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Additional file 1 S1: Job categories assigned a high likelihood of exposure to pesticides by CLIC-JEM and their prevalence among parents of children included in the study. S2: Directed Acyclic Graphs (DAG) of known and suspected associations with childhood cancers (Potential confounders for which data were available and which were considered in the analyses are shown in bold). S3: Exposure prevalence among parents of children included in the analysis based on CLIC-JEM and reported job categories at censuses 1990 and 2000. S4: Frequency of paternal and maternal occupational exposure to pesticides among children included in both analyses (n = 1,407,503). S5: Association between potential confounders and likelihood of paternal exposure to pesticides. S6: Association between potential confounders and likelihood of maternal exposure to pesticides. S7: Cases of childhood cancers included in analyses and likelihood of parental occupational exposure to pesticides. S8: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort. S9: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort stratified by census year of entry (only outcomes with evidence of interaction shown). S10: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort, classifying non-economically active parents as missing. S11: Sensitivity analysis classifying mothers reporting “housework” as having high likelihood of exposure if the father reported an occupation in agriculture. S12: Additional analysis comparing children for whom at least one parent had high likelihood of exposure to children whose parents both had no or minimal exposure. S13: Change of parental occupational pesticides exposure between 1990 and 2000.

Chromosomal instability is one of the hallmarks of cancer and caused by chromosome missegregation during mitosis, a process frequently associated with micronucleus formation. Micronuclei are formed when chromosomes fail to join a daughter nucleus during cell division and are surrounded by their own nuclear membrane. Although it has been commonly assumed that the gain or loss of specific chromosomes is random during compromised cell division, recent data suggest that the size of chromosomes can impact on chromosome segregation fidelity. To test whether chromosome missegregation rates scale with chromosome size in primary human cancer cells, we assessed chromosome sequestration into micronuclei in patient-derived primary NCH149 glioblastoma cells, which display high-level numerical chromosome instability (CIN), pronounced spontaneous micronucleus formation but virtually no structural CIN. The cells were analysed by interphase fluorescence-in-situ-hybridization (FISH) using chromosome-specific painting probes for all chromosomes. Overall, 33% of early passage NCH149 cells harbored micronuclei. Entrapment within a micronucleus clearly correlated with chromosome size with larger chromosomes being significantly more frequently missegregated into micronuclei than smaller chromosomes in primary glioblastoma cells. These findings extend the concept that chromosome size determines segregation fidelity by implying that size-specific micronucleus entrapment occurs in primary human cancer cells as well. This article is protected by copyright. All rights reserved.

In hemophilia A and B, analysis of the F8 and F9 gene variants enables carrier and prenatal diagnosis and prediction of risk for the development of inhibitors. The PedNet Registry collects clinical, genetic, and phenotypic data prospectively on more than 2000 children with hemophilia. The genetic reports of F8/F9 gene variants were classified uniformly to Human Genome Variation Society nomenclature and reevaluated using international population- and disease-specific databases, literature survey and, where applicable, computational predictive programs. We report 88 novel variants in the F8 and F9 genes, 80 fulfilling criteria for Class 5 (pathogenic), six for Class 4 (likely pathogenic) and two fulfilling criteria for Class 3 (variant of unknown significance) of the American College of Medical Genetics and Genomics/Association for Molecular Pathologyguidelines together with information on the respective phenotype and inhibitor formation. The study highlights the need to reevaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in light of changed nomenclature and new guidelines.

Additional file 1 S1: Job categories assigned a high likelihood of exposure to pesticides by CLIC-JEM and their prevalence among parents of children included in the study. S2: Directed Acyclic Graphs (DAG) of known and suspected associations with childhood cancers (Potential confounders for which data were available and which were considered in the analyses are shown in bold). S3: Exposure prevalence among parents of children included in the analysis based on CLIC-JEM and reported job categories at censuses 1990 and 2000. S4: Frequency of paternal and maternal occupational exposure to pesticides among children included in both analyses (n = 1,407,503). S5: Association between potential confounders and likelihood of paternal exposure to pesticides. S6: Association between potential confounders and likelihood of maternal exposure to pesticides. S7: Cases of childhood cancers included in analyses and likelihood of parental occupational exposure to pesticides. S8: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort. S9: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort stratified by census year of entry (only outcomes with evidence of interaction shown). S10: Association between parental occupational exposure to pesticides and risk of childhood cancer in the Swiss National Cohort, classifying non-economically active parents as missing. S11: Sensitivity analysis classifying mothers reporting “housework” as having high likelihood of exposure if the father reported an occupation in agriculture. S12: Additional analysis comparing children for whom at least one parent had high likelihood of exposure to children whose parents both had no or minimal exposure. S13: Change of parental occupational pesticides exposure between 1990 and 2000.