Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the SACS gene around the world. Besides French Canadians, SACS genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered SACS mutations in several other countries. SACS mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the SACS gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.

World War II and its Impact on French Canadians

This research takes the perspective of a Romanian-born philologist after having lived, studied, and taught in the Quebec public educational system for nearly 12 years. The main purpose of this study is to discuss the important influences World War II had on the evolution of Quebec society. Examining Quebec's social life and culture from a historic standpoint is a primordial step for immigrants and their integration into Quebec's society. An analysis of the corpus selected for this study, namely, Roch Carrier's La guerre, yes sir!, Jean Jules Richard’s Neuf jours de haine, Jean Vaillancourt’ s Les Canadians errants, and Gabrielle Roy’s Bonheur d’ occasion, reveals that World War II marked in different ways the disturbance of the traditional, pastoral, and agrarian life, which triggered some modernist influences in people’s lives. For instance, the war changed women’s condition. When Canadian French men were shipped out to Europe to fight in the war, women were employed in Quebec’s factories and plants. Even though they were paid less than men, they became independent and autonomous. Another example is the presence of British soldiers in Quebec, which disturbed the traditional lifestyle of French Canadians. It was difficult for English soldiers to understand the locals’ culture, who in turn, perceived them as dangerous and responsible for the war. Nowadays, Quebecers’ mentality is influenced by the various cultures they are surrounded by, yet, they still preserve some values which are originated during World War II.

How multicultural is Canada really? An investigation of the inclusion and exclusion of culturally diverse groups in English Canadians‘ representations of Canadian nationhood and identity

<p>The current thesis aimed to contribute to a national psychology for Canada by examining majority group (i.e., English Canadians) representations of nationhood and national identity as they relate to the cultural diversity comprising the nation. This dissertation took a macro-level approach to examine the content of English Canadians‘ representations, situating the research within a theoretical framework consisting of two families of existing social psychological theories of social representations (i.e., Social Representations Theory; Moscovici, 1961; and Social Representations of History; Liu & Hilton, 2005) and social identity (i.e., Social Identity Theory; Tajfel & Turner, 1979; and Self-Categorization Theory; Turner, Hogg, Oakes, Reicher, & Wetherell, 1987). A multi-method approach using a mix of qualitative and quantitative techniques was employed to examine societal- and individual-level representations of Canadian nationhood and identity. The thesis had three major goals: 1) To determine the content of Canadian nationhood and identity; 2) To investigate if minority groups (i.e., French Canadians, Aboriginal peoples, and newer immigrants and their descendants) are included in and/or excluded from English Canadians‘ representations of Canadian nationhood and identity; and 3) To examine whether individuals‘ representations reflected government and mass media representations. The dissertation begins by reviewing existing literature on the content of Canadian nationhood, identity and diversity, providing an interpretive analysis using the guiding social psychological theories. Three empirical studies follow, which examined different aspects of representations of nationhood and identity. Study 1 used Critical Discourse Analysis (van Dijk, 1993) to investigate English Canadian print media representations of nationhood and identity by analysing the media response to two events concerned with the integration and accommodation of religious and cultural minorities, and immigrants. Study 2 examined ordinary citizens‘ representations of Canadian history through the use of survey methods. Study 3 examined implicit and explicit associations between ethnicity and Canadian nationhood. The findings revealed that governmental, media and individuals‘ representations of nationhood and identity were highly similar to one another, allowing us to advance a model of the content of Canadian identity. It was found that cultural groups are incorporated in English Canadians‘ representations of nationhood and identity in different ways from each other, depending on the context. It was shown that French Canadians represent a non-negligible component of nationhood and identity, but that they are sometimes reluctantly included in representations when they make demands on the majority. Aboriginal peoples are symbolically represented in English Canadians‘ representations of Canadian history, but are almost entirely absent from discussions of present day society and diversity. Newer immigrants and their descendants are sometimes included in present day representations of Canadian nationhood and identity, but are absent from historical representations. The Enlightenment Values of equality, freedom, democracy and reason (Michael, 2000) emerged as a crucial component of Canadian nationhood and identity, and this research suggests that they may represent why French Canadians are included in representations, as well as the key that newer immigrants and their descendants need to use to achieve inclusion (or conversely, warrant exclusion if they violate these values). Over all it was found that multiculturalism is not in itself a Canadian value, as has previously been suggested (Adams, 2007; Kymlicka, 2003), but it is instead a respect for the Enlightenment Values and an accommodation of diversity within these values that English Canadians treasure. Potential limitations and suggestions for future research are discussed. The thesis concludes with a consideration of how the results can be applied to increase the inclusion of minority groups in the majority group‘s conceptions of nationhood and identity. This work should serve as a launching point for discussions between the cultural groups about inclusion and exclusion.</p>

