A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Cultural History of Luxembourg: The Luxembourg Identity is more than a question of language

Also published on http://www.tageblatt.lu/meinung/forum/kulturgeschicht-letzebuerg-letzebuerger-identiteit-ass-mei-wei-just-sprooch

Consultations infirmières en cancérologie (rédaction et évaluation de documents pharmaceutiques)

PARIS-BIUP (751062107) / SudocSudocFranceF

Near-shore island lizard fauna shaped by a combination of human-mediated and natural dispersal

Aim: Island biotas provide opportunities to study colonization and adaptation to novel environments. Islands, especially near-shore islands, may have a long record of human habitation such that some lineages result from human-assisted introductions. Here, we combine phylogenetic analyses with fossil data and historical specimen records to reconstruct colonization histories, characterize among-island divergence and assess the role of humans in shaping the evolutionary history of lizards inhabiting a near-shore island archipelago. Location: Channel Islands and adjacent mainland of California, United States. Taxa: Western fence lizard (Sceloporus occidentalis), southern alligator lizard (Elgaria multicarinata), common side-blotched lizard (Uta stansburiana). Methods: We sequenced mitochondrial DNA (ND1, cyt-b) from each of three lizard species, covering their entire island distributions plus the adjacent mainland. For each, we estimated diversity within and among each island, obtained maximum likelihood bootstrapped phylogenies, constructed haplotype networks and tested for population expansion. We used museum specimen records and microfossil evidence to infer colonization scenarios. Results: Sceloporus occidentalis is characterized by a single island-colonization event, and exhibits the deepest divergences from mainland relatives and the highest among-island divergence. Elgaria multicarinata and Uta stansburiana each have at least three distinct colonization events, with fossil and historical data indicating that some of these occurred after humans arrived to the islands. Main Conclusions: The evolution of Channel Island lineages for two lizard taxa has been mediated by ancient and contemporary anthropogenic activity, while the evolution of the third is shaped by natural dispersal and vicariance caused by sea-level rise. Genetic divergence corroborates the treatment of S. occidentalis as an endemic island species, Sceloporus becki. The unique histories of these three taxa are synthesized with other Channel Island lineages highlighting that taxa inhabiting islands with long histories of human activity should be carefully studied to assess the role of people in facilitating colonization and subsequent gene flow

Alternate Title: For the Girls

First Line: Now little Willie Newton knew his countryFirst Line of Chorus: He's doing his bit for the girlsTitle of Larger Work: Tempest and SunshineKey: B Flat Majo

Additional file 1: Table S1. of Farewell to GBM-O: Genomic and transcriptomic profiling of glioblastoma with oligodendroglioma component reveals distinct molecular subgroups

Targeted amplicon DNA sequencing coding exons. (XLSX 91 kb