Author Interviews, Biomarkers, Cancer Research, ENT / 13.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31235" align="alignleft" width="154"]Jacek Majewski PhD Associate Professor Department of Human Genetics McGill University and Genome Quebec Innovation Centre Montreal, Canada Dr. Jacek Majewski[/caption] Jacek Majewski PhD Associate Professor Department of Human Genetics McGill University and Genome Quebec Innovation Centre Montreal, Canada  MedicalResearch.com: What is the background for this study? Response: Our lab, in collaboration with Dr. Nada Jabado, has been investigating the molecular genetics of pediatric glioblastoma – a deadly brain cancer. Several years ago, in the majority of our patients’ tumors we discovered mutations in genes that encode histone proteins. Those mutations disrupt the epigenome - that is the way the DNA is modified, silenced, or activated in the cancer cells. It appears that epigenome-modifying mutations are particularly important in pediatric cancers, and our hypothesis is that they act by diverting the normal developmental pathways into unrestrained proliferation. Many other studies have highlighted the significance of epigenome disruption in a number of cancers.
Author Interviews, Baylor College of Medicine Houston, Genetic Research, NEJM / 09.01.2017

MedicalResearch.com Interview with: Jennifer E Posey MD, PhD Assistant Professor Department of Molecular and Human Genetics Baylor College of Medicine Tamar Harel MD, PhD Clinical Genetics Academic Research Fellow Department of Molecular and Human Genetics Baylor College of Medicine Current affiliation: Department of Genetic and Metabolic Diseases Hadassah-Hebrew University Medical Center Jerusalem, Israel MedicalResearch.com: What is the background for this study? What are the main findings? Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health. In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests. The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected. In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition.
Abuse and Neglect, Genetic Research, Schizophrenia, UCSD / 06.01.2017

MedicalResearch.com Interview with: [caption id="attachment_31016" align="alignleft" width="200"]Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125 Dr. Brian Head[/caption] Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125 MedicalResearch.com: What is the background for this study? What are the main findings? Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia. SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015). Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms.
Asthma, Author Interviews, Genetic Research, Pediatrics / 04.01.2017

MedicalResearch.com Interview with: [caption id="attachment_26649" align="alignleft" width="100"]Donata Vercelli, MD Professor of Cellular and Molecular Medicine, University of Arizona Director, Arizona Center for the Biology of Complex Diseases Associate Director, Asthma and Airway Disease Research Center The BIO5 Institute, Rm. 339 Tucson, AZ 85721 Dr. Donata Vercelli[/caption] Donata Vercelli, MD Professor of Cellular and Molecular Medicine Director, Arizona Center for the Biology of Complex Diseases Director, Molecular Genomics, Asthma and Airway Disease Research Center The University of Arizona The BIO5 Institute Tucson, AZ 85721 MedicalResearch.com: What is the background for this study? Response: Asthma is the most prevalent chronic disease of childhood. Epidemiological evidence suggests that the disease often begins during the pre-school years even when chronic symptoms appear much later in life. However, firm criteria to pinpoint how early a child’s trajectory to asthma truly begins are currently lacking. The mechanisms underlying asthma inception also remain largely unknown. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception.
Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017

