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- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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- Dellenmark-Blom, Michaela, 1983, et al.
(författare)
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Establishment of a condition-specific quality-of-life questionnaire for children born with esophageal atresia aged 2-7 across 14 countries
- 2023
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Ingår i: Frontiers in Pediatrics. - 2296-2360. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEsophageal atresia (EA) is a rare congenital anomaly characterized by a discontinuity of the esophagus. Following surgical repair, survival rates have improved dramatically the past decenniums and today exceed 90%, but the children commonly present with esophageal and respiratory morbidity. In 2018, a condition-specific quality-of-life questionnaire for children with esophageal atresia (EA) aged 2-7 in Sweden-Germany was finalized (The EA-QOL questionnaire). The study aim was to describe the evaluation of the new translations across 12 new countries in Europe, Asia, Africa, Central-and North America.MethodsFollowing forward-backward translation into the new languages, the 17-item EA-QOL questionnaire was tested in cognitive debriefing interviews with parents of children with EA aged 2-7. Parents rated if each item was easy to understand (clarity) and sensitive to answer (interference with personal integrity). They could skip responding to a non-applicable/problematic item and give open comments. Predefined psychometric criteria were used; item clarity >= 80%/item sensitive to answer <= 20%/item feasibility <= 5% missing item responses. The decision to modify the translation was based on native expert, patient stakeholder, and instrument developer review, and the need for harmonization between translations.ResultsSimilar to findings in the Swedish-German cognitive debriefing, the cross-cultural analysis of input from 116 parents from 12 new countries (4-14 parents, median 9 parents/country) showed that all items in the EA-QOL questionnaire fulfilled the criteria for item clarity >= 80% and sensitive to answer (ranging from 1%-4.5%), although results varied between countries. Four items had missing responses between 5.2% and 13.4%, three within the same domain and were in line with parents' explanations. Poor translations and feasibility were improved.ConclusionsBased on parent input, the collaboration between native experts, patient stakeholders, and instrument developers, a linguistic version of the EA-QOL questionnaire for children aged 2-7 for use in and across 14 countries has been established. These efforts have set the conditions for a cross-cultural field test of the EA-QOL questionnaire and will open the doors for a new chapter in outcome research, registries, and clinical practice concerning children with EA. In the long-term, this will help increase knowledge of the disease's burden, promote patient-centeredness, exchange of information between nations, and strengthen evidence-based treatments for children born with EA.
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| 5. |
- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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- Ure, Agustin, et al.
(författare)
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Characterization of the complete genomes of Camelus dromedarius papillomavirus types 1 and 2
- 2011
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 92:8, s. 1769-1777
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Tidskriftsartikel (refereegranskat)abstract
- Camel papillomatosis has been described previously, but the genome of the suspected papillomavirus (PV) has not been identified. An outbreak of papillomatosis occurred in a dromedary farm of 55 animals in Sudan during August 2009. The disease was only present in young animals aged about 3-7 months, of which 44% (11/25) were affected with lesions, mainly on the lips and lower jaw. This study reports for the first time the complete genomes of Camelus dromedarius papillomavirus types 1 (CdPV1) and 2 (CdPV2), isolated from a cauliflower-like nodule and a round oval raised nodule, respectively. Pairwise comparisons of their L1 nucleotide sequences revealed 69.2% identity, and phylogenetic analyses suggested that these two PV types are grouped within the genus Deltapapillomavirus. Both viruses were isolated from fibropapillomas, although no putative E5 proteins homologous to that of bovine papillomavirus type 1 were identified. The genetic information will be useful for evolutionary studies of the family Papillomaviridae, as well as for the development of diagnostic methods for surveillance of the disease in dromedaries.
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| 7. |
- Korolija, D, et al.
(författare)
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Evaluation of quality of life after laparoscopic surgery: evidence-based guidelines of the European Association for Endoscopic Surgery.
- 2004
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 18:6, s. 879-897
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Tidskriftsartikel (refereegranskat)abstract
- Background Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research. Methods An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research. Results Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function. Conclusions Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.
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| 10. |
- Lucidarme, J., et al.
(författare)
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An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015
- 2016
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Ingår i: Eurosurveillance. - Stockholm, Sweden : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 21:45, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.
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| 12. |
- Ure, A, et al.
(författare)
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Using HPV-meta for human papillomavirus RNA quality detection
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 13058-
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Tidskriftsartikel (refereegranskat)abstract
- In the era of cervical cancer elimination, accurate and validated pipelines to detect human papillomavirus are essential to elucidate and understand HPV association with human cancers. We aimed to provide an open-source pipeline, “HPV-meta”, to detect HPV transcripts in RNA sequencing data, including several steps to warn operators for possible viral contamination. The “HPV-meta” pipeline automatically performs several steps, starting with quality trimming, human genome filtering, HPV detection (blastx), cut-off settlement (10 reads and 690 bp coverage to make an HPV call) and finishing with fasta sequence generation for HPV positive samples. Fasta sequences can then be aligned to assess sequence diversity among HPV positive samples. All RNA sequencing files (n = 10,908) present in the cancer genome atlas (TCGA) were analyzed. “HPV-meta” identified 25 different HPV types being present in 488/10,904 specimens. Validation of results showed 99.98% agreement (10,902/10,904). Multiple alignment from fasta files warned about high sequence identity between several HPV 18 and 38 positive samples, whose contamination had previously been reported. The “HPV-meta” pipeline is a robust and validated pipeline that detects HPV in RNA sequencing data. Obtaining the fasta files enables contamination investigation, a non very rare occurrence in next generation sequencing.
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