Bowen-Conradi syndrome is a lethal autosomal recessive disorder affecting Hutterite infants, characterized by severe growth and psychomotor retardation, and leading to death at an average age of thirteen months. Linkage analysis and sequencing identified an A>G mutation in EMG1 as the probable cause of the disease. This gene is implicated in ribosome biogenesis, and the mutation results in an unstable EMG1 protein. The reduction in available EMG1 causes a transient delay in processing of the ribosomal small subunit 18S rRNA, leading to cell cycle delay at G2/M and a subsequent reduction in cell proliferation rates in patient lymphoblasts. A mouse model of Bowen-Conradi syndrome also displayed severe developmental delay, with prominent effects in the cranial central nervous system. Embryos died prematurely during development, probably due to decreased proliferation rates accompanied by apoptosis. These results shed light on the etiology of Bowen-Conradi syndrome, and open the door for development of treatments.

Limb girdle muscular dystrophies (LGMDs) are a clinically and genetically heterogeneous group of myopathies characterized by weakness and wasting of the proximal musculature. There are currently seventeen loci associated with different LGMDs, seven with an autosomal dominant mode of inheritance (LGMD1A–1G) and 10 with an autosomal recessive mode of inheritance (LGMD2A– 2J). The cumulative worldwide prevalence of LGMD is thought to be ~1/15,000. In the Hutterite population of North America there is an over-representation of autosomal recessive LGMD with a prevalence estimated to be >1/400. The objective of this work was to delineate the genetic basis of LGMD in this large genetically isolated population. A genome-wide scan was performed on Hutterite LGMD patients and their families in order to locate the mutant gene. This allowed us to identify a novel locus at chromosome region 9q31-33 that was named LGMD2H. Extensive haplotyping and mutation screening led to the discovery of c.1459G>A in TRIM32 as the causative mutation of LGMD2H. We then found that this same mutation was the cause of another previously described myopathy in the Hutterites, sarcotubular myopathy (STM)[reference awaiting publishers decision]. Analysis of the TRIM32 gene product revealed that it is a potential E3-ubiquitin ligase, is expressed in many human tissues including muscle and brain, and has a punctate cytoplasmic distribution. During the analysis of the LGMD2H region, it became apparent that there were Hutterite LGMD patients not linked to the LGMD2H locus. In order to identify the causative gene(s) in the remaining families, we performed a genome-wide scan. A locus at chromosome 19q13 was found to correspond to disease inheritance, the site of a previously described LGMD locus, LGMD2I. No causative gene had yet been identified at this locus so haplotyping and mutation screening was performed. We were able to identify c.826C>A in FKRP as the causative mutation in our remaining cohort of LGMD patients. The same mutation has since been found in many other populations, and is apparently a relatively common cause of LGMD. We obtained DNA from 19 non-Hutterite LGMD2I patients of diverse origins with c.826C>A and determined that it is an old founder mutation. There is no further evidence of any other loci causing autosomal recessive myopathy in the Hutterites. With the identification of c.1459G>A in TRIM32 and c.826C>A in FKRP we appear to have delineated the genetic cause of all myopathies of increased prevalence in the Hutterite population. To date, we have been able to provide accurate, non-invasive, diagnosis to over 70 patients and have provided carrier testing to approximately 120 at-risk family members. This kind DNA-based approach is not feasible in the general population due the enormous amount of locus, allelic, and clinical heterogeneity among myopathy patients.

