NSC seminar October 28th, 2011: High-throughput Sequencing – Applications and Analyses

PROGAMME

10.00 – 10.10  Welcome and opening remarks by Dag Undlien, Oslo University Hospital, Institute of Medical Genetics Ullevål

10.10 – 11.00  “I have half my mother’s genes yet am 98% identical to a chimpanzee” by Prof. Ken Dewar, McGill University

Genomic technologies continue to lay a foundation for further health research and are becoming increasingly present in clinical settings. At the same time, genomics is becoming widely accessible throughout all of the life sciences and is impacting research into microbes and infectious diseases, biotechnological applications for improving food safety supply, and new methodologies for assessing and improving environmental health. The McGill University and Genome Quebec Innovation Centre in Montreal is a genomics and bioinformatics core for Quebec and eastern Canada. The presentation will summarize several ongoing projects and highlight how genomic sciences are advancing research in combating the bacterial pathogen Clostridium difficile, identifying fungal genes for breaking down forest waste materials, and developing a genomic framework in the vervet monkey as a model for complex human behaviours.

11.00 – 11.50  “Cichlidomics: uncovering the molecular basis of diversification in East African cichlid fishes” by Dr. Walter Salzburger, Zoological Institute, University of Basel, Switzerland

More than 150 years after the publication of Charles R. Darwin’s The Origin of Species, the identification of the processes governing the emergence of novel species remains a fundamental question to biology. Why is it that some groups have diversified in a seemingly explosive manner, while other lineages have remained unvaried over millions of years? And what are the external factors and environmental conditions that promote diversification? A key to these and related questions is the comparative study of exceptionally diverse yet relatively young species assemblages that have radiated in geographically well-defined areas, such as the Darwin’s finches on the Galapagos archipelago or the cichlid fishes in the Great Lakes of East Africa. Lakes Tanganyika, Malawi, and Victoria are each teeming with a unique set of hundreds of endemic cichlid species, which are likely to have evolved in the last few millions to several thousands of years only. East Africa’s cichlid species differ greatly in ecologically relevant, hence naturally selected, characters such as mouth morphology and body shape, but also in sexually selected traits such as coloration. One of the most fascinating aspects of cichlid evolution is the frequent occurrence of evolutionary parallelisms, which has led to the question whether selection alone is sufficient to produce these parallel morphologies, or whether a developmental or genetic bias has influenced the direction of diversification. The availability of five cichlid genomes now greatly enhances the quest for the molecular basis of diversification in cichlid fishes.

11.50 – 12.00  Discussion

12.00 – 13.00  Lunch

13.00 – 13.50  “Pathogenic alleles, clan genomics and the complex genetic architecture of human disease” by Prof. James R. Lupski, Department of Molecular and Human Genetics, Baylor College of Medicine

Mendelian disorders and common complex conditions have traditionally been considered separate categories of human disease, with distinct genetic architectures. Emerging data suggest that the genetic contributions to human disease most likely result from a genome wide mutational burden contributing to the totality of pathogenic alleles.  Human diseases may be caused by alleles across the full range of variant types including simple nucleotide variants (SNV), small indels, structural variants and copy number variants (CNV), and may involve variants across the allele frequency spectrum (i.e. including rare and common), regardless of disease category and disease frequency. The availability of whole genome sequences of several individuals from multiple populations, 1000 Genomes Project pilot studies, and targeted genomic sequences derived from very large sample sizes, have shown that the prevalence of rare variants is perhaps greater than anticipated. These new data and the subsequent fundamental shift in perspective have important ramifications for approaches to discovery and diagnostics in human disease. A new synthesis is required to interpret the totality of variation within personal genomes in the context of complete individual genetic variation data, population genetics, and evolution. Ultimately, the genetic health of individuals, i.e. genomic variation conveying susceptibility to disease or resulting in protection from disease, may be influenced much more by recent mutation than older mutations that occurred in distant ancestors.

13.50 – 14.40  “Ensembl and incorporation of new sequence technology data” by Prof. Steve Searle, Wellcome Trust Sanger Institute

Ensembl is an established project providing genomic data for more than 10 years. It aims to produce high quality gene annotation, comparative genomic, variation genomic and functional genomic data in a fully integrate resource for more than 55 species. The influx of new sequence technology data has provided opportunities for extending and improving Ensembl annotation. One major consequence is that the number of species being sequenced has expanded dramatically recently. Also RNASeq is being used in gene annotation and ChIP-Seq in regulatory region annotation. It has also lead to some challenges, in particular around processing and presenting the sheer volumes of data, but also in qualitative changes in the data, such as changes in the characteristics of assemblies based on new sequence technology data, and generating complete transcript models from the short RNASeq reads. I will present Ensembl and some of the recently incorporated new sequence technology data.

14.40 – 15.30  “Single Molecule, Real-Time Sequencing on the PacBio^™ RS platform: Technology and Applications” by Dr. Deepak Singh, Pacific Biosciences Europe

A Pacific Biosciences 'PacBio RS' platform has been ordered by the NSC – and will be in place during the fourth quarter of 2011. The 'PacBio RS' platform employs revolutionary SMRT biology that incorporates single molecule real-time sequencing techniques. This technology delivers unprecedented sequence read lengths and allows researchers to obtain results in less than a day. These enabling capabilities of the technology are expanding the range of applications in all areas of genomic research which will be shared and discussed during this presentation.

15.30 – 15.45  Discussion and closing remarks by Nils Chr. Stenseth and Kjetill S. Jakobsen, Centre for Ecological & Evolutionary Synthesis, University of Oslo

 

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Please note that the NSC is organising a course in basic applications and bioinformatics analysis of High Throughput Sequencing data Oct. 25-28, i.e. the days prior to the seminar. For more information on the course, and for applying to participate, visit the course website.