Paternal Grandfather’s Access to Food Predicts All-Cause and Cancer Mortality in Grandsons

MedicalResearch.com Interview with:

Denny Vågerö  PhD MSc CHESS, Centre for Health Equity Studies Department of Public Health Sciences Stockholm University, Stockholm, Sweden

Dr. Vågerö

Denny Vågerö  PhD MSc
CHESS, Centre for Health Equity Studies
Department of Public Health Sciences
Stockholm University, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transgenerational, epigenetic, response, has been shown in studies of animals and plants. Does it apply to humans?

Previous findings of associations between grandparents early nutrition and grandchildren’s mortality have been controversial.  Two reasons for this: evidence in human studies has been based on rather small numbers and potential mechanisms are not very well understood.

We have tested the hypothesis that there is “a male line transgenerational response” to nutritional events in pre-puberty in a study much larger than previous ones.

We find support for this hypothesis in that boys who enjoyed unusually good access to food during their “slow growth period” (aged 9-12 years) seem to transmit a mortality risk on their grandsons but not granddaughters, in particular for cancer.

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Some Anti-Tumor Drugs May Promote Delayed Aggressive Cancers

MedicalResearch.comInterview with:
Alexandra Avgustinova PhD
Postdoctoral fellow at the Institute for Research in Biomedicine (IRBBarcelona)

Dr. Avgustinova
Dr. Avgustinova

MedicalResearch.com:  What is the background for this study?

Response: The basis of this study was the strong association between closed chromatin and high mutation rate reported several years ago. We were surprised to see this observation being widely interpreted as a causal association, as it was largely based on correlative studies without experimental backing. Therefore we decided to experimentally test for the first time whether indeed altering chromatin opening would affect mutation rate or distribution within tumours.

MedicalResearch.com: What are the main findings?

Response: We found that, despite significantly increasing chromatin opening, loss of the histone methyltransferase G9a did not have any major influence on the mutation rate or distribution within cutaneous squamous cell carcinomas. These results demonstrate that chromatin opening does not play a major role in determining the mutation rate within tumours, and we speculate that other, confounded factors (e.g. replication timing or H3K36me3 levels) are likely causal for the observed association. This, however, remains to be proven experimentally.

Another major conclusion of our study was that although tumour initiation was delayed and tumour burden decreased in the absence of G9a, the tumours that did develop were highly aggressive due to selection for more aggressive tumour clones. This finding was contrary to many published reports suggesting G9a as a good candidate for clinical targeting, highlighting the need for long-term follow-up in pre-clinical studies.

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Using of Big Data to Estimate Prevalence of Defective DNA Repair Variants in the US

MedicalResearch.com Interview with:

Kenneth H. Kraemer,M.D.
Chief DNA Repair Section
Laboratory of Cancer Biology and Genetics, Center for Cancer Research
National Cancer Institute

MedicalResearch.com:  What is the background for this study?

Response: At the National Cancer Institute, we have been examining patients with xeroderma pigmentosum (XP), a rare, recessively inherited, cancer-prone disease for many years. Therefore, with the increasing use of exome sequencing, we decided to see how closely”big data” corresponded with our clinical observations.  

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Genome Analysis Can Overestimate Incidence of Chronic Kidney Disease

MedicalResearch.com Interview with:

Hila Milo Rasoul, PhD Postdoctoral research scientist Ali Gharavi Lab Columbia University

Dr. Milo Rasouly

Hila Milo Rasouly, PhD
Postdoctoral research scientist
Ali Gharavi Lab
Columbia University

MedicalResearch.com: What is the background for this study?

Response: Genome sequencing is increasingly used in clinical medicine to help make a clinical diagnosis and make predictions about potential future complications. The diagnostic yield and limitations for different indications are still being worked out.  We are interested in studying the applications of genome sequencing for chronic kidney diseases. It is estimated that 10% of adults have chronic kidney disease (CKD), and amongst them, 10% are caused by single-gene (Mendelian) forms of disease.

