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Author Interviews, BMJ, Genetic Research, Vitamin D / 19.11.2014

MedicalResearch.com Interview with: Børge G Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Herlev Hospital, Copenhagen University Hospital Dept. Clinical Biochemistry Herlev Ringvej Herlev, Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Nordestgaard: Many people take vitamin D supplements with the hope of reducing morbidity and mortality. However, it is unclear whether low vitamin D per se is a direct cause of increased mortality or whether it is simply a marker of poor lifestyle in general and/or underlying hidden disease. Our study involved 95,766 white participants of Danish descent from three cohorts in Copenhagen, who had genetic variants known to affect vitamin D levels. We found that genetically low vitamin D levels were associated with increased all-cause mortality, cancer mortality, and other mortality, but not with cardiovascular mortality. This is important as such genetics studies cannot be explained by poor lifestyle or hidden disease, as neither can change your genes. (more…)
Author Interviews, Genetic Research, Nature, NYU / 06.11.2014

Leslie Mitchell, PhD New York University Langone Medical Center Boeke Lab, Institute for Systems Genetics NY NY, 10016MedicalResearch.com Interview with: Leslie Mitchell, PhD New York University Langone Medical Center Boeke Lab, Institute for Systems Genetics NY NY, 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: One of our major interests is building synthetic chromosomes. Typically we construct synthetic chromosomes using a bottom-up approach, first designing the sequence in silico and then synthesizing and piecing together the DNA to build the designer molecule. While eukaryotic chromosomes are usually linear in structure, oftentimes we build our designer synthetic chromosomes as circular molecules to take advantage of cloning technologies available in E. coli, an organism that tolerates only circular chromosomes. We developed the telomerator as a means by which to convert circular synthetic chromosomes into linear molecules, which more closely resemble the native chromosomes found in eukaryotic cells. We discovered that the telomerator is an extremely effective tool for generating linear derivatives of circular synthetic chromosomes. There are two main reasons for this.
  • First, the action of the telomerator can be assessed using a simple phenotypic assay so it is easy to differentiate cells that encode linear synthetic chromosomes from those with the circular format.
  • Second, the telomerator encodes ‘telomere seed sequences’ that are exposed and recognized by the cell upon linearization, thus the ends of a newly linearized chromosome are protected, which ensures its stability over generations. We put the telomerator to the test by integrating it in 54 different positions on a circular synthetic yeast chromosome called synIXR (Dymond et al. 2011). In 51 of the 54 positions we could successfully linearize the synIXR chromosome and recover viable cells, however many of the different linear derivatives conferred growth defects. We determined the mechanism underlying both the growth defects and lethality associated with linearization to be telomere position effect. In other words, when essential genes were re-positioned near telomeres their reduction in expression due to subtelomeric silencing was detrimental to the cell.
(more…)
Alcohol, Author Interviews, Genetic Research / 05.11.2014

Victor M. Karpyak, M.D., Ph.D. Medical Director, Intensive Addiction Treatment Program Director, Mayo Clinic Addiction Services Consultant, Department of Psychiatry and Psychology Assistant Professor of Psychiatry Mayo Clinic College of Medicine MedicalResearch.com Interview with: Victor M. Karpyak, M.D., Ph.D.  Medical Director, Intensive Addiction Treatment Program Director, Mayo Clinic Addiction Services Consultant, Department of Psychiatry and Psychology Assistant Professor of Psychiatry  Mayo Clinic College of Medicine Medical Research: What is the background for this study? Dr. Karpyak: The staggering costs of alcohol use disorders call for the development and implementation of evidence-based treatment strategies. Several medications (acamprosate, naltrexone, and disulfiram) were approved for treatment of alcohol use disorders; yet, only a fraction of patients respond to each medication. Clearly, response predictors are needed to improve treatment efficacy and personalize recommendations for treatment selection. It is expected that pharmacogenomic research will aid the discovery of such predictors. (more…)
Author Interviews, Genetic Research, Infections / 25.10.2014

