Emmanuel Peprah
Emmanuel Peprah
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Associate Professor of Global and Environmental Health
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Professional overview
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Dr. Emmanuel Peprah’s research interests lie at the confluence of understanding what, why, and how some evidence-based interventions work in some populations and not others. The programattic focus of his research is understanding the contextual factors that influence the burden of co-morbidity in people living with HIV/AIDS (PLWH), with a particular focus on cardiovascular disease risk factors and mental health. As the burden of non-communicable diseases (NCDs) continues to increase, there is an opportunity to integrate NCD management into HIV care with implemention strategies that leverage the global infrasturcture designed to improve care delivery for PLWH. Dr. Peprah has built collaborations with multidisciplinary teams of investigators, both nationally and internationally, to address the high burden of comorbidity in PLWH globally. He is also the founder of the Baakoye Foundation, a nonprofit philanthropic organization dedicated to serving people in sub-Saharan Africa, and co-founder of the Washington Leaders Index (WLI), which aims to empower the next generation of emerging leaders through active, innovative, and inclusive leadership programs. Both nonprofit organizations serve the needs of children and people globally within the domains of education and health.
Before joining GPH, Dr. Peprah was a senior program official at the National Institutes of Health (NIH), where he worked with senior leadership to oversee strategic planning, initiative development, and implementation of research priorities in the areas of translational research, implementation science, and global health. He led and managed HIV/AIDS programs and a $10 million portfolio as part of the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine Program. He was instrumental in launching the Human, Heredity, and Health in Africa (H3Africa) Initiative, a multimillion trans-NIH program, and served on its executive board. Dr. Peprah has received several awards for strategic planning, management, and implementation of large-scale NIH programs.
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Education
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BS, Biology, Texas A&M University, Commerce, TXPhD, Molecular Biology & Biomedical Science, Meharry Medical College, Nashville, TN
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Honors and awards
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NIH Director’s Award for Leadership H3Africa Stage II Team: For exceptional leadership and dedication in implementing Stage II of the Human Heredity and Health in Africa program (2018)NHLBI’s Director's for Outstanding Service (2018)NHLBI’s Director's for Outstanding Service Partnership/Collaboration Award for bringing multiple disciplines together to understand HIV-related co-morbidities and prepare for the challenges presented by the complex conditions of the new HIV era (2018)NHLBI’s Director's for Outstanding Translational Science Award for demonstrating exemplary leadership and service in advancing translation research (2017)Federal Service Career Promotion (2016)NHLBI’s Director's for Outstanding Translational Science Award as part of the Center for Translational Research and Implementation Science (CTRIS) Leadership Team for demonstrating exemplary leadership and service in advancing CTRIS’s translation (2016)NHLBI’s Director's for Breath of Fresh Air (Innovation) award for exemplary work evaluating NHLBI’s support for multi-project research grants and proposing creative and innovative enhancements to the NHLBI’s program project grants (PPG) (2016)NHLBI’s Director's for Learning Environment Award for fostering a learning environment through effective administration, knowledge sharing, and thoughtful implementation of the NHLBI R35 Program (2016)NHLBI’s Director's for Partnership/Collaboration in recognition of outstanding collaborative efforts in developing a conceptual framework for the NHLBI R35 program to provide greater funding stability and flexibility to investigators (2015)NIH Director's Common Fund Leadership Award for the NIH Common Fund Early Independence Award Program (2013)NIH Director's Award as a member of the Common Fund Global Health Leadership Team for outstanding service in the coordination of the Common Fund Global Health Initiatives (2012)Certificate of Appreciation for Invited Presenter, NIH Seminar Series, STEM Careers (2012)Certificate of Appreciation for Invited Presenter, Washington Mathematics Science Technology Public Charter High School, Washington, DC (2012)Leadership Award, Postdoctoral Fellows Research Symposium Committee, Emory University, Atlanta, GA (2008)
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Areas of research and study
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Dissemination and Implementation of Evidence-based ProgramsHIV/AIDSImplementation scienceInter-organizational NetworksTranslational science
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Publications