How multicultural is Canada really? An investigation of the inclusion and exclusion of culturally diverse groups in English Canadians‘ representations of Canadian nationhood and identity

<p>The current thesis aimed to contribute to a national psychology for Canada by examining majority group (i.e., English Canadians) representations of nationhood and national identity as they relate to the cultural diversity comprising the nation. This dissertation took a macro-level approach to examine the content of English Canadians‘ representations, situating the research within a theoretical framework consisting of two families of existing social psychological theories of social representations (i.e., Social Representations Theory; Moscovici, 1961; and Social Representations of History; Liu & Hilton, 2005) and social identity (i.e., Social Identity Theory; Tajfel & Turner, 1979; and Self-Categorization Theory; Turner, Hogg, Oakes, Reicher, & Wetherell, 1987). A multi-method approach using a mix of qualitative and quantitative techniques was employed to examine societal- and individual-level representations of Canadian nationhood and identity. The thesis had three major goals: 1) To determine the content of Canadian nationhood and identity; 2) To investigate if minority groups (i.e., French Canadians, Aboriginal peoples, and newer immigrants and their descendants) are included in and/or excluded from English Canadians‘ representations of Canadian nationhood and identity; and 3) To examine whether individuals‘ representations reflected government and mass media representations. The dissertation begins by reviewing existing literature on the content of Canadian nationhood, identity and diversity, providing an interpretive analysis using the guiding social psychological theories. Three empirical studies follow, which examined different aspects of representations of nationhood and identity. Study 1 used Critical Discourse Analysis (van Dijk, 1993) to investigate English Canadian print media representations of nationhood and identity by analysing the media response to two events concerned with the integration and accommodation of religious and cultural minorities, and immigrants. Study 2 examined ordinary citizens‘ representations of Canadian history through the use of survey methods. Study 3 examined implicit and explicit associations between ethnicity and Canadian nationhood. The findings revealed that governmental, media and individuals‘ representations of nationhood and identity were highly similar to one another, allowing us to advance a model of the content of Canadian identity. It was found that cultural groups are incorporated in English Canadians‘ representations of nationhood and identity in different ways from each other, depending on the context. It was shown that French Canadians represent a non-negligible component of nationhood and identity, but that they are sometimes reluctantly included in representations when they make demands on the majority. Aboriginal peoples are symbolically represented in English Canadians‘ representations of Canadian history, but are almost entirely absent from discussions of present day society and diversity. Newer immigrants and their descendants are sometimes included in present day representations of Canadian nationhood and identity, but are absent from historical representations. The Enlightenment Values of equality, freedom, democracy and reason (Michael, 2000) emerged as a crucial component of Canadian nationhood and identity, and this research suggests that they may represent why French Canadians are included in representations, as well as the key that newer immigrants and their descendants need to use to achieve inclusion (or conversely, warrant exclusion if they violate these values). Over all it was found that multiculturalism is not in itself a Canadian value, as has previously been suggested (Adams, 2007; Kymlicka, 2003), but it is instead a respect for the Enlightenment Values and an accommodation of diversity within these values that English Canadians treasure. Potential limitations and suggestions for future research are discussed. The thesis concludes with a consideration of how the results can be applied to increase the inclusion of minority groups in the majority group‘s conceptions of nationhood and identity. This work should serve as a launching point for discussions between the cultural groups about inclusion and exclusion.</p>

A.4 A Novel Recessive TNNT1 Congenital Core-Rod Myopathy in French Canadians

Background: Mutations in the slow skeletal muscle troponin T (TNNT1) gene cause a congenital nemaline myopathy resulting in death from respiratory insufficiency in early infancy. We report on four French Canadians with a novel congenital TNNT1 myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy and genetic testing. TNNT1 expression in muscle was assessed by quantitative PCR and immunoblotting. Wild type or mutated TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess for rescue of the morphant phenotype. Results: Four patients shared a novel missense homozygous mutation in TNNT1. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of rhabdomyolysis. Older patients remained ambulatory into their sixties. Lower extremity MRI showed symmetrical myopathic changes. Paraspinal MRI showed diffuse fibro-fatty involution. Biopsies showed multi-minicores. Nemaline rods were seen in half the patients. TNNT1 mRNA expression was similar in controls and patients, while levels of TNNT1 protein were reduced in patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to do so. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel mutation.

