| 1. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 2. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
- Ozsahin, Hulya, et al.
(författare)
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Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:1, s. 439-45
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Tidskriftsartikel (refereegranskat)abstract
- Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.
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| 4. |
- Johnell, Kristina, et al.
(författare)
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Anxiolytic-hypnotic drug use associated with trust, social participation, and the miniaturization of community: A multilevel analysis
- 2006
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Ingår i: Social Science and Medicine. - : Elsevier BV. - 1873-5347 .- 0277-9536. ; 62:5, s. 1205-1214
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Tidskriftsartikel (refereegranskat)abstract
- The concept of social capital has gained wide interest in public health research in recent years. However, we suggest a concept that was introduced and developed by Fukuyama, named "miniaturization of community".. as an alternative to that of social capital. The concept of miniaturization of community emphasizes that a high level of social participation can be accompanied by a low level of trust, both at the individual and at the community level, which may in turn result in social disorder and lack of social cohesion. When society becomes more disordered, people may tend to feel more insecure and anxious. Use of anxiolytic-hypnotic drugs (AHDs) could under such circumstances be a coping strategy. In this study, we first wanted to investigate whether the contextual component of the miniaturization of community concept (i.e. area high social participation and low trust) is associated with individual AHD use, over and above individual characteristics. Secondly, we aimed to study whether people living in the same municipality share a similar probability of AHD use, after adjusting for individual characteristics, and if so, how large this contextual phenomenon is. We used data on 20,319 women and 17,850 men aged 18-79 years from 58 municipalities in six regions in central Sweden, who participated in the Life & Health year 2000 postal survey. We applied multilevel logistic regression analysis with individuals at the first level and areas at the second level. Our results suggest that living in an area with a high level of miniaturization of community seems to be associated with individual AHD use, beyond people's individual characteristics including their own level of social participation and trust. The concept of miniaturization of community may be an extension of the classic concept of social capital and may increase our understanding of contextual effects on health. (c) 2005 Elsevier Ltd. All rights reserved.
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| 5. |
- Rosvall, Maria, et al.
(författare)
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Contribution of main causes of death to social inequalities in mortality in the whole population of Scania, Sweden
- 2006
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 6:79
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Tidskriftsartikel (refereegranskat)abstract
- Background: To more efficiently reduce social inequalities in mortality, it is important to establish which causes of death contribute the most to socioeconomic mortality differentials. Few studies have investigated which diseases contribute to existing socioeconomic mortality differences in specific age groups and none were in samples of the whole population, where selection bias is minimized. The aim of the present study was to determine which causes of death contribute the most to social inequalities in mortality in each age group in the whole population of Scania, Sweden. Methods: Data from LOMAS ( Longitudinal Multilevel Analysis in Skane) were used to estimate 12-year follow-up mortality rates across levels of socioeconomic position (SEP) and workforce participation in 975,938 men and women aged 0 to 80 years, during 1991 - 2002. Results: The results generally showed increasing absolute mortality differences between those holding manual and non-manual occupations with increasing age, while there were inverted u-shaped associations when using relative inequality measures. Cardiovascular diseases (CVD) contributed to 52% of the male socioeconomic difference in overall mortality, cancer to 18%, external causes to 4% and psychiatric disorders to 3%. The corresponding contributions in women were 55%, 21%, 2% and 3%. Additionally, those outside the workforce (i.e., students, housewives, disability pensioners, and the unemployed) showed a strongly increased risk of future mortality in all age groups compared to those inside the workforce. Even though coronary heart disease (CHD) played a major contributing role to the mortality differences seen, stroke and other types of cardiovascular diseases also made substantial contributions. Furthermore, while the most common types of cancers made substantial contributions to the socioeconomic mortality differences, in some age groups more than half of the differences in cancer mortality could be attributed to rarer cancers. Conclusion: CHD made a major contribution to the socioeconomic differences in overall mortality. However, there were also important contributions from diseases with less well understood mechanistic links with SEP such as stroke and less-common cancers. Thus, an increased understanding of the mechanisms connecting SEP with more rare causes of disease might be important to be able to more successfully intervene on socioeconomic differences in health.
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| 6. |
- Sánchez, Elena, et al.
(författare)
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Identification of a new putative functional IL18 gene variant through an association study in systemic lupus erythematosus
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:19, s. 3739-3748
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. In this study, we aimed to determine the potential role of the IL18 gene in SLE. To define the genetic association of the IL18 and SLE, we have genotyped nine SNPs in an independent set of Spanish cases and controls. The IL18 polymorphisms were genotyped by PCR, using a predeveloped TaqMan allele discrimination assay. Two SNPs were still significant after fine mapping of the IL18 gene. The SNP (rs360719) surviving correction for multiple tests was genotyped in two replication cohorts from Italy and Argentina. After the analysis, a significance with rs360719 C-allele remained across the sets and after the meta-analysis (Pooled OR = 1.37, 95% CI 1.21-1.54, combined P = 3.8E-07, Pc = 1.16E-06). Quantitative real-time PCR was performed to assess IL18 mRNA expression in PBMC from subjects with different IL18 rs360719 genotypes. We tested the effect of the IL18 rs360719 polymorphism on the transcription of IL18 by electrophoretic mobility shift assay and western blot. We found a significant increase in the relative expression of IL18 mRNA in individuals carrying the rs360719 C-risk allele; in addition we show that the polymorphism creates a binding site for the transcriptional factor OCT-1. These findings suggest that the novel IL18 rs360719 variant may play an important role in determining the susceptibility to SLE and it could be a key factor in the expression of the IL18 gene.
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