Dr R.E.W. (Bob) Hancock, OC, OBC, FRSC {Canada Research Chair and Professor, Department of Microbiology and Immunology,UBC} Director, Centre for Microbial Diseases and Immunity Research University of British Columbia, Vancouver, British Columbia, CanadaMedicalResearch.com Interview with: Dr R.E.W. (Bob) Hancock, OC, OBC, FRSC {Canada Research Chair and Professor, Department of Microbiology and Immunology,UBC} Director, Centre for Microbial Diseases and Immunity Research University of British Columbia, Vancouver, British Columbia,  Canada MedicalResearch: What is the background for this study? What are the main findings? Dr. Hancock: We wanted to understand how patients transitioned from the hyperinflammatory phase (cytokine storm) of sepsis to the hypoinflammatory (immunosuppressive) phase of sepsis (inability to respond appropriately to infections). About 15% of patients die in this first phase and 20% in the second phase, making sepsis one of the most deadly syndromes (35% overall mortality, 5 million deaths [8.3% of all deaths] annually worldwide). We hypothesized that immunosuppression was characterized by a state termed endotoxin tolerance a cellular amnesia (termed cellular reprogramming) in which cells fail to respond to microbial cues. Overall we found that an Endotoxin Tolerance gene signature is significantly associated with the subsequent development of confirmed sepsis and new organ dysfunction in patients who had suspected sepsis. All 620 sepsis patients in retrospective and new analyses presented with an expression profile strongly associated with the endotoxin tolerance signature (p<0.01; AUC 96.1%). This occurred in fact very early in sepsis and in a new clinical study we found that the signature could be detected already in the emergency ward at first clinical  presentation and 24-48 hours prior to definitive diagnosis. Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. (more…)
Author Interviews, Genetic Research / 24.10.2014

Dr. Toomas Kivsild PhD Department of Archaeology and Anthropology University of Cambridge, CambridgeMedicalResearch.com Interview with: Dr. Toomas Kivsild PhD Department of Archaeology and Anthropology University of Cambridge, Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Kivsild: Native populations of Siberia are known to have certain physiological characteristics such as high basal metabolic rate, and high blood pressure and low levels of serum lipids, that have been explained as traits that have evolved as a consequence of the adaptation of Siberians to their cold environment. Genetic basis of cold adaptation is still poorly understood. In our previous study using genome-wide genotyping scans we detected a 3 Mbp region of high haplotype homozygosity in chromosome 11 as a candidate of strong positive selection in Northeast Siberians. There were 79 protein coding genes mapping to this homozygosity region but we could not determine which of the genes was driving the signal we observed. In this forthcoming paper we have used high coverage whole genome sequences from 25 individuals from Northeast Siberia and we were able to determine the most likely SNP that is responsible for the high haplotype homozygosity in the chromosome 11 in Northeast Siberians maps to CPT1A gene which is a key regulator of long-chain fatty-acid oxidation in mitochondria. What makes this finding most interesting is that the same SNP had previously been found in Greenland and Canadian Inuits in association with high infant mortality and hypoketotic hypoglycemia. There are only a few other similar cases, like the sickle cell and APOL1 alleles, where disease associated genetic variants may have risen to high frequency in modern day populations due to the adaptive advantage they have presented in the past populations. (more…)
Author Interviews, Bipolar Disorder, Genetic Research, Nature / 21.10.2014

Edward I. Ginns, MD, PhD, Director Program in Medical Genetics and Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School Reed Rose Gordon Building, Room 137 Shrewsbury, MA 01545MedicalResearch.com: Interview with: Edward I. Ginns, MD, PhD, Director Program in Medical Genetics and Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School Reed Rose Gordon Building, Room 137 Shrewsbury, MA 01545 Medical Research: What are the main findings of the study? Dr. Ginns: Our study identified that sonic hedgehog signaling, an important brain pathway, is involved in bipolar affective disorder. This finding shows a mechanism and provides new targets for drug development. It suggests that sonic hedgehog signaling can be modulated to help manage bipolar symptoms in adults by using drugs already being studied in clinical trials for other medical conditions. The new findings were uncovered by decades of translational research in the Old Order Amish families of Pennsylvania, where in a few special families in the Amish Study there is a high incidence of both bipolar disorder and a rare genetic dwarfism, Ellis van‐Creveld (EvC) syndrome. No person with EvC had bipolar disorder despite forty years of documented research across multiple generations, suggesting that the genetic cause of this rare dwarfism was protective of bipolar affective disorder. (more…)
Author Interviews, Diabetes, Diabetologia, Exercise - Fitness, Genetic Research / 01.10.2014

