| 1. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Bernatsky, S, et al.
(författare)
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An International Cohort Study of Cancer in Systemic Lupus Erythematosus
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 52:5, s. 1481-1490
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. Methods. We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. Results. The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). Conclusion. These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.
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| 4. |
- Bernatsky, S., et al.
(författare)
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Mortality in systemic lupus erythematosus
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 54:8, s. 2550-2557
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.
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| 5. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 6. |
- Bernatsky, Sasha, et al.
(författare)
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Lymphoma risk in systemic lupus: effects of disease activity versus treatment
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:1, s. 138-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
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| 7. |
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| 8. |
- Bernatsky, Sasha, et al.
(författare)
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Cancer risk in systemic lupus: An updated international multi-centre cohort study
- 2013
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 42, s. 130-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To update estimates of cancer risk in SLE relative to the general population. Methods: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Results: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% Cl 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). Conclusion: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing. (C) 2013 Elsevier Ltd. All rights reserved.
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| 9. |
- Chioza, Barry A., et al.
(författare)
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Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14
- 2009
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 87:2-3, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.
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