Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark

Adherence to instruction for use after endovascular repair of popliteal artery aneurysm

Objectives: Endovascular repair (ER) of popliteal artery aneurysm (PAA) is an alternative to open repair. However, there is no standardized protocol for when to opt for ER and the decision is therefore at the discretion of the clinician. This study aims to evaluate the adherence to the Instruction For Use (IFU) in patients undergoing ER for PAA and factors associated with stent graft patency at one year. Methods: The adherence to IFU provided by the manufacturer in 55 patients treated with Gore Viabahn® Endoprosthesis with Heparin Bioactive Surface for PAA between 2009 and 2019 were retrospectively analyzed. Duplex follow-up was performed at 30 days and one year. Results: The two groups of patients treated within (n = 10) and not within (n = 45) IFU did not differ in patient demographics, diagnostic assessment, treatment or outcome. Forty-five patients (81.8%) received stent graft placement with at least one deviation according to IFU. Distal oversizing >20% was the most frequent deviation against IFU (n = 22, 40.0%). Primary patency at one year was 72%. Diameter size difference >1 mm between overlapping stent grafts (6/14 [43%], p = 0.013) and renal insufficiency (5/12 [42%], p = 0.0086) were associated with lower primary patency at one year. Age-adjusted analysis of tortuosity index (HR 1.78/SD, 95% CI 1.17–2.71; p = 0.0071) and maximal PAA angle (HR 1.73/SD, 95% CI 1.018–2.95; p = 0.043) were associated with major amputation/mortality at end of follow-up. Conclusion: The majority of patients undergoing ER for PAA were not treated within IFU. Diameter size difference >1 mm between overlapping stent grafts was associated with a higher loss of primary patency at one year. Multi-center studies with larger sample size and long-term follow up of patency are warranted