Dr. Yann C Klimentidis, PhD Assistant professor of Epidemiology and Biostatistics Mel and Enid Zuckerman College of Public Health University of Arizona Medical CenterMedicalResearch.com Interview Invitation with: Dr. Yann C Klimentidis, PhD Assistant professor of Epidemiology and Biostatistics Mel and Enid Zuckerman College of Public Health University of Arizona Medical Center   Medical Research: What are the main findings of the study? Dr. Klimentidis: The main finding is that the association of physical activity with type-2 diabetes risk is weakest among those who are at high genetic risk for type-2 diabetes. Furthermore, we find that this trend is stronger among women as compared to men, and that it appears to be driven mainly by genetic risk to insulin resistance, as opposed to genetic risk for reduced beta-cell function. (more…)
Author Interviews, Genetic Research, Nature, Prostate Cancer / 18.09.2014

Dr. Jyotsna Batra QUT Institute of Health and Biomedical Innovation's Queensland University of Technology Queensland, AustraliaMedicalResearch.com Interview with: Dr. Jyotsna Batra QUT Institute of Health and Biomedical Innovation's Queensland University of Technology Queensland, Australia   Medical Research: What are the main findings of the study? Dr Batra: Prostate cancer is a disease with upto 40% genetic component. Previous Genome-wide association studies have identified 77 risk loci associated with prostate cancer. This study is further extension of previous GWASs and also involved meta-analysis of multi-ethnic populations. Through this large study involving approximately 90,0000 individuals, 23 new susceptibility loci were identified to be associated with prostate cancer, 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. (more…)
Author Interviews, Cancer Research, Genetic Research, University of Pennsylvania / 12.09.2014

Renata Afi Rawlings-Goss, Ph.D. Postdoctoral Fellow Tishkoff Lab, University of PennsylvaniaMedicalResearch.com Interview with: Renata Afi Rawlings-Goss, Ph.D. Postdoctoral Fellow Tishkoff Lab, University of Pennsylvania   Medical Research: What are the main findings of the study? Dr. Rawlings-Goss: We found genetic mutations in key gene regulators that have been linked to ethnic disparities in cancer. Our investigation identified more than 30 previously undescribed mutations in important regulatory molecules called microRNAs. Individual microRNA molecules can regulate large numbers of genes in some cases over 6000 genes at once. Therefore, mutations in these genes have been linked to numerous diseases. By and large, however, microRNA mutations have not been studied in people of diverse ethnic backgrounds. (more…)
Author Interviews, Genetic Research, Hematology, Johns Hopkins, NEJM / 27.08.2014

Jerry Spivak, M.D Professor of Medicine and Oncology Director, Center for the Chronic Myeloproliferative Disorders John Hopkins MedicineMedicalResearch.com Interview with: Jerry Spivak, M.D Professor of Medicine and Oncology Director, Center for the Chronic Myeloproliferative Disorders John Hopkins Medicine Medical Research: What are the main findings of the study? Dr. Spivak: The main findings of this study are that polycythemia vera occurs in two clinical forms: an indolent form in which only phlebotomy may be necessary and a more aggressive form requiring myelosuppressive therapy and that these two forms of the disease can be distinguished genetically. (more…)
Aging, Author Interviews, Genetic Research / 26.08.2014

Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain.MedicalResearch.com Interview with: Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. Medical Research: What are the main findings of the study? Dr. Serrano: We investigated the contribution of rare genetic variation to human exceptional longevity (EL, individuals with ≥100 years of age) by exome-sequencing long-lived siblings in three different families where exceptional longevity clustered. We found only one gene that harbored rare variants that was likely to contribute to human longevity across all three families and this gene was the Apolipoprotein B gene (APOB). We further found that the frequency of these rare APOB variants associated with familial exceptional longevity was greater in a cohort of 206 nonfamilial cases of exceptional longevity compared to the control population, though this association did not reach statistical significance. In addition, we found rare variants in many genes within individual families that are likely to contribute to human longevity given previous studies in animals. (more…)
Author Interviews, Breast Cancer, Genetic Research, NEJM / 07.08.2014