The American College of Medical Genetics and Genomics developed guidelines on how to interpret genetic variants in order to make a genetic diagnosis. Our lab has been engaged in studying the yield and impact of genetic testing for  CKD, and in the course of our research, we realized that a very large number of individuals have genetic variants that may be classified as pathogenic based on automated application of the guidelines. However, in majority of these cases, the genetic variant was much too frequent in the population to be plausibly disease-causing or did not match up well with the clinical diagnosis. This led us to wonder about the risk of false-positive genetic diagnosis. To analyze this risk for false-positive genetic diagnosis, we analyzed the genome sequence of 7,974 self-reported healthy adults.

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Eczema Determined by Genetics or Environment?

MedicalResearch.com Interview with:
“Eczema” by NIAID is licensed under CC BY 2.0Hans Bisgaard, MD, DMSc

Professor of Pediatrics
C‌openhagen U‌niversity H‌ospital, H‌erlev-G‌entofte
Copenhagen

MedicalResearch.com: What is the background for this study? What are the main findings?

 Response: The uniqueness of this study, is that we for the first time have day-to-day recordings of symptoms and use og local treatment during the first 3 years of life showing the disease peaks at 2 years of age and children start outgrowing thereafter.Previous studies including our own have analyzed eczema at a certain age.Since eczema is highly variable over time, our disease description is novel.This has allowed us a more reliable analyses of factors determining eczema in young children 

MedicalResearch.com: What should readers take away from your report?

Response: What we see it that eczema is determined by genetics and with no know external factors causing or deteriorating the severity.

 MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are currently aiming to analyze the interaction between genetics and the environment. In other words though eczema is highly genetically determined, we have reason to believe that external factors triggers such genes.
 No conflicts of interest   

Citation:  

Thorsteinsdottir S, Stokholm J, Thyssen JP, et al. Genetic, Clinical, and Environmental Factors Associated With Persistent Atopic Dermatitis in Childhood. JAMA Dermatol. Published online November 14, 2018. doi:10.1001/jamadermatol.2018.4061

 

Nov 15, 2018 @ 12:52 pm

  The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. 

Genetic Variant is Risk Factor for Two Different Types of Interstitial Lung Disease

MedicalResearch.com Interview with:

Joyce S. Lee, MD Associate Professor Director, Interstitial Lung Disease Program Department of Medicine Division of Pulmonary Sciences and Critical Care Medicine University of Colorado School of Medicine

Dr. Lee

Joyce S. Lee, MD
Associate Professor
Director, Interstitial Lung Disease Program
Department of Medicine
Division of Pulmonary Sciences and Critical Care Medicine
University of Colorado School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Rheumatoid arthritis (RA) is a common inflammatory arthritis that can be complicated by interstitial lung disease (ILD). Patients with RA-ILD share clinical characteristics with another ILD called idiopathic pulmonary fibrosis (IPF).

Given the similar clinical phenotype, our goal was to see if these lung diseases (IPF and RA-ILD) shared a common genetic risk factor. The MUC5B promoter variant is the most common risk factor (genetic and otherwise) for the development of IPF.

Our findings demonstrate the MUC5B promoter variant is also a strong risk factor for the development of RA-ILD among patients with RA.

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Genetic Locus Linked to Migraine Risk in African American Children

MedicalResearch.com Interview with:
"DNA model" by Caroline Davis2010 is licensed under CC BY 2.0Hakon Hakonarson, MD, PhD
Corresponding Author
Xiao Chang, PhD
Lead Author
The Center for Applied Genomics
Children’s Hospital Philadelphia
PhiladelphiaPennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Migraine is a genetic disorder characterized by recurrent and intense headaches often accompanied by visual disturbances. Genome-wide association studies (GWASs) are a powerful hypothesis-free tool for investigating the genetic architecture of human disease. Currently, multiple GWASs have been conducted on European adults with migraine that have successfully identified several migraine susceptibility genes involved in neuronal and vascular functions.

