Workshop: Mammalian Genes, Genomes, Transcriptomes and Networks
23-06-2015: University of Copenhagen, 13:25-16:30, Orangeriet, Dyrlægevej 36 at Frederiksberg Campus.
Registration is not necessary. Refreshments will be served (first come, first served).
Jan Gorodkin, University of Copenhagen
|13:30-14:15||Pig genomes: A story about natural and human mediated admixture and selection
Martien Groenen, Wageningen UR
|14:15-14:45||Of mice and men -"A transcriptomics look on atopic dermatitis- like mice and humans"
Thomas Litman, Leo Pharma
|15:15-16:00||Genome-wide detection of translated loci using spectral analysis of ribosomal footprints
Uwe Ohler, Max Delbruck Center for Molecular Medicine
|16:00-16:30||Gene association networks: Large-scale integration of data and text
Lars Juhl Jensen, CPR, University of Copenhagen
Pig genomes: A story about natural and human mediated admixture and selection.
Martien Groenen, Wageningen UR. (https://www.vcard.wur.nl/Views/Profile/View.aspx?id=3344)
Whole genome sequencing of hundreds of individual pigs representing different species, as well as a variety of domestic and wild populations from Sus scrofa, the pig species domesticated by humans, showed that admixture between different species and populations played an important role both during speciation and domestication. Our data highlight the importance of past cyclical climatic fluctuations in the speciation of the family Sus on the islands of South East Asia and subsequent admixture events between different species of this family.
In domestic pigs, genomes have been shaped by a complex demographic history, independent domestication in Asia and Anatolia and human mediated admixture. About 10,000 years ago pigs were domesticated independently in Anatolia and Asia from local wild boars that had diverged around 1My ago. This resulted in distinct European and Asian pig breeds, each with discrete phenotypic characteristics. However gene-flow from wild to domestic pigs continued to be an important post-domestication process in pigs. Despite this gene-flow, the genomes of domestic pigs show strong signatures of selection at loci that affect behaviour and morphology and our results suggest independent parallel sweeps in the two independent domestication areas (China and Anatolia) at loci linked to morphological traits.
In the late 18th - early 19th century, the domesticated descendants of these divergent populations were hybridized as Asian pigs were used to improve Western pigs. This hybridization can be identified in the genome of European pigs as relatively long haplotypes shared with Asian pigs. Since the initial introgression, subsequent bottlenecks and selection have resulted in specific Asian haplotypes to reach high frequencies in European breeds. We demonstrate both the presence of introgressed Asian haplotypes in these European domestic pigs and selection signatures on loci in those regions. These signatures are often subtle and rarely result in a complete sweep, possibly because of the quantitative nature of the associated traits. The identified Asian introgressed haplotypes are associated with regions harboring genes involved in meat quality, development and fertility. Our findings suggest that increased fertility and fatness both were important breeding goals for early nineteenth century pig farmers, and that specific Asian variants were selected during the development of modern European pig breeds.
Of mice and men -"A transcriptomics look on atopic dermatitis- like mice and humans"
Thomas Litman, Leo Pharma. (http://www.researchgate.net/profile/Thomas_Litman)
Atopic dermatitis (AD) is caused by a complex interplay between immune and epidermal barrier abnormalities.
While many mouse models have been used to simulate AD, their molecular phenotypes are not fully understood, and a comparison of key models to human AD is lacking.
We are currently evaluating the molecular phenotype of common models to determine how these relate to human AD. Thus, transcriptomics analysis by microarrays and subsequent validation by qRT-PCR has been performed on biopsies from seven mouse models. It is data from this study that will be presented and discussed in relation to the different immune and barrier aspects of AD.
Genome-wide detection of translated loci using spectral analysis of ribosomal footprints
Uwe Ohler, Max Delbruck Center for Molecular Medicine (https://ohlerlab.mdc-berlin.de/profiles/uohler/)
RNA-based sequencing technologies have made it possible to quantify gene expression regulation at each individual step, from transcription to protein synthesis. A recent protocol, called Ribosome Profiling, specifically collects the RNA fragments protected by ribosomes. Several studies have used this approach to provide global insights into the extent of pervasive translation and the coding potential of putative long non-coding RNAs. However, with the high resolution and depth obtained in recent experiments, ribosome profiling lets us pinpoint the exact codons that are processed by the translation machinery. More precisely, the profiles exhibit a three-nucleotide periodicity pattern of footprints along the reading frame.
To take full advantage of this information, we have developed a new computational strategy based on spectral analysis methods. This principled approach allows us to quantify the statistical significance of periodic patterns individually for each candidate locus, and unravels the presence of high-confidence coding loci outside of canonical coding sequences. Based on newly generated, deep data for the human cell line HEK293, we define hundreds of translated small Open Reading Frames, located mostly in the 5'UTR of coding transcripts, but also in annotated lincRNA and other non-coding genes. Comparison with shotgun mass-spectrometry data demonstrates this strategy to be at least on par with very deep proteomics datasets.
Gene association networks: Large-scale integration of data and text
Lars Juhl Jensen, CPR, KU (http://www.cpr.ku.dk/staff/staff_all/?pure=en/persons/343848)
Methodological advances have in recent years given us unprecedented information on the molecular details of living cells. However, it remains a challenge to collect all the available data on individual genes and to integrate the highly heterogeneous evidence available with what is described in the scientific literature.
In the presentation he will describe the STRING database (http://string-db.org), which is widely used in the proteomics community. It aims to provide critical assessment and comprehensive integration of protein–protein interactions, including both direct physical interactions and indirect functional associations. The latest version of STRING covers more than 2000 organisms for which it includes evidence from a diverse range of curated databases, raw data repositories, automatic text mining of biomedical literature, and computational prediction methods.
It will also briefly introduce a new suite of web resources that apply the same strategy to study subcellular localization (http://compartments.jensenlab.org), tissue expression (http://tissues.jensenlab.org), and disease associations (http://diseases.jensenlab.org).