Poster Abstracts - S518
Articles
- IdentificationPowell, OwenCan genomics enable genetic evaluations with phenotypes recorded on smallholder dairy farms?
Owen Powell1, R. Chris Gaynor1, Janez Jenko1, Gregor Gorjanc1, Okeyo Mwai2, Raphael Mrode2,3 & John M. Hickey1
1The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Research Centre, Midlothian EH25 9RG, UK; 2ILRI, International Livestock Research Institute; 3Scotland's Rural College (SRUC), Peter Wilson Building, Kings Buildings, West Mains Road, Edinburgh, EH9 3JG
Background: Genetic evaluation is a central component of genetic improvement programs. In advanced economies, most genetic evaluations depend on large quantities of data that are recorded on commercial farms. Large herd sizes and widespread use of artificial insemination enable the genetic and environmental components of an individual animal's phenotype to be accurately separated. In contrast to this, herds are neither large nor have high genetic connectedness in smallholder farming systems, such as in East Africa. This limits genetic evaluation with pedigree information. Genomic information keeps track of shared haplotypes rather than animals. This information could capture and strengthen connectedness between herds and through this may enable genetic evaluations based on phenotypes recorded on smallholder dairy farms. The objective of this study was to use simulation to quantify the power of genomic information to enable genetic evaluation under such conditions.
Results: The results from this study show; (i) GBLUP produced higher accuracies than PBLUP at all population sizes and herd sizes, (ii) Models with herd fitted as a random effect produced equal or higher accuracies than the model with herd fitted as a fixed effect across all herd size scenarios, (iii) At low levels of genetic connectedness, with four offspring per sire and one to two animals per herd, GBLUP produced EBV accuracies greater than 0.5. Generally, a decrease in the number of sires mated per generation showed consistently higher accuracies compared to when more sires were used.
Conclusions: This study has demonstrated the potential of genomic information to be an enabling technology in smallholder dairy economies by facilitating genetic evaluations with records collected from farms with herd sizes of four cows or less. The inclusion of smallholder dairy data in genetic evaluations could provide increases in local and national milk production, in regions such as East Africa, with downstream impacts upon wider societal, nutritional and economic outcomes.
- IdentificationRahelinirina, SoanandrasanaFirst molecular detection of pathogenic Leptospira in livestock from slaughterhouses in Madagascar
Soanandrasana Rahelinirina1, Mark Moseley2, Minoarisoa Rajerison1, Rakotoharinome Vincent Michel3, Sandra Telfer1,2
1Institut Pasteur de Madagascar, 2The University of Aberdeen, 3Direction des Services Vétérinaires Madagascar
Although leptospirosis has not been considered a significant health problem for humans or livestock in Madagascar, a recent serological study has shown evidence of exposure in humans and identified contact with cattle as a key risk factor. However, the real role of livestock such as cattle and pig in the epidemiology of human leptospirosis in Madagascar remains to be elucidated. The aims of this study were to determine the prevalence of Leptospira among livestock in Madagascar and characterize the pathogenic Leptospira species found. Kidney and urine samples from 105 cattle and 100 pigs were collected from four slaughterhouses in Madagascar in 2015. The samples were tested by a quantitative real-time PCR TaqMan assay targeting the 16sRNA gene specific to pathogenic Leptospira. Where possible, sequencing of 200-300bp of the lfb1 gene was used to identify infecting Leptospira species. Cattle had a significantly higher overall prevalence than pigs (19% vs 5%). Cattle had 13 infections detected in kidney samples and 11 in urine samples, with only 4 individuals testing positive for both sample types. Of the positive pigs, only one infection was detected in kidney compared to four infections detected in urine.
Sequencing identified L. borgpetersenii and L. kirschneri in cattle. No lfb1 sequences were obtained from positive pig samples. This is the first molecular evidence of leptospirosis in livestock in Madagascar. The high prevalence in cattle provides further evidence that they could be an important source of infection for humans and also suggest that leptospirosis may have significant impacts on animal health and productivity. Moreover, our results highlight the need to consider sampling methodology when comparing studies and planning surveillance. Our results reinforce the need to take a one health approach for zoonoses like leptospirosis.