MedicalResearch.com Interview with: [caption id="attachment_30921" align="alignleft" width="150"]Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol Dr. Beate St Pourcain[/caption] Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses. As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence - the ability to socially engage with other people successfully - in participants of a population-based birth cohort during development. Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder. "The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development", explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence.
Author Interviews, Blood Pressure - Hypertension, Genetic Research, PLoS, Race/Ethnic Diversity, Social Issues / 25.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30767" align="alignleft" width="132"]Connie J. Mulligan, PhD Professor, Department of Anthropology University of Florida Gainesville, FL Dr. Connie J. Mulligan[/caption] Connie J. Mulligan, PhD Professor, Department of Anthropology University of Florida Gainesville, FL MedicalResearch.com: What is the background for this study? Response: Lance Gravlee (UF Dept of Anthropology, UF Genetics Institute) started this research over 10 years ago. As a cultural anthropologist, Lance uses ethnographic (open-ended questions) interviews and discovered that over half of the participants in our study talked about experiences of discrimination that happened to people close to them. As a geneticist (UF Dept of Anthropology, UF Genetics Institute), I came into the project because I was interested in seeing how genetics and sociocultural stressors, like discrimination, interact. In our project, we look at blood pressure because hypertension is a disease that shows racial disparities and also because it is a complex disease that is caused by both genetic and environmental factors (like discrimination).
Author Interviews, Electronic Records, Genetic Research, Heart Disease, Lipids, Science / 25.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30763" align="alignleft" width="133"]Michael F. Murray MD Geisinger Health System Danville, PA 17822 Dr. Michael Murray[/caption] Michael F. Murray MD Geisinger Health System Danville, PA 17822 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease.
Author Interviews, Cancer Research, Columbia, Genetic Research, Personalized Medicine / 23.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30757" align="alignleft" width="200"]Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University Dr. Kai Wang[/caption] Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment. iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile. What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment.
Author Interviews, Genetic Research, Lancet, Pediatrics, Schizophrenia / 22.12.2016

MedicalResearch.com Interview with: Dr Lucy Riglin Division of Psychological Medicine and Clinical Neurosciences MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University School of Medicine Cardiff UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: Schizophrenia is a mental disorder that usually occurs after puberty. However, previous research suggests that individuals who go on to develop schizophrenia often presented cognitive, social, behavioural, and emotional impairments in childhood. Our study found that, in a general population sample, genetic risk for schizophrenia was associated with these childhood impairments as early as age 4 years.
Author Interviews, Genetic Research, Nature, Weight Research / 21.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30700" align="alignleft" width="100"]Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France Prof. Jamal Tazi[/caption] Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France MedicalResearch.com: What is the background for this study? What are the main findings? Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss.
Author Interviews, Genetic Research, JAMA / 16.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30502" align="alignleft" width="142"]C. Anthony Blau, M.D. Professor of Medicine, Division of Hematology University of Washington School of Medicine Co-Director, University of Washington Institute for Stem Cell and Regenerative Medicine Director, Center for Cancer Innovation Dr. C. Anthony Blau[/caption] C. Anthony Blau, M.D. Professor of Medicine, Division of Hematology University of Washington School of Medicine Co-Director, University of Washington Institute for Stem Cell and Regenerative Medicine Director, Center for Cancer Innovation MedicalResearch.com: What is the background for this study? What are the main findings? Response: Matching cancer treatment to the molecular composition of a patient’s tumor holds promise for making cancer therapies more effective, and molecular testing for cancer patients has become widespread in recent years. Recently molecular testing of tumor samples has been complemented by blood tests that characterize tumor DNA that has been shed into the bloodstream.  Blood tests are attractive because they are much less invasive than obtaining tumor tissue via biopsies.
Author Interviews, Breast Cancer, Genetic Research, JAMA / 12.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30290" align="alignleft" width="160"]Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute Dr. Adrian Lee[/caption] Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The goal of this study was to understand molecular changes which occur when breast cancers metastasize to the brain, with the eventual of identifying new therapeutic strategies. Brain metastases occur in 10-15% of patients with metastatic breast cancer and are a major clinical challenge. Limited therapeutic options exist for patients with brain metastases. We analyzed molecular changes in pairs of patient-matched primary breast cancers and brain metastases. We found that brain metastases tended to have the same intrinsic subtype as the primary breast cancer, however, there were many genes which changes in gene expression and may represent therapeutic targets. The most common change was an increase in ErbB2/HER2 which can be targeted clinically.
Author Interviews, Genetic Research, Leukemia, NYU/NYMC / 11.12.2016