Dr Marc Tischkowitz MD PhD University Lecturer (Associate Professor) and Honorary Consultant Physician in Medical Genetics Department of Medical Genetics, University of CambridgeMedicalResearch.com Interview with: Dr Marc Tischkowitz MD PhD University Lecturer (Associate Professor) and Honorary Consultant  Physician in Medical Genetics Department of Medical Genetics, University of Cambridge Medical Research: What are the main findings of the study? Dr. Tischkowitz: The PALB2 gene was first identified in 2006 and linked to breast cancer in 2007 but until now we have not had good breast cancer risk estimates for women who have inherited PALB2 mutations. This study was started in 2009 by an group of research institutions (The PALB2 Interest Group) in Canada, US, Europe (UK, Belgium, Greece, Italy, Finland) and Australia. We studied 362 individuals with PALB2 mutations from 154 families. We found that awomen with a PALB2 mutation will on average have a 35% risk of developing breast cancer by the age of 70, rising to 58% if there is a strong family history. Our study will help clinicians to better advise and manage such women. There are several new aspects.
  • It is by far the largest study to date and provides the most accurate risk estimates for PALB2 mutation carriers.
  • It shows that the breast cancer risk is modified by the family history. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 31.07.2014

Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HXMedicalResearch.com Interview with: Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HX Medical Research: What are the main findings of the study? Dr. Ronald: Psychotic experiences, such as paranoia, hallucinations and disorganised thinking, are commonly reported by adolescents. Until now it has not been understood whether mild variations in psychotic experiences in the community are part of the same construct as more severe psychotic experiences in adolescence. Our findings suggest that they are. In our study, over 10,000 16-year-old adolescents in England and Wales were assessed on measures of psychotic experiences. The study identified a close link between normal, less frequent psychotic experiences and more severe and frequent experiences in the general population. A classic twin design was employed, which enabled us to conduct analyses investigating the role of genetic and environmental influences on psychotic experiences. The same genetic influences appeared to play a role across the spectrum of severity of psychotic experiences. The study found that psychotic experiences are moderately heritable in adolescence in the general population. This suggests it would be worth directing molecular genetic endeavours towards this area, which has so far received very little attention in terms of causal explanations. We also show that psychotic experiences have considerable environmental influence; in fact, environmental influence appears to play a larger role in causing psychotic experiences in adolescence than for diagnosed psychotic disorders in adults, such as schizophrenia. This result suggests a fruitful avenue will be to tackle what environmental risk factors influence adolescents to have psychotic experiences. (more…)
Author Interviews, Genetic Research, JCEM, Weight Research / 31.07.2014

Dr. Agatha van der Klaauw, PhD Wellcome Trust Postdoctoral Clinical Fellow Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge Metabolic Research Laboratories Addenbrooke's Hospital Cambridge, United KingdomMedicalResearch.com Interview with: Dr. Agatha van der Klaauw, PhD Wellcome Trust Postdoctoral Clinical Fellow Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge Metabolic Research Laboratories Addenbrooke's Hospital Cambridge, United Kingdom   Medical Research: What are the main findings of the study? Dr. van der Klaauw: Obesity occurs when we eat more calories than we burn which is often easy to do as many foods are highly palatable and high in calories. Highly palatable foods such as chocolate trigger signals in the brain that give a feeling of pleasure and reward (sometimes called cravings) which can contribute to overeating. These signals are processed in the reward centres in the brain, where sets of neurons release chemicals such as dopamine. However, very little is known about whether the reward centres of the brain work differently in some people who are overweight. In this study, we were interested in studying overweight people who had a problem with the melanocortin 4 receptor (MC4R) gene. About 1% of obese people have a problem in this gene which contributes to weight gain from a young age. We compared three groups of people: people who were overweight due to a problem in the MC4R gene, people who were overweight but the gene was normal and some people who were normal weight. We performed functional Magnetic Resonance Imaging (fMRI) scans to look at how the reward centres in the brain were activated by pictures of appetizing food such as chocolate cake compared to bland food such as rice or broccoli and non-food items such as staplers. We found that in normal weight people, the reward centres are activated (light up) when they are shown pictures of cake or chocolate and the same was seen in overweight people with a problem in the MC4R gene. But we found that the reward centres were underactive in overweight volunteers (in whom the gene was normal). (more…)
Author Interviews, Genetic Research, Mental Health Research / 30.07.2014

