reported about 5 years ago, in a publication led by my colleagues Dr. Jeramiah Smith at the University of Kentucky and Dr. Weiming Li at Michigan State University.  It turns out that many aspects of the lamprey genome are similar to ours, particularly in the central nervous system. Therefore, we think it is a reasonable expectation that what we learn from lamprey could give us some relevant clues about what might be different about the responses in mammals and other animals that are not good at regenerating their spinal cord. In this study, we found that the expression of many genes in the spinal cord and brain of lampreys change during their recovery from spinal cord injury. Some of the genes that get activated are similar to what happens when our peripheral nervous system is injured, which is better at regenerating than the central nervous system. We also identified that a pathway called the Wnt pathway plays an important role in the regeneration and recovery process. This is a large, complex network of genes that are important in many biological processes, from embryological development in fruit flies to cancer in humans. (more…)
Author Interviews, Genetic Research, JAMA, Neurology, Parkinson's / 25.01.2018 Interview with: Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003 What is the background for this study? What are the main findings?  Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features. To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score. We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08). (more…)
Author Interviews, Emory, Genetic Research, JAMA, Ophthalmology / 24.01.2018 Interview with: Eldon E. Geisert, PhD Professor of Ophthalmology Emory School of Medicine What is the background for this study? What are the main findings? Response: In the late 1990s a group of doctors began a study of glaucoma patients to determine if there were phenotypes that are predictive for developing glaucoma. In this Ocular Hypertension Treatment Study (OHTS) one of the highly correlated ocular traits was central corneal thickness (CCT). The early clinical studies found that people with thinner corneas were at a higher risk of developing glaucoma. In two large studies, examining thousands of people a number of genes were identified that were risk factors for glaucoma or that controlled CCT in humans. In both cases the identified genes accounted for less than 10% of the genetic risk for glaucoma and less than for 10% of the genetic control for CCT. There was little data linking the genetic control of CCT to the glaucoma risk. Our group has taken an indirect approach to the question, using well-defined mouse genetic system to identify genes modulating CCT and then interrogating human glaucoma data to determine if these genes are associated with glaucoma risk.   (more…)
Author Interviews, FDA, Genetic Research, Ophthalmology / 15.01.2018 Interview with: Dr. Stephen Rose PhD Chief Research Officer Foundation Fighting Blindness (FFB) Dr. Rose comments on the announcement of the FDA approval of voretigene neparvovec (LUXTURNA™) gene therapy for inherited blindness due to mutations in the RPE65 gene. What is the background for this announcement? What were the main findings from the study? Response: While it has been 30 years since the RPE65 gene was identified as causing Leber’s Congenital Amaurosis, this shows that it is possible to have an effective gene therapy for an inherited disease. As the first gene therapy for the eye or for an inherited disease, LUXTURNA is a historic milestone in the search for cures for all inherited retinal diseases (IRDs). As a one-time gene therapy, LUXTURNA will not only be life-changing for patients with vision loss due to mutations in the RPE65 gene, it also provides critical momentum for gene therapies - for the eye and other diseases - now in the clinic.  (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Genetic Research, University of Pittsburgh / 07.01.2018 Interview with: Xiangwei Xiao, M.D., Ph.D. Assistant Professor of Department of Surgery, Children’s Hospital of Pittsburgh University of Pittsburgh School of Medicine, Pittsburgh, PA What is the background for this study? Response: Diabetes is a prevalent chronic disease characterized by persistently high blood glucose. Diabetes has two main subtypes, type 1 diabetes and type 2 diabetes. In type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In type 2 diabetes, the beta cells do not produce enough insulin or the body is not able to use insulin effectively. (more…)
Author Interviews, Genetic Research, Pharmaceutical Companies / 17.12.2017 Interview with: Alexander S Hauser, PhD student MRC Laboratory of Molecular Biology Cambridge UK Department of Drug Design and Pharmacology, University of Copenhagen Copenhagen, Denmark What is the background for this study? What are the main findings? Response: The prevalence and impact of genetic variation among all human G protein coupled receptors (GPCRs) that are targeted by FDA-approved drugs remain unknown. In this study, we present a comprehensive analysis and map of the pharmacogenomics landscape of GPCR drug targets. The key highlights are: - GPCRs targeted by drugs show extensive genetic variation in the human population - Variation occurs in functional sites and may result in altered drug response - Understanding GPCR genetic variation may help reduce global healthcare expenses (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, JAMA / 15.12.2017 Interview with: Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115 What is the background for this study? What are the main findings? Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (FDA-CDs) has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall. The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol.  These modifications include, for example, the testing of other tumor types that may carry targetable variants, different types of input specimen preparations available in pathology such as cytology smears or other fresh specimens rather than paraffin blocks, and availability of different methods of DNA quantification that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result. Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. (more…)
Author Interviews, Genetic Research, Melanoma / 14.12.2017 Interview with: Hildur Helgadottir, M.D., Ph.D. Department of Oncology Karolinska University Hospital What is the background for this study? What are the main findings? Response: Malignant melanoma of the skin is one of the fastest increasing cancer types in the West. The main risk factors for melanoma are UV light exposure and hereditary factors. It is therefore relatively common for the afflicted to have family members with the disease. Inherited mutations of the tumour suppressor gene CDKN2A are the strongest known risk factors for familial melanoma and mutations in this gene also increase the risk of other cancers. Children, siblings or parents of mutation carriers have a 50-50 chance of also having the mutation, which can be identified with a gene test. The present study included Swedish and American families with inherited CDKN2A mutations. The researchers studied whether family members who have not inherited the mutation have any higher than normal risk of developing melanoma or other cancers. Melanoma, but no other cancers, was more common in the non-carriers in these families compared to the normal population. The phenomenon whereby non-carriers of a specific mutation copy the phenotype (in this case melanoma) from their mutation-carrying relatives is known as phenocopy. Phenocopy can be caused by other risk-modifying genes or exposure patterns that increase the probability of the specific phenotype manifesting itself. Previous studies have shown that people with the mutation who also have certain pigmentation variants run an even higher risk of melanoma. Even though the CDKN2A mutation should be present in all populations, it has almost exclusively been identified in families with a Caucasian heritage.This suggests that dark-skinned people with this mutation probably don’t develop melanoma as often and are therefore not tested for this specific mutation, presumably because they lack the risk-modifying pigmentation variants that increase the risk of melanoma. The researchers believe that such pigmentation variants also contribute to a higher melanoma risk in the family members who do not carry the mutation. (more…)
Author Interviews, Genetic Research, Weight Research / 08.12.2017 Interview with: David Meyre PhD Associate Professor, McMaster University, Dept. of Health Research Methods, Evidence, and Impact Hamilton, Ontario Canada Visiting Professor, University of Lorraine, Inserm Nutrition-Genetics-Environmental Risks What is the background for this study? What are the main findings? Response: While the average body mass index has reached a plateau in Western countries such as the United States, extreme forms of obesity are still on the rise. The origins of super obesity are still poorly understood. We studied the effects of 37 well-established obesity genes on body-mass index in 75,230 adults with European ancestry using innovative statistical methods (conditional quantile regression and meta-regression models). We found that nine of the 37 genes (24%) make individuals gain more weight if they already have a high body mass index. The effect of these genes is amplified by four times, if we compare the 10% of the population at the low end of the body mass index, compared to the 10% at the high end. The plausible explanation is that there are interactions between these snowball obesity genes and risk environmental factors. (more…)
Author Interviews, Genetic Research, Weight Research / 05.12.2017 Interview with: “Scale model” by brett jordan is licensed under CC BY 2.0William Barrington, PhD lead author on the study Recently graduated PhD student from the Threadgill lab David Threadgill, PhD Texas A&M College of Medicine and College of Veterinary Medicine & Biomedical Sciences, senior author What is the background for this study? What are the main findings? Response: Obesity and diet-induced diseases, such as cardiovascular disease, have reached epidemic proportions. The United States has offered universal dietary recommendations for decades, but they have been largely unsuccessful in reducing diet-induced diseases. These recommendations are largely built upon population-level data, which examines a large number of individuals and determines the average response to a dietary intervention. However, if there is large variation in responses within a population, then population-level data may be inadequate to improve health across genetically diverse individuals. Our study used four genetically diverse types of mice to examine how one’s genetics interact with diet to influence obesity and risk factors for cardiometabolic disease. The study compared four popular human diets (American, Mediterranean, Japanese, and Maasai/ketogenic). While all mice suffered detrimental effects from the American diet, the severity of disease varied widely across the types of mice. In comparison, no single diet improved health across all strains, but there was one or more diets that improved health in each strain. (more…)
