A diverse array of genetic factors contribute to the pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number variation have also been identified; and an effect of ethnicity on susceptibility has been described.http://dx.doi.org/10.1186/1750-1172-8-2IS

Characterization of bacterium types isolated from commercial laying hen farms in Ogun State Nigeria

This study investigated the distribution of bacterium categories isolated from poultry feces and litters on commercial laying hen farms in Remo and Egba local government areas, Ogun State, Nigeria. In total 29 species of lactose and non-lactose fermenters were recovered. Bacteria isolated from feces included Aeromonas hydrophila (27.5%), Providencia stuartii (15.5%), Actinobacillus sp. (9.1%), Burkholderia cepacia (7.7%), Serratia marcescens (4.9%), Citrobacter diversus (4.9%), Klebsiella oxytoca (4.2%), and Enterobacter gergoviae (4.2%). Others were Escherichia coli (2.1%), Plesiomonas shigelloides (2.1%), Vibrio alginolyticus (2.1%), Morganella morganii (2.1%), Pantoea agglomerans (1.4%), Vibrio mimicus (1.4%), Pseudomonas aeruginosa (1.4%), Burkholderia pseudomallei (1.4%), Salmonella arizonae (0.7%), Klebsiella pneumonia (0.7%), Acinetobacter iwoffii (0.7%), Vibrio vulnificus (0.7%), Shewanella putrefaciens (0.7%), Proteus mirabilis (0.7%) and Proteus vulgaris (0.7%). There was 66.7% similarity between the bacterium profile of litters and that of feces; some additional strains were identified in the litters. No variation (p = 0.64) was observed in the number of isolated bacterium types from feces and litter samples. However, the number of bacterium types isolated from fecal samples differed (p = 0.002) between the two studied areas. Results suggest that there is a potential risk of wide-range bacterial transmission within poultry populations, and to humans in close contact with them

Hydrochemical Investigation of Saline Water Intrusion into Aquifers in Part of Eastern Dahomey Basin, Southwestern Nigeria

This study is a major attempt at delineating presence and lateral extent of saline water intrusions into aquifers at the easternmost part of Dahomey basin which falls essentially in the sedimentary terrain of Ondo State of Nigeria. 61 water samples were collected from hand dug wells, shallow boreholes, and ponds across the study area and analyzed for relevant parameters such as pH, conductivity, total hardness, calcium hardness, magnesium hardness, total dissolved solids, alkalinity and concentrations of the following anions and cations; chloride, calcium, Sulphate, bicarbonate, magnesium and sodium. Equivalent salinity was calculated from the water sample analysis results. The hydrochemical analysis results reveals possible saline water intrusion in the coastal area, especially the southeastern part and Agbabu in the north central part of the study area as evident from high concentration values of chloride (372 - 1500 mg/l), alkalinity (105 - 330 mg/l), equivalent salinity (135 - 2808 mg/l), total dissolved solid (181 - 1005 mg/l), high pH values (4.4 - 8.6 pH) and conductivity values (541 - 1500 µs/cm). Keywords: Saline water intrusion, saline-freshwater boundary, hydrochemical and equivalent salinity.

Hydrochemical Investigation of Saline Water Intrusion into Aquifers in Part of Eastern Dahomey Basin, Southwestern Nigeria

This study is a major attempt at delineating presence and lateral extent of saline water intrusions into aquifers at the easternmost part of Dahomey basin which falls essentially in the sedimentary terrain of Ondo State of Nigeria. 61 water samples were collected from hand dug wells, shallow boreholes, and ponds across the study area and analyzed for relevant parameters such as pH, conductivity, total hardness, calcium hardness, magnesium hardness, total dissolved solids, alkalinity and concentrations of the following anions and cations; chloride, calcium, Sulphate, bicarbonate, magnesium and sodium. Equivalent salinity was calculated from the water sample analysis results. The hydrochemical analysis results reveals possible saline water intrusion in the coastal area, especially the southeastern part and Agbabu in the north central part of the study area as evident from high concentration values of chloride (372 - 1500 mg/l), alkalinity (105 - 330 mg/l), equivalent salinity (135 - 2808 mg/l), total dissolved solid (181 - 1005 mg/l), high pH values (4.4 - 8.6 pH) and conductivity values (541 - 1500 µs/cm). Keywords: Saline water intrusion, saline-freshwater boundary, hydrochemical and equivalent salinity.

Tailoring consent to context: designing an appropriate consent process for a biomedical study in a low income setting

Background Currently there is increasing recognition of the need for research in developing countries where disease burden is high. Understanding the role of local factors is important for undertaking ethical research in developing countries. We explored factors relating to information and communication during the process of informed consent, and the approach that should be followed for gaining consent. The study was conducted prior to a family-based genetic study among people with podoconiosis (non-filarial elephantiasis) in southern Ethiopia. Methodology/Principal Findings We adapted a method of rapid assessment validated in The Gambia. The methodology was entirely qualitative, involving focus-group discussions and in-depth interviews. Discussions were conducted with podoconiosis patients and non-patients in the community, fieldworkers, researchers, staff of the local non-governmental organisation (NGO) working on prevention and treatment of podoconiosis, and community leaders. We found that the extent of use of everyday language, the degree to which expectations of potential participants were addressed, and the techniques of presentation of information had considerable impact on comprehension of information provided about research. Approaching podoconiosis patients via locally trusted individuals and preceding individual consent with community sensitization were considered the optimal means of communication. Prevailing poverty among podoconiosis patients, the absence of alternative treatment facilities, and participants' trust in the local NGO were identified as potential barriers for obtaining genuine informed consent. Conclusions Researchers should evaluate the effectiveness of consent processes in providing appropriate information in a comprehensible manner and in supporting voluntary decision-making on a study-by-study basis