dr_zachary_kaminskyMedicalResearch.com Interview with: Zachary A. Kaminsky, Ph.D. Assistant Professor Johns Hopkins University School of Medicine Department of Psychiatry Baltimore, MD, 21205 Medical Research: What are the main findings of the study? Dr. Kaminsky: A DNA methylation increase at the SKA2 gene was identified and observed across three post mortem brain tissue cohorts and was associated with suicide. The DNA methylation at the SKA2 gene was associated with lower gene expression of the gene. The same association was found in blood allowing us to attempt to predict suicidal behaviors in living individuals. (more…)
Author Interviews, Breast Cancer, Diabetes, Genetic Research, Nature, Vanderbilt / 23.07.2014

MedicalResearch.com Interview with: Qiuyin Cai, M.D., Ph.D. Associate Professor of Medicine Vanderbilt University Medical Research: What are the main findings of the study? Dr. Cai: We conducted a genome-wide association study in East Asians to search for additional genetic changes that are linked to breast cancer development. The study was conducted as part of the Asia Breast Cancer Consortium, which includes 22,780 women with breast cancer and 24,181 control subjects. We found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk. These results were also replicated in a large consortium, including 16,003 breast cancer cases and 41,335 control subjects of European ancestry. (more…)
Author Interviews, Breast Cancer, Genetic Research, Nature / 23.07.2014

MedicalResearch.com Interview with Dr Lim Weng Khong Research Fellow, National Cancer Centre Singapore. Medical Research: What are the main findings of the study? Dr Lim Weng Khong: This study uncovered the genetic cause fibroadenomas, which are very common benign breast tumours in women. The team from National Cancer Centre Singapore, Singapore General Hospital and Duke-NUS Graduate Medical School identified a critical gene called MED12 that has frequent durations in a remarkable 60 per cent of fibroadenomas studied. Their findings have been published in the top-ranked journal Nature Genetics. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research, NEJM, Pediatrics / 03.07.2014

Dr. Daniel AgardhMedicalResearch.com Interview with: Dr. Daniel Agardh M.D., Ph.D Department of Pediatrics Diabetes and Celiac Disease Unit Skåne University Hospital Malmo, Sweden, MedicalResearch: What are the main findings of the study? Dr. Agardh: In this study, we stratify the risk of celiac disease among children according to their HLA genotype and country of residence. We confirm that HLA-DQ2/2 genotype is the major risk factor for early celiac disease, but also show how the risk differs between the participating countries despite of sharing similar HLA risk. This points to the direction of an interaction between HLA and the environment that eventually lead to an autoimmune response in genetic susceptible children. (more…)
Author Interviews, Diabetes, Genetic Research, Nature / 30.06.2014

Dr. Domenico Accili MD Professor of Medicine Department of Medicine Columbia University College of Physicians and Surgeons New York, New York 10032MedicalResearch.com: Interview with Dr. Domenico Accili MD Professor of Medicine Department of Medicine Columbia University College of Physicians and Surgeons New York, New York 10032 MedicalResearch: What are the main findings of the study? Dr. Accili: By switching off a single gene (foxo1), scientists at Columbia University’s Naomi Berrie Diabetes Center have converted human gastrointestinal cells into insulin-producing cells, demonstrating in principle that a drug could retrain cells inside a person’s GI tract to produce insulin. (more…)
ADHD, Author Interviews, Genetic Research, Nature / 19.06.2014

