Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 16.08.2013

MedicalResearch.com Interview with: Dr. Ramon Trullas Research Professor CSIC Institute of Biomedical Research of Barcelona MedicalResearch.com: What are the main findings of the study? Answer: The findings reported in this manuscript that we consider can be underscored are: 1) Asymptomatic subjects at risk of developing sporadic Alzheimer’s disease (AD), as well as symptomatic patients diagnosed with probable sporadic AD show a low concentration of circulating cell free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF). 2) Pre-symptomatic subjects carrying pathogenic PSEN1 gene mutations which cause early onset familial AD, also exhibit low mtDNA content in CSF. 3) Reduced mtDNA content in CSF occurs in preclinical PSEN1 mutation carriers at least one decade before patients are expected to manifest clinical signs of dementia and well before any alteration in currently known AD biomarkers. 4) Low mtDNA content in CSF distinguishes patients diagnosed with AD from either controls or patients with fronto-temporal lobar degeneration. These findings indicate that the amount of circulating cell-free mtDNA content in CSF may be a novel biomarker for the early detection of AD in the preclinical stage of AD. Moreover, the observation that low mtDNA content in the CSF is associated with both sporadic and familial forms of AD suggests that, independently of the etiology, regulation of mtDNA content is a converging factor in the pathophysiology of AD. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Nature / 16.08.2013

MedicalResearch.com Interview with: Steve Estus PhD Dept. of Physiology University of Kentucky Office: Room 332 Sanders-Brown Building 800 S. Limestone Street Lexington, KY 40536-0230 MedicalResearch.com: What are the main findings of the study? Answer: We report evidence for the function of a Alzheimer's genetic risk factor. This protective allele of the polymorphism decreases the splicing efficiency of exon 2 in CD33, a receptor protein that regulates microglial activation. Loss of exon 2 appears to produce a dormant CD33 protein, resulting in increased microglial phagocytosis activity. Overall, these findings confirm and extend recent papers in Neuron and Nature Neuroscience (discussed further in our report) that described decreased CD33 activity with the protective SNP allele. (more…)
Author Interviews, Genetic Research, Kidney Disease, Nature, University of Pennsylvania / 12.08.2013

MedicalResearch.com Interview with: Dr. Wen-Ya Ko, Ph.D. Postdoctoral Fellow, First author of the paper Department of Genetics School of Medicine University of Pennsylvania 426 Clinical Research Building 415 Curie Boulevard Philadelphia, PA 19104-6145 Dr. Wen-Ya Ko, Ph.D. Postdoctoral Fellow, First author of the paper Department of Genetics School of Medicine University of Pennsylvania 426 Clinical Research Building 415 Curie Boulevard Philadelphia, PA 19104-6145 Dr. Sarah Tishkoff, Ph.D., Senior author of the paper David and Lyn Silfen University Professor Departments of Genetics and Biology School of Medicine School of Arts and Sciences University of Pennsylvania Dr. Sarah Tishkoff, Ph.D., Senior author of the paper David and Lyn Silfen University Professor Departments of Genetics and Biology School of Medicine School of Arts and Sciences University of Pennsylvania MedicalResearch.com: What are the main findings of the study? Answer: In humans the APOL1 gene codes for Apolipoprotein L1, a major component of the trypanolytic factor in serum. The APOL1 gene harbors two risk alleles (G1 and G2) associated with chronic kidney disease (CKD) among individuals of recent African ancestry. We studied APOL1 across genetically and geographically diverse ethnic groups in Africa. We have discovered a number of novel variants at the APOL1 functional domains that are required to lyse trypanosome parasites inside human blood vessels. We further identified signatures of natural selection influencing the pattern of variation on chromosomes carrying some of these variants. In particular, we have identified a haplotype (a cluster of genetic variants linked along a short region of a chromosome), termed G3, that has evolved adaptively in the Fulani population who have been practicing cattle herding which has been historically documented as early as in the medieval ages (but which could have begun thousands of years earlier). Many of the novel variants discovered in this study are candidates to play a role conferring protection against trypanosomiasis and/or to play a role in susceptibility of CKD in humans. (more…)
Asthma, Author Interviews, Genetic Research, Smoking, UCLA / 06.08.2013

MedicalResearch.com Interview with: Virender Rehan, MD Professor of Pediatrics Chief, Division of Neonatology Director, Neonatal Intensive Care Unit Director, Neonatal-Perinatal Fellowship Training Program Co-Director Perinatal Research Center Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA Torrance, CA, 90502 MedicalResearch.com: What are the main findings of the study? Dr. Rehan: The main findings of the study include the likelihood of transmission of asthma to third generation offspring following maternal smoking during pregnancy even when child’s mother didn’t smoke. And these effects seem to be more profound in the upper airways of males compared to that in females. (more…)
Asthma, Author Interviews, Duke, Genetic Research, Lancet, NEJM / 10.07.2013

