70 research outputs found
Analyses of sequence divergence using completely sequenced genomes
No full text>Magister Scientiae - MScUsing the complete genome, Saccharomyces cerevisiae, which duplicated after its
speciation fuom Kluyveromyces lactics, a dataset of 119 putative S. cerevisiae - K.
lactis ortholog-pairs was constructed. S. cerevisiae paralogous pairs that are likely to
have duplicated during the whole genome duplication of S. cerevisiae were obtained
and the approach taken in our previous work (Nembaware et al., 20OZ), was repeated
to test whether the presence of a paralogue in S. cerevisiae had an effect on the rate
of sequence divergence of the 119 pairs of orthologous genes. We found, however,
that substitutions at synonymous sites had reached saturation and this prevented us
from being able to repeat the previous finding with S. cerevistae and K. lactis . From
this study a publicly available web-server (http://hamlyn.sanbi.ac.zal-victoria) that
automates the calculation of Ka:Ks values given a pairs homologous CDS sequences
is presented
Genome-wide survey and analysis of allele-specific mRNA splicing in human and mouse
No full textIncludes abstract.Includes bibliographical references (leaves 125-145).This dissertation aims to examine allele-specific splicing in human and mouse using publicly available datasets. Such datasets, which have been generated from multiple tissue sources and from individuals of diverse backgrounds, are rich and cheap reservoirs of transcript isoforms resulting from alternative splicing as well as isoforms resulting from mutations or polymorphisms (allele-specific isoforms). Published tools were used to analyse microarray and genomic data. However, for the assessment of allele-specific splicing using publicly available high-throughput transcript sequences, we present two novel methods: a heuristic method for quantifying the prevalence of allele-specific splicing and a more sophisticated maximum likelihood method for the detection of individual examples of allele-specific splicing. These methods make use of transcripts that can be mapped to both polymorphisms and computationally predicted mRNA isoforms. Inference of polymorphic alleles from transcripts is laborious hence a pre-computed database was created for the human data and made publicly available for use by the wider research community
Risk factors associated with blood pressure variation in sickle cell disease in Cameroon
No full textBackground: In SCD patients, studies have shown that increased Blood Pressure (BP) is associated with higher risk of stroke and mortality, even in a range of systolic BP(SBP) and diastolic BP(DBP) that are considered relatively normal for the general population (i.e., lower than 140 mmHg). SCD patients, generally, have lower systolic, diastolic, and mean BP compared to age and sex-matched controls. Relative Systemic Hypertension (RSH) for SCD patients is defined as BP ranging from 120–139/70–89 mmHg, and Systemic Hypertension for SCD patients with BP above 140/90 mmHg. BP may be a potential modulator of clinical severity in SCD patients. BP is a heritable trait with estimates indicating that 30–70% of the trait variance is attributable to genetic variation. A recurrent deleterious and loss of function mutations in genes associated with lowering BP, e.g., variants in CLCN6, have been recently associate with long survival in SCD in Cameroon. Additionally, demographic, biological, and anthropometric factors have been reported to be associated with BP in SCD patients. Understanding the aetiology of BP variation in SCD patients and assessment of up-to-date evidence is key to early prediction of potential BP-related complications in SCD patients. Early prediction of BP-related complications in SCD patients could lead to better prevention and treatment of SCD and its associated causes of mortality. Herein, we investigated (clinical, genetic, and epidemiological) risk factors associated with RSH or Systemic Hypertension in SCD patients in Cameroon to gain insight into the pathophysiology of BP variation in this disease in an African setting. Objectives: 1) A systematic review and meta-analysis on BP variation (Normal, Relative Systemic Hypertension(RSH) and Hypertension) among SCD patients; 2) Investigate clinical and epidemiological risk factors for RSH and Systemic Hypertension in 815 SCD patients in Cameroon; 3) Identification of genetic variants associated to BP variation in SCD patients in Cameroon using a Genome-wide Association study; 4) Functional analysis on pathways and mechanisms underlying BP variation in SCD patients. Methods: Systematic review and meta-analysis: A protocol was developed and registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42020168798. A search was conducted on the following electronic databases: PubMed, Scopus, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta- analysis (PRISMA) served as a template for reporting the review and meta-analysis. Independently, in collaboration with another reviewer, we screened studies, extracted relevant data, assessed methodological quality and risk of bias on each included study. A retrospective analysis to investigate risk factors associated with RSH or Systemic Hypertension in SCD patients in Cameroon. Participants who had incomplete/out of range BP readings were excluded from this analysis. Categorical variables were compared using Chi squared test or Fisher exact test if the expected count in a cell was less than five while continuous variables were compared according to BP category with the Kruskal–wallis test. Multivariate multinomial logistic regression modelling was used to examine the effects of the demographic, anthropometric, clinical, and laboratory factors to determine the potential independent risk factors for RSH and Systemic Hypertension. A final model was created that included all the predictors and interactions that were significantly associated at the level of P 18 years (P < 0.001), weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.046), creatinine (P < 0.001), eGFR (P < 0.001) and haemoglobin (P = 0.020) . Multivariate analyses found that age [OR = 1.02, (95% CI = 1.01–1.05), P = 0.021], creatinine [OR = 1.310, 95% CI = 1.05–1.63, P = 0.016], BMI [OR = 1.09, (95% CI = 1.03– 1.16), P = 0.002] were independent risk factors for high BP values in SCD patients with RSH compared with SCD patients with normal BP values. Genome-wide analysis and meta-analysis: For SBP, we found two genetic loci including independent and suggestive SNPs. The first locus was found in RP11-727A23.5 on chromosome 11 (rs146072506, P=4.88x10-08), the second locus was found on DLGAP1 gene on chromosome 18 (rs35715722, P=3.408x10-08). Two other SNPs were found in the intergenic regions. For DBP, the only significant SNP was in the intergenic region. Additionally, we found one SNP (rs186536474, p=8.90x10-09) located on GPR39 gene on chromosome 2 with a statistically significant p-value associated with BMI. Identified variants in intergenic regions may play a role in specific genes regulating BP or BMI. The meta-analysis of the Cameroon SCD cohort and Silent Infarct Transfusion Trial (SITT) cohorts, and African American cohort of SCD patients, did not find significant SNPs. After performing genetic analysis and Gene-set analysis with none of the identified genes or gene-set reached a significant threshold. Additionally, tissue expression analysis did not reach significant thresholds. Conclusion: This is the first in-depth investigation of the non-genetic and genetic risk factors associated with BP variation (RSH or Systemic Hypertension) in SCD patients in Africa, i.e., Cameroon. Age, male gender, BMI was found to be statistically significant independently associated factors of RSH and Hypertension in the SCD patients in Cameroon. The GWAS analysis identified a few SNPs which were statistically associated with BP and BMI in Cameroonian SCD patients. These SNPs require follow up studies in larger SCD cohorts. Tailored interventions that consider both genetic and non-genetic risk factors have potential to lead to better management of BP pressure in SCD patients and prevent possibly prevent development of severe SCD complications
A formative evaluation of an instant messaging-based HIV and AIDS helpline in South Africa
No full textIncludes abstract.Includes bibliographical references.Widespread adoption of mobile phone-based innovative interventions hinge on clear guidelines and standards being established on how such programmes should be designed and implemented to promote high impact levels. This report is a formative evaluation of RedChatZone, a pilot instant messaging-based programme implemented in 2009 to provide an HIV and AIDS helpline via Mxit, an instant messaging platform
SMARTLife Data Dictionary used for a comparative study
No full textThis is a tool used to collect data from research administrators and managers
SmartLife Infographic
No full textComparative analyses of responses from Research Administrators and Managers located in the UK and Africa to identify key issues that could inform training particularly impact equitable partnerships.</div
Patient-centric research in the time of COVID-19: conducting ethical COVID-19 research in Africa
No full textResearch practices should be ethical and transparent, prioritising patient benefits and provision of health carehealthcare, and respecting participant autonomy.Priority should be given to research studies with the potential for immediate translated patient benefits based on realistic interventions appropriate to an African context. Institutional Ethics Review Boards should be supported to ensure high-quality, rapid review of research proposals. Informed consent models should reflect research risk level and the heightened vulnerability of the study population during a health crisis. Consideration should be made for patients who are too ill to give consent, and inclusion of data from deceased patients. Participant information must be accessible and relevant to participants, in local languages, and include clear, realistic descriptions of potential benefits and risks. Community engagement using appropriate media channels can be effective in providing information and counter dissemination of false information. Funders and journal editors can provide additional checks and balances to ensure funded and published research from Africa is ethical, patient-centric, relevant and transparent
The African genomic medicine training initiative (AGMT) : showcasing a community and framework driven genomic medicine training for nurses in Africa
No full textThe potential of genomic medicine in improving the quality of healthcare both at population
and individual-level is well-recognized globally. However, successful adoption of genetic
and genomic evidence into clinical practice depends on training the healthcare workforce
and clinical researchers in genomic medicine. Due to limited expertise in the medical
genetics and genomics field, widespread uptake largely depends on task-shifting for the
implementation of genomic medicine implementation to key healthcare professionals such
as nurses. Their knowledge would be developed through courses aimed at professional
development. Globally, trainers, and training initiatives in genomic medicine are in early
stages of development, but resource limited settings such as the African continent face