Michele Jacob, Ph.D. Professor of Neuroscience Sackler School of Graduate Biomedical Sciences Tufts UniversityMedicalResearch.com Interview with Michele Jacob, Ph.D. Professor of Neuroscience Sackler School of Graduate Biomedical Sciences Tufts University MedicalResearch: What are the main findings of the study? Dr. Jacob: Autistic-like behaviors and cognitive impairments associate with loss of the Adenomatous Polyposis Coli (APC) gene.  We deleted APC chiefly from excitatory neurons in the mouse developing forebrain; the mice exhibited changes in synapse maturation and density, reduced social interest, increased repetitive behaviors, and learning deficits.  In addition, we found  molecular changes that define a novel role for APC in linking to and regulating the levels of particular proteins that function in synaptic adhesion complexes and signaling pathways that are required for normal learning and memory consolidation. (more…)
Author Interviews, Clots - Coagulation, Genetic Research / 18.06.2014

MedicalResearch.com Interview with: David Ldr_david_l_brown. Brown, MD, FACC Professor of Medicine Cardiovascular Division Washington University School of Medicine St. Louis, MO 63110 MedicalResearch: What are the main findings of the study? Dr. Brown: This meta-analysis of randomized controlled trials showed that using a genotype-based warfarin dosing algorithm did not improve the process or outcomes of anticoagulation compared to using a clinical dosing algorithm. (more…)
Author Interviews, Genetic Research, Mayo Clinic, Schizophrenia / 11.06.2014

Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in DenmarkMedicalResearch.com Interview with: Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in Denmark MedicalResearch: What are the main findings of the study? Dr. Nykjaer: It is well known that ADHD is a complex condition caused by a number of factors including genetic and environment. However, approximately 75% etiology is considered to be genetic and a large body of investigations suggests that it is multiple genes each with a moderate effect that is responsible for conferring susceptibility to ADHD. We have here found one single gene the dysfunction of which is sufficient to trigger the disease.  The gene encodes a receptor, SorCS2, which ensures correct wiring our reward system during embryonic development. Malfunction of the receptor causes ADHD-like symptoms in mice. It is well accepted that ADHD predisposes to psychiatric disorders and genetic reports have linked variations in the SorCS2 gene with schizophrenia. Studies are currently ongoing to evaluate if mutations disrupting the function of SorCS2 may also result in schizophrenia. If this is the case we have come closer to an explanation for the link between ADHD and psychiatric disorders. In the future when prenatal genetic screening becomes established, non-sense mutations in the SorCS2 gene can be used to predict that the child will develop ADHD with 100% certainty.   (more…)
Author Interviews, Genetic Research, OBGYNE / 02.06.2014

MedicalResearch.com Interview with : Dr. Francesco FiorentinoMedicalResearch.com Interview with : Dr. Francesco Fiorentino CEO and Lab Director ROME - ITALY MedicalResearch: What are the main findings of the study? Dr. Fiorentino: This study describes findings from first and second of a three-phase strategy to validate the use of next-generation sequencing (NGS) for comprehensive aneuploidy screening, as a preclinical step toward its routine use in the diagnosis of chromosomal aneuploidy on embryos. The first phase  involved a large preclinical validation study on single cells, and demonstrated that the NGS-based 24-aneuploidy screening protocol was accurate and reliable. The results provided 100% consistency for aneuploid embryo call with array-CGH, the highly validated method of aneuploidy screening. The second phase of the study, instead, focused on the clinical application of the NGS-based protocol for the detection of all chromosomes in embryos. A prospective trial involving analysis of human embryos at the blastocyst stage of development was designed for this purpose, in order to establish similar levels of chromosome-specific NGS copy number assignment concordance compared with 24sure array as those observed in the first phase of the study. Consistency of NGS-based aneuploidy detection was assessed matching the results obtained with array-CGH–based diagnoses, Embryos obtained from 55 consecutive clinical PGS cycles, blindly assessed in parallel with both NGS and array-CGH techniques, displayed 100% concordance for aneuploid embryo call. Consistency obtained during this investigation was similar to those obtained in the first phase of the study that used NGS to examine single cell samples, demonstrating the reliability of the NGS-based method in detection of chromosome aneuploidy also in embryos at blastocyst stage derived from clinical preimplantation genetic screening (PGS)  cycles. The clinical outcomes obtained in this study from preimplantation genetic screening cycles performed with the NGS approach were very encouraging, resulting in a clinical pregnancy rate per embryo transfer of 63.8% (mean age 38.5+2.1 years) and an ongoing implantation rate of 64.0%, values that are comparable with recent results from other comprehensive chromosome screening approaches. In conclusion, the results achieved in this study demonstrate the reliability of the NGS-based protocol for detection of whole chromosome aneuploidies, mosaicism occurrences and segmental changes in embryos. (more…)
Author Interviews, BMJ, Genetic Research, Heart Disease / 22.05.2014

