Male monogamous prairie voles vary in the way they use space, with some males intruding extensively on the territories of others, while others do not. We hypothesize that individual differences in the way males set up their territories is due to individual differences in their cognition and neural peptide receptor expression. Indeed, our lab has identified individual differences in vasopressin receptor expression in the retrosplenial cortex that are associated with differences in space use in the wild; this brain variation is predicted in part by sequence variants in the avpr1a gene. To test this hypothesis we first tested different behavioral paradigms that could be used to assess social cognition in the monogamous prairie vole. We tested the voles in a test of scent mark memory. We tried to establish conditioned place preference for male urine or postpartum estrus urine. Lastly, we developed a novel Barnes maze paradigm for looking at vi socio-spatial memory associated with escape. Male voles improved their performance in the Barnes maze over the course of 4 days, but did not respond to the overmark task or the conditioned place preference test. Next we used the Barnes maze to assess whether males of HI and LO RSC-V1aR genotypes perform differently in the task. Males of different genotypes did not perform differently in the Barnes maze. We also looked at V1aR expression levels in the brains of the animals that were tested in the Barnes maze. V1aR expression in the RSC did not correlate to Barnes maze performance. In addition to genetic influences, RSC-V1aR is known to be affected by neonatal exposure to oxytocin antagonist. Here we show preliminary results indicating that the RSC V1aR expression is reduced in LO animals, but not in HI animals. In addition, V1aR expression the anterior medial BNST was affected by neonatal exposure to OTA. The posterior lateral and ventral BNST, medial and lateral DT, and LS were not affected by neonatal exposure to OTA. / text

No description available.

Although many genetic factors have been successfully identified for human diseases in genome-wide association studies (GWAS), genes discovered to date only account for a small proportion of overall genetic contributions to many complex traits. Association studies have difficulty in detecting the remaining true genetic variants that are either common variants with weak allelic effects, or rare variants that have strong allelic effects but are weakly associated at the population level. In this work we applied a goodness-of-fit test for detecting sets of common and rare variants associated with quantitative or binary traits by using whole genome sequencing (WGS) data. This test has been proved optimal for detecting weak and sparse signals in the literature, which fits the requirements for targeting the genetic components of missing heritability. Furthermore, this p-value-combining method allows one to incorporate different data and/or research results for meta-analysis. The method was used to simultaneously analyse the WGS and GWAS data of Genetic Analysis Workshop (GAW) 18 for detecting true genetic variants. The results show that goodness-of-fit test is comparable or better than the influential sequence kernel association test in many cases.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the field of Paediatrics. Johannesburg, 2015 / The introduction of combined antiretroviral treatment (cART) reduced HIV related mortality more than 70% and the rate of new infection in children continue to decrease considerably. However this benefit is threatened by the emergence of drug resistant strains of HIV. Studies exploring the patterns of drug resistance in the paediatric population are crucial for policy makers and for individual patients’ management. In sub-Saharan Africa where HIV-1 subtype C is more prevalent, there is a limited number of paediatric studies exploring the drug resistance patterns. To get more insight on this problem, we explored the drug resistance mutations (DRMs) patterns in a paediatric population attending a referral public paediatric HIV clinic. Methodology The study was a cross-sectional retrospective descriptive study. Convenience sampling method was used and all paediatric patients (0-14 years) who underwent genotypic HIV drug resistance testing at Empilweni Clinic between January 1st, 2004 and February 28th, 2012 were included. Demographic and clinical data were collected from the clinical electronic database and DRM frequencies related to treatment exposure were presented. Results During our study period, 63 patient samples were sent for HIV genotyping drug resistance testing. Eleven samples did not meet the inclusion criteria. Among the 52 patient samples retained, 44 patients (84.6%) had a successful HIV amplification and all were infected with HIV-1 subtype C. Ninety one percent (n=40) of the patients had at least one DRM isolated but in only 78% (n=34) did these mutations translate into genotypic drug resistance to at least one antiretroviral drug (ARV) used in South Africa. Nucleotide reverse transcriptase inhibitors (NRTI) mutations were the most commonly identified with M184V being the most prevalent (64.4%; n=29). This was associated with thymidine analogue mutations (TAMs) in 36.3% of the patients (n=16). TAMs were identified in 25% (n=11) of the patients. K65R and Q151M were rarely identified in our cohort. V106M and K103N were the most common non-nucleotide reverse transcriptase inhibitors (NNRTI) mutations and were both identified in 21.9% (n=7) of the patients exposed to NNRTI-based regimen. V82A was the most commonly identified protease gene (PR) mutation in 29.3% (n=12) of the cases. Forty eight percent of the patients (n=21) had a dual class resistance and 11.4% (n=5) had resistance to ARVs from all the three classes. Over a quarter (27.2%, n=12) of the patients in our cohort were still sensitive to all ARVs used in South Africa. The development of drug resistance was not associated with any clinical characteristic in our cohort. Conclusion The drug resistance mutations identified in paediatric patients failing cART show a complex pattern with some failing patients still sensitive to all ARVs while others harbour complex resistance mutations. Therefore, regular counselling to optimize adherence and regular viral load monitoring for early detection of failure may be important tools for continued cART success. Given the complexity of the DRMs patterns in paediatric patients, the HIV drug resistance test is warranted to guide the choice of appropriate cART regimens.