Limb girdle muscular dystrophies (LGMDs) are a clinically and genetically heterogeneous group of myopathies characterized by weakness and wasting of the proximal musculature. There are currently seventeen loci associated with different LGMDs, seven with an autosomal dominant mode of inheritance (LGMD1A–1G) and 10 with an autosomal recessive mode of inheritance (LGMD2A– 2J). The cumulative worldwide prevalence of LGMD is thought to be ~1/15,000. In the Hutterite population of North America there is an over-representation of autosomal recessive LGMD with a prevalence estimated to be >1/400. The objective of this work was to delineate the genetic basis of LGMD in this large genetically isolated population. A genome-wide scan was performed on Hutterite LGMD patients and their families in order to locate the mutant gene. This allowed us to identify a novel locus at chromosome region 9q31-33 that was named LGMD2H. Extensive haplotyping and mutation screening led to the discovery of c.1459G>A in TRIM32 as the causative mutation of LGMD2H. We then found that this same mutation was the cause of another previously described myopathy in the Hutterites, sarcotubular myopathy (STM)[reference awaiting publishers decision]. Analysis of the TRIM32 gene product revealed that it is a potential E3-ubiquitin ligase, is expressed in many human tissues including muscle and brain, and has a punctate cytoplasmic distribution. During the analysis of the LGMD2H region, it became apparent that there were Hutterite LGMD patients not linked to the LGMD2H locus. In order to identify the causative gene(s) in the remaining families, we performed a genome-wide scan. A locus at chromosome 19q13 was found to correspond to disease inheritance, the site of a previously described LGMD locus, LGMD2I. No causative gene had yet been identified at this locus so haplotyping and mutation screening was performed. We were able to identify c.826C>A in FKRP as the causative mutation in our remaining cohort of LGMD patients. The same mutation has since been found in many other populations, and is apparently a relatively common cause of LGMD. We obtained DNA from 19 non-Hutterite LGMD2I patients of diverse origins with c.826C>A and determined that it is an old founder mutation. There is no further evidence of any other loci causing autosomal recessive myopathy in the Hutterites. With the identification of c.1459G>A in TRIM32 and c.826C>A in FKRP we appear to have delineated the genetic cause of all myopathies of increased prevalence in the Hutterite population. To date, we have been able to provide accurate, non-invasive, diagnosis to over 70 patients and have provided carrier testing to approximately 120 at-risk family members. This kind DNA-based approach is not feasible in the general population due the enormous amount of locus, allelic, and clinical heterogeneity among myopathy patients.

Thesis (Ph.D.)--Lehigh University, 2007.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (p. 156-158).

Grainview: A Beginning Teacher's Experiences on a Hutterite colony in novel form. Hutterite colonies dot the Canadian prairie landscape like grain elevators. Where did they come from? What do the people called Hutterites believe? Accalia McConnell was bright, feisty, newly graduated teacher. Her first teaching assignment was on an Alberta Hutterite colony. As her first seven years of teaching unfold, "Caley" is continuously confronted with new challenges, contradictions, and compromises necessitated when two divergent cultures collide in one small classroom. The Hutterian life is ostensibly based on the biblical interpretations of their erstwhile leader. Jakob Hutter, who seized communal life has defied probability and flourished over their four hundred year history. However, in contemporary society the technological advances threaten one of the basic tenets of Hutterian life: isolaton. When the Hutterites emigrated to the West it was negotiated that the colony members were to be educated in local curricula. This price of admission presented the dilemma of maintaining traditional ways in the face of modern advancements. The flashpoint for this cultural collision is the classroom of Caley McConnell. As the anecdotal stories of education in the schoolhouse unfold, Caley is forced to cotinuously balance the myriad of viewpoints surrounding her: those of the superintendent, the preacher, Daniel the domineering farm boss, the illegitimate child, runaways and Caley's own set of values. These stories intertwine numerous challenges that inexorably lead to a breaking point. In searching for an understanding of Hutterian culture, Caley ultimately discovers herself. / xix, 118 p. ; 28 cm.

<p>Recent evidence suggests that vitamin D may be important for immune function. Canadian studies have reported varying prevalences of low levels of vitamin D. Whether these low vitamin D levels are associated with susceptibility to respiratory tract infections (RTIs) and infection severity remains unclear given the inconsistent association in recent studies. Influenza virus as a cause of RTI is of particular interest given its prevalence, morbidity and economic burden. Vaccination is a key strategy in prevention, but little is known about the effect of vitamin D on influenza vaccine response.</p> <p>A prospective cohort study of children 3 to 15 years old living in Hutterite communities in Alberta, Saskatchewan and Manitoba was conducted to assess the prevalence and predictors of low vitamin D levels and evaluate the association between vitamin D and the incidence and severity of laboratory proven respiratory tract infections. In those who received influenza vaccination, the relationship between vitamin D and influenza vaccine immunogenicity was examined.</p> <p>A total of 743 children were included in the study. The median serum 25-hydroxyvitamin D level (25[OH]D) was 62.0 nmol/L (interquartile range 51.0, 74.0). Levels lower than 50 nmol/L were present in 152 children (20.5%) and lower than 75 nmol/L in 565 children (76%). Lower serum 25(OH)D levels were associated with increased risk of RTI. No association was found between serum 25(OH)D level and disease severity. There was also no relationship found between serum 25(OH)D level and seroprotection or seroconversion from inactivated influenza vaccine.</p> <p>In conclusion, low serum 25(OH)D levels are a significant problem in Canadian Hutterite communities. Furthermore, low serum 25(OH)D levels were associated with increased risk of proven upper RTIs. Studies evaluating the role of vitamin D supplementation to reduce the burden of disease are warranted, and strategies to improve vitamin D status in rural communities in Canada are needed.</p> / Master of Science (MSc)

No description available.

