Challenges for the study of disease in the 21 st century • Characterise the function of every gene in the mammalian genome • Generate mutations in every gene in the mouse genome • Characterise the phenotype of every mutant mice • Identify models of human disease Genome Function Disease
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Challenges for the study of disease in the 21 st century Characterise the function of every gene in the mammalian genome Generate mutations in every gene.
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Challenges for the study of disease in the 21st century
• Characterise the function of every gene in the mammalian genome
• Generate mutations in every gene in the mouse genome
• Characterise the phenotype of every mutant mice
• Identify models of human disease
Genome
Function
Disease
European Mouse Programmes
• EUCOMM
• Developing mouse mutants for most of the genes in the mouse genome
• EUMORPHIA
• Development and standardisation of mouse phenotyping platforms
• EUMODIC - European Mouse Disease Clinic
• Undertake a major pilot programme to utilise standardised phenotyping platforms for the analysis of a large number of mouse mutants
Challenges for the study of disease in the 21st century
• Characterise the function of every gene in the mammalian genome
• Generate mutations in every gene in the mouse genome
• Characterise the phenotype of every mutant mice
• Identify models of human disease
Genome
Function
Disease
European Mouse Programmes • EUCOMM 2006-2009
• European Conditional Mouse Mutagenesis program
• Major Participants - GSF, Sanger, Univ. Frankfurt, Max Planck, Berlin, Harwell, Univ. Dresden, Strasbourg, CNR & EMBL, Monterotondo, RZPD
• 20,000 gene trap and targeted null/conditional ES lines - library archived at RZPD, Heidelberg for distribution
• 320 mouse lines generated and re-archived for distribution to the community
• 20 new Cre expressing mouse strains generated
• Complementary programmes in Canada - NorCOMM (underway), and US - KOMP (RFA)
The European Conditional Mouse Mutagenesis Program
EUCOMM1. GSF National Center, Munich, Germany
W. Wurst (coordinator), Hrabe de Angelis2. Wellcome Trust Sanger Institute,
Hinxton, UKA. Bradley (coordinator), W. Skarnes, P. Liu
3. University Frankfurt, GermanyH. von Melchner
4. Max-Planck-Institute of Molecular Genetics, Berlin, GermanyP. Ruiz
5. University Dresden, GermanyF. Stewart
6. Gene Bridges, Dresden, Germany
G. Stevens7. Institute Clinique de la Souris (ICS),
Strasbourg, FranceP. Chambon
8. EMBL, Monterotondo, ItalyN. Rosentahl
9. Medical Research Council, Harwell, UKS. Brown
10. National Research Council, Monterotondo, ItalyG. Tocchini-Valentini
11. German Rsesource Center of Genome Research (RZPD), HeidelbergB. Korn
European Mouse Programmes • EUCOMM 2006-2009
• European Conditional Mouse Mutagenesis program
• Major Participants - GSF, Sanger, Univ. Frankfurt, Max Planck, Berlin, Harwell, Univ. Dresden, Strasbourg, CNR & EMBL, Monterotondo, RZPD
• 20,000 gene trap and targeted null/conditional ES lines - library archived at RZPD, Heidelberg for distribution
• 320 mouse lines generated and re-archived for distribution to the community
• 20 new Cre expressing mouse strains generated
• Complementary programmes in Canada - NorCOMM (underway), and US - KOMP (RFA)
Challenges for the study of disease in the 21st century
• Characterise the function of every gene in the mammalian genome
• Generate mutations in every gene in the mouse genome
• Characterise the phenotype of every mutant mice
• Identify models of human disease
Genome
Function
Disease
Challenges of Phenotyping
• Developing a comprehensive phenotyping platform able to deliver phenotypic information for all body systems
• Standardising phenotyping protocols so that we can share and compare phenotype data from mouse genetics centres throughout the world
The importance of standardisation
• Better reproducibility of test outcome
• Better comparability of test outcome
• Sharing of phenome results
AcrossTime
AcrossLabs
UnifiedDatabase
Eumorphia Phenotype screens for mice
Developing an integrated platform
EUMORPHIA - the consortium MRC Mammalian Genetics Unit, UK