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| 2. |
- Moens, Lotte N, et al.
(författare)
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Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23450-
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence - both genetic and functional - indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that similar to 90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.
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| 3. |
- Adolfsson, Rolf
(författare)
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A review of Swedish crop residue statistics used in the greenhouse gas inventory
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Factors for recalculating primary crops into the nitrogen content of crop residues for different arable crops are compiled and summarised here. The data is included in the calculation of nitrous oxide from the turnover in crop residues and was used in the inventory of greenhouse gases in the 2006 Submission. The data is compared to data for both Denmark and Finland. In addition, sources of uncertainty are discussed. The suggested revision decreases the estimated emissions from crop residues by 18 % in 2003. The emissions from crop residues correspond to 6 % of the N2O emissions from agriculture in this year.
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| 4. |
- Adolfsson,, Rolf
(författare)
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A review of Swedish crop residue statistics used in the greenhouse gas inventory
- 2005
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The IPCC (Intergovernmental Panel on Climate Change) calculation model for nitrous oxide (N2O) emissions from agricultural land includes emissions from the nitrogen turnover in crop residues. The nitrogen content of crop residues is calculated using primary crop statistics in combination with recalculation factors, that is, the ratios of crop residue/primary crop and the nitrogen content in crop residues. In addition, information on removed crop residues is used to subtract that part of the crop residues that is not turned over on agricultural land.A comparison between data used in different countries reveals great differences.1 Variations in climate, soil fertility and production methods across different countries partly explain some of the differences. Nevertheless, it is likely that these differences also depend on different definitions as well as on variations in the trial data. A more systematic comparison of the recalculations for different countries requires well-documented sources of information
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| 5. |
- Adolfsson, Rolf
(författare)
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Documentation of data on landfills
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this report some vital data on landfills, used in Sweden’s greenhouse gas inventory to the UNFCCC, are controlled according to current guidelines. Quality aspects of historic surveys on deposited wastes are considered and compared over time. Plant specific data on recovered methane gas from landfills have been scanned into a database, which has been used as a tool for quality control.Despite of some minor differences, the historic quantities of deposited wastes seem to be consistently estimated. There seem to be no systematic differences between the surveys with data on deposited waste amounts, but the variability in the earliest surveys is probably greater.Data on recovered methane are accurate in general, since they mainly depend on sold energy; information that is well documented at the plants. Some unexplained deviations are however identified, when comparing the plant specific values over time. In some cases, it may be possible to increase the quality of the data by renewed contacts with the respondents. Much data were however collected some years back in time, which probably will make a systematic revision of the data unrealistic. A revision of a few values would probably only have minor impacts on the total amount of recovered methane. In the future, the quality of data input could be improved, by immediate consistency checks with older data. The collected data could be stored in a waste database, such as DIA (a database created within the project Data om hushållsavfall), to simplify this procedure.
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| 7. |
- Lindholm, Eva, et al.
(författare)
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Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree
- 2004
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Ingår i: Psychiatric Genetics. - Philadelphia : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 14:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 1 0p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.
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| 8. |
- Massat, Isabelle, et al.
(författare)
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Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association Study of affective disorders
- 2002
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 114:2, s. 177-85
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Tidskriftsartikel (refereegranskat)abstract
- Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/ 133 C subjects, and for DRD3: 325 BPAD/ 325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age ( plus minus five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P=0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.
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| 9. |
- Wikström, Helene, et al.
(författare)
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Field Burning of Crop Residues
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Emissions of greenhouse gases from field burning of crop residues have been estimated to very low levels in 2002. The emissions of CO and NOx may however be considered as not negligible. Information provided by experts support a decreasing trend of field burning as an agricultural practice, but there are only usable activity data for one single year (1997).Due to lack of activity data from beginning of the nineties and very low emission levels, the study concludes that Sweden should report trace gas emissions from field burning of crop residues as not occurring "NO" in the emission inventories.
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| 10. |
- Åberg, Karolina, et al.
(författare)
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Human QKI, a New Candidate Gene for Schizophrenia Involved in Myelination
- 2005
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics. - Malden : Wiley. - 1552-4841 .- 1552-485X. ; 141B:1, s. 84-90
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that chromosome 6q25-6q27 includes a susceptibility locus for schizophrenia in a large pedigree from northern Sweden. In this study, we fine-mapped a 10.7 Mb region, included in this locus, using 42 microsatellites or SNP markers. We found a 0.5 Mb haplotype, likely to be inherited identical by decent, within the large family that is shared among the majority of the patients (69%). A gamete competition test of this haplotype in 176 unrelated nuclear families from the same geographical area as the large family showed association to schizophrenia (empirical P-value 0.041). The only gene located in the region, the quaking homolog, KH domain RNA binding (mouse) (QKI), was investigated in human brain autopsies from 55 cases and 55 controls using a high-resolution mRNA expression analysis. Relative mRNA expression levels of two QKI splice variants were clearly downregulated in schizophrenic patients (P-value 0.0004 and 0.03, respectively). The function of QKI has not been studied in humans, but the mouse homolog is involved in neural development and myelination. In conclusion, we present evidence from three unrelated sample-sets that propose the involvement of the QKI gene in schizophrenia. The two family based studies suggest that there may be functional variants of the QKI gene that increase the susceptibility of schizophrenia in northern Sweden, whereas the case-control study suggest that splicing of the gene may be disturbed in schizophrenic patients from other geographical origins. Taken together, we propose QKI as a possible target for functional studies related to the role of myelination in schizophrenia.
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