| 1. |
- Appelqvist, Frida, et al.
(author)
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Deletion of the MGMT gene in familial melanoma
- 2014
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In: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 53:8, s. 703-711
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Journal article (peer-reviewed)abstract
- The DNA repair gene MGMT (O-6-methylguanine-DNA methyltransferase) is important for maintaining normal cell physiology and genomic stability. Alterations in MGMT play a critical role in the development of several types of cancer, including glioblastoma, lung cancer, and colorectal cancer. The purpose of this study was to explore the function of genetic alterations in MGMT and their connection with familial melanoma (FM). Using multiplex ligation-dependent probe amplification, we identified a deletion that included the MGMT gene in one of 64 families with a melanoma predisposition living in western Sweden. The mutation segregated with the disease as a heterozygous deletion in blood-derived DNA, but a homozygous deletion including the promoter region and exon 1 was seen in tumor tissue based on Affymetrix 500K and 6.0 arrays. By sequence analysis of the MGMT gene in the other 63 families with FM from western Sweden, we identified four common polymorphisms, nonfunctional, as predominantly described in previous studies. We conclude that inherited alterations in the MGMT gene might be a rare cause of FM, and we suggest that MGMT contributes to melanoma predisposition.
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| 2. |
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| 3. |
- Bjursell, Cecilia, 1971, et al.
(author)
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PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families.
- 2000
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In: Human mutation. - 1098-1004 .- 1059-7794. ; 16:5, s. 395-400
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Journal article (peer-reviewed)abstract
- Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.
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| 4. |
- Erlandson, Anna, et al.
(author)
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Epigenetic mutations in CDKN2A in western Swedish families with hereditary malignant melanoma
- 2008
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In: Molecular Medicine Reports. - Athens, Greece : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 1:1, s. 89-91
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Journal article (peer-reviewed)abstract
- This study aimed to identify the molecular genetic variations associated with an increased risk of hereditary malignant melanoma (HMM) in the western Swedish population. In 68 families with increased hereditary susceptibility to malignant melanoma, we previously reported a low frequency of alterations in the CDKN2A gene, which is regarded as the major melanoma predisposition gene. Among these alterations, we identified a novel mutation in 3 families (Asp108Tyr). In the present study, we focused on the possible role of heritable epimutations as a cause of the silencing of the CDKN2A gene. We used two different technical approaches to detect changes in CpG methylation in the promoter region of the CDKN2A gene; methylation-specific PCR (MSP) analysis of bisulfite-converted DNA and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). From families who tested negative for germ-line CDKN2A mutations, 64 unrelated patients with hereditary melanoma were included in the study. We showed a consistent lack of hypermethylation in the promoter region of CDKN2A in patients with HMM in our western Swedish population. A putative germ-line methylation of the CDKN2A, if any, is therefore likely to be a rare event in hereditary melanoma. This study demonstrates that there are probably additional and as yet unknown genetic factors present in western Swedish HMM families.
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| 5. |
- Erlandson, Anna
(author)
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Genotype/ phenotype correlation of two neuropsychiatric diseases. A genetic study of CDG1a and Rett syndrome
- 2003
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to investigate the effects of mutations in the genes that cause the two neuropsychiatric diseases congenital disorder of glycosylation (CDG) type Ia and Rett syndrome. These two diseases affect children's central and peripheral nervous systems, causing mental retardation and neuronal impairment. CDG type Ia patients also have cerebellar atrophy and, in most cases, liver dysfunction and skeletal abnormalities. CDG type Ia is a recessive autosomal disease. The gene involved in the pathogenesis of CDG type Ia is phosphomannomutase 2 (PMM2) located in chromosome region 16p13. Rett syndrome debutes after 6-18 months of normal development, and one of the most intriguing features of the disease is that it affects females almost exclusively. As the disease proceeds, they develop autistic behaviour, learning disabilities and characteristic hand-wringing movements, resembling hand washing. The majority of Rett syndrome cases are sporadic, and inheritance is dominant X-linked in the few familial cases. The methyl CpG-binding protein 2 gene (MECP2), located in chromosome region Xq28, contains mutations in approximately 80% of Rett patients.In summary, we detected 20 different mutations in a comprehensive mutation screening of PMM2 in a large group of CDG type Ia patients. We found PMM2 mutations with DNA sequencing and single-stranded conformation polymorphism (SSCP) in more than 95% of the patients. The dominating genotype was 357C>A/ 422G>A. The mutations detected in PMM2 were then used in an evaluation of the recently developed mutation detection technique denaturing high-performance liquid chromatography (DHPLC). We confirmed 19 of 20 mutations with DHPLC, and concluded that this technique is suitable for a first screening of PMM2 in CDG type Ia patients. Subsequenty, we performed a genotype/ phenotype correlation study with essentially the same group of patients. We were able to report some phenotypic trends in patient groups with the same mutation, i.e. mutation 548T>C correlated with mild disease, and mutation 691G>A correlated with severe disease. In contrast, the most common genotype (357C>A/ 422G>A) was related to the whole spectrum of clinical presentations. The enzyme activity of PMM, measured in fibroblasts from patients, did not correlate to either genotype or phenotype. Our haplotype study, combined with data on the geographical origin of the patients, resulted in the location of two mutations to regions in southern and mid-eastern Sweden, most likely as a result of founder mutations (common ancestry).Furthermore, we performed a mutation screening of MECP2 with DNA sequencing in 16 classical Rett women, and found that 13 had de novo MECP2 mutations. Three of these were novel, and three were hot-spot mutations. In order to improve the mutation detection rate, we tested another mutation detection method, multiplex ligation-dependent probe amplification (MLPA). Using this method, we found large deletions in three of eleven classical Rett patients, who had previously been considered to lack mutations, when analysed with DNA sequencing. We concluded that MLPA is useful as a complement to DNA sequencing for finding mutations in Rett patients.
