The unstable (CTG)$\sb{\rm n}$ trinucleotide repeat associated with myotonic dystrophy: What it does and where it came from

Myotonic dystrophy (DM), an autosomal dominant disorder mapping to human chromosome 19q13.3, is the most common neuromuscular disease in human adults.^ Following the identification of the mutation underlying the DM phenotype, an unstable (CTG)$\sb{n}$ trinucleotide repeat in the 3$\prime$ untranslated region (UTR) of a gene encoding a ser/thr protein kinase named DM protein kinase (DMPK), the study was targeted at two questions: (1) the identification of the disease-causing mechanism(s) of the unstable repeat, and at a more basic level, (2) the identification of the origin and the mechanism(s) involved in repeat instability. The first goal was to identify the pathophysiological mechanisms of the (CTG)$\sb{n}$ repeat.^ The normal repeat is transcribed but not translated; therefore, initial studies centered on the effect on RNA transcript levels. The vast majority of DM affecteds are heterozygous for the mutant expansion, so that the normal allele interferes with the analysis of the mutant allele. A quantitative allele-specific RT-PCR procedure was developed and applied to a spectrum of patient tissue samples and cell lines. Equal levels of unprocessed pre-mRNA were determined for the wild type (+) and disease (DM) alleles in skeletal muscle and cell lines of heterozygous DM patients, indicating that any nucleosome binding has no effect at the level of transcriptional initiation and transcription of the mutant DMPK locus. In contrast, processed mRNA levels from the DM allele were reduced relative to the + allele as the size of the expansion increased. The unstable repeat, therefore, impairs post-transcriptional processing of DM allele transcripts. This phenomenon has profound effects on overall DMPK locus steady-state transcript levels in cells missing a wild type allele and does not appear to be mediated by imprinting, decreased mRNA stability, generation of aberrant splice forms, or absence of polyadenylation of the mutant allele.^ In Caucasian DM subjects, the unstable repeat is in complete linkage disequlibrium with a single haplotype composed of nine alleles within and flanking DMPK over a physical distance of 30 kb. A detailed haplotype analysis of the DM region was conducted on a Nigerian (Yoruba) DM family, the only indigenous sub-Saharan DM case reported to date. Each affected member of this family had an expanded (CTG)$\sb{n}$ repeat in one of their DMPK alleles. However, unlike all other DM populations studied thus far, disassociation of the (CTG)$\sb{n}$ repeat expansion from other alleles of the putative predisposing haplotype was found. Thus, the expanded (CTG)$\sb{n}$ repeat in this family was the result of an independent mutational event. Consequently, the origin of DM is unlikely the result of a single mutational event, and the hypothesis that a single ancestral haplotype predisposes to repeat expansion is not compelling. (Abstract shortened by UMI.) ^

Primary health care management in Nigeria

This research sets out to assess if the PHC system in rural Nigeria is effective by testing the research hypothesis: `PHC can be effective if and only if the Health Care Delivery System matches the attitudes and expectations of the Community'. The field surveys to accomplish this task were carried out in IBO, YORUBA, and HAUSA rural communities. A variety of techniques have been used as Research Methodology and these include questionnaires, interviews and personal observations of events in the rural community. This thesis embraces three main parts. Part I traces the socio-cultural aspects of PHC in rural Nigeria, describes PHC management activities in Nigeria and the practical problems inherent in the system. Part II describes various theoretical and practical research techniques used for the study and concentrates on the field work programme, data analysis and the research hypothesis-testing. Part III focusses on general strategies to improve PHC system in Nigeria to make it more effective. The research contributions to knowledge and the summary of main conclusions of the study are highlighted in this part also. Based on testing and exploring the research hypothesis as stated above, some conclusions have been arrived at, which suggested that PHC in rural Nigeria is ineffective as revealed in people's low opinions of the system and dissatisfaction with PHC services. Many people had expressed the view that they could not obtain health care services in time, at a cost they could afford and in a manner acceptable to them. Following the conclusions, some alternative ways to implement PHC programmes in rural Nigeria have been put forward to improve and make the Nigerian PHC system more effective.

The empire beats on: Oyo, Bata drums and hegemony in nineteenth-century Cuba

The Lukumí people of Cuba, currently known as Yoruba, are descendants of one of the mightiest West African kingdoms, the Oyo, Empire. The Oyo-Yoruba were important cultural contributors to certain areas of the New World such as Cuba, Brazil, Trinidad, and to some degree Haiti and the Lesser Antilles. Anthropologist William Bascom has said that “no African group has had greater influence on New World culture than the Yoruba.” ^ After the devastation of the empire around 1825, two new Oyos resuscitated. The first, New Oyo, was established about 80 miles south of the ancient site around 1830. The second Oyo was instituted on the other side of the Atlantic Ocean, in the city of Havana and its surrounding towns. Much of Oyo lie, as ancient Oyo is now called, was transported to the New World, reformed and adapted according to its new surroundings, and, it preserved its reign over its “subjects” through the retention and dissemination of its cultural and religious practices. ^ Using an interdisciplinary approach, this investigation will argue that of all the African groups brought to Cuba, the Oyo-Yoruba were the most influential in shaping Afro-Cuban culture since their introduction in the nineteenth century. The existence of batá drums in Cuba and the cultural components of this musical genre will serve as one of many examples to illustrate the vitality of Oyo cultural hegemony over Afro-Cubans. It is arguable that these drums and the culture that surrounded them were very important instruments used by the Oyo to counter the acculturation of many Africans in Cuba. Likewise, this culture became acculturative in itself by imposing its religious world views on non-Oyo ethnics and their descendants. Oral histories and narratives collected among Lukumí practitioners on the island and abroad have been invaluable archives to supplement and/or complement primary and secondary sources of information. ^

The Anagó Language of Cuba

This thesis investigates the socio-linguistic factors that led to the emergence of a new language in Cuba known as Anagó. This language emerged from contact between multiple dialects of the West African Yoruba language and Spanish. Language contact between the Yoruba language and Spanish took place in Cuba beginning in the nineteenth century after the introduction of large numbers of Yoruba speakers into Cuba during the trans-Atlantic slave trade. This thesis argues against the opinion that Anagó is simply a corrupted and imperfect form of Yoruba. Instead, it maintains that Anagó is a new language that emerged in Cuba and became a functional vehicle for the transmission of ideas and culture. Additionally, this study will present evidence that the Anagó speaking community was a constituent part of Cuban society since the nineteenth century, and is therefore an inextricable part of Cuban cultural patrimony. Twentieth century examples of Anagó language are examined as evidence of a vital Anagó speaking transnational community.