additional logistical and institutional challenges. The African Genomic Medicine Training
(AGMT) Initiative was conceived during a combined conference of the African Society
of Human Genetics (AfSHG) and the Human Heredity and Health in Africa Consortium
(H3Africa) in 2016, Senegal, in response to the needs for developing knowledge and
skills in genomic medicine. AGMT was established to implement a sustainable genomic
medicine training initiative primarily for healthcare professionals who are not geneticists but
are nurses, doctors, and pharmacists in Africa. This paper reports on the establishment
of the AGMT initiative and the strategies developed and piloted by this initiative in
designing and implementing an accredited frame-work and community-based blended
learning course for nurses across 11 African countries. The global implementation
experiences, outcomes and lessons learnt are highlighted. The AGMT initiative strategy
takes advantage of existing research consortia and networks to train and create a pool of
trainers and has adopted evidence-based approaches to guide curriculum and content
development/adaptation. This initiative established the first Africa-wide online blended
learning genomic medicine course which forms the basis from which to develop courses
for other healthcare professionals and the wider public.The National Human Genome Research
Institute (NHGRI) and the Office of The Director (OD),
the National Institutes of Health.http://www.frontiersin.org/Geneticsam2020Immunolog
A <it>plant natriuretic peptide-like </it>gene in the bacterial pathogen <it>Xanthomonas axonopodis </it>may induce hyper-hydration in the plant host: a hypothesis of molecular mimicry
No full textAbstract Background Plant natriuretic peptides (PNPs) are systemically mobile molecules that regulate homeostasis at nanomolar concentrations. PNPs are up-regulated under conditions of osmotic stress and PNP-dependent processes include changes in ion transport and increases of H2O uptake into protoplasts and whole tissue. Presentation of the hypothesis The bacterial citrus pathogen Xanthomonas axonopodis pv. Citri str. 306 contains a gene encoding a PNP-like protein. We hypothesise that this bacterial protein can alter plant cell homeostasis and thus is likely to represent an example of molecular mimicry that enables the pathogen to manipulate plant responses in order to bring about conditions favourable to the pathogen such as the induced plant tissue hyper-hydration seen in the wet edged lesions associated with Xanthomonas axonopodis infection. Testing the hypothesis We found a Xanthomonas axonopodis PNP-like protein that shares significant sequence similarity and identical domain organisation with PNPs. We also observed a significant excess of conserved residues between the two proteins within the domain previously identified as being sufficient to induce biological activity. Structural modelling predicts identical six stranded double-psi β barrel folds for both proteins thus supporting the hypothesis of similar modes of action. No significant similarity between the Xanthomonas axonopodis protein and other bacterial proteins from GenBank was found. Sequence similarity of the Xanthomonas axonopodis PNP-like protein with the Arabidopsis thaliana PNP (AtPNP-A), shared domain organisation and incongruent phylogeny suggest that the PNP-gene may have been acquired by the bacteria in an ancient lateral gene transfer event. Finally, activity of a recombinant Xanthomonas axonopodis protein in plant tissue and changes in symptoms induced by a Xanthomonas axonopodis mutant with a knocked-out PNP-like gene will be experimental proof of molecular mimicry. Implication of the hypothesis If the hypothesis is true, it could at least in part explain why the citrus pathogen Xanthomonas campestris that does not contain a PNP-like gene produces dry corky lesions while the closely related Xanthomonas axonopodis forms lesions with wet edges. It also suggests that genes typically found in the host, horizontally transferred or heterologous, can help to explain aspects of the physiology of the host-pathogen interactions.</p
Knowledge, Attitude, and Perceptions of Pharmacists and Pharmacy Students towards Pharmacogenomics in Zimbabwe
No full textThe potential of pharmacogenomics (PGx) to positively impact health outcomes and quality of healthcare is well-established. However, the application of available evidence into clinical practice is still limited due to limited knowledge among healthcare professionals, including pharmacists. As a start towards building capacity for PGx education, we assessed knowledge, attitudes, and perceptions about PGx among practising pharmacists and pharmacy students. A cross-sectional study was conducted among pharmacists and undergraduate pharmacy students selected using a convenient sampling method—a 37-question survey instrument was used to obtain information regarding PGx among the participants. Out of a total of 131 participants, 56% of respondents showed fair-to-good PGx knowledge. Respondents’ self-reported assessment indicated that 88% had average and above knowledge scores in PGx. Practising pharmacists in Zimbabwe have positive attitudes towards PGx and would support its application to improve treatments. However, there were concerns about security and discrimination when genomics data is used by those who do not understand its meaning. Participants agreed that they would play a leading role in PGx testing if provided with appropriate training. The interest in PGx is challenged by their limited knowledge and understanding of genetics, suggesting a need to update curricula for pharmacy students and for continuing health education programmes
- …