Publications
The Importance of Conducting Stroke Genomics Research in African Ancestry Populations
Xu, H., Mitchell, B. D., Peprah, E., Kittner, S. J., & Cole, J. W. (n.d.).Publication year
2017Journal title
Global HeartVolume
12Issue
2Page(s)
163-168A global perspective on using implementation research to address hypertension-associated target organ damage
AbstractPeprah, E., Lopez-Class, M., Shero, S., John-Sowah, J., & Engelgau, M. (n.d.).Publication year
2016Journal title
Ethnicity and DiseaseVolume
26Issue
3Page(s)
395-398AbstractHypertension, a major risk factor for cardiovascular disease, imposes a significant public health burden and challenge to address it worldwide. Scaling up delivery of proven, effective interventions for hypertension could significantly advance the goal of reducing the global burden. Although significant progress has been made in many countries, some lament that large-scale initiatives focused on reducing blood pressure in global populations have not effectively addressed this challenge. Late-stage implementation research plays a critical role in determining effective and sustainable scale-up of these initiatives. In this article, we briefly discuss some of the global initiatives that have been funded by the National Heart, Lung, and Blood Institute of the US National Institutes of Health. Intervention delivery strategies in low resource settings must have demonstrated effectiveness and consideration for the social, cultural and physical context (eg, access, affordability, and availability of medications) in which a program is being delivered in order to be sustainable nationally and globally. Hence, the use of implementation research is central to determining sustainable delivery of evidence-based and tailored interventions focused on hypertension control. The sustained control of hypertension in global populations holds tremendous potential for reducing morbidity, premature mortality, and the adverse economic impact of cardiovascular disease in all regions.A strategic framework for utilizing late-stage (t4) translation research to address health inequities
AbstractLopez-Class, M., Peprah, E., Zhang, X., Kaufmann, P. G., & Engelgau, M. M. (n.d.).Publication year
2016Journal title
Ethnicity and DiseaseVolume
26Issue
3Page(s)
387-394AbstractAchieving health equity requires that every person has the opportunity to attain their full health potential and no one is disadvantaged from achieving this potential because of social position or other socially determined circumstances. Inequity experienced by populations of lower socioeconomic status is reflected in differences in health status and mortality rates, as well as in the distribution of disease, disability and illness across these population groups. This article gives an overview of the health inequities literature associated with heart, lung, blood and sleep (HLBS) disorders. We present an ecological framework that provides a theoretical foundation to study late-stage T4 translation research that studies implementation strategies for proven effective interventions to address health inequities.Building a Platform to Enable NCD Research to Address Population Health in Africa: CVD Working Group Discussion at the Sixth H3Africa Consortium Meeting in Zambia
Peprah, E., Wiley, K., Troyer, J., Adebamowo, S. N., Adu, D., Mayosi, B. M., Ramsay, M., Motala, A. A., Adebamowo, C., Ovbiagele, B., & Owolabi, M. (n.d.).Publication year
2016Journal title
Global HeartVolume
11Issue
1Page(s)
165-170Burden of diarrhea in the eastern mediterranean region, 1990-2013: Findings from the global burden of disease study 2013
AbstractKhalil, I., Colombara, D. V., Forouzanfar, M. H., Troeger, C., Daoud, F., Moradi-Lakeh, M., El Bcheraoui, C., Rao, P. C., Afshin, A., Charara, R., Abate, K. H., Abd El Razek, M. M., Abd-Allah, F., Abu-Elyazeed, R., Kiadaliri, A. A., Akanda, A. S., Akseer, N., Alam, K., Alasfoor, D., … Mokdad, A. H. (n.d.).Publication year
2016Journal title
American Journal of Tropical Medicine and HygieneVolume
95Issue
6Page(s)
1319-1329AbstractDiarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low-and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015
Failed generating bibliography.AbstractPublication year
2016Journal title
The Lancet HIVVolume
3Issue
8Page(s)
e361-e387AbstractBackground Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1–3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5–2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6–40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7–1·9 million) in 2005, to 1·2 million deaths (1·1–1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Funding Bill & Melinda Gates Foundation, and National Institute of Mental Health and National Institute on Aging, National Institutes of Health.Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013
AbstractMokdad, A. H., Forouzanfar, M. H., Daoud, F., El Bcheraoui, C., Moradi-Lakeh, M., Khalil, I., Afshin, A., Tuffaha, M., Charara, R., Barber, R. M., Wagner, J., Cercy, K., Kravitz, H., Coates, M. M., Robinson, M., Estep, K., Steiner, C., Jaber, S., Mokdad, A. A., … Murray, C. J. (n.d.).Publication year
2016Journal title
The Lancet Global HealthVolume
