The value of gametoclonal variation in breeding for quantitative traits in flue-cured tobacco (Nicotiana tabacum L.)

Summary In tobacco (Nicotiana tabacum L.), anther-derived doubled haploid populations have been shown to exhibit large amounts of unexpected genetic variation and a severe depression in cured leaf yield when compared to conventionally inbred genotypes from comparable sources. A previous study had predicted that the yield depression observed in a doubled haploid population-derived from a near homozygous cultivar, NC95, might be overcome through a recurrent selection program. In the current study, progress from three cycles of full-sib family selection for improved yield in an anther-culture derived population of NC95 was measured, as well as the remaining genetic variation within the population. A design II experiment was conducted in the population following three cycles of selection. Results indicate that the NC95 yield level has been recovered in the third selection cycle population. Although most of the genetic variation in the population appears to be exhausted, the additive genetic variance among maternal half-sib families for yield is significant, and it appears that continued yield improvement can be made through recurrent selection. Significant additive-genetic variance for yield was found among maternal half-sib families but was essentially zero among the paternal half-sib families, suggesting that remaining genetic variation is not being transmitted through pollen. One possible explanation results from the phenomenon of DNA amplification that can occur during the anther culture process, and that may enable extraordinary recombinational events and reduce the viability of male gametes.     

Comparing the Immunogenicity of AS03-Adjuvanted 2009 Pandemic H1N1 Vaccine with Clinical Protection in Priority Risk Groups in England

In England, during pandemic 2009 H1N1, vaccine efficacy and immunogenicity population studies in priority groups were rolled out in parallel to evaluate the pandemic vaccination programme. This provided a unique opportunity to compare immunogenicity and clinical protection in the same population and thus provide insights into the correlates of protection for the pandemic H1N1 2009 vaccine in risk groups. While clinical protection from AS03-adjuvanted pandemic 2009 H1N1 vaccine was high in those aged <25 years and pregnant women, effectiveness in older adults with chronic conditions has been found to be surprisingly poor. Here we present results from the immunogenicity study derived from the same population. Individuals from priority groups eligible for pandemic vaccination attending participating general practices were recruited. Pre and post-vaccination blood samples were collected and HI antibody testing to assess immune response to vaccination performed. The final cohort consisted of 610 individuals: 60 healthy children aged <5 years; 32 healthy pregnant women; 518 individuals from risk groups. Seroconversion rate in healthy children aged <5 years (87%, 95% CI: 75% to 94%) was higher than that of risk groups combined (65%, 95% CI: 61% to 69%) (p<0.001). Multivariable analysis of risk groups showed that the size of response in those who did seroconvert was lower in those who received the 2009/10 seasonal TIV (Fold effect: 0.52, 0.35 to 0.78). Predicted immunological boosting from higher pre-vaccine titres after 2009 pandemic H1N1 vaccination only occurred in children (seroconversion rate = 92%) and not in individuals aged 10 to 39 from risk groups (seroconversion rate = 74%). The lack of clinical protection identified in the same population in older adults from risk groups could be attributed to these lower seroresponses. Current immunogenicity licensing criteria for pandemic influenza vaccine may not correlate with clinical protection in individuals with chronic disease or immunocompromised.     

Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system

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PhyloWGS: Reconstructing subclonal composition and evolution from whole-genome sequencing of tumors

Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations. We describe a new method, PhyloWGS, which can be applied to whole-genome sequencing data from one or more tumor samples to reconstruct complete genotypes of these subpopulations based on variant allele frequencies (VAFs) of point mutations and population frequencies of structural variations. We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods. PhyloWGS is free, open-source software, available at https://github.com/morrislab/phylowgs.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0602-8) contains supplementary material, which is available to authorized users.