Christopher Labos MD CM, FRCPC, MSc candidate Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec CanadaMedicalResearch.com Interview with: Christopher Labos MD CM, FRCPC, MSc candidate Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec Canada MedicalResearch: What are the main findings of the study? Dr. Labos: A higher genetic risk score (GRS) composed of a set of recently discovered genetic markers strongly linked to cardiovascular disease is associated with an earlier age of first acute coronary syndromes (ACS). We also found that other traditional risk factors such as smoking, obesity and male sex were also associated with an earlier ACS. Two medication classes were also associated with age of first ACS: hormone replacement therapy was associated with earlier ACS while aspirin was associated with ACS occuring at a later age. (more…)
Author Interviews, Endocrinology, Genetic Research, Metabolic Syndrome, Weight Research, Yale / 14.05.2014

MedicalResearch Interview with: Arya Mani, M.D. Department of Internal Medicine and Genetics Yale Cardiovascular Research Center Yale, New Haven CT Arya Mani, M.D. Department of Internal Medicine and Genetics Yale Cardiovascular Research Center Yale, New Haven CT MedicalResearch: What are the main findings of the study? Dr. Mani: Our group has identified a gene that when mutated it causes a form of truncal (central) obesity that is associated with a cluster of coronary artery disease risk factors, including high blood pressure, insulin resistance and possibly elevated blood lipids. These associated risk factors are collectively known as the metabolic syndrome, which may lead to development of diseases such as diabetes and coronary artery disease, both of which were very prevalent in the populations we studied. All identified mutations by our group have been so far gain of function mutations, which means they increased the activity of the gene in pathways related to adipogenesis and gluconeogenesis. (more…)
Author Interviews, Breast Cancer, Genetic Research / 29.04.2014

Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of TorontoMedicalResearch.com Interview with: Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto MedicalResearch.com: What are the main findings of the study? Dr. Bombard: The main finding of the study is that gene expression profiling tests play a critical role when women with early-stage breast cancer decide whether to have chemotherapy, but many of them do not fully understand what some of the test results mean. For many the gene expression profiling test was the main factor in their treatment decision. The women we interviewed understood the test would indicate whether chemotherapy would be beneficial to them. But many thought the test reflected their unique circumstances and did not understand that their test result was based on larger population statistics. Patients often viewed their gene expression profiling results as providing information that was more scientifically valid, uniquely personalized and emotionally significant than any other information they had received. For many, the test was a transformational element that empowered them, allowed them to feel confident in their decisions and may even have rescued them from unnecessary chemotherapy. Patients described emotionally and socially complex reasons why they valued gene expression profiling testing in making their treatment decisions. Patients valued the test because it provided them with certainty amidst confusion, with options and a sense of empowerment, and with personalized, authoritative information. (more…)
Author Interviews, Dengue, Ebola, Genetic Research, Infections, NEJM, NIH / 24.04.2014

