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Biology subjects

Vermaat, M.

Publications and source records attributed to Vermaat, M..

3 recordsLinked to original sources

Mutalyzer 2: Next Generation HGVS Nomenclature Checker

Unambiguous variant descriptions are of utmost importance in clinical genetic diagnostics, scientific literature, and genetic databases. The Human Genome Variation Society (HGVS) publishes a comprehensive set of guidelines on how variants should be correctly and unambiguously described. We present the implementation of the Mutalyzer 2 tool suite, designed to automatically apply the HGVS guidelines so users do not have to deal with the HGVS intricacies explicitly to check and correct their variant descriptions. Mutalyzer is profusely used by the community, having processed over 133 million descriptions since its launch. Over a five year period, Mutalyzer reported a correct input in approximately 50% of cases. In 41% of the cases either a syntactic or semantic error was identified and for approximately 7% of cases, Mutalyzer was able to automatically correct the description.

bioinformatics↗

Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic diversity in the lion (Panthera leo)

BackgroundPrevious phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting. ResultsIn this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail. ConclusionsThe results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management of ex situ populations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity.

evolutionary biology↗

Full-length mRNA sequencing uncovers a widespread coupling between transcription and mRNA processing

The multifaceted control of gene expression requires tight coordination of regulatory mechanisms at transcriptional and post-transcriptional level. Here, we studied the interdependence of transcription, splicing and polyadenylation events on single mRNA molecules by full-length mRNA sequencing. In MCF-7 breast cancer cells, we found 2,700 genes with interdependent alternative transcription, splicing and polyadenylation events, both in proximal and distant parts of mRNA molecules. The analysis of three human primary tissues revealed similar patterns of interdependency between transcription and mRNA processing events. We predict thousands of novel Open Reading Frames from the sequence of full-length mRNAs and obtained evidence for their translation by shotgun proteomics. The mapping database rescued 358 previously unassigned peptides and improved the assignment of others. By recognizing sample-specific amino-acid changes and novel splicing patterns, full-length mRNA sequencing improved proteogenomics analysis of MCF-7 cells. Our findings demonstrate that our understanding of transcriptome complexity is far from complete and provides a basis to reveal largely unresolved mechanisms that coordinate transcription and mRNA processing.

molecular biology↗