4Issue
10Page(s)
e704-e713AbstractBackground The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Funding Bill & Melinda Gates Foundation.A global health strategy to capitalize on proven-effective interventions for heart, lung, and blood diseases
Engelgau, M. M., Peprah, E., Sampson, U. K., & Mensah, G. A. (n.d.).Publication year
2015Journal title
Global HeartVolume
10Issue
1Page(s)
87-91DS-Connect: A Promising Tool to Improve Lives and Engage Down Syndrome Communities Worldwide
AbstractPeprah, E. K., Parisi, M. A., Kaeser, L., Bardhan, S., Oster-Granite, M. L., & Maddox, Y. T. (n.d.).Publication year
2015Journal title
Global HeartVolume
10Issue
4Page(s)
337-340AbstractDown syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities in the United States with an estimated birth prevalence of 1:691 births; however, worldwide estimates of the number of individuals with intellectual and developmental disabilities, including DS, remain speculative. Little is known about the global health impact of DS, such as heart defects, gastrointestinal malformations, and other medical and behavioral issues. Further research is needed to develop the next generation of novel therapies and compounds aimed at improving cognition, reducing dementia, and mitigating other manifestations of DS. To address these challenges, the National Institutes of Health has created the first web-based, voluntary registry and data resource called DS-Connect: The Down Syndrome Registry to collect demographic and health information about individuals with DS.Endothelial dysfunction: A unifying hypothesis for the burden of cardiovascular diseases in sub-Saharan Africa
AbstractSampson, U. K., Engelgau, M., Peprah, E. K., & Mensah, G. A. (n.d.).Publication year
2015Journal title
Cardiovascular Journal of AfricaVolume
26Issue
2Page(s)
S56-S60AbstractIt is well established that the leading causes of death and disability worldwide are cardiovascular diseases (CVD), chief among which is ischaemic heart disease. However, it is also recognised that ischaemic heart disease frequently coexists with other vascular conditions, such as cerebrovascular, renovascular and peripheral vascular disease, thus raising the notion of a common underlying pathobiology, albeit with differing manifestations, dictated by the implicated vascular bed. The understanding that common metabolic and behavioural risk factors as well as social determinants and drivers are convergent in the development of CVD evokes the idea that the dysfunction of a common bio-molecular platform is central to the occurrence of these diseases. The state of endothelial activation, otherwise known as endothelial dysfunction, occurs when reactive oxygen signalling predominates due to an uncoupled state of endothelial nitric oxide synthase (eNOS). This can be a physiological response to stimulation of the innate immune system or a pathophysiological response triggered by cardiovascular disease risk factors. The conventional wisdom is that the endothelium plays an important role in the initiation, progression and development of CVD and other non-communicable diseases. Consequently, the endothelium has remarkable relevance in clinical and public health practice as well as in health education, health promotion, and disease- and risk-factor prevention strategies. It also presents a plausible unifying hypothesis for the burden of CVD seen globally and in sub-Saharan Africa. Importantly, the heterogeneity in individual responses to metabolic, behavioural, and social drivers of CVD may stem from a complex interplay of these drivers with genomic, epigenetic and environmental factors that underpin eNOS uncoupling. Therefore, further biomedical research into the underlying genetic and other mechanisms of eNOS uncoupling may enlighten and shape strategies for addressing the burden of CVD in sub-Saharan Africa and other regions of the world.Genome-wide association studies in Africans and African Americans: Expanding the framework of the genomics of human traits and disease
AbstractPeprah, E., Xu, H., Tekola-Ayele, F., & Royal, C. D. (n.d.).Publication year
2015Journal title
Public Health GenomicsVolume
18Issue
1Page(s)
40-51AbstractGenomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions.H3Africa comes of age
Mensah, G. A., Peprah, E. K., Sampson, U. K., & Cooper, R. S. (n.d.).Publication year
2015Journal title
Cardiovascular Journal of AfricaVolume
26Issue
2Page(s)
S3-S5Opportunities and Challenges in Chronic Chagas Cardiomyopathy
Mensah, G. A., Burns, K. M., Peprah, E. K., Sampson, U. K., & Engelgau, M. M. (n.d.).Publication year
2015Journal title
Global HeartVolume
10Issue
3Page(s)
203-207Understanding decreased fertility in women carriers of the FMR1 premutation: A possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency (FXPOI)
AbstractPeprah, E. (n.d.).Publication year
2014Journal title
Reproductive HealthVolume
11Issue
