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- Eisfeldt, J., et al.
(författare)
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Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements
- 2019
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Ingår i: PLOS Genetics. - : NLM (Medline). - 1553-7390 .- 1553-7404. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated.
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- Nilsson, D., et al.
(författare)
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Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights the Importance of Microhomology in the Mechanism of Formation
- 2017
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 38:2, s. 180-192
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Tidskriftsartikel (refereegranskat)abstract
- Most balanced translocations are thought to result mechanistically from nonhomologous end joining or, in rare cases of recurrent events, by nonallelic homologous recombination. Here, we use low-coverage mate pair whole-genome sequencing to fine map rearrangement breakpoint junctions in both phenotypically normal and affected translocation carriers. In total, 46 junctions from 22 carriers of balanced translocations were characterized. Genes were disrupted in 48% of the breakpoints; recessive genes in four normal carriers and known dominant intellectual disability genes in three affected carriers. Finally, seven candidate disease genes were disrupted in five carriers with neurocognitive disabilities (SVOPL, SUSD1, TOX, NCALD, SLC4A10) and one XX-male carrier with Tourette syndrome (LYPD6, GPC5). Breakpoint junction analyses revealed microhomology and small templated insertions in a substantive fraction of the analyzed translocations (17.4%; n = 4); an observation that was substantiated by reanalysis of 37 previously published translocation junctions. Microhomology associated with templated insertions is a characteristic seen in the breakpoint junctions of rearrangements mediated by error-prone replication-based repair mechanisms. Our data implicate that a mechanism involving template switching might contribute to the formation of at least 15% of the interchromosomal translocation events.
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- Syk, Ingvar, et al.
(författare)
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Postoperative fever, bowel ischaemia and cytokine response to abdominal aortic aneurysm repair--a comparison between endovascular and open surgery
- 1998
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Ingår i: European Journal of Vascular and Endovascular Surgery. - 1532-2165. ; 15:5, s. 398-405
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study bowel ischaemia in transfemorally placed endoluminal grafting (TPEG) for abdominal aortic aneurysms, and any relation to cytokine response or postoperative fever. DESIGN: Prospective not randomised. University hospital setting. MATERIAL: Fourteen cases of conventional surgery and 23 cases of endovascular technique for infrarenal abdominal aortic aneurysm repair. METHODS: Tonometry was used for sigmoid colon pH, and ELISAs for serum IL-6. RESULTS: Mucosal pH in the sigmoid colon fell significantly during clamping and reperfusion in both groups. Lowest measured sigmoid colon pH was 7.10 in the open group, compared to 7.22 in the TPEG group (p < 0.05). The IL-6 levels in serum peaked after 4 h of reperfusion; 249 pg/ml in the open group, compared to 89 pg/ml in the TPEG group (p < 0.05). High levels of IL-6 in the postoperative period and persisting low sigmoidal pH were associated with serious complications. Postoperative temperature did not differ significantly between the groups, and no significant correlation could be found with sigmoid colon pH or IL-6 levels. CONCLUSIONS: The less pronounced perioperative bowel ischaemia in TPEG patients indicates an advantage of the TPEG technique. Splanchnic ischaemia was not related to postoperative fever, nor the IL-6 or TNF response.
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