| 1. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Claassen, Y. H. M., et al.
(författare)
-
International comparison of treatment strategy and survival in metastatic gastric cancer
- 2019
-
Ingår i: BJS Open. - : JOHN WILEY & SONS LTD. - 2474-9842. ; 3:1, s. 56-61
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn the randomized Asian REGATTA trial, no survival benefit was shown for additional gastrectomy over chemotherapy alone in patients with advanced gastric cancer with a single incurable factor, thereby discouraging surgery for these patients. The purpose of this study was to evaluate treatment strategies for patients with metastatic gastric cancer in daily practice in five European countries, along with relative survival in each country. MethodsNationwide population-based data from Belgium, Denmark, the Netherlands, Norway and Sweden were combined. Patients with primary metastatic gastric cancer diagnosed between 2006 and 2014 were included. The proportion of gastric resections performed and the administration of chemotherapy (irrespective of surgery) within each country were determined. Relative survival according to country was calculated. ResultsOverall, 15 057 patients with gastric cancer were included. The proportion of gastric resections varied from 81 per cent in the Netherlands and Denmark to 183 per cent in Belgium. Administration of chemotherapy was 392 per cent in the Netherlands, compared with 632 per cent in Belgium. The 6-month relative survival rate was between 390 (95 per cent c.i. 378 to 402) per cent in the Netherlands and 541 (521 to 569) per cent in Belgium. ConclusionThere is variation in the use of gastrectomy and chemotherapy in patients with metastatic gastric cancer, and subsequent differences in survival.
|
|
| 5. |
- Clark, Andrew G., et al.
(författare)
-
Evolution of genes and genomes on the Drosophila phylogeny
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
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.
|
|
| 6. |
|
|
| 7. |
- Eriksson, Daniel, et al.
(författare)
-
Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
|
|
| 8. |
- Forsberg, Simon, et al.
(författare)
-
The Shepherds' Tale : A Genome-Wide Study across 9 Dog Breeds Implicates Two Loci in the Regulation of Fructosamine Serum Concentration in Belgian Shepherds
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus is a serious health problem in both dogs and humans. Certain dog breeds show high prevalence of the disease, whereas other breeds are at low risk. Fructosamine and glycated haemoglobin (HbA1c) are two major biomarkers of glycaemia, where serum concentrations reflect glucose turnover over the past few weeks to months. In this study, we searched for genetic factors influencing variation in serum fructosamine concentration in healthy dogs using data from nine dog breeds. Considering all breeds together, we did not find any genome-wide significant associations to fructosamine serum concentration. However, by performing breed-specific analyses we revealed an association on chromosome 3 (rho(corrected) approximate to 1:68 x 10(-6)) in Belgian shepherd dogs of the Malinois subtype. The associated region and its close neighbourhood harbours interesting candidate genes such as LETM1 and GAPDH that are important in glucose metabolism and have previously been implicated in the aetiology of diabetes mellitus. To further explore the genetics of this breed specificity, we screened the genome for reduced heterozygosity stretches private to the Belgian shepherd breed. This revealed a region with reduced heterozygosity that shows a statistically significant interaction (rho = 0.025) with the association region on chromosome 3. This region also harbours some interesting candidate genes and regulatory regions but the exact mechanisms underlying the interaction are still unknown. Nevertheless, this finding provides a plausible explanation for breed-specific genetic effects for complex traits in dogs. Shepherd breeds are at low risk of developing diabetes mellitus. The findings in Belgian shepherds could be connected to a protective mechanism against the disease. Further insight into the regulation of glucose metabolism could improve diagnostic and therapeutic methods for diabetes mellitus.
|
|
| 9. |
|
|
| 10. |
- Hayami, Masaru, et al.
(författare)
-
Population-Based Cohort Study from a Prospective National Registry : Better Long-Term Survival in Esophageal Cancer After Minimally Invasive Compared with Open Transthoracic Esophagectomy
- 2022
-
Ingår i: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 29:9, s. 5609-5621
-
Tidskriftsartikel (refereegranskat)abstract
- Background Recent research indicates long-term survival benefits of minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) for patients with esophageal and gastroesophageal junction (GEJ) cancers, but there is a need for more population-based studies. Methods We conducted a prospective population-based nationwide cohort study including all patients in Sweden diagnosed with esophageal or junctional cancer who underwent a transthoracic esophagectomy with intrathoracic anastomosis. Data were collected from the Swedish National Register for Esophageal and Gastric Cancer in 2006-2019. Patients were grouped into OE and MIE including hybrid MIE (HMIE) and totally MIE (TMIE). Overall survival and short-term postoperative outcomes were compared using Cox regression and logistic regression models, respectively. All models were adjusted for age, sex, American Society of Anesthesiologists (ASA) score, clinical T and N stage, neoadjuvant therapy, year of surgery, and hospital volume. Results Among 1404 patients, 998 (71.1%) underwent OE and 406 (28.9%) underwent MIE. Compared with OE, overall survival was better following MIE (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.55-0.94), TMIE (HR 0.67, 95% CI 0.47-0.94), and possibly also after HMIE (HR 0.76, 95% CI 0.56-1.02). MIE was associated with shorter operation time, less intraoperative bleeding, higher number of resected lymph nodes, and shorter hospital stay compared with OE. MIE was also associated with fewer overall complications (odds ratio [OR] 0.70, 95% CI 0.47-1.03) as well as non-surgical complications (OR 0.64, 95% CI 0.40-1.00). Conclusions MIE seems to offer better survival and similar or improved short-term postoperative outcomes in esophageal and GEJ cancers compared with OE in this unselected population-based cohort.
|
|
