Organisers

Niels Tommerup, Wilhelm Johannsen Centre for Functional Genome Research, Dept. of Cellular and Molecular Medicine, Panum Institute, Blegdamsvej 3B, 2200 Copenhagen N

Introduction

The terms gene, genotype and phenotype was coined by the Danish geneticist Wilhelm Johannsen in 1909 [1], and the Wilhelm Johannsen Centre for Functional Genome Research was established in 2001 by the Danish National Research Foundation which will be ending in 2011[2]. To celebrate that and honour Wilhelm Johannsen a workshop is planned looking into his ideas from today’s technological developments. The first part of the workshop will focus on to what extent the emerging high-throughput sequencing technologies may influence the concept of the gene as a functional unit, from classical protein coding genes to the growing world of non-coding RNA-genes including microRNA genes (David Haussler, USA [3]; Wang Jun, China [4]). Furthermore, the celebration will focus on how molecular genetics have identified the genotype behind numerous genetics disorders, with suprising examples of lumping and splitting of clinical entities, and how this will be accellerated by novel sequencing strategies (Han Brunner, The Netherlands) [5]. One area where this may revolutionise both the discovery phase and eventually diagnostics, may be the many neurodevelopmental and psychiatric disorders, including mental retardation, autism, and schizophrenia, where a majority of the high heritability in these disorders have remained unexplained as a dark matter of heritability, despite numerous genome-wide association studies. A likely explanation for this is an enormous genetic heterogeneity, with the presence of many new mutations. The workshop will address the latest developments in the molecular dissection of these disorders, from the first detection of pathogenic mutations in autism, schizophrenia and idiopathic epilepsy in the form of recurrent copy number variants to the likelihood that deep sequencing will be able to reveal a molecular basis for other classical genetic terms like reduced penetrance and genetic variability in neurodevelopmental and psychiatric disorders (Hans-Hilger Ropers, Germany [6]; Evan Eichler, US [7]).

The multitude of genetic variants that will be detected by deep sequencing, e.g. by exome sequencing, will necessitate roper control data from the population, and a better understanding of the Systems Biology of the relevant disease. The workshop will address the first of these issues by describing the results of the so far largest exome sequencing effort involving 2000 Danes (Oluf B. Pedersen, Denmark [8]), and how this population resource may facilitate genetic research in the future. The concept and development of tools for Systems Biology research will be addressed by one of the pioneers in the field (Søren Brunak, Denmark) [9] and exemplified by the recent description of the Systems Biology of congenital heart disease (Lars Allan Larsen, Denmark) [10]. The Danish exome resource will be combined with a Systems Biology model of neurodevelopmental and psychiatric disorders and with large scale deep sequencing in an effort to dissect the molecular basis for cognitive comorbidity (Niels Tommerup, Denmark). The establishment of a genotype-phenotype relationsship by the detection of a mutation necessitates functional analyses of the specific gene and mutation involved. Traditionally, this is done by knock-out or knock-down experiments of single genes, e.g. in animal or cellular models. However, the future deep- sequencing based molecular dissection of more complex disorders and more complex molecular basis of disease, including polygenic inheritance and epigenetic modifiers, will necessitate the development of patient- and tissue specific models. This will be especially important for disorders affecting the central nervous system, with human specific phenotypes, e.g. speech defects and dyslexia. The latest developments in the generation of human specific disease models by generation and differentiation of human induced stem cells (hiPS) will be addressed by Juan Izpisúa-Belmonte, Spain [11]. The complex molecular mechanisms related to epigenetic modifications that may modify genotype-phenotype relationships is addressed by Dirk Schübeler, Switzerland [12]. New developments in high-throughput microscopy can address the phenotype at cellular level (Rainer Pepperkok, Germany) [13].

The keynote speakers will be supplemented by selected and related presentations given by the young participants.

[1] Johannsen, W. (1909) Elemente der exakten Erblichkeitslehre. Gustav Fischer, Jena.
[2] Wilhelm Johannsen Centre for Functional Genome Research. http://www.wjc.ku.dk/
[3] Pruitt KD, et al. Genome Res. 2009;19:1316-23.
[4] Heard E, et al. Nat Rev Genet. 2010;11:723-33.
[5] Krawitz PM, et al. Nat Genet. 2010 Aug 29. [Epub ahead of print].
[6] Ropers HH. Annu Rev Genomics Hum Genet. 2010;11:161-87.
[7] Eichler EE, et al. Nat Rev Genet. 2010;11:446-50.
[8] LuCamp. Lundbeck Foundation Centre for applied medical genomics in personalised disease protection, prevention and care. http://www.lucamp.org/#/172977/
[9] Lage et a. Nat Biotechnol 2007;25:309-16.
[10] Lage et a. Mol Syst Biol. 2010;6:381.
[11] Raya A, et al. Nat Protoc. 2010;5:647-60.
[12] Schübeler D. Nature 2009;462:296-7.
[13] Neumann B, et al. Nature 2010; 464:721-7

Venue

The meeting will be held at the Panum Institute, Dam Auditorium, Blegdamsvej 3, 2200-Copenhagen N (Nørre Campus of the University of Copenhagen).

For travel to the Panum Institute, please see links at: http://www.wjc.ku.dk/travel/index.php?subpage=maps

The Dam Auditorium is located above the main entrance on the first floor, in front of the circular stairs.

Speakers

David Haussler, Santa Cruz, USA
Wang Jun, Shenzen, China
Han Brunner, Nijmegen, The Netherlands
Hans-Hilger Ropers, Berlin, Germany
Evan Eichler, Seattle, USA
Oluf B. Pedersen, Copenhagen, Denmark
Søren Brunak, Lyngby, Denmark
Lars Allan Larsen, Wilhelm Johannsen Centre, Denmark
Niels Tommerup, Wilhelm Johannsen Centre, Denmark
Juan Izpisúa Belmonte, Barcelona, Spain
Rainer Pepperkok, Heidelberg, Germany
Dirk Schübeler, Basel, Switzerland

Draft Programme

Day 1: 100 years with the terms gene, genotype and phenotype
Welcome: Niels Tommerup
Morning session:
The gene as a concept: David Haussler, Santa Cruz, CA
The gene in the era of deep sequencing. Wang Jun, Beijing.
Oral presentations by 3 young participants

Afternoon session:
Genotype and Phenotype. Han Brunner, Nijmegen, The Netherlands.
Oral presentations by 3 young participants

Day 2: The interplay of genes in complex disorders
Morning session:
Next generation sequencing in mental retardation: Hans-Hilger Ropers, Berlin.
Genomic cognition disorders: Evan Eichler, Seattle.
Oral presentations by 3 young participants

Afternoon session:
Systems Biology. Søren Brunak, Lyngby.
Large scale exome sequencing. Oluf B. Pedersen, Copenhagen.
Oral presentations by 3 young participants

Day 3: From Interaction Networks to Phenotypes
Morning session:
From Interaction Networks to Phenotype in congenital heart disease. Lars Allan Larsen, Copenhagen.
Genotype-phenotype relations in cognitive comorbidity: Niels Tommerup, Copenhagen.
Oral presentations by 3 young participants.

Afternoon session:
Induced Stem Cells as disease models. Juan Izpisúa-Belmonte, Barcelona.
Epigenetics: Dirk Schübeler, Basel.
High-throughput microscopy: Rainer Pepperkok, Heidelberg.
Oral presentations by 3 young participants.

Registration

Registration is now closed.