Single nucleotide polymorphisms (SNPs) in various taste receptor genes have previously been linked to outcomes such as differences in taste thresholds, food liking, and body mass index, but no studies of this sort have examined sour taste. This study genotyped 501 young adults for PKD2L1 rs603424 and administered a Food Frequency Questionnaire and Tanita body composition testing to look for associations between the noted SNP, dietary intake, and body composition. Intake of citrus fruit, vitamin C, caffeine, and alcohol were significantly associated with genotype in two-way ANOVA analyses looking at the effect of genotype and race or sex on dietary intake. Regarding body composition, genotype was significantly associated with BMI, but not body fat percentage or fat free mass. These findings suggest that rs603424 may influence intake of certain sour and bitter dietary components; however, further research will be needed to confirm these findings.

No description available.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand , in fulfillment of the requirements for the degree of Master of Science in Medicine, 2013 / Sequence analysis from HIV-1 (human immunodeficiency virus type 1) subtype B and more recently subtype C infected patients has revealed that mutations in the HIV-1 protease region that confer drug resistance to boosted protease inhibitor (PIs) are rarely detected at the time of virological failure. Mutations in the HIV-1 subtype B gag-pol cleavage sites are thought to be compensatory mutations which arise as a result of PI use. This study investigated the presence of compensatory mutations in the HIV-1 subtype C gag-pol cleavage sites and matched pol genotypes from South African patients failing a boosted PI-based regimen, as compared to antiretroviral drug naïve patients. A new amplification protocol encompassing the near full-length gag, PR and partial RT was established and used to sequence the HIV-1 gag-pol cleavage sites from 23 proviral DNA samples (p24 antigen cultured peripheral blood mononuclear cells; PBMCs), and 51 patient samples (23 antiretroviral drug-naïve, 26 failing second-line lopinavir/ritonavir containing regimens), all attending the Charlotte Maxeke Johannesburg Hospital. Nucleotide sequences were aligned and codon positions S373Q, A431V, I437T/V, L449P or P453L associated with known gag-pol cleavage site mutations were analysed and compared. The pol genotypes were established using an in house assay. Antiretroviral drug resistant primary virus isolates were grown from samples from patients enrolled on the CIPRA-SA study, and propagated in coculture with PHA-activated, IL-2 stimulated PBMCs. HIV-1 gag-pol cleavage sites and pol genotypes for all primary virus isolates were established as described above. Fifty one of 74 patient samples, used to establish the in-house gag-pol cleavage site assay, were successfully amplified and sequenced. Detailed analysis of the five known gag-pol cleavage sites revealed that 5 patient samples (4 PI-exposed, 1 unknown regimen) encoded for the previously described mutations that impact on gag-pol cleavage in the absence of any major PR mutations. A further five samples from patients on the failing PI-based regimen had major PR mutations. No known mutations in the gag-pol region were identified in patients failing a first line regimen. The pol mutations described in this study were similar to the findings reported for treatment failures in South African HIV-1 subtype C infected patients. Primary virus was grown from only 25 of the 91 PBMC CIPRA samples. None of the 25 CIPRA-SA primary virus isolates had gag-pol cleavage site mutations, and only 9 harboured known RT antiretroviral drug resistant mutations. Overall, the presence of HIV-1 gag-pol cleavage site mutations may account for virological treatment failure in 5 of the South African patient samples analysed. Although the gag-pol cleavage site mutations detected in the current study are only present in a small proportion of treatment-experienced South African patients, this may increase due to more patients accessing second line PI-containing regimens. Thus, future genotyping work incorporating the analysis of the gag-pol cleavage sites in addition to the PR and RT regions is warranted. The antiretroviral drug resistant primary viruses obtained provide valuable reagents for future phenotyping studies.

The region of eastern and southern Africa is very diverse in environments and agronomic practices. The region has one of the highest per capita consumption of maize (Zea mays. L), which is predominantly produced by smallholder farmers. Some important constraints facing these farmers include drought and low fertility. For decades, the International Center for Wheat and Maize Improvement (CIMMYT) has been involved in developing maize genotypes that have high grain yields and are tolerant to drought, low fertility and other important constraints. This germplasm is developed for wide adaptation. However, the development of superior germplasm is significantly affected by interaction between genotypes and the environment (i.e., genotype by environment interaction, GEI). To estimate and understand GEI maize genotypes are evaluated in a range of environments representing as much variability of the target growing areas as possible. Because of dwindling resources needed to conduct testing in the region, it may not be possible to test in all potential target areas. Therefore, a careful process of site selection for testing is essential to improve efficiencies in cultivar testing and deployment. The objective of this research was to characterize the maize testing locations of the eastern and southern Africa region. Historical data from CIMMYT Regional Trials from 1999 to 2003 was used to characterize the environments and estimate genetic parameters. Environmnent and GEI showed consistently high contributions to the total variation observed among genotypes for grain yield. Environment contributed over 60% and sometimes up to 85% of total variation observed. Sequential retrospective pattern analysis (Seqret) was conducted on the adjusted standardized grain yield. A total of 7 groups of environments were identified. Repeatabilites, a measure of the proportion of phenotypic variation that is due to genetic differences, was reduced under stress conditions. The relationship among traits showed that anthesis-silking interval (ASI) is an important selective trait, which can improve selection efficiency for grain yield under stress conditions. Stability analysis provided an opportunity to observe the response and adaptation of genotypes to a wide range of environments. Variety ZM621 was a stable and high yielding genotype.

Thesis (M.S.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains ix, 106 p. : ill. (some col.), map (part col.). Includes abstract. Includes bibliographical references.