Considering the prevalence of migraines varies across ethnicities, the genetic risk factors may be different in patients of African ancestries and European ancestries. In addition, if migraine presents at an early age (childhood), it may reflect elevated biological predisposition from genetic factors or increased susceptibility to environmental risk factors.

We performed the first GWAS to investigate the susceptibility genes associated with migraine in African-American children. The main out come was that common variants at the 5q33.1 locus in the human genome are associated with migraine risk in African-American children. The genetic underpinnings at this locus responsible for this finding are less relevant in patients of European ancestry.  Continue reading

Strong Genetic Component to Psychotic-Like Experiences with Cannabis

MedicalResearch.com Interview with:
Dr. Nicole Karcher, PhD
Post-doctoral scholar with the NIMH Training in Clinical Sciences fellowship
Department of Psychiatry
Washington University School of Medicine  

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For over fifteen years, researchers have debated the role that cannabis use plays in the development of both psychotic disorders as well as subthreshold psychotic symptoms, such as psychotic-like experiences (PLEs). There is still a lack of consensus regarding the nature of the association between cannabis use and psychosis risk, with some research finding evidence for genetic overlap, while other research finds evidence for potentially causal pathways.

The current study examined data from twins and siblings from two different samples, the U.S.-based Human Connectome Project and the Australian Twin Registry, with a total of 4,674 participants. Overall, psychotic-like experiences were associated with three separate cannabis use variables [frequent (≥100 times) use, a Cannabis Use Disorder diagnosis, and current cannabis use]. Furthermore, the current research found evidence for both shared genetic and individual-specific contributions to the association between PLEs and these three cannabis use variables. More specifically, while the association between cannabis use and psychotic-like experiences was largely attributable to shared genetic factors, cannabis users were more likely to endorse PLEs in comparison to the relative who used cannabis less.  Continue reading

Paternal Smoking Can Affect Multiple Generations of Descendants

MedicalResearch.com Interview with:
"Photo booth: The Smoking Man" by simpleinsomnia is licensed under CC BY 2.0Pradeep G. Bhide, Ph.D.
Professor | Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience
Director, Center for Brain Repair
Department of Biomedical Sciences
Florida State University College of Medicine
Tallahassee, FL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Until now, much attention had been focused on the adverse effects of cigarette smoking by pregnant women on their children’s cognitive development. Some reports suggested that cigarette smoking during pregnancy can produce harmful effects in multiple generations of descendants (transgenerational effects).

Not much had been known about the effects of paternal smoking, although more men smoke cigarettes than women. Our study shows that paternal nicotine exposure can be deleterious to the offspring in multiple generations. That is, cognitive function may be compromised in children and grandchildren of a nicotine-exposed male. Of course, our study was done in mice and not men.  However, since studies done in mice on maternal nicotine exposure produced results consistent with studies done in women and children, we believe that he findings from our present study likely can be extrapolated to humans.  Continue reading

Breast Cancer: Gene Expression of Receptors on a Chip Can Enhance Precision Diagnosis

MedicalResearch.com Interview with:
"JFK Plaza/ Breast Cancer Awareness" by nakashi is licensed under CC BY 2.0Univ.- Prof. Dr. Wolfgang Schreiner
Section Biosimulation and Bioinformatics
Center for Medical Statistics, Informatics, and Intelligent Systems
Medical University of Vienna
General Hospital
WIEN / AUSTRIA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The choice of correct individualized therapy for breast cancer depends on correct diagnosis: receptors for estrogen, progesterone and HER2 are determined routinely. However 5-10% of these routine diagnostics are inaccurate and may entail suboptimal therapy.

We have paved the way for additional diagnostics from gene expression data so as to increase precision of diagnostics. Continue reading

Gene Variants Can Alter Glucose Absorption and Cardiometabolic Risks

MedicalResearch.com Interview with:

Scott David Solomon, MD Director, Noninvasive Cardiology Professor, Harvard Medical School Brigham and Women's Hospital

Dr. Solomon

Scott David Solomon, MD
Director, Noninvasive Cardiology
Professor, Harvard Medical School
Brigham and Women’s Hospital 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The sodium glucose transport proteins are known to be important in regulating uptake of glucose. SGLT-1 is predominantly located in the gut and is responsible for uptake of glucose and galactose in the small intestine. Individuals born with severe mutations of this gene have severe malabsorption syndrome.