1AbstractFragile X syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5′ untranslated region of the fragile X mental retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine-guanine (CGG) triplet repeats, causes FXS. Individuals with 55-199 CGG repeats, classified as premutation carriers, are affected by two distinct disorders depending on their premutation status. Disorders associated with premutation carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similarities of FXTAS and FXPOI (e.g. overabundance of FMR1 transcript and intranuclear inclusions) suggest that similar molecular mechanisms underlie both FXTAS and FXPOI. The current hypothesis describes the underlying mechanism for FXTAS as an mRNA gain-of-function mutation, however the underlying mechanism for FXPOI remains unresolved. New data suggests that repeat associated non-AUG (RAN) translation could underlie FXPOI.Biomedical research, a tool to address the health issues that affect African populations
AbstractPeprah, E., & Wonkam, A. (n.d.).Publication year
2013Journal title
Globalization and HealthVolume
9Issue
1AbstractTraditionally, biomedical research endeavors in low to middle resources countries have focused on communicable diseases. However, data collected over the past 20 years by the World Health Organization (WHO) show a significant increase in the number of people suffering from non-communicable diseases (e.g. heart disease, diabetes, cancer and pulmonary diseases). Within the coming years, WHO predicts significant decreases in communicable diseases while non-communicable diseases are expected to double in low and middle income countries in sub-Saharan Africa. The predicted increase in the non-communicable diseases population could be economically burdensome for the basic healthcare infrastructure of countries that lack resources to address this emerging disease burden. Biomedical research could stimulate development of healthcare and biomedical infrastructure. If this development is sustainable, it provides an opportunity to alleviate the burden of both communicable and non-communicable diseases through diagnosis, prevention and treatment. In this paper, we discuss how research using biomedical technology, especially genomics, has produced data that enhances the understanding and treatment of both communicable and non-communicable diseases in sub-Saharan Africa. We further discuss how scientific development can provide opportunities to pursue research areas responsive to the African populations. We limit our discussion to biomedical research in the areas of genomics due to its substantial impact on the scientific community in recent years however, we also recognize that targeted investments in other scientific disciplines could also foster further development in African countries.DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome
AbstractXu, H., Rosales-Reynoso, M. A., Barros-Núñez, P., & Peprah, E. (n.d.).Publication year
2013Journal title
BMC research notesVolume
6Issue
1AbstractBackground: Fragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. The mechanisms of repeat expansion are dependent on the presence of cis elements and the absence of trans factors both of which are not mutually exclusive and contribute to repeat instability. Expansions associated with trans factors are due to the haploinsuffient or reduced expression of several DNA repair/metabolizing proteins. The reduction of expression in trans factors has been primarily conducted in animal models without substantial examination of many of these expansion mechanisms and trans factors in humans. Results: To understand the trans factors and pathways associated with trinucleotide repeat expansion we have analyzed two microarray datasets which characterized the transcript expression in patients with FXS and in controls. Conclusion: We observed significant down regulation of DNA damage/repair pathway transcripts. This observation was consistent in both datasets, which used different populations. Within these datasets, several transcripts overlapped in the direction of association and fold change. Further characterization of these genes will be critical to understand their role in trinucleotide repeat instability in FXS.Fragile X Syndrome: The FMR1 CGG Repeat Distribution Among World Populations
AbstractPeprah, E. (n.d.).Publication year
2012Journal title
Annals of Human GeneticsVolume
76Issue
2Page(s)
178-191AbstractFragile X syndrome (FXS) is characterized by moderate to severe intellectual disability, which is accompanied by macroorchidism and distinct facial morphology. FXS is caused by the expansion of the CGG trinucleotide repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. The syndrome has been studied in ethnically diverse populations around the world and has been extensively characterized in several populations. Similar to other trinucleotide expansion disorders, the gene-specific instability of FMR1 is not accompanied by genomic instability. Currently we do not have a comprehensive understanding of the molecular underpinnings of gene-specific instability associated with tandem repeats. Molecular evidence from in vitro experiments and animal models supports several pathways for gene-specific trinucleotide repeat expansion. However, whether the mechanisms reported from other systems contribute to trinucleotide repeat expansion in humans is not clear. To understand how repeat instability in humans could occur, the CGG repeat expansion is explored through molecular analysis and population studies which characterized CGG repeat alleles of FMR1. Finally, the review discusses the relevance of these studies in understanding the mechanism of trinucleotide repeat expansion in FXS.Examination of FMR1 transcript and protein levels among 74 premutation carriers
