Contrasting exome constancy and regulatory region variation in the gene encoding CYP3A4: an examination of the extent and potential implications.

OBJECTIVE: CYP3A4 expression varies up to 100-fold among individuals, and, to date, genetic causes remain elusive. As a major drug-metabolizing enzyme, elucidation of such genetic causes would increase the potential for introducing personalized dose adjustment of therapies involving CYP3A4 drug substrates. The foetal CYP3A isoform, CYP3A7, is reported to be expressed in ∼10% of European adults and may thus contribute towards the metabolism of endogenous substances and CYP3A drug substrates. However, little is known about the distribution of the variant expressed in the adult. METHODS: We resequenced the exons, flanking introns, regulatory elements and 3'UTR of CYP3A4 in five Ethiopian populations and incorporated data from the 1000 Genomes Project. Using bioinformatic analysis, we assessed likely consequences of observed CYP3A4 genomic variation. We also conducted the first extensive geographic survey of alleles associated with adult expression of CYP3A7 - that is, CYP3A7*1B and CYP3A7*1C. RESULTS AND CONCLUSION: Ethiopia contained 60 CYP3A4 variants (26 novel) and more variants (>1%) than all non-African populations combined. No nonsynonymous mutation was found in the homozygous form or at more than 2.8% in any population. Seventy-nine per cent of haplotypes contained 3'UTR and/or regulatory region variation with striking pairwise population differentiation, highlighting the potential for interethnic variation in CYP3A4 expression. Conversely, coding region variation showed that significant interethnic variation is unlikely at the protein level. CYP3A7*1C was found at up to 17.5% in North African populations and in significant linkage disequilibrium with CYP3A5*3, indicating that adult expression of the foetal isoform is likely to be accompanied by reduced or null expression of CYP3A5

Review of \u3ci\u3e Native American Representations: First Encounters, Distorted Images, and Literary Appropriations\u3c/i\u3e Edited by Gretchen M. Bataille

The misrepresentation, commodification, and distortion of indigenous identities have existed from the moment of first contact between Native peoples and Europeans, Editor Gretchen Bataille observes in the introduction to Native American Representations. The problems are familiar to literary scholars: power relations produced by colonization determine who has the authority to represent Native peoples in the broader culture, and these representations in turn tend to reinforce European dominance and to obfuscate the violence, and even the fact, of colonization. The questions of how Native peoples have been represented throughout the centuries of colonialism, by whom, and for what purposes comprise the focus of this anthology. Most of its contributors analyze the problems raised by historical and contemporary representations in a series of essays that examine a range of interdisciplinary materials including postcolonial theory, WPA papers of the 1930s, popular films, and the production of collaborative personal narratives. Other contributors examine the ways in which Native thinkers and scholars engage and contest conventional representations, defining their societies and cultures on their own terms and providing critical perspectives on European colonization in such forms as fiction, oral histories, films, and traditional stories. The contributors are newer as well as established scholars in Native American studies, including Native writers Katherine Shanley and Louis Owens. Together, they aim both to provide critical perspectives on conventional representations and, in some cases, to offer challenging alternatives more consistent with the concerns of Native communities. The essays cover a wide range of subjects that focus for the most part on the twentieth century, and they include a number of topics that have already received scholarly attention as well as more original and innovative studies. Because one of the goals of Native American Representations is to examine critically who has the authority to represent Native peoples, a subject that has also been the focus of recent debates in the field, the collection would have been strengthened by more contributions by Native scholars and a greater emphasis on Native perspectives. In addition, the collection as a whole (with a couple of notable exceptions) is remarkably inattentive to images and voices of Native women, even though the silencing and marginalization of Native women is one consequence of the colonial processes that the volume seeks to criticize. Overall, however, Native American Representations provides a valuable addition to the growing body of scholarship in the field on the complicated relationships among race, colonialism, and representation