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| 6. |
- Erlandson, Anna, et al.
(author)
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MECP2 abnormality phenotypes: clinicopathologic area with broad variability
- 2005
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In: J Child Neurol. - 0883-0738. ; 20:9, s. 727-32
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Journal article (peer-reviewed)abstract
- Rett syndrome is a neurodevelopmental disorder that occurs worldwide and predominantly affects girls. The MECP2 gene has been put forward as the underlying gene. Interestingly, other clinical presentations in addition to Rett syndrome have been reported to be the results of deviations in MECP2. This prompted us to outline a working hypothesis of how these diverse phenotypes are connected. Our aim was to summarize the clinical picture of deviations in MECP2 at this moment to obtain a comprehensive overview. Thus, we have attempted to create a gradient, starting at the left with the most severely affected MECP2-deviant subgroups, represented by boys who are diseased in the intrauterine phase or as neonates, and at the right, the most mildly affected subgroup, female asymptomatic carriers. In the center, with dominant numbers, we have placed classic Rett syndrome presentations, together with the late-onset Rett syndrome variant and preserved speech variant. In conclusion, we feel that it is important to emphasize that Rett syndrome is a strictly clinical diagnosis that is not identical to the far broader concept of MECP2 deviations.
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| 7. |
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| 8. |
- Erlandson, Anna, et al.
(author)
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Novel CDKN2A mutations detected in western Swedish families with hereditary malignant melanoma
- 2007
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In: Journal of Investigative Dermatology. - : NATURE PUBLISHING GROUP. - 0022-202X .- 1523-1747. ; 127:6, s. 1465-1467
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Journal article (peer-reviewed)abstract
- We have examined alterations in the cyclin-dependent kinase inhibitor 2A (CDKN2A), a major melanoma predisposing gene, in a western-Swedish hereditary melanoma population comprising 107 patients from 68 families. Using sequence analysis and multiplex ligation-dependent probe amplification, we found a novel mutation (Asp108 Tyr), segregating with the disease in three families. This mutation has previously been detected as a somatic mutation in other cancers. We found a previously described Swedish founder mutation (ins113Arg) in one family and a large duplication encompassing the CDKN2A gene locus in another family. Moreover, a debated polymorphism (Ala148Thr) was found in nine families, in which the polymorphism did not segregate with the disease.
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| 9. |
- Erlandson, Anna
(author)
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The visible and the invisible
- 2014
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In: Claiming the City. - Uppsala : Uppsala University. - 9789198039153 ; , s. 86-94
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Book chapter (other academic/artistic)
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| 10. |
- Jonsson, Anna-Carin, 1964-, et al.
(author)
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Teachers’ implicit theories of intelligence : influences from different disciplines and scientific theories
- 2012
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In: European Journal of Teacher Education. - : Informa UK Limited. - 0261-9768 .- 1469-5928. ; 35:4, s. 387-400
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Journal article (peer-reviewed)abstract
- A sample of 226 Swedish high school teachers from various knowledge domains completed self-report measures of intelligence regarding implicit theories and scientific theories of intelligence. A mixed ANOVA showed that teachers from language, social science and practical disciplines had a significant preference for an incremental theory of intelligence compared to an entity theory of intelligence whilst the teachers in mathematics did not. One of the conclusions was that entity theories of intelligence may be more pronounced among teachers in mathematics. Second there is a significant relation between naïve beliefs in intelligence as fixed and inborn, entity theories, and the scientific g-factor theory. Last, it was the oldest and most experienced and youngest and least experienced teachers who preferred an entity theory of intelligence the most
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| 11. |
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| 12. |
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| 13. |
- Lundvall, Mikael, et al.
(author)
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Aetiology of severe mental retardation and further genetic analysis by high-resolution microarray in a population-based series of 6- to 17-year-old children.