AbstractPeprah, E., He, W., Allen, E., Oliver, T., Boyne, A., & Sherman, S. L. (n.d.).Publication year
2010Journal title
Journal of Human GeneticsVolume
55Issue
1Page(s)
66-68AbstractFragile X-associated disorders are caused by a CGG trinucleotide repeat expansion in the 5′-untranslated region of the FMR1 gene. Expansion of the CGG trinucleotide repeats to >200 copies (that is, a full mutation) induces methylation of the FMR1 gene, with transcriptional silencing being the eventual outcome. Previous data have shown that FMR1 premutation carriers (individuals with 55-199 repeats) have increased FMR1 mRNA levels with decreased protein (fragile X mental retardation protein (FMRP)) levels. However, the point at which this translational inefficiency occurs, given the increased transcription mechanism, has not yet been explored and remains to be elucidated. We examined the repeat length group, FMR1 transcript and FMRP levels in 74 males with a wide range of repeat lengths using analysis of covariance to better characterize this association. Results showed that the mean FMRP level among carriers with 80-89 repeats was significantly higher than the mean levels among lower (54-79) and higher (90-120) premutation carriers, in spite of the increasing transcript level with repeat length. Taken together, these results suggest that the 80-89-repeat group may lead to different properties that increase the efficiency of translation compared with other premutation repeat size groups.Genetic diversity of the Fragile X syndrome Gene (FMR1) in a large sub-saharan West African population
AbstractPeprah, E. K., Allen, E. G., Williams, S. M., Woodard, L. M., & Sherman, S. L. (n.d.).Publication year
2010Journal title
Annals of Human GeneticsVolume
74Issue
4Page(s)
316-325AbstractSummary: Fragile X syndrome (OMIM #300624) is caused by the expansion of a CGG trinucleotide repeat found in the 5′ untranslated region of the X-linked FMR1 gene. Although examinations of characteristics associated with repeat instability and expansion of the CGG repeat upon transmission from parent to offspring has occurred in various world populations, none has been conducted in large Sub-Saharan African populations. We have examined the FMR1 CGG repeat structure in a sample of 350 males drawn from the general population of Ghana. We found that Ghanaians and African Americans have similar allele frequency distributions of CGG repeat and its flanking STR markers, DXS548 and FRAXAC1. However, the distribution of the more complex marker, FRAXAC2, is significantly different. The haplotype structure of the FMR1 locus indicated that Ghanaians share several haplotypes with African Americans and Caucasians that are associated with the expanded full mutation. In Ghanaians, the majority of repeat structures contained two AGG interruptions, however, the majority of intermediate alleles (35-49) lacked AGG interruptions. Overall, we demonstrate that allelic diversity of the FMR1 locus among Ghanaians is comparable to African Americans, but includes a minority of CGG array structures not found in other populations.Characterization of the mitochondrial inner membrane protein translocator Tim17 from Trypanosoma brucei
AbstractSingha, U. K., Peprah, E., Williams, S., Walker, R., Saha, L., & Chaudhuri, M. (n.d.).Publication year
2008Journal title
Molecular and Biochemical ParasitologyVolume
159Issue
1Page(s)
30-43AbstractMitochondrial protein translocation machinery in the kinetoplastid parasites, like Trypanosoma brucei, has been characterized poorly. In T. brucei genome database, one homolog for a protein translocator of mitochondrial inner membrane (Tim) has been found, which is closely related to Tim17 from other species. The T. brucei Tim17 (TbTim17) has a molecular mass 16.2 kDa and it possesses four characteristic transmembrane domains. The protein is localized in the mitochondrial inner membrane. The level of TbTim17 protein is 6-7-fold higher in the procyclic form that has a fully active mitochondrion, than in the mammalian bloodstream form of T. brucei, where many of the mitochondrial activities are suppressed. Knockdown of TbTim17 expression by RNAi caused a cessation of cell growth in the procyclic form and reduced growth rate in the bloodstream form. Depletion of TbTim17 decreased mitochondrial membrane potential more in the procyclic than bloodstream form. However, TbTim17 knockdown reduced the expression level of several nuclear encoded mitochondrial proteins in both the forms. Furthermore, import of presequence containing nuclear encoded mitochondrial proteins was significantly reduced in TbTim17 depleted mitochondria of the procyclic as well as the bloodstream form, confirming that TbTim17 is critical for mitochondrial protein import in both developmental forms. Together, these show that TbTim17 is the translocator of nuclear encoded mitochondrial proteins and its expression is regulated according to mitochondrial activities in T. brucei.