La littérature de jeunesse constitue un objet culturel essentiel pour nous aider à cerner une société à un moment précis de son histoire, par exemple à travers les enjeux, les idées ou les grands principes qui l’animent, les changements qui s’y opèrent ou les individus qui la composent. En effet, puisqu’elle a souvent une vocation éducative, elle tend à refléter le contexte social dans laquelle elle est produite, à dépeindre des modèles ou des comportements souhaités, et à transmettre une vision particulière du monde – généralement celle des adultes qui y gravitent. Cette thèse porte spécifiquement sur la littérature de jeunesse huttérite – jusqu’à maintenant largement méconnue – et s’intéresse aux ouvrages produits par cette communauté établie en territoire canadien et étatsunien depuis plus de 100 ans et dont les pratiques découlent d’une approche rigoriste de l’anabaptisme. Le projet vise essentiellement à illustrer comment et dans quelle mesure ce genre transpose, à l’écrit, l’environnement du groupe, son identité unique et son héritage socioculturel, linguistique, religieux et historique. Pour ce faire, deux éléments ont été utilisés pour former le corpus de recherche : 1) les œuvres, notamment analysées avec une perspective issue de la narratologie, et 2) des questionnaires, construits de manière à recueillir l’opinion de membres de la collectivité et ainsi à comprendre leur vision quant aux différents enjeux (littéraires, langagiers, pédagogiques ou moraux) entourant cette littérature. D’abord, le projet montre que les auteur·es de la communauté proposent au lectorat des ouvrages où les pratiques présentées et ce que nous pourrions appeler un « savoir-être » huttérite sont valorisés et viennent conforter l’affiliation identitaire et socioculturelle des jeunes à l’huttérisme. Les trames narratives, composées entre autres par les thématiques, les péripéties ou les personnages des récits, véhiculent les grands fondements idéologiques du groupe, témoignent de ce qui est attendu des enfants, notamment leur rôle et leur place dans la collectivité, et les adultes, qui permettent l’accès aux œuvres, exposent dès lors ce qui constitue une lecture appropriée pour les jeunes ou confirment implicitement que certains sujets demeurent sensibles ou tabous. Ensuite, notre analyse montre comment le plurilinguisme unique des huttérites, qui parlent un dialecte qui leur est propre, l’huttérien, ainsi que l’anglais et l’allemand, se retrouve dans l’objet littéraire, de quelle manière les différentes langues s’y entremêlent, et comment ces livres « interlinguaux » illustrent le « parler multilingue » du groupe. Bien que l’anglais occupe dans les documents un espace considérable et paraisse reléguer l’huttérien à l’arrière-plan, ce dernier apparait comme un élément fondamental pour symboliser et légitimer l’univers mental du lectorat. Certain·es auteur·es stipulent même que leur ouvrage s’inscrit dans une démarche visant à maintenir, voire à revitaliser le dialecte, alors que l’anglais prend de plus en plus de place au quotidien. Si la littérature de jeunesse huttérite semble essentiellement destinée au lectorat de la communauté, elle ne se restreint pas à ce destinataire : elle offre, au contraire, à quiconque le souhaite, l’occasion de découvrir et de démystifier une collectivité dont le parcours original et les contributions littéraires mériteraient de susciter davantage l’intérêt. / Children’s literature forms an essential cultural asset that can help us understand a society at a specific point in its history, for example the issues, the ideas or the major principles driving it, the changes taking place or the people that are part of it. In fact, because it often has an educational purpose, it tends to reflect the social context in which it is produced, to depict role models or desired behaviours, and to convey a unique vision of the world – generally the one of a group or of a particular society. This thesis focusses on Hutterite children’s literature – until now largely unknown – and examines the works of this community, which established itself in Canada and in the Unites-States over 100 years ago, and whose religious practices result from a rigorous following of Anabaptism. The research corpus of this thesis is based on two components: 1) books of Hutterite’s children’s literature, analyzed with a perspective from the field of narratology, and 2) surveys, designed to gather the opinions of the Hutterite society, and therefore understand its point of view on different issues concerning this type of literature (literary, language, pedagogical or moral concerns). First, the study shows that authors from the community offer readership books in which the practices depict what we could call an ideal “Hutterite citizen” reinforcing the identity and the sociocultural affiliation