MedicalResearch.com Interview with: Jason Saliba PhD Perlmutter Cancer Center New York University Langone Medical Center New York, NY MedicalResearch.com: What is the background for this study? What are the main findings? Response: The outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically over the last four decades, but the prognosis for those who relapse remains dismal, especially for those who relapse while on therapy. In fact, relapsed disease remains a leading cause of cancer related mortality in children. To date, various studies have discovered a number of somatic alterations that contribute to driving relapse and have provided profound insight into the selective forces that lead to clonal outgrowth of drug resistant populations. However, the timing of the initial emergence of the driving mutations along with the speed of clonal outgrowth is unknown. Whole exome sequencing (WES) was run on available diagnosis, germline (remission), and relapse samples collected from thirteen pediatric ALL patients treated according to Nordic NOPHO ALL protocols. Analyses were then performed to find somatic missense mutations enriched in the relapse samples versus their patient matched diagnosis and/or germline samples. Candidate relapse driving missense mutations were identified as present at high levels (>20%) in the relapse sample, but were undetectable in germline or low to absent in the diagnosis sample. Eight of the thirteen patients contained mutations in genes previously reported to be enriched at relapse. Interestingly, a majority of the patients contained novel candidate relapse specific genes involved in a wide array of cellular processes such as cell adhesion/migration, RNA polymerase II/transcription, circadian rhythm, the unfolded protein response, RNA transport, epigenetic regulation, DNA methylation, and kinases.
Author Interviews, Genetic Research, Nature, NIH, Weight Research / 09.12.2016

MedicalResearch.com Interview with: [caption id="attachment_30390" align="alignleft" width="200"]Audrey Chu, Ph.D. Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health Dr. Audrey Chu[/caption] Audrey Chu, Ph.D. Division of Intramural Research National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk. In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds. Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes.
Alcohol, Author Interviews, Biomarkers, Genetic Research / 28.11.2016

MedicalResearch.com Interview with: Chunyu Liu, PhD The Population Sciences Branch, Division of Intramural Research The Framingham Heart Study, National Heart, Lung and Blood Institute Framingham, MA Department of Biostatistics Boston University School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use.
Author Interviews, Gastrointestinal Disease, Genetic Research / 23.11.2016

MedicalResearch.com Interview with: Mauro D’Amato Ikerbasque Research Professor Head, Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases BioDonostia Health Research Institute San Sebastian, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Irritable bowel syndrome (IBS) is a very common condition, whose underlying pathophysiology is poorly understood. People with IBS often complain certain foods trigger their symptoms and, at least in some patients, incomplete breakdown of carbohydrates may result in malabsorption with diarrhoea, bloating and abdominal pain. At the extreme of the spectrum of such clinical manifestations, this is what happens in a hereditary form of sucrose intolerance, the congenital sucrase-isomaltase deficiency (CSID) due to mutations in the Si gene that lead to defective enzymatic disaccharidase activity in the gut. Because IBS shows genetic predisposition, we tested the hypothesis that mutations and DNA variants affecting SI enzyme function may confer increased risk of IBS. We studied almost 2000 individuals from several clinics from Europe and USA, and found out that rare SI mutations and other more common defective DNA variants are indeed more frequent in patients than healthy controls.
Author Interviews, Dermatology, Genetic Research / 22.11.2016

MedicalResearch.com Interview with: Prof. Dr. Regina Betz and Dr. Buket Basmanav Ünalan (first author) Institute of Human Genetics University of Bonn Bonn, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: Up to know, the cause for uncombable hair was totally unknown. We identified now mutations in three genes, all being responsible for uncombable hair syndrome. Of interest, the corresponding proteins, namely, PADI3, TGM3 and TCHH, are all in the same cascade that is responsible for the formation and mechanical strengthening of the hair shaft.
ADHD, Author Interviews, Genetic Research, Pediatrics / 01.11.2016