Daniel Belsky, PhD NIA Postdoctoral Fellow Center for the Study of Aging and Human Development Duke University MedicalResearch.com Interview with: Daniel Belsky, PhD NIA Postdoctoral Fellow Center for the Study of Aging and Human Development Duke University Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study MedicalResearch.com: What are the main findings of the study? Dr. Belsky : We looked to the largest-ever genome-wide association study of asthma (that study by the GABRIEL Consortium included more than 26,000 individuals) to identify genetic variants that could be used to construct a genetic profile of asthma risk. We then turned to The Dunedin Multidisciplinary Health and Development Study, a unique cohort of 1,000 individuals who have been followed from birth through their fourth decade of life with extensive measurements of asthma and related traits. We computed a “genetic risk score” for each person based on the variants identified in GWAS. Then, we looked at who developed asthma, when they developed asthma, and what that asthma looked like in terms of allergic response and impaired lung function. What we found: (1) People with higher genetic risk scores were more likely to develop asthma and they developed asthma earlier in life. (2) Among children who developed asthma, the ones at higher genetic risk were more likely to have persistent asthma through midlife. (3) Genetic risk was specifically associated with allergic asthma that resulted in chronic symptoms of impaired lung function. (4) People with higher genetic risk score developed more severe cases of asthma. As compared to people with a lower genetic risk, they were more often absent from school and work because of asthma and they were more likely to be hospitalized for asthma. (5) The genetic risk score provided new information about asthma risk that could not be obtained from a family history. (more…)
Author Interviews, Cancer Research, Genetic Research, Lung Cancer / 26.05.2013

MedicalResearch.com Authors’ Interview: Sophie Rousseaux and Saadi Khochbin INSERM, U823; Université Joseph Fourier, Grenoble 1; Institut Albert Bonniot, Grenoble F-38700, France. MedicalResearch.com: What are the main findings of the study? Answer: We first discovered that all cancer cells lose the ability to maintain gene silencing and therefore activate genes that should normally remain silent. Although present in all cells, some genes are normally expressed (or “active”) only in one cell type. For example, normal lung cells do not express genes that are only active in germ cells (i. e., cells that will become spermatozoa), but lung cancerous cells activate some of these germ cells-specific genes. In this work we designed a specific approach to detect these aberrant gene expressions and found that they occur in all cancers of all origins. We then decided to exploit this phenomenon to help the detection of cancers and predict their evolution. For this purpose, we chose to focus on lung cancer to establish “a proof of principle”. We found that, among all the genes wrongly expressed in the tumour cells, the activation of 26 of them enabled us to identify the most aggressive lung cancers. Compared with the existing information currently available for doctors (i.e.; tumour size, its pathological subtype…), our approach brings much more precision in predicting the evolution of the tumours and the prognosis of the patients. (more…)
Author Interviews, Breast Cancer, Genetic Research, PNAS / 03.04.2013

MedicalResearch.com eInterview with Dr. Mathieu Lupien PhD Dr. Mathieu Lupien PhD Princess Margaret Cancer Centre, University Health Network Ontario Cancer Institute (OCI) Assistant Professor Department of Medical Biophysics University of Toronto Princess Margaret Cancer Centre, University Health Network Ontario Cancer Institute (OCI) Assistant Professor Department of Medical Biophysics University of Toronto MedicalResearch.com: What are the main findings of the study? Dr. Lupien: Approximately 50% of breast cancer patients fail to respond to the standard of care based on endocrine (hormonal) therapy. Our research identifies a mechanism that accounts for this resistance. Drugs against this mechanism are already tested for other diseases. Hence, our discovery should rapidly help reposition these drugs against endocrine therapy resistant breast cancer. (more…)
Author Interviews, Duke, Genetic Research, Leukemia, MD Anderson, UT Southwestern / 23.03.2013

MedicalResearch.com Author Interview: Jun J. Yang, Ph.D. Assistant Member Dept. of Pharm. Sci. St. Jude Children's Research Hospital 262 Danny Thomas Pl., MS313 Memphis, TN 38105 MedicalResearch.com: What are the main findings of the study? Dr. Yang: We performed a comprehensive survey of inherited genetic variations for their contribution to the susceptibility of acute lymphoblastic leukemia (ALL), the most common cancer in children. This is by far the largest study of its kind (in terms of the number of subjects involved), and also the first one to include multi-ethnic populations. We identified 4 genomic loci related to the predisposition to ALL, 2 of which contributed to racial differences in the incidence of ALL. This study provided unequivocal evidence for inherited susceptibility of childhood ALL and pointed to novel biology of the pathogenesis of this disease. (more…)