- IdentificationSmith, Edward
Genomic Characterization of Zambian Indigenous Cattle Breeds
Edward Smith
Virginia Polytechnic Institute and State University, Animal and Poultry Sciences, Blacksburg, VA
Breed characterization is a primary step in designing appropriate management and conservation programs of livestock in developing countries. Since cattle represent a major food animal species in Zambia, its conservation is a major goal for both the government and non-governmental organizations. To support the conservation effort, the objective of this thesis research was to assess the phenotypic and molecular characteristics of indigenous Zambian cattle breeds including Angoni, Barotse, Tonga, and Baila based on body measurements and randomly amplified polymorphic DNA (RAPD) markers, respectively. A total of 100 animals, 25 from each of the four breeds associated with different tribes and region of Zambia, were used in the molecular analysis research. Additionally, 10 Holstein x Jersey crossbred animals were used as a reference and to test the extent of cross-breeding, if any, of the indigenous stock with exotic breeds. To further compare the Zambian indigenous breeds, morphometric measurements including body length, heart girth, and height at withers on 50 animals of each breed were measured. Blood was collected from animals at randomly selected farms and DNA isolated by standard protocols in Zambia. A total of 10 primers, of the 20 evaluated for informativeness, were used in the RAPD-PCR analyses. Differences among the four breeds for all the three morphometric measurements were significant with the Barotse significantly higher than the other three (P<0.05). The average number of bands per primer was 7.1 and the percentage of polymorphic bands per primer ranged from 40 to 71.4 with an average of 64.8%. Breed divergence was highest between the Tonga and the Barotse and lowest between the Tonga and Baila breeds. Both the morphometric measurements and RAPD-based distance estimates suggest that the Barotse may be different from the other indigenous breeds while the Tonga and Baila were more closely related. In addition, the genetic distance estimates imply that the Holstein x Jersey crosses are different from the four Zambian indigenous cattle breeds evaluated. This thesis research provides, for the first time, the basic genetic information necessary for conservation of Zambian cattle breeds and the use of these populations for effective crossbreeding. The data suggest that though there is isolated by geographic distance and cultural differences among the tribes, two of the breeds are significantly related.
- IdentificationTshabalala, ElizabethGenetic diversity of pharmacogenes in a Bantu-speaking cohort and evaluation of variants associated with tenofovir-induced nephrotoxicity
E. Sibongile Tshabalala1, Ananyo Choudhury2, Natasha Beeton-Kempen1, Faheem Seedat3 and Ebrahim Variava3, Neil Martinson4, Michèle Ramsay2, 5 and Dalu Mancama1
1CSIR, Biosciences Unit, South Africa: 2Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, South Africa; 3Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 4Perinatal HIV Research Unit, Baragwanath Hospital and Faculty of Health Sciences, University of the Witwatersrand, South Africa; 5Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, South Africa
Recent South African studies report an increase in hospital admissions due to adverse drug reactions (ADRs), including to tenofovir disoproxil fumarate (TDF). Growing evidence suggests a genetic contribution to TDF-related ADRs. Given the high genetic diversity observed in African populations, the aim of this study was to elucidate the pharmacological implications of such diversity by identifying and characterizing known and novel pharmacogenetic variants and evaluating their possible association with TDF-induced nephrotoxicity. Using targeted next generation sequencing to screen 40 Bantu-speaking individuals for variants in 65 genes, 1687 variants were identified; including 129 novel and 22 potential loss-of-function variants. Based on allele frequency (MAF>0.1) and prior association with ADRs, nine SNPs within five genes were prioritised for a genetic association study for TDF-induced nephrotoxicity (clinically manifesting as acute kidney injury (AKI)). A total of 137 HIV positive patients on TDF treatment were subsequently genotyped using TaqMan® assays, 53 of whom presented with AKI. Association analysis was performed with alleles, genotypes and haplotypes using χ2 tests. The ABCC2 1249A allele and ABCC2 haplotypes AAC and AAT displayed associations with TDF-induced AKI (p≤0.05). The ABCC2 GTT haplotype (p=0.02) appeared to be protective against TDF-induced AKI. However, the associations were not significant following corrections for multiple testing. Further evaluation of these ABCC2 variants in larger cohorts is warranted to establish their role, if any, in TDF-induced AKI.
