BackgroundLocalising regulatory variants that control gene expression is a challenge for genome research. Several studies have recently identified non-coding polymorphisms associated with inter-individual differences in gene expression. These approaches rely on the identification of signals of association against a background of variation due to other genetic and environmental factors. A complementary approach is to use an Allele-Specific Expression (ASE) assay, which is more robust to the effects of environmental variation and trans-acting genetic factors.Methodology/Principal FindingsHere we apply an ASE method which utilises heterozygosity within an individual to compare expression of the two alleles of a gene in a single cell. We used individuals from three HapMap population groups and analysed the allelic expression of genes with cis-regulatory regions previously identified using total gene expression studies. We were able to replicate the results in five of the six genes tested, and refined the cis- associated regions to a small number of variants. We also showed that by using multi-populations it is possible to refine the associated cis-effect DNA regions.Conclusions/SignificanceWe discuss the efficacy and drawbacks of both total gene expression and ASE approaches in the discovery of cis-acting variants. We show that the ASE approach has significant advantages as it is a cleaner representation of cis-acting effects. We also discuss the implication of using different populations to map cis-acting regions and the importance of finding regulatory variants which contribute to human phenotypic variation.

Animals are commonly used for scientific purposes in Africa and the Middle East. However, this field is often inadequately regulated, with many countries lacking national legislation, policies, or guidelines for the care and use of animals used for research, testing, or education. This results in an essentially uncontrolled system where scientific quality and animal wellbeing cannot robustly be guaranteed, which may hinder acceptance (i.e., publication) of results by the scientific community and limit public confidence. Though accepted international guidelines and best practice recommendations exist that could be adopted or adapted to meet local needs, the responsible conduct of research and animal welfare may not be prioritized in regions that are affected by instability, poverty, disease, or malnutrition. Some notable exceptions do, however, exist in individual countries or institutions where ethical review processes, oversight of animal health and welfare, the competence of personnel, and other scientific standards are appropriately regulated and implemented. These countries and institutions represent nodes of expertise that could act as platforms of support for surrounding regions in terms of the provision of education, training, and sharing of experience and resources. To make such regional capacity-strengthening efforts sustainable will require regional cooperation, the establishment of regional networks, harmonization of policies, pooled resources, and long-term investment in education, training, and infrastructure. An overarching system is needed to oversee the efficient promotion of scientific and ethical standards and the dissemination of information on laboratory animal science in Africa and the Middle East, while each country should remain able to maintain a system of oversight that reflects its own cultures, traditions, religions, laws, and regulations. This article provides an overview of the governance of the care and use of animals for scientific purposes in different regions of Africa and the Middle East as a foundation for coordinated future advancement.

An overview of the successes and current challenges in implementing and raising awareness of the Three Rs in South Africa