Sergio D. Rosenzweig, MD, PhD Director, Primary Immunodeficiency Clinic (PID-C) LHD, NIAID, NIH Head of the Infectious Diseases Susceptibility Unit at the Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD, 20892MedicalResearch.com Interview with: Sergio D. Rosenzweig, MD, PhD Director, Primary Immunodeficiency Clinic (PID-C) Head of the Infectious Diseases Susceptibility Unit at the Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD, 20892 MedicalResearch.com: What are the main findings of the study? Dr. Rosenzweig: We diagnosed a disease called CDG-IIb in two siblings with severe development issues and very low levels of immunoglobulins, which include infection-fighting antibodies. These children were referred to the NIAID Primary Immunodeficiency Clinic through the NIH Undiagnosed Diseases Program. CDG-IIb is an extremely rare congenital disorder of glycosylation (CDG), with only one other case reported. The genetic defect of the disease disrupts glycosylation, the process for attaching and trimming sugars from proteins. Almost 50% of our proteins have sugars attached, and these are called glycoproteins. They include immunoglobulins and also some viral glycoproteins that are made when cells are infected by a virus. The spread of some viruses, including HIV and influenza, depend on viral glycoproteins in order to infect additional cells and form viral protective shields. We found that this type of virus was less able to replicate, infect other cells, or create adequate protective shields in CDG-IIb patient cells because of the glycosylation defect. In comparison, adenovirus, poliovirus, and vaccinia virus, which either do not rely on glycosylation or do not form protective glycoprotein shields, replicated normally when added to both CDG-IIb and healthy cells. (more…)
Author Interviews, Cancer Research, Genetic Research, Journal Clinical Oncology / 20.04.2014

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Assistant Professor of Medicine and of Health Research and Policy Divisions of Oncology and Epidemiology Allison W. Kurian, M.D., M.Sc. Assistant Professor of Medicine and of Health Research and Policy Divisions of Oncology and Epidemiology and James M. Ford, MD Associate Professor of Medicine Pediatrics and Genetics, Division of Oncology, Stanford University School of MedicineJames M. Ford, MD Associate Professor of Medicine Pediatrics and Genetics, Division of Oncology, Stanford University School of Medicine MedicalResearch.com: What are the main findings of the study? Answer: We found that 11% of women who met standard clinical criteria for BRCA1 and BRCA2 (BRCA1/2) mutation testing, yet had tested negative, actually carried an actionable mutation in another cancer-related gene.  We found that patients were highly motivated to learn about their genetic test results and new recommendations for cancer risk reduction.  Over a short follow-up period, colonoscopy screening resulted in early detection of a tubular adenoma in a patient found to have a high-risk MLH1 mutation, and thus the multiple-gene testing in our study has likely prevented at least one cancer to date.  We conclude that multiple-gene sequencing can benefit appropriately selected patients. (more…)
Author Interviews, Genetic Research, Nature, Social Issues / 14.04.2014

MedicalResearch.com Interview with: Prof Dr Isabelle Mansuy Lab of Neuroepigenetics University/ETH Zürich Brain Research Institute Zürich SwitzerlandProf Dr Isabelle Mansuy Lab of Neuroepigenetics University/ETH Zürich Brain Research Institute Zürich Switzerland MedicalResearch.com: What are the main findings of the study? Prof. Mansuy: The mains findings are that the transmission of the effects of traumatic stress in early life involves small non-coding RNAs in sperm. The study shows that some microRNAs are in excess in the sperm of adult males subjected to trauma during early postnatal life, but are also altered in the brain and in blood, and that these alterations are associated with behavioral and metabolic symptoms including depressive behaviors, reduced risk assessment and altered glucose/insulin metabolism. Injecting sperm RNA in fertilized oocytes reproduces these symptoms and confirm that RNA are the responsible factors. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, NIH / 10.04.2014

Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, GermanyMedicalResearch.com Interview with: Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, Germany MedicalResearch.com: What are the main findings of the study? Prof. Dr. med. Piotr Lewczuk: In our study, we investigated the concentrations of four isoforms of amyloid beta peptides in the blood of healthy young volunteers without memory complains. The participants were stratified into three groups according to their apolipoprotein E (APOE) genotype, which is the mostly investigated and generally accepted genetic risk factor for sporadic Alzheimer’s Disease (AD). It is known that the alterations of the amyloid beta metabolism are the earliest changes in the course of AD, occurring many years (or even decades) before the onset of the clinical symptoms, but it is actually not known how early these alterations start. Correspondingly, we wanted to investigate if healthy persons with genetic risk factor show changes in their amyloid beta metabolism already 30-40 years before the age when AD is usually diagnosed. We did not find any differences between the groups with and without APOE-driven risk, which might be carefully interpreted as no signs of Alzheimer’s Disease pathology in persons at risk at such an early life stage. Taken together, we think that the Alzheimer’s Disease pathology starts some 10-20 years before the beginning of the clinical symptoms, but not earlier. (more…)