Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of the retinal dystrophy genes still await discovery. In this thesis we aimed to study the genetic background of two inherited retinal diseases, X-linked cone-rod dystrophy and Åland Island eye disease. X-linked cone-rod dystrophy (CORDX) is characterized by progressive loss of visual function in school age or early adulthood. Affected males show reduced visual acuity, photophobia, myopia, color vision defects, central scotomas, and variable changes in fundus. The disease is genetically heterogeneous and two disease loci, CORDX1 and CORDX2, were known prior to the present thesis work. CORDX1, located on Xp21.1-11.4, is caused by mutations in the RPGR gene. CORDX2 is located on Xq27-28 but the causative gene is still unknown. Åland Island eye disease (AIED), originally described in a family living in Åland Islands, is a congenital retinal disease characterized by decreased visual acuity, fundus hypopigmentation, nystagmus, astigmatism, red color vision defect, myopia, and defective night vision. AIED shares similarities with another retinal disease, congenital stationary night blindness (CSNB2). Mutations in the L-type calcium channel α1F-subunit gene, CACNA1F, are known to cause CSNB2, as well as AIED-like disease. The disease locus of the original AIED family maps to the same genetic interval as the CACNA1F gene, but efforts to reveal CACNA1F mutations in patients of the original AIED family have been unsuccessful. The specific aims of this study were to map the disease gene in a large Finnish family with X-linked cone-rod dystrophy and to identify the disease-causing genes in the patients of the Finnish cone-rod dystrophy family and the original AIED family. With the help of linkage and haplotype analyses, we could localize the disease gene of the Finnish cone-rod dystrophy family to the Xp11.4-Xq13.1 region, and thus establish a new genetic X-linked cone-rod dystrophy locus, CORDX3. Mutation analyses of candidate genes revealed three novel CACNA1F gene mutations: IVS28-1 GCGTC>TGG in CORDX3 patients, a 425 bp deletion, comprising exon 30 and flanking intronic regions in AIED patients, and IVS16+2T>C in an additional Finnish patient with a CSNB2-like phenotype. All three novel mutations altered splice sites of the CACNA1F gene, and resulted in defective pre-mRNA splicing suggesting altered or absent channel function as a disease mechanism. The analyses of CACNA1F mRNA also revealed novel alternative wt splice variants, which may enhance channel diversity or regulate the overall expression level of the channel. The results of our studies may be utilized in genetic counseling of the families, and they provide a basis for studies on the pathogenesis of these diseases. In the future, the knowledge of the genetic defects may be used in the identification of specific therapies for the patients.

The influence of school smoking policy and school prevention programs on the smoking behaviour of high school students in Prince Edward Island, Canada

The aim of the study was to examine the influence of school smoking policy and school smoking prevention programs on the smoking behaviour of students in high schools in Prince Edward Island using the School Health Action Planning Evaluation System (SHAPES). A total sample included 13,131 observations of students in grades 10-12 in ten high schools in Prince Edward Island over three waves of data collection (1999, 2000, and 2001). Changes in prevalence of smoking and factors influencing smoking behaviour were analyzed using descriptive statistics and Chi-Square tests. Multi-level logistic regression analyses were used to examine how both school and student characteristics were associated with smoking behaviour (I, II, III, IV). Since students were located within schools, a basic 2-level nested structure was used in which individual students (level 1) were nested within schools (level 2). For grade 12 students, the combination of both school policies and programs was not associated with the risk of smoking and the presence of the new policy was not associated with decreased risk of smoking, unless there were clear rules in place (I). For the grade 10 study, (II) schools with both policies and programs were not associated with decreased risk of smoking. However, the smoking behaviour of older students (grade 12) at a school was associated with younger students’ (grade 10) smoking behaviour. Students first enrolled in a high school in grade 9, rather than grade 10, were at increased risk of occasional smoking. For students who transitioned from grade 10 to 12 (III), close friends smoking had a substantial influence on smoking behaviour for both males and females (III). Having one or more close friends who smoke (Odds Ratio (OR) = 37.46; 95% CI = 19.39 to 72.36), one or more smokers in the home (OR = 2.35; 95% CI = 1.67 to 3.30) and seeing teachers and staff smoking on or near school property (OR=1.78; 95% CI = 1.13 to 2.80), were strongly associated with increased risk of smoking for grade 12 students. Smoking behaviour increased for both junior (Group 1) and senior (Group 2) students (IV). Group 1 students indicated a greater decrease in smoking behaviour and factors influencing smoking behaviour compared to those of Group 2. Students overestimating the percentage of youth their age who smoke was strongly associated with increased likelihood of smoking. Smoking rates showed a decreasing trend (1999, 2000, and 2001). However, policies and programs alone were not successful in influencing smoking behaviour of youth. Rather, factors within the students and schools contextual environment influenced smoking behaviour. Comprehensive approaches are required for school-based tobacco prevention interventions. Keywords: schools, policy, programs, smoking prevention, adolescents Subject Terms: school-based programming, public health, health promotion

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.