CMB&RM seminar: High-throughput skeletal phenotyping of KO mice from the International Mouse Phenotyping Consortium; new biology and opportunities for data integration
| Dates: | 30 May 2019 |
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| Times: | 14:00 - 15:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Graham R Williams |
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The International Knockout Mouse Consortium (IMPC) aims to generate knockout mice for all 20,000 protein coding genes in C57BL6/N mice and decipher their function. To date around 8,000 KO lines have been generated in 19 centres worldwide, with over 2,500 lines contributed by the Sanger Institute and MRC Harwell. A broad primary phenotype screen reports 233 variables covering 26 physiological systems and offers a wealth of open access data, although available skeletal analysis lacks sensitivity and functional information. The Wellcome Trust-funded "Origins of Bone and Cartilage Disease" (OBCD) programme has developed rapid-throughput analysis of bone and joint phenotypes in IMPC KO mice to (i) advance understanding of skeletal biology and bone & joint disease pathophysiology, (ii) uncover new susceptibility alleles for skeletal disorders, and (iii) provide in vivo models to elucidate the molecular mechanisms of disease. OBCD analysis determines multiple phenotype parameters relating to the structure and function of bone, and to the characteristics of subchondral bone, joint surface and articular cartilage in the knee joint. Bone phenotyping has been completed in >1000 KO lines, and novel techniques for joint phenotyping have been developed and validated with comprehensive phenotyping completed in >50 KO lines. These datasets are growing, they represent the largest skeletal phenotype resource worldwide and are already being integrated with (i) IMPC phenotype data from other physiological systems (ii) international GWAS in osteoporosis and osteoarthritis, and (iii) transcriptomic datasets from skeletal cell lineages, the Single Cell Expression Atlas and other EMBL-EBI platforms. This presentation will highlight how collaboration can be applied to accelerate gene discovery and functional annotation in skeletal disease and discuss further opportunities for data integration in the future.
Speaker
Graham R Williams
Role: Professor
Organisation: Imperial College London
Travel and Contact Information
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Lecture Theatre
Michael Smith Building
Manchester