Impact of social stigma on the process of obtaining informed consent for genetic research on podoconiosis: a qualitative study

Background The consent process for a genetic study is challenging when the research is conducted in a group stigmatized because of beliefs that the disease is familial. Podoconiosis, also known as 'mossy foot', is an example of such a disease. It is a condition resulting in swelling of the lower legs among people exposed to red clay soil. It is a very stigmatizing problem in endemic areas of Ethiopia because of the widely held opinion that the disease runs in families and is untreatable. The aim of this study was to explore the impact of social stigma on the process of obtaining consent for a study on the genetics of podoconiosis in Southern Ethiopia. Methods We adapted a rapid assessment tool validated in The Gambia. The methodology was qualitative involving focus-group discussions (n = 4) and in-depth interviews (n = 25) with community members, fieldworkers, researchers and staff of the Mossy Foot Treatment and Prevention Association (MFTPA) working on prevention and treatment of podoconiosis. Results We found that patients were afraid of participation in a genetic study for fear the study might aggravate stigmatization by publicizing the familial nature of the disease. The MFTPA was also concerned that discussion about the familial nature of podoconiosis would disappoint patients and would threaten the trust they have in the organization. In addition, participants of the rapid assessment stressed that the genetic study should be approved at family level before prospective participants are approached for consent. Based on this feedback, we developed and implemented a consent process involving community consensus and education of fieldworkers, community members and health workers. In addition, we utilized the experience and established trust of the MFTPA to diminish the perceived risk. Conclusion The study showed that the consent process developed based on issues highlighted in the rapid assessment facilitated recruitment of participants and increased their confidence that the genetic research would not fuel stigma. Therefore, investigators must seek to assess and address risks of research from prospective participants' perspectives. This involves understanding the issues in the society, the culture, community dialogues and developing a consent process that takes all these into consideration

Mapping of disease-associated variants in admixed populations

Recent developments in high-throughput genotyping and whole-genome sequencing will enhance the identification of disease loci in admixed populations. We discuss how a more refined estimation of ancestry benefits both admixture mapping and association mapping, making disease loci identification in admixed populations more powerful

Prediction of HLA class II alleles using SNPs in an African population

BACKGROUND: Despite the importance of the human leukocyte antigen (HLA) gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs). However, the utility of these methods in African populations has not been systematically evaluated. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1) alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit) resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia. CONCLUSIONS/SIGNIFICANCE: We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit) resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countrie

Genome scan linkage analysis comparing microsatellites and single-nucleotide polymorphisms markers for two measures of alcoholism in chromosomes 1, 4, and 7

BACKGROUND: We analyzed 143 pedigrees (364 nuclear families) in the Collaborative Study on the Genetics of Alcoholism (COGA) data provided to the participants in the Genetic Analysis Workshop 14 (GAW14) with the goal of comparing results obtained from genome linkage analysis using microsatellite and with results obtained using SNP markers for two measures of alcoholism (maximum number of drinks -MAXDRINK and an electrophysiological measure from EEG -TTTH1). First, we constructed haplotype blocks by using the entire set of single-nucleotide polymorphisms (SNP) in chromosomes 1, 4, and 7. These chromosomes have shown linkage signals for MAXDRINK or EEG-TTTH1 in previous reports. Second, we randomly selected one, two, three, four, and five SNPs from each block (referred to as Rep1 – Rep5, respectively) to conduct linkage analysis using variance component approach. Finally, results of all SNP analyses were compared with those obtained using microsatellite markers. RESULTS: The LOD scores obtained from SNPs were slightly higher but the curves were not radically different from those obtained from microsatellite analyses. The peaks of linkage regions from SNP sets were slightly shifted to the left when compared to those from microsatellite markers. The reduced sets of SNPs provide signals in the same linkage regions but with a smaller LOD score suggesting a significant impact of the decrease in information content on linkage results. The widths of 1 LOD support interval of linkage regions from SNP sets were smaller when compared to those of microsatellite markers. However, two linkage regions obtained from the microsatellite linkage analysis on chromosome 7 for LOG of TTTH1 were not detected in the SNP based analyses. CONCLUSION: The linkage results from SNPs showed narrower linkage regions and slightly higher LOD scores when compared to those of microsatellite markers. The different builds of the genetic maps used in microsatellite and SNPs markers or/and errors in genotyping may account for the microsatellite linkage signals on chromosome 7 that were not identified using SNPs. Also, unresolved map issues between SNPs and microsatellite markers may be partly responsible for the shifted linkage peaks when comparing the two types of markers