MedicalResearch.com Interview with: Dr. Josephine Elia, M.D. Neuroscience Center Department of Child and Adolescent Psychiatry Nemours/Alfred I. DuPont Hospital for Children MedicalResearch.com: What is the background for this study? What are the main findings? Response: Glutamate neurotransmission may play an important role in ADHD and other neuropsychiatric disorders. The purpose of this study is to determine the frequency of genetic mutations involving specific genes (GRM network genes) which influence glutamatergic neurotransmission. A total of 23 study sites across the USA enrolled 1,013 children, aged 6-17 years who had been previously diagnosed with ADHD. Saliva samples were submitted to The Center for Applied Genomics (CAG) at CHOP for analysis of mutations of interest. Information on medical history, including other neuropsychiatric diagnoses and family history as well as areas of academic and social concern were also collected. Overall, the mutation frequency was 22%, with a higher prevalence of 25% observed in patients aged 6-12. When compared to mutation negative ADHD patients, the patients with the mutations of interest were more likely to have concerns about anger control and disruptive behaviors.
Anemia, Author Interviews, Genetic Research, Hematology / 27.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29185" align="alignleft" width="133"]Peter M. Glazer, MD, PhD Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Department of Therapeutic Radiology Yale University Dr. Peter M. Glazer[/caption] Peter M. Glazer, MD, PhD Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Department of Therapeutic Radiology Yale University MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is generally recognized that gene editing in blood stem cells could provide a strategy for treatment of inherited disorders such as sickle cell disease and thalassaemia. Recent excitement has focused on CRISPR/Cas9 technology because of it is so easy to use. However, the CRISPR approach introduces an active DNA cutting enzyme into cells, which can lead to off-target cuts in the genome. As an alternative, we have pursued triplex-forming peptide nucleic acids (PNAs) designed to bind site-specifically to genomic DNA via strand invasion and formation of PNA/DNA/PNA triplexes. PNAs consist of a charge-neutral peptide-like backbone and nucleobases enabling hybridization with DNA with high affinity. PNA/DNA/PNA triplexes recruit the cell’s own DNA repair machinery to initiate site-specific editing of the genome when single-stranded ‘donor DNAs’ are co-delivered as templates containing the desired sequence modification. We found that triplex-forming PNAs substituted at the gamma position yielded high levels of gene editing in blood stem cells in a mouse model of human β-thalassaemia. Injection of thalassemic mice with nanoparticles containing gamma PNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood hemoglobin levels into the normal range and up to 7% β-globin gene correction in stem cells, with extremely low off-target effects. We conclude that the combination of nanoparticle delivery and next generation PNAs may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration.
Author Interviews, Genetic Research, Menopause / 21.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29054" align="alignleft" width="136"]Carolyn J. Crandall, MD, MS, FACP Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, California Dr. Carolyn Crandall[/caption] Carolyn J. Crandall, MD, MS, FACP Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, California MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scientists have suspected that genes may contribute to the risk of getting hot flashes and night sweats, but studies so far have been few in number and only focused on small parts of the human gene code (for example, the gene coding for estrogen receptors). No study has ever comprehensively sampled gene variations that span the entire human genome to look for associations between genetic variation and risk of hot flashes and night sweats. This was the first study of its kind, performed in more than 17.000 postmenopausal women participating in the Women’s Health Initiative Study. We examined 11,078,977 single-nucleotide polymorphisms, or SNPs, which are gene variants, in a genome-wide association study. Our main results were that 14 gene variants (SNPs) that were significantly associated with increased risk of having hot flashes. All of these variants were located in chromosome 4, in the gene that codes for the tachykinin receptor 3.
Alzheimer's - Dementia, Author Interviews, JAMA, Neurological Disorders / 20.10.2016