- IdentificationWalusansa, AbdulNon-typhoidal Salmonella and Zoonotic E. coli as Potential Drivers of Antimicrobial Resistance in Pastoralist Communities in Kasese District, Uganda
Abdul Walusansa
School of Medicine, Islamic University in Uganda
August 2017
Introduction: Non-prescribed use of antimicrobials in Agriculture incurs a transfer risk of resistant pathogens to humans. The aim of this study was to determine the potential of non-typhoidal Salmonella spp and Zoonotic E. coli to serve as drivers of Antimicrobial resistance among animals and humans.
Methodology: A laboratory based cross-sectional study was done using archived Salmonella spp and E. coli isolates previously obtained from individuals among pastoralist communities of Kasese district, Uganda. Recovery of the isolates was done by conventional culture and Identification by biochemical methods, serotyping and PCR. Antimicrobial resistance profiling was done by using Kirby bauer disc diffusion method. Following this; the isolates were screened for resistance mechanisms including Extended Spectrum β-lactamase, Carbapenemase and AmpC production using disc diffusion based methods.
Results: The prevalence of Enterohemorrhagic E.coli (EHEC) and Non Typhoidal salmonella were 16% (28/180) and 50% (1/2) respectively. Of the EHEC, 94% (26/28) were of phylogroup B1, A (3%, 1/28) and B2 (3%, 1/28). The most prevalent virulence gene in the EHEC was Stx1 (100%, 28/28) followed by Stx2e (94%, 26/28), none was Stx2 positive. Highest resistance was seen to Cotrimoxazole (89%, 25/28), Tetracycline (71%,20/28), Ampicillin (65%,18/28) and Nitrofurantoin (28%,8/28), these are commonly used in the agricultural sector, whereas minimal resistance was observed to those commonly used in human medicine especially the β-lactams, β-lactam inhibitors and Carbapenems. 17%, (5/28) of the EHEC were ESBL positive, of these one (3%, 1/28) was a Carbapenemase producer. Though only one Non-typhoidal Salmonella isolate was found, it is worrying to note that it showed resistance to all the three antimicrobial agents (Nalidixic acid, Chloramphenicol and Ciprofloxacin) that are most recommended for treatment of Salmonellosis in this setting.
Conclusion: There is a high prevalence of highly pathogenic and resistant zoonotic E. coli and low prevalence of Non typhoidal salmonella among humans in pastoralist communities in Uganda. We suspect that these pathogens, along with their AMR genes, were acquired from animals because the zoonotic E. coli (EHEC) largely contained the animal specific Vero toxin gene VT2e and majority belonged Pylo-group B1 which has been documented as the most common EHEC phylo-group inhabiting domestic animals. Therefore, it is highly likely that zoonotic bacteria are potential drivers of antimicrobial resistance to humans in these settings and we recommend that studies involving relatedness of drug resistant isolates from humans and animals should be conducted to ascertain the role of enterohemorrhagic E. coli in the zoonotic spread of antimicrobial resistance in pastoralist communities. We recommend that a one health approach should be used to establish drivers of MDR spread in pastoralist communities.
- IdentificationAkindele, AkeemAssociation of the Tumor Necrosis Factor α- 308G/A Polymorphism with Malaria and Hepatitis B Virus Infection among Nigerian Pregnant Women
Akeem Abiodun Akindele1, Ebunoluwa Adediran1, Olusola Ojurongbe1*
1Ladoke Akintola University of Technology, Ogbomoso, Nigeria
Background: Malaria and Hepatitis B Virus (HBV) could be detrimental to pregnant women and their fetus. Tumor necrosis factor (TNF-α) is believed to be a critical factor in susceptibility and progression of infectious diseases. This study investigated the contribution of TNF-308G/A genetic polymorphism to Malaria and HBV infections in pregnant women.
Methods: A total of 225 Nigerian pregnant women were enrolled into the study after obtaining a signed informed consent. Malaria was diagnosed by microscopic examination of Giemsa stained blood smears, while HBV was diagnosed by using HBV serological markers test kit. ARMS-PCR was used for TNF-α genotyping.