We looked at genetic variants that lead to reduced function of the protein, but not complete loss of function, in a large cohort of individuals in the NIH funded Atherosclerosis Risk in Communities Study. We found that those with mutations in the gene had reduced glucose uptake, as measured by an oral glucose tolerance test, as well as less obesity, diabetes, heart failure and death.

Continue reading

Genetic Risk Score Improves Ability To Predict Diabetics at Risk of Coronary Disease

MedicalResearch.com Interview with:

Mario Luca Morieri

Dr. Morieri

Mario Luca Morieri MD
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center
Department of Medicine, Harvard Medical School, Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Coronary artery disease (CAD) is one of the most important complications of diabetes.

Similarly to other complex disorders, CAD is influenced by both environmental and genetic factors. Over the last decade, our understanding of the genetic factors contributing to CAD has dramatically improved and hundreds of new genetic markers associated with increased cardiovascular risk have been identified.

In this study, we showed that combining these genetic markers into a single score (a so called genetic risk score) can improve our ability to the identify those patients with type 2 diabetes who are at higher risk of experiencing a coronary event. 

MedicalResearch.com: What should readers take away from your report? 

Response: One take-away message is that the genetic markers associated with CAD in persons without diabetes have a similar effect in people with diabetes. Another is that prediction of increased risk of CAD in people with diabetes can be improved with the combination of genetic markers with “classic” known markers of CAD such as high cholesterol and high blood pressure. Improving cardiovascular risk prediction will allow physicians to focus their effort on people at higher risk, making the allocation of health-care resources more efficient. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We were able to replicate our findings (from the ACCORD trial) in another study including diabetic patients with similar characteristics (the ORIGIN trial). However, to improve the generalizability of the genetic risk score, its performance should be tested in populations with different clinical characteristics. With the detailed information provided in the paper, other researchers should be able to do this. Also, the genetic score reported in our paper applies to Whites as it was derived from genetic markers discovered in that ethnic group. It would be important to build a similar genetic risk score for people of different ancestry using genetic markers specific to those populations.

MedicalResearch.com: Is there anything else you would like to add? 

Response: We showed in the paper that the identification of an increasing number of genetic markers of CAD risk over the last 8 years has resulted into a progressive improvement in the performance of genetic risk scores for prediction of CAD risk. Thus, if new genetic markers of CAD continue to be identified over the next few years, the usefulness of these genetic scores may continue to increase. 

Citation:

Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial

Mario Luca Morieri, He Gao, Marie Pigeyre, Hetal S. Shah, Jennifer Sjaarda, Christine Mendonca,Timothy Hastings, Patinut Buranasupkajorn, Alison A. Motsinger-Reif, Daniel M. Rotroff, Ronald J. Sigal,Santica M. Marcovina, Peter Kraft, John B. Buse, Michael J. Wagner, Hertzel C. Gerstein, Josyf C. Mychaleckyj, Guillaume Parè and Alessandro Doria

Diabetes Care 2018 Sep; dc180709.https://doi.org/10.2337/dc18-0709

Sep 29, 2018 @ 6:39 pm 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Most Patients Who Carry BRCA1/2 Pathogenic Variants Are Unaware

MedicalResearch.com Interview with:

Michael F. Murray, MD, FACMG, FACP Director for Clinical Operations in the Center for Genomic Health Yale School of Medicine

Dr. Murray

Michael F. Murray, MD, FACMG, FACP
Director for Clinical Operations in the Center for Genomic Health
Yale School of Medicine

MedicalResearch.com: What is the background for this study?