MedicalResearch.com Interview with: [caption id="attachment_29020" align="alignleft" width="132"]Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London Dr David Lynch[/caption] Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2011 it was discovered that mutations in a gene called CSF1R cause a rare syndrome of early onset dementia often accompanied by movement disorders, spasticity and seizures, which is named adult onset leukoencephalopathy with axonal spheroids (ALSP). The hallmarks of ALSP are a characteristic appearance on MRI imaging and findings in brain pathological specimens - axonal swellings or 'spheroids'. We manage a multidisciplinary group with expertise in leukoencephalopathies and have previously identified patients with mutations in CSF1R. However, we also found patients with a syndrome typical of ALSP who did not carry mutations in CSF1R. In this study, we showed that some of these patients carry recessive mutations in a different gene, AARS2. This included a patient with characteristic axonal spheroids in brain tissue and typical ALSP clinical and imaging features.
Author Interviews, Genetic Research, JAMA, Schizophrenia / 14.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28772" align="alignleft" width="96"]Panagiotis (Panos) Roussos, MD, PhD Assistant Professor Department of Genetics and Genomic Sciences and Department of Psychiatry Icahn Institute for Genomics and Multiscale Biology Friedman Brain Institute Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029 Dr. Roussos[/caption] Panagiotis (Panos) Roussos, MD, PhD Assistant Professor Department of Genetics and Genomic Sciences and Department of Psychiatry Icahn Institute for Genomics and Multiscale Biology Friedman Brain Institute Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Schizophrenia is a complex neuropsychiatric illness and multiple genetic risk factors contribute to the disease. However, it is unclear how these genetic risk factors act and which molecular functions are affected in brain cells of patients with schizophrenia. In this study, we used neurons derived from pluripotent stem cells of patients with schizophrenia and control samples with no history of neuropsychiatric disease. We identified changes related to the way DNA transcribes (a.k.a. gene expression) in schizophrenia compared to controls during activation of the neurons. These changes affect genes that have been genetically associated with schizophrenia. Our study provides evidence that multiple genetic risk factors might lead to schizophrenia because of a damaging effect on the activity of neurons.
Author Interviews, Dermatology, Genetic Research, Nature / 13.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28848" align="alignleft" width="200"]Richard Spritz, Director of the Human Medical Genetics and Genomics Program at the University of Colorado School Medicine, led a recent study that explored the genetic links between eye color and serious skin conditions like vitiligo and melanoma. (Marla R. Keown/Aurora Sentinel) Dr. Richard Spritz,[/caption] Richard A. Spritz, M.D. Professor and Director, Human Medical Genetics and Genomics Program University of Colorado School of Medicine. Aurora, CO 80045 USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease. In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance.
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity / 10.10.2016

MedicalResearch.com Interview with: [caption id="attachment_28675" align="alignleft" width="200"]Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre Dr Tamara Shiner[/caption] Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although in the past believed to be sporadic, there is much emerging evidence for a significant genetic contribution to Dementia with Lewy bodies (DLB). Hetrozygosity for common mutations in the GBA gene have been shown to be more frequent among DLB patients and Parkinson's disease patients than in the general population. We found that GBA mutations are in fact exceptionally frequent among Ashkenazi Jewish (AJ) patients with Dementia with Lewy bodies. Our results indicate that one in three of all Ashkenazi DLB patients carry mutations in this specific gene (compared to approximately 6% in the general Ashkenazi Jewish population). We also found that those who carry these mutations have a more severe disease phenotype.
Author Interviews, Autism, Genetic Research, Kidney Disease, Nature / 28.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28407" align="alignleft" width="200"]Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK Prof. Adrian Woolf[/caption] Prof Adrian S. Woolf Chair, Professor of Paediatric Science University of Manchester, UK MedicalResearch.com: What is the background for this study? Response: Several years ago, Laurent Fasano discovered that the Drosophila teashirt gene was needed to pattern the body of embryonic flies. He then found that this transcription factor had three similar genes in mammals. Working with Adrian Woolf in the UK, they found that Teashirt-3 (Tshz3) was needed in mice to make muscle form in the ureter When the gene was mutated, mice were born with ureters that were 'blown-up' and they failed to milk urine from the kidney with the bladder.
Aging, Author Interviews, Genetic Research / 23.09.2016

Dr-Bastiaan-Heijmans.jpg MedicalResearch.com Interview with: Dr. Bastiaan Heijmans Leiden University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response.
Author Interviews, Breast Cancer, Cancer, Genetic Research, UT Southwestern / 23.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28272" align="alignleft" width="96"]Roshni Rao, M.D Breast Surgery University of Texas Southwestern Dr. Roshni Rao[/caption] Roshni Rao, M.D Breast Surgery University of Texas Southwestern MedicalResearch.com: What is the background for this study? What are the main findings? Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer. TNBC is more common in young, African American women, but can be found in other ethnic groups as well. This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer.
Author Interviews, Case Western, Genetic Research / 22.09.2016

MedicalResearch.com Interview with: [caption id="attachment_28236" align="alignleft" width="200"]Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio Dr. Carlos E. Crespo-Hernández[/caption] Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio MedicalResearch.com: What is the background for this study? What are the main findings? Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival.