hvp5: meeting summary and thoughts - garry cutting
TRANSCRIPT
Meeting summary and thoughts
Garry Cutting, MDMcKusick Nathans Institute of Genetic Medicine
Johns Hopkins
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KudosScientific Programme CommitteeRichard G. H. Cotton (Melbourne, Australia)Raymond Dalgleish (Leicester, United Kingdom)Johan T. den Dunnen (Leiden, Netherlands)Marc Greenblatt (Burlington, VT, United States)Aida Falcon de Vargas (Caracas, Venezuela)Finlay Macrae (Melbourne, Australia)Martina Witsch-Baumgartner (Innsbruck, Austria)
Organising SecretariatRania Horaitis, ICOHeather Howard, ICOHelen Robinson , ICOTimothy Smith, ICOCasimiro Vizzini, UNESCO
And finish on time
Don’t be boring
Annotating variation in the human genome
• The challenge
• Potential solutions
The Cambridge Wine Blogger http://cambridgewineblogger.blogspot.com/2011/06/on-breadth-vs-depth-in-tasting.html
Stylianos Antonarakis, Session VIII
Rapid increase in the number of genes associated with mendelian phenotypes
Source: OMIMYears
Num
ber o
f gen
es
Number of variants reported per gene in the Leiden Open Variation Database (LOVD)
Variants from LOVD databases version 2.0-24 or higher and with properly configured reference sequences were used to extract the number of unique alleles reported per gene. If a gene was present in multiple databases (duplicate instances), the raw data was parsed such that the highest number of variants per a given gene was reported. Data courtesy of Ivo F.A.C. Fokkema and Johan T. den Dunnen.
Figures courtesy of Melissa Lee Cutting GR AJHG 2014
• Increasing number of genes associated with mendelian disease
• Increasing number of variants per gene
Perfect Storm of Variants
Interpretive gap: Difference between rate of variant discovery and rate of
variant annotation
Variants identified Interpretive gap
Annotated
Cost of sequencing
Time
$$
Cutting GR AJHG 2014
Quantifying the interpretive gap
CFTR
137 for OMIM, 1301 for HGMD, 345 for LOVD
HBA1HBB
Gene matched counts of variants per gene, sorted by length
Christopher Cassa, Session X
Stylianos Antonarakis, Session VIII
Thomy de Ravel, Session II
Nik Nor Liza Nik Hassan, Session II
Raj Ramesar, Session III
Dwomoa Adu, Session III
Enock Matovu, Session III
Stylianos Antonarakis, Session VIII
Ted Kalbfleisch, Session IV
Moris Swertz, Session IV
Stylianos Antonarakis, Session VIII
Peter Taschner, Session V
Raymond Dalgleish, Session V
Ada Hamosh, Session V
Stylianos