Author Interviews, Dermatology, Genetic Research / 04.12.2017 Interview with: Alicia R. Martin PhD, Postdoc Department of Genetics Stanford University Department of Medicine, Massachusetts General Hospital and Harvard Medical School Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA and Brenna M. Henn, Phd, Assistant Professor Department of Ecology and Evolution SUNY Stony Brook, NY What is the background for this study? What are the main findings? Response: Skin pigmentation varies more in Africa than in any other continent, and yet genetic studies of this and other traits are massively underrepresented there. Previous Eurasian study biases have instead focused on populations that vary less and have fewer variants contributing to baseline skin color. In our study, we compiled quantitative skin color measurements from a large, globally diverse set of individuals and populations to show that pigmentation varies more closer to the equator than in high latitude populations. We focused on the ‡Khomani San and Nama populations from South Africa, which diverged early along the modern human lineage from other populations and have lighter skin than equatorial Africans. We showed that skin pigmentation is roughly 100% heritable, but that previously identified genes make up a tiny fraction (~10%) of the variation present in these populations. We identified both known and new genes contributing to this variability. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 15.11.2017 Interview with: Hao Yu Chen, MSc Department of Medicine McGill University Montreal, Quebec, Canada Senior author: George Thanassoulis, MD, MSc What is the background for this study? Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated. Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  (more…)
Author Interviews, Autism, Genetic Research, Nature / 12.11.2017 Interview with: Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960 What is the background for this study? What are the main findings? Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions. Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown. Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes. Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability. (more…)
Abuse and Neglect, Author Interviews, Genetic Research, OBGYNE, Pediatrics / 10.11.2017 Interview with: Professor Sir Nicholas Wald FRCP FRS Professor of Preventive Medicine Wolfson Institute of Preventive Medicine Barts and The London School of Medicine and Dentistry Queen Mary University of London London What is the background for this study? Response: Prenatal screening for Down’s syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) by maternal plasma DNA analysis has an improved screening performance compared with conventional screening but is too expensive to be performed routinely and has a technical failure rate. The aim of the study was to take advantage of the improved screening performance of the DNA analysis in conjunction with the existing methods thereby providing a seamless testing interface between the “old” and the “new” methods that would detect a larger proportion of affected pregnancies with a much lower false-positive rate, at a much reduced cost compared with universal DNA testing and with no failed tests. The novel approach was to conduct a conventional screening test using a screening cut-off level that identifies about 10% of women with the highest risks of having an affected pregnancy (much higher than in conventional screening) and then to perform a DNA test using a portion of the original blood sample collected for the conventional test. Progressing to the DNA test was automatic for these high risk women without their having to be recalled for counseling and a fresh blood sample (ie as a reflex response hence the term “reflex DNA screening”). (more…)
Author Interviews, Genetic Research, Ophthalmology / 07.11.2017 Interview with: Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting Blindness Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics' Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes. Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder? Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness. iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration. There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Genetic Research, Nature / 07.11.2017 Interview with: Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain What is the background for this study? What are the main findings? Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer's disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer's patients than in human controls of the same age; and it is lower in the elderly with respect to young adults. Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho. (more…)