Response: Population screening for the cancer risk associated with the BRCA1 and BRCA2 genes has been suggested by some.  We screened a cohort of about 50,000 adult patient volunteers at Geisinger Health System in Pennsylvania for this risk.  Continue reading

Age, Sex and Genetics Can Identify Groups at Higher Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD Department of Clinical Biochemistry Rigshospitalet, Blegdamsvej & Deputy Head Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen

Dr. Frikke-Schmidt

Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD
Department of Clinical Biochemistry
Rigshospitalet, Blegdamsvej &
Deputy Head
Department of Clinical Medicine
Faculty of Health and Medical Sciences
University of Copenhagen

MedicalResearch.com: What is the background for this study?

 

Response: Alzheimer’s disease and other forms of dementia are devastating, neurodegenerative disorders affecting more than 47 million people in 2015, a number projected to triple by 2050 (1,2). Available curative treatments are lacking, and no useful risk prediction tools exist. The potential for prevention is however substantial, emphasized by the recently observed incidence decline in Western societies, likely caused by improved treatment and prevention of vascular risk factors (1,3,4). Population growth and aging, will however triple dementia prevalence by 2050, if no action is taken. Acting now with ambitious preventive interventions, delaying onset of disease by five years, is estimated to halve the prevalence globally (1,5).

Despite important preventive efforts over the last decades – resulting in decreased smoking, lower blood pressure and lower cholesterol levels in the general population – physical inactivity, overweight, and diabetes remain threats for our health care system, and in particular for cardiovascular disease and dementia. Intensifying preventive efforts in general is thus of crucial importance, and especially for those patients at highest risk who most likely will benefit the most from early and targeted prevention. Risk stratification and specific treatment goals according to the estimated absolute 10-year risk, has been implemented in cardiovascular disease for years (6,7). There is an un-met need for similar strategies in dementia, underscored by the publication of several randomized multicomponent trials that seem to improve or maintain brain function in at-risk elderly people from the general population (8-10) Continue reading

Genetics of Aggressive Skin Cancers in Patients with ‘Butterfly’ Skin Identified

MedicalResearch.com Interview with:

Dr Andrew South, PhD, Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University) 

Dr. South

Dr Andrew South, PhD,
Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University) 

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Butterfly Syndrome or recessive dystrophic epidermolysis bullosa?

Response: Epidermolysis Bullosa, or EB, is a group of genetic diseases caused by mutations in genes which play a role in maintaining skin integrity. An EB patients’ skin can be very fragile which has been likened to butterfly wings, which are also very fragile. Skin blisters are common in EB patients and in some cases large wounds can result from the slightest mechanical trauma, hence the term Butterfly Syndrome.

Skin cancer is a major complication of patients with the recessive dystrophic subtype of EB, known as recessive dystrophic epidermolysis bullosa or RDEB, and these cancers, called squamous cell carcinoma (SCC), are very aggressive. SCC is the leading cause of death in patients with RDEB. SCC also arise very early, affecting RDEB patients in their 20’s and 30’s. Our study used genetic analysis of cancers collected from patients to try and determine what causes the cancer at such an early age and what causes these cancers to be so fatal. Skin SCC arising in the general population as a result of sun exposure are generally benign and occur much later in life, regular skin SCC patients are predominantly over the age of 60, therefore something must be different about RDEB SCC.  Continue reading

Significant Sex Differences in Genetic Associations with Longevity

MedicalResearch.com Interview with:

Yi Zeng, Ph.D.| Professor, Center for Study of Aging and Human Development and Geriatrics Division, School of Medicine, Duke University Professor, National School of Development, Chief Scientist of Raissun Institute for Advanced Studies, Peking University Distinguished Research Scholar, Max Planck Institute for Demographic Research Foreign member of the Royal Netherlands Academy of Arts and Sciences

Dr. Yi Zeng

Yi Zeng, Ph.D.|
Professor, Center for Study of Aging and Human Development and Geriatrics Division, School of Medicine, Duke University
Professor, National School of Development, Chief Scientist of Raissun Institute for Advanced Studies, Peking University
Distinguished Research Scholar, Max Planck Institute for Demographic Research
Foreign member of the Royal Netherlands Academy of Arts and Science

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized healthcare.