“A Curse or a Blessing?”: Montreal Jews and the Politics of 1960s Quebec

In this article, the author argues that the politics of the Quiet Revolution in Quebec in the 1960s invigorated Montreal Jews as a religious and cultural minority rather than marginalizing or alienating them. While Jewish activists remained critical of the expanding ambitions of the Quebec state and the rise of nationalism in the province, they took the opportunity to advance Jewish claims and adopted a largely positive outlook on their communal future in Quebec. In fact, Montreal Jews, like their francophone neighbours, but perhaps unlike the anglophone majority, had motives to share in Quebec’s collective thrill during the 1960s: it created opportunities to discuss and advance cultural continuity. This perspective is crucial to nuance the popular assumption that animosity and reluctance alone characterized Quebec Jews’ reaction to the Quiet Revolution, leading many to find solace in Toronto after the election of the Parti québécois and in reaction to long-smouldering tensions. By exploring the themes of education, French language, and nationalism in Jewish English-language newspapers and institutional sources from the 1960s, the author reveals more nuanced dynamics between Jews and French Canadians at the time of the Quiet Revolution.

DNA and historical evidence indicate many colonial French Canadians were of Sephardic Jewish ancestry

The Spanish Inquisition in 1492 resulted in the deaths of thousands of Spanish Jews and the exile of around 150,000. The Huguenots and Acadians who settled in Colonial French Canada are assumed to be of Christian faith and ancestry. To support this hypothesis, the researcher uses a novel combination of methods drawn from historical records and artifacts, genealogies and DNA testing. In recent years, this combination of methods has led to the discovery that several of the Plymouth Colony settlers, Central Appalachian Colonial settlers, and Roanoke Colony settlers were of Sephardic Jewish origin. Thus, using the new methodology of ancestral DNA tracing, the researcher document that the majority of Huguenot and Acadian colonists in French Canada were of Sephardic Jewish ancestry. They are most likely descended from Sephardic Jews who fled to France from the Iberian Peninsula in the late 1300s and early 1500s. The researcher additionally propose that some members of both groups continued to practice Judaism in the new world, thus becoming secret Jews or crypto-Jews. The researcher also finds evidence of Ashkenazi Jewish ancestry in both groups.

Becoming Québécois: Édouard and the Duchesse de Langeais between Old Worlds and New in the work of Michel Tremblay

Our identity is formed in large part by the way we see others and the way others, in their turn, see us. This is true both of Québec and of Édouard, one of the principal characters of the fictionalised Montréal universe of Michel Tremblay. A representative of the pre-1970s socio-economic inequality of French-Canadians, Édouard is further marginalised by his homosexuality. In his transvestite persona as the Duchesse de Langeais, a revised version of a Balzacian heroine, he undertakes a mocking critique of the injustices of his society from the ‘external’ point of view of this supposed French aristocrat before seizing the opportunity of an actual visit to France, hoping to find there a freer and more equitable society. But the Old World turns out to be unwelcoming and antiquated, making Édouard more aware of the hitherto unperceived advantages of his life in Montréal. Returning home, his only option is to resume his role as a provocative duchess, preparing the ground for the advent in 1976 of a modern Québec, a francophone society of the New World, internationally recognised for its openness of mind and its cultural dynamism.

The Genetic Analyses of French Canadians of Quebec Facilitate the Characterization of New Cancer Predisposing Genes Implicated in Hereditary Breast and/or Ovarian Cancer Syndrome Families

The French Canadian population of the province of Quebec has been recognized for its contribution to research in medical genetics, especially in defining the role of heritable pathogenic variants in cancer predisposing genes. Multiple carriers of a limited number of pathogenic variants in BRCA1 and BRCA2, the major risk genes for hereditary breast and/or ovarian cancer syndrome families, have been identified in French Canadians, which is in stark contrast to the array of over 2000 different pathogenic variants reported in each of these genes in other populations. As not all such cancer syndrome families are explained by BRCA1 and BRCA2, newly proposed gene candidates identified in other populations have been investigated for their role in conferring risk in French Canadian cancer families. For example, multiple carriers of distinct variants were identified in PALB2 and RAD51D. The unique genetic architecture of French Canadians has been attributed to shared ancestry due to common ancestors of early settlers of this population with origins mainly from France. In this review, we discuss the merits of genetically characterizing cancer predisposing genes in French Canadians of Quebec. We focused on genes that have been implicated in hereditary breast and/or ovarian cancer syndrome families as they have been the most thoroughly characterized cancer syndromes in this population. We describe how genetic analyses of French Canadians have facilitated: (i) the classification of variants in BRCA1 and BRCA2; (ii) the identification and classification of variants in newly proposed breast and/or ovarian cancer predisposing genes; and (iii) the identification of a new breast cancer predisposing gene candidate, RECQL. The genetic architecture of French Canadians provides a unique opportunity to evaluate new candidate cancer predisposing genes regardless of the population in which they were identified.