- 2012
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In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:1, s. 85-91
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Journal article (peer-reviewed)abstract
- Aim: To investigate the prevalence, co-morbidities and aetiologies of severe mental retardation (SMR) in a cohort of Swedish children and to further penetrate aetiologies in the group with undetermined causes by application of updated clinical-genetic methods. Methods: The study was population-based and included children living in the County of Halland in western Sweden in 2004 (born 1987-1998; 46000 children). Patients were identified through habilitation centres, paediatric clinics and school health services. Patients with unclear prenatal aetiology were investigated with single nucleotide polymorphism (SNP)-array. Results: Severe mental retardation was identified in 133 children from 132 families, corresponding to a prevalence of 2.9 per 1000 children. There were more males than females (90:43).The aetiology was prenatal in 82 (62%), perinatal in 14 (10%) and postnatal in 8 (6%). In 29 (22 %) children, mainly males with autism, the cause could not be related to the time of birth. In the prenatal group, genetic causes dominated, but still 23 children remained undiagnosed; in 5/19 of these patients, a diagnosis could be made after SNP-array analysis. One or more associated neurological handicaps were found in more than half of the children. Conclusion: Prevalence and co-morbidity were similar to previous Scandinavian studies. High-resolution chromosomal micro-array techniques are valuable diagnostic tools, reducing the number of patients with unexplained SMR.
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| 14. |
- Rajaei, Saideh, et al.
(author)
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Early infantile onset ''congenital'' Rett syndrome variants: Swedish experience through four decades and mutation analysis.
- 2011
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In: Journal of child neurology. - : SAGE Publications. - 1708-8283 .- 0883-0738. ; 26:1, s. 65-71
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Journal article (peer-reviewed)abstract
- The early infantile onset ''congenital'' variant of Rett syndrome presents with deviations of behavior from very early infancy. Here, we report on a clinical-genetic study in a collected series of 14 Swedish girls with early infantile onset Rett syndrome phenotype. The clinical diagnosis was based on symptom onset before the age of 6 months and the patients fulfilled 3 or more Rett variant criteria and 5 or more supportive criteria. Genotype-phenotype correlation studies in the CDKL5-gene have recently shown clinical associations to early infantile onset Rett variants. Mutation analyses for both the MECP2-gene and the CDKL5-gene were, therefore, performed. Of interest, we found a large deletion covering 2 exons in MECP2, which underlines the importance of MECP2 mutation screening even for the ''atypical'' early infantile onset variants of Rett syndrome. No early infantile onset Rett syndrome patients in this study had the previously well-known hotspot mutations in the MECP2-gene.
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| 15. |
- Rönnerman, Karin, 1952, et al.
(author)
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Doktorander som kreativa brobyggare – samtal om läraryrkets praktik ur ett nordiskt perspektiv
- 2013
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In: Paper presenterat på Högskolepedagogisk konferens vid Göteborgs universitet(HKG2013), 17 oktober 2013..
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Conference paper (other academic/artistic)abstract
- En vanlig undervisningsform i forskarutbildningen är föreläsningar av en kunnig forskare inom sitt område. En annan är seminarier där litteraturen bearbetas, diskuteras och reflekteras över. Ofta avslutas en kurs på forskarnivå med ett individuellt skriftligt paper där doktoranden ska relatera kursinnehållet till sin avhandling. Mindre vanligt är att det förekommer interaktiva former för doktoranders lärande. I detta paper presenteras en interaktiv workshop, i vilken 12 doktorander och två lärare deltog. Temat för detta event var nordisk forskning om lärarprofessionen. Syftet med paperet är att presentera och diskutera lärandet hos doktoranderna utifrån att de deltagit i både planering och genomförandet av en workshop där de tagit ansvar för både helheten och specifika delar. Planeringen av workshopen tog ungefär ett år, en tid då samtliga doktorander var delaktiga i de olika diskussioner och urval som krävdes för att hitta ett antal forskare att bjuda in. I ett första steg gjordes en inventeringen av nordiska avhandlingar publicerade mellan 2002-2011 som handlade om läraryrket och som resulterade i den bibliografi omfattade 15 A4 sidor. I ett andra steg valdes några avhandlingar från varje land och i ett tredje avgränsades publikationsår. Sista steget innebar en sammanställning av sex avhandlingar utifrån majoritetsprincipen. I doktorandgruppen har urvalet diskuterats vid flera seminarier. Doktoranderna har valt en avhandling var som de önskade fördjupa sig i. Diskussioner har förts kring vilka frågor kring innehållet som är relevanta samt hur workshop skulle planeras och genomföras. Både innehåll och form har således varit aktuellt. De områden och frågor som diskuterats fram låg till grund för genomförandet av workshopen som varade i två dagar. Varje inbjuden författare fick ca 20 minuter att presentera sin avhandling därefter ställde två doktorander fördjupande frågor till innehållet under ca 20 minuter. Forskaren avslutade seminariet med att berätta hur hen gått vidare med sin forskning efter disputation. Hela workshopen avslutades med en paneldebatt ledd av de tolv doktoranderna med utgångspunkt i de områden de lyft fram som kunde hittas i samtliga avhandlingar. Resultatet av workshopen kan betecknas i termer av en lärandegemenskap där doktoranderna själva uttrycker att de lärt av processen och fått perspektiv på sitt eget avhandlingsarbete. Lärandet kan betraktas i termer av både färdigheter, kritisk analys och. En sista steg i arbetet kommer att ske genom att färdigställa en rapport av workshopen, i vilken doktorandernas lärande kommer att beskrivas.
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