Author Interviews, Dental Research, Genetic Research / 07.11.2017 Interview with: “Dental Mold_002” by Ano Lobb is licensed under CC BY 2.0Alexandre R. Vieira, DDS. MS, PhD Professor, Director of Clinical Research,  Director of Student Research Department of Oral Biology Center for Craniofacial and Dental Genetics Department of Pediatric Dentistry School of Dental Medicine Department of Human Genetics Graduate School of Public Health Clinical and Translational Sciences Institute University of Pittsburgh What is the background for this study? What are the main findings? Response: One aspect is the dilemma between continuing to use dental amalgams and the perception that composite resins are not as durable. We show that composite resin restorations can perform similarly to dental amalgams for the first 5 years. But the most remarkable is that composite resin failures may be related to certain individual risk factors, such as genetic variation. (more…)
Aging, Author Interviews, Gender Differences, Genetic Research / 02.11.2017 Interview with: Dr Mandy Peffers BSc MPhil PhD BVetMed FRCVS Wellcome Trust Clinical Intermediate Fellow Institute of Ageing & Chronic Disease Faculty of Health & Life Sciences University of Liverpool Liverpool UK What is the background for this study? Response: The project was an extension of Louise Pease’s MSc research project in bioinformatics which aimed to re-analyse existing RNA-seq data to determine age related changes in gene expression in musculoskeletal tissues that may lead to the development of degenerative diseases.  From existing literature we identified that degenerative diseases such as osteoarthritis and tendinitis were more prevalent in females and became more frequent following menopause.  We looked at the biology of the cohort we were trying to assess and discovered a gender imbalance, we hypothesised that this was why few results had been obtained from the original analysis. So we developed a research proposal that detailed extending the existing data to publicly available data and merging the experiments; to increase the number of replicates available and balance the experimental design.  We conducted multiple analyses and discovered that splitting samples by age and gender obtained the most significant results, and that whilst in a lot of cases the same genes were being differentially expressed, they were changing in opposite directions.  Louise remembered her statistics lecturer Gerard Cowburn (Ged) taught her about the assumptions of statistical tests, in particular covariance analysis (which has previously been used to show that age and gender do not affect gene expression) assumed that under the conditions being tested data points were not opposites.  Realising that this assumption had been violated by the data she began to think about what other assumptions we were working with and how to test their validity. (more…)
Author Interviews, Genetic Research, PLoS / 07.10.2017 Interview with: Colin Sharpe School of Biology Institute of Biomolecular and Biomedical Science School of Biological Sciences University of Portsmouth Portsmouth, United Kingdom What is the background for this study? What are the main findings? Response: We have long been fascinated by the question of what underpins the increasing complexity of multicellular animals. In a recent publication we looked at changes to the diversity of the NCoR family corepressors (NCoRs) across the Deuterostomes and found an increase in diversity from sea urchins to humans (1). This is due to gene duplication, an increase in alternative splicing and the encorporation of more protein motifs and domains. In this study we devised a measure of functional diversity based on these three factors and calculated this value for over 12000 genes involved in transcription in nine species from the nematode worm to humans. Orthologues whose increase in diversity correlated with the increase in complexity of these animals were then selected and we looked for common features and interactions between the selected genes. We found that proteins that regulate the dynamic organisation of chromatin were significantly enriched within the selection. (more…)
Author Interviews, Clots - Coagulation, Genetic Research, JAMA, Surgical Research / 04.10.2017 Interview with: Anne R. Bass, MD Associate Professor of Clinical Medicine Weill Cornell Medical College Rheumatology Fellowship Program Director Hospital for Special Surgery New York, NY 10021 What is the background for this study? Response: Blood thinners are used after orthopedic surgery to prevent blood clots from forming in the legs and traveling to the lungs. They are also used in patients with certain heart diseases to prevent strokes. Blood thinners, like warfarin, are effective but can be associated with serious bleeding complications, especially if the wrong dose is given. Genetic testing can help doctors predict the right warfarin dose to use in an individual patient. In this trial, ≈1600 elderly patients undergoing hip or knee replacement were randomly assigned to receive warfarin dosing based on genetics plus clinical factors (like height, weight and gender), or based on clinical factors alone. The specific genes tested wereVKORC1, CYP2C9, and CYP4F2 which influence warfarin metabolism and the body’s ability to produce clotting factors. (more…)