Results: Out of the 225 pregnant women screened, 57(25.3%) and 44(20%) were positive for P. falciparum parasitaemia and HBsAg respectively. The prevalence of P. falciparum parasitaemia and HBsAg co-infection was 11(4.5%). The frequency of TNF-α 308 GG genotype (54.40%) was higher compared to GA (38.60%) and AA (7.02%) in the study population. No significant difference was observed when the genotype GG of healthy control was compared with Malaria, HBV and Malaria-HBV co-infection. None of the other two genotypes (GA and AA) showed any significant difference between cases and healthy control. Both G and A alleles did not show any significant difference between cases and healthy control.
Conclusion: High prevalence of malaria and HBV among pregnant women was observed in the study area. Genotypes and alleles of TNF-α 308 G/A do not play significant role in malaria and HBV infections among the study population.
Keywords: Tumor necrosis factor, Malaria, Hepatitis B Virus, pregnant women
- IdentificationAladejana, OluwatoyinOccurrence and Multiple-Antibiotics Resistance Profile of Enterobacteriaceae Isolated from Bats Faecal Samples in Osun State, Nigeria
Aladejana Oluwatoyin Modupe1*, Oluduro Antonia Olufunke2, Famurewa Oladiran1, Thonda Oluwakemi Abike1, Olawoye Abimbola Abosede1.
1 Department of Biological Sciences, Microbiology Unit, Kings University, Odeomu, Osun State Nigeria; 2Department of Microbiology, Faculty of Science, Obafemi Awolowo University, Ile-ife, Osun State, Nigeria
*Corresponding Author
Members of Enterobacteriaceae are important human pathogens and increasing number of antibiotic-resistant strains among the members are detected worldwide. Bats are one of the most widely distributed mammals in the world, they are known as either reservoirs or carriers of several zoonosis. A total of 48 faecal samples were collected with 142 isolates recovered from Obafemi Awolowo University Ile Ife, 23 faecal samples were collected with 84 isolates recovered from Nigeria machine Tools, Osogbo and 30 faecal samples were collected with 111 isolates recovered from Oba's Palace Area, Ilesa, all in Osun State South West Nigeria. Of the 41 different genera detected, 13 were common to the three study locations. Their resistance to fifteen different antibiotics revealed that antibiotic resistance patterns of the Gram-negative bacteria recovered from the different locations correlated well. In all, the susceptibility and resistance patterns of the bacterial isolates varied and 35.9% of the multiple antibiotic-resistant isolates tested for were Extended Spectrum β - Lactamase (ESBL) producers. The level of multiple antibiotic resistance and ESBL producers among isolates in the study areas is of great public health concern considering the health implications.
- IdentificationAlimohamed, MohamedRoutine use of targeted NGS panel in a Dutch cardiomyopathy cohort
Mohamed Z. Alimohamed, Lennart F. Johansson, Ludolf G. Boven, Krista van Dijk, Paul van der Zwaag, Richard J. Sinke, Rolf H. Sijmons, Birgit Sikkema-Raddatz, Jan D H Jongbloed
Departments of Genetics, University Medical Center Groningen, Groningen, The Netherlands
Background:
Next generation sequencing is increasingly used for clinical evaluation of patients with cardiomyopathies because it allows for simultaneous evaluation of multiple genes known to be associated with the disease. However, the diagnostic yield is variable in routine clinical practice. Furthermore, analysis of copy number variations is still not routinely performed.
Objectives:
(1) To determine the diagnostic yield of our custom targeted NGS gene panel used in routine clinical diagnostics in a Dutch cohort of over 2000 cardiomyopathy patients. (2) Examine the impact on the yield of analyzing this cohort for single or multiple exon duplications and deletions.
Methods:
Up to 61 genes known to be implicated in cardiomyopathies were selected for enrichment and analysis on DNA isolated from peripheral blood from patients as a routine procedure. Patients directed for genetic testing to our clinical genetics laboratory having a referral diagnosis for various types of cardiomyopathies were included in this study [N=2002]. A written informed consent was obtained for all patients referred to our clinical genetics laboratory. Classification of variants was based on guidelines for variant interpretation recommended by the American College of Medical Genetics and Genomics. Diagnostic yield was calculated using cases where a likely pathogenic or pathogenic variant was detected. Putative exonic deletions/duplications were analyzed using CoNVaDING and XHMM tools using settings previously described.
Results and Conclusion:
An overall diagnostic yield of 23% was achieved. CNVs were detected in 16 patients. Variants of unknown clinical significance were identified in 39% patients. These results illustrate the need to further reassess disease variant classification.