Continue reading

Breast and Ovarian Cancers: More Genes Than BRCA1 and BRCA2

MedicalResearch.com Interview with:
Ambry GeneticsShuwei Li, PhD
Principal Statistical Geneticist
Ambry Genetics

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Breast cancer is the most commonly diagnosed cancer, while ovarian cancer is the fifth leading cause of death due to cancer, in US women. Since the discovery of BRCA1 and BRCA2, multiple genes have been reported as risk factors; however, it is still unclear whether the known findings represent the complete genetic landscape of breast and ovarian cancers.

Our team performed exome sequencing on more than 10,000 breast and/or ovarian cancer patients and nearly 4,000 controls. We observed increased risk of breast cancer associated with PALB2, ATM, CHEK2 and MSH6 genes, and increased risk of ovarian cancer associated with MSH6, RAD51C, TP53 and ATM genes.   Continue reading

Women Whose Mothers Lived to 90, Likely To Have Health Old Age

MedicalResearch.com Interview with:

Aladdin H. Shadyab, PhD  MS, MPH, CPH Department of Family and Preventive Medicine UCSD twitter.com/TheDrAladdin

Dr. Aladdin Shadyab

Aladdin H. Shadyab, PhD  MS, MPH, CPH
Department of Family Medicine and Public Health
University of California, San Diego
twitter.com/TheDrAladdin

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous studies have shown that offspring of long-lived parents are not only likely to live longer but to also avoid major chronic diseases (e.g., coronary heart disease), have fewer chronic disease risk factors, and to have better cognitive and physical function in late life. However, few studies have examined parental longevity in relation to an overall measure of successful aging that included reaching old age free of both major diseases and disabilities.

The objective of our study was to determine if parental longevity predicted healthy aging, defined as survival to age 90 without any major age-related diseases (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. The participants of our study were from the Women’s Health Initiative, a large, longitudinal study among postmenopausal women from the United States.

We observed that women whose mothers survived to at least age 90 years were 25% more likely to achieve healthy aging. We also observed that women whose fathers only lived to age 90 did not have increased likelihood of healthy aging. However, women whose mother and father both lived to age 90 were the most likely to achieve healthy aging.

Continue reading

Gastric Cancer: Gene Mutation Predictive of Response to Immunotherapy

MedicalResearch.com Interview with:

Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082

Prof. Zhang

Wei Zhang, Ph.D.
Hanes and Willis Family Professor in Cancer
Director
Cancer Genomics and Precision Oncology
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, NC  27157-1082

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years.

Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice.

There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy.

Continue reading

Genes From Dad Influence How Mom Cares for Babies

MedicalResearch.com Interview with:
“Family” by IsaacVakeroKonor is licensed under CC BY 3.0Professor Rosalind John
Head of Biomedicine Division, Professor
School of Biosciences
Cardiff University
Cardiff UK

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: I have been studying a really remarkable family of genes called “imprinted genes” for the last 20 years. For most genes, we inherit two working copies — one from our mother and one from our father. But with imprinted genes, we inherit only one working copy – the other copy is switched off by epigenetic marks in one parent’s germline. This is really odd because we are all taught at school that two copies of a gene are important to protect us against mutations, and much safer than only one copy. So why turn off one copy?

Maternal care boosted by paternal imprinting in mammals

Maternal care boosted by paternal imprinting in mammals

When my research group were studying these genes in mice, we found out that one of them, called Phlda2, plays an important role in the placenta regulating the production of placental hormones. Placental hormones are critically important in pregnancy as they induce adaptations in the mother required for healthy fetal growth. There was also some indirect evidence that placental hormones play a role in inducing maternal instinct. Women are not born with a maternal instinct –  this behaviour develops during pregnancy to prepare the mother-to-be for the new and demanding role of caring for her baby. This led to my idea that this gene expressed in the offspring’s placenta could influence maternal behaviour, which was entirely novel. 