of children to Hutterites beliefs. Narrative frameworks, such as the themes, the plots and the characters in the stories convey the group’s ideological basis, indicating what is expected of children, in particular their role and place in the community. As a result, the Hutterite community, which ultimately decides what books are a suitable reading for children, implicitly confirms that some topics remain sensitive or taboo. Furthermore, this research shows how the unique multilingualism of the Hutterites, who speak their own dialect, Hutterisch, as well as English and German, is reflected in their children’s literature: children’s literary works, often “interlingual books”, usually combine different languages, using the “multilingual speech” of the group. Although English is predominantly used in Hutterite children’s literature, Hutterites words and phrases appear to emphasize and legitimize Hutterite culture and beliefs. Some authors are proud to highlight the fact their work provides the means of maintaining and even revitalizing the dialect, as the English language is encroaching on their society. Though Hutterite children’s literature seems to be destined essentially to the community’s readership, it is not limited to it: on the contrary, it offers everyone the opportunity to discover and to demystify a communal group whose journey and literary contributions deserve our attention. / Kinderliteratur ist ein wesentliches Kulturgut, das uns ermöglicht, eine Gesellschaft zu einem bestimmten Zeitpunkt ihrer Geschichte zu erfassen. Man kann beispielsweise an die folgenden Punkte denken: die Herausforderungen, die Ideen oder die wichtigen Prinzipien, die diese Minderheitsgruppe anregt, die Veränderungen, die geschehen, oder die Individuen, die sie bilden. Da sie häufig eine pädagogische Aufgabe erfüllt, zielt sie meistens darauf ab, den sozialen Hintergrund widerzuspiegeln, Vorbilder oder gewünschte Verhalten zu schildern oder ein bestimmtes Weltbild zu vermitteln – i.d.R. die Denkweise der Erwachsenen. Die vorliegende These befasst sich mit der Kinderliteratur der Hutterer*innen – bisher größtenteils unbekannt – und beschäftigt sich mit den Werken dieser Gemeinschaft, die sich seit über hundert Jahren sowohl in Kanada als auch in den USA befindet, und deren Gepflogenheiten auf einer rigoristischen Herangehensweise beruhen. Das Projekt veranschaulicht, wie und inwiefern Kinderliteratur sowohl den gesellschaftlichen Kontext dieser Gruppe als auch ihre einzigartige Identität und ihr soziokulturelles, sprachliches, religiöses und historisches Erbe auf Papier überträgt. Dafür formen zwei Elemente den Forschungskorpus: 1) die Werke, die u.a. mit Hilfe der Narratologie analysiert werden und 2) Fragebögen, die die Meinung einiger Mitglieder der Gemeinschaft sammeln sollten und ihre Weltanschauung bezüglich verschiedener Themen, die diese Literatur betreffen (z.B. literarische, sprachliche, pädagogische oder moralische Fragen), demonstrieren sollten. Zuerst beweist das Forschungsprojekt, dass hutterische Autor*innen der Leserschaft Bücher bieten, in denen die vorgestellten Herangehensweisen und ein „typisch hutterisches“ Verhalten wertgeschätzt werden und die identische und soziokulturelle Zugehörigkeit der Kinder bestärken. Die Erzählstrukturen der Werke, u.a. die Themen, die Handlungen oder die Figuren, vermitteln die ideologischen Grundlagen der Gemeinschaft und zeigen, was von der Leserschaft erwartet wird, neben ihrer Rolle und ihrem Platz in der Gesellschaft. Die Erwachsenen, die die Werke zugänglich machen, deuten außerdem darauf hin, welche Lektüre für Kinder geeignet ist, und bestätigen dabei implizit, welche Themen nach wie vor sensibel sind oder tabuisiert werden. Danach stellt die Analyse dar, wie die besondere Mehrsprachigkeit der Hutterer*innen, die einen einzigartigen Dialekt (Hutterisch), Englisch und Hochdeutsch sprechen, in den Werken verkörpert wird, auf welche Weise die verschiedenen Sprachen sich mischen, und wie „interlinguale“ Bücher das „mehrsprachige Sprechen“ dieser Gruppe schildern. Trotz des großen Platzes, den das Englische einnimmt, und des Eindrucks, dass das Hutterische in den Hintergrund rückt, ist der Dialekt in der Tat ein grundlegendes Element, um die Gedankenwelt der Leserschaft zu symbolisieren und zu legitimieren. Einige Autor*innen erwähnen sogar ausdrücklich, dass das Buch zum Erhalten und zur Wiederbelebung des Dialekts beitragen soll – da die englische Sprache immer mehr Platz in ihrem Alltag einnimmt. Obgleich diese Literatur sich eher an die Kinder der Gemeinschaft zu richten scheint, beschränkt sie sich nicht auf diese Leserschaft. Sie bietet jungen Leser*innen die Möglichkeit, eine Gemeinschaft zu entdecken und zu entmystifizieren, deren einzigartige Geschichte und literarische Beiträge weitaus mehr Interesse erwecken sollten.