Key words:
Cardiomyopathy, NGS-panel, Diagnostic-yield - IdentificationAnumudu, ChiakaImproving schistosomiasis control using genomics and proteomics tools
Chiaka Anumudu1, Olugbenga Onile2, Adewale Adebayo1,3, Henrietta Awobode4, Raphael Isokpehi5
1Cellular Parasitology Programme, Department of Zoology, University of Ibadan, Ibadan Nigeria; 2Elizade University, Ilara Mokin, Ondo State Nigeria; 3King's College London UK; 4Parasitology Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria; 5College of Engineering and Sciences, Bethune Cookman University, Daytona Beach, Florida, USA
Validated diagnostic markers are key to the early detection and treatment of cancer. Indeed, if these biomarkers can be readily extracted and detected in bodily fluids, a simple, diagnostic test can be developed that would be of extreme value to patients especially in rural and resource-poor settings.
For urinary schistosomiasis, we are looking for such a marker, which can be used for the detection of Schistosoma associated bladder damage and schistosomiasis, in a low-tech-test. We have used proteomics and microbiome methods to search for such markers in our previous works, and identified a large number of targets. Using a cross sectional study design, we collected 371 blood and urine samples from adults resident in Eggua. The urine was screened by centrifugation for eggs of the parasite Schistosoma haematobium and later 49 samples by proteomics methods for molecules that could be uniquely indicative of schistosomiasis and bladder damage. Participants were also tested by ultrasound for bladder pathologies. Microbiome analysis was performed on 70 blood and urine samples using NGS and bioinformatics pipeline. A total of 1306 proteins, and 9701 unique peptides were observed, and 54 human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies. Due to the interesting biomarkers identified from these proteomic and microbiome studies, we are currently engaged in a research collaboration to repeat the studies and validate the results with a larger sample. Further work may be of interest in to make a comparative analysis of the usefulness of each of the 54 identified biomarkers for the diagnosis of schistosomiasis.
- IdentificationChibnik, Lori
Neuropsychiatric genetics in Africa: Building the research and the researchers together
Lori B. Chibnik1,2, Dickens Akena3, Lukoye Atwoli4, Symon M. Kariuki5,6, Charles R.J.C Newton5,6, Kristianna Post1,2, Dan J. Stein7, Anne Stevenson1,2, Rocky E. Stroud1,2, Solomon Teferra8, Zukiswa Zingela9, Bizu Gelaye1,2, Karestan C. Koenen1,2
1Harvard T.H. Chan School of Public Health, Boston, USA
2Broad Institute of MIT and Harvard, Cambridge, USA
3Makerere University, Kampala, Uganda
4 Moi University, Eldoret, Kenya
5KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
6University of Oxford, Oxford, UK
7University of Cape Town, Cape Town, South Africa
8Addis Ababa University, Addis Ababa, Ethiopia
9Walter Sisulu University, Mthatha, South Africa
Both global mental health and neuropsychiatric genetics have made enormous strides in the past decade. However, these two fields have grown on parallel tracks, with little to no interaction. While recent advances in psychiatric genetics have identified over 100 genetic loci associated with schizophrenia that are now being used to inform translational research, large-scale genetic studies have primarily used only genomes with European ancestry. If this pattern continues, advances in genetics will be limited with the ensuing risk that therapeutic innovations leave out large segments of the global population. Researchers have launched a new initiative with the objective of improving the existing science and addressing issues of equity by growing research capacity through mentoring and training young scientists. This new program, the Neuropsychiatric Genetics of African Populations, includes a study on psychosis (NeuroGAP-Psychosis) which began collection in 2018 and aims to collect DNA and phenotypic data from more than 17,000 cases (schizophrenia and bipolar disorder) and 17,000 controls from four countries in Africa: Ethiopia, Kenya, South Africa, and Uganda, combined with a capacity building program, the Global Initiative for Neuropsychiatric Education in Research (GINGER).
Through a two-year Fellowship program GINGER combines in-person research workshops, virtual classroom activities and a series of courses run in collaboration with partner institutions in Africa. By combining research with training and mentoring we hope to ensure that the next generation is adequately prepared to take an active role in NeuroGAP-Psychosis, carry the research forward and be future leaders in the field of global neuropsychiatric genetics.
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