Until now direct experimental evidence to support the theory that placental hormones trigger this “motherly love” by acting directly on the brain of the mother has been lacking. To test the theory that our imprinted gene could influence the mother’s behaviour by regulating placental hormones, we generated pregnant mice by IVF carrying embryos with different copies of Phlda2. We used IVF to keep all the mothers genetically identical. This resulted in genetically identical pregnant female mice exposed to different amounts of placental hormones – either low, normal or high.

We found that female mice exposed in pregnancy to low amounts of placental hormones were much more focused on nest building (housekeeping) and spent less time looking after their pups or themselves than normal mice. In contrast, female mice exposed to high placental hormones neglected their nests and spent more time looking after their pups and more time self-grooming. We also found changes in the mother’s brain before the pups were born so we know that the change in priorities started before birth. 

MedicalResearch.com: What should readers take away from your report?

Response: This study is important because it shows, for the first time, that genes from the dad expressed in the placenta influence the quality of care mothers gives to their offspring. Perhaps more significantly, this study highlights the importance of a fully functional placenta for high quality maternal care.

We have shown in a mouse model that genes in the placenta and placental hormones are important for priming maternal nurturing in an animal model. Human placenta have the same imprinted genes and also manufactures placental hormones. It is possible that problems with the placenta could misprogram maternal nurturing in a human pregnancy and these mothers may not bond well with their newborn. It is also possible that problems with the placenta could contribute to depression in mothers. We are all familiar with postnatal depression but many more mothers experience depression in pregnancy with 1 in 7 mothers reporting clinically significant symptoms. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: After we found out that Phlda2 could influence maternal behaviour in mice, we asked whether there were changes in this gene in human placenta from pregnancies where women were either diagnosed with clinical depression or self reported depression in pregnancy. Phlda2 seems to be OK but we found another gene that belongs to the same imprinted gene family called PEG3 that is expressed at lower than normal levels in women with depression. Strangely, this seems to only be in placenta from boys. 

MedicalResearch.com: Is there anything else you would like to add?

Response: To explore this further, we have just started our own human cohort study called “Grown in Wales” at Cardiff University focused on prenatal depression. We are now looking at placental hormones in the mother’s blood and gene expression in the placenta to test the idea that the genes we are studying in mice are misregulated in the placenta of pregnancies where the mothers suffer with depression. This work is now funded by the Medical Research Council.

Citation: 

Maternal care boosted by paternal imprinting in mammals

D. J. Creeth, G. I. McNamara,, S. J. Tunster, R. Boque-Sastre,, B. Allen,, L. Sumption, J. B. Eddy,A. R. Isles, R. M. John PLOS
Published: July 31, 2018

Aug 2, 2018 @ 11:48 pm 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Alzheimer’s Disease: Genes Modify Effect of High Fat Diet

MedicalResearch.com Interview with:
The Jackson LaboratoryCatherine Kaczorowski, Ph.D.

Associate Professor and Evnin Family Chair in Alzheimer’s Research
Kristen O’Connell, Ph.D., Assistant Professor
Amy Dunn, Ph.D., Postdoctoral Associate
The Jackson Laboratory


MedicalResearch.com: What is the background for this study? What are the main findings?
 

Dr. Amy Dunn: “Alzheimer’s disease is complex, with both genetic and environmental factors determining symptom onset and disease progression, though our current understanding of how genetic and environmental factors interact to influence disease risk is incomplete. We recently developed a panel of genetically diverse mice carrying human familial AD mutations (AD-BXDs) that better model human AD in order to determine how genetics and diet interact to modify disease onset and severity.

We fed a high fat diet to AD-BXDs and monitored metabolic and cognitive function over the duration of the HFD feeding.  We observed accelerated working memory decline in most of the AD-BXD mouse strains, however, the impact of high fat diet on memory was dependent on individual genetic differences across the panel, with some AD-BXD strains maintaining cognitive function on high fat diet (resilient strains).

Our data suggest that diet and genetic background interact to mediate vulnerability to AD pathogenesis, and that metabolic factors (e.g. obesity, body composition) that may contribute to cognitive decline differentially in normal aging versus AD. “

Continue reading

PITS Gene Linked To Rare Neurologic Disorders

MedicalResearch.com Interview with: 

Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030

Dr. Marcogliese

Paul C Marcogliese, Ph.D.
Postdoctoral Associate,
Laboratory of Dr. Hugo Bellen
Department of Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas 77030

Loren D. Pena, MD PhD Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC

Dr. Peña


Loren D. Pena, MD PhD
Division of Human Genetics
Cincinnati Children’s Hospital Medical Center
Department of Pediatrics
University of Cincinnati
Cincinnati, OH 45229


MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined.

Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression.

Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans.

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Genetic Testing Could Identify Individuals At Risk of Osteoporosis

MedicalResearch.com Interview with:

Stuart Kim - PhD Professor of Developmental Biology, Emeritus Bio-X Affiliated Faculty James H. Clark Center Stanford University

Dr. Kim

Stuart Kim PhD
Professor of Developmental Biology, Emeritus
Bio-X Affiliated Faculty
James H. Clark Center
Stanford University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Osteoporosis is caused by a reduction in bone mass, and leads to a high incidence of bone fracture because the weakened bone is less able to withstand the stress of slips and falls. Osteoporosis affects millions of elderly, is responsible for as many as 50% of fractures in women and 25% of fractures in men over the age of 50, and accounts for $19 billion in annual health care costs in the US. Identification of people with an increased genetic risk for osteoporosis could reduce the incidence of bone fracture. Low BMD is also a risk factor for stress fractures. For athletes and military personnel undergoing harsh rigors of training, stress fractures are common injuries that limit playing time, military effectiveness and competitive success.

Using data from UK Biobank, a genome-wide association study identified 1,362 independent SNPs that clustered into 899 loci of which 613 are new. These data were used to train a genetic algorithm using 22,886 SNPs as well as height, age, weight and sex as predictors. Individuals with low genetic scores (about 2% of those tested) showed a 17-fold increase in risk for osteoporosis and about a 2-fold increase in risk of fractures. Continue reading

Novel Models of Late-Onset Alzheimer’s Disease Based on GWAS

MedicalResearch.com Interview with:

Gregory Carter

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Animal models for late-onset Alzheimer’s disease (LOAD) will be of significant benefit for the discovery and characterization of links between specific genetic factors and the molecular pathways associated with the disease. To date, most animal models have been based on rare, early-onset Alzheimer’s disease genes that incompletely capture the complexity of LOAD and have not translated well to therapies. Therefore, developing and utilizing animal models based on genes hypothesized to play a role in LOAD will provide new insights into its basic biological mechanisms.  Continue reading

Whole-Exome Analysis of Late-Onset Alzheimer’s Disease Reveals Novel Candidate Genes Involved in Cognitive Function

MedicalResearch.com Interview with:

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Late-onset Alzheimer’s disease (LOAD) is the most common form of the disease and the major cause of dementia in the aging population. To date, the complex genetic architecture of LOAD has hampered both our ability to predict disease outcome and to establish research models that effectively replicate human disease pathology.

Therefore, most basic research into Alzheimer’s disease has focused on early-onset forms caused by mutations in specific genes, which has provided key biological insights but to date has not translated to effective disease preventatives or cures.

Our study analyzes both common and rare human genetic variants to identify those significantly associated with .late-onset Alzheimer’s disease, beginning with a large data set from the Alzheimer’s Disease Sequencing Project. We also analyzed RNA sequencing data from post-mortem human and mouse model samples to prioritize candidate genes.

We found a new common coding variant significantly associated with disease, in addition to those in genes previously associated with late-onset Alzheimer’s disease. We also found five candidate genes conferring a significant rare variant burden.  Continue reading