| 1. |
- Humble, E., et al.
(författare)
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A draft fur seal genome provides insights into factors affecting SNP validation and how to mitigate them
- 2016
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 16:4, s. 909-921
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Tidskriftsartikel (refereegranskat)abstract
- Custom genotyping arrays provide a flexible and accurate means of genotyping single nucleotide polymorphisms (SNPs) in a large number of individuals of essentially any organism. However, validation rates, defined as the proportion of putative SNPs that are verified to be polymorphic in a population, are often very low. A number of potential causes of assay failure have been identified, but none have been explored systematically. In particular, as SNPs are often developed from transcriptomes, parameters relating to the genomic context are rarely taken into account. Here, we assembled a draft Antarctic fur seal (Arctocephalus gazella) genome (assembly size: 2.41 Gb; scaffold/contig N-50: 3.1 Mb/27.5 kb). We then used this resource to map the probe sequences of 144 putative SNPs genotyped in 480 individuals. The number of probe-to-genome mappings and alignment length together explained almost a third of the variation in validation success, indicating that sequence uniqueness and proximity to intron-exon boundaries play an important role. The same pattern was found after mapping the probe sequences to the Walrus and Weddell seal genomes, suggesting that the genomes of species divergent by as much as 23 million years can hold information relevant to SNP validation outcomes. Additionally, reanalysis of genotyping data from seven previous studies found the same two variables to be significantly associated with SNP validation success across a variety of taxa. Finally, our study reveals considerable scope for validation rates to be improved, either by simply filtering for SNPs whose flanking sequences align uniquely and completely to a reference genome, or through predictive modelling.
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| 2. |
- Humble, Mats B., 1952-, et al.
(författare)
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Paroxetine concentrations in obsessive-compulsive disorder : Support for a therapeutic interval
- 2017
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Ingår i: European psychiatry. - : Elsevier. - 0924-9338 .- 1778-3585. ; 41:Suppl., s. S322-S322
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Previous studies of concentrations of serotonin reuptake inhibitors (SRIs) versus therapeutic efficacy have yielded inconsistent results. Even if the relationships between the individual's serotonergic system and the clinical symptoms of obsessive-compulsive disorder (OCD) are poorly understood, the SRIs are consistently effective in OCD. However, studies on SRI concentrations in OCD treatment are rare.Objectives/aims: To identify possible links between paroxetine concentrations and anti-obsessive response.Methods: In a randomised, double-blind trial, comparing clomipramine, paroxetine and placebo in OCD treatment, serum paroxetine levels were measured after 1 week and after 4 weeks of treatment in 18 patients. Anti-obsessive response was assessed with Yale-Brown obsessive compulsive scale (Y-BOCS) and patients’ global evaluation (PGE), after 12 weeks of treatment.Results: Serum paroxetine concentrations after 4 weeks suggested a therapeutic interval between 50 and 240 nmol/L (13–63 ng/mL). The mean Y-BOCS decrease was 54% inside versus 7% outside this interval (t = 3.96; P = 0.0011).Conclusions: Paroxetine levels seemingly predicted clinical outcome. Studies with a greater number of patients are necessary in order to confirm this finding and to discern whether it is useful in clinical practice.
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| 3. |
- Stoffel, M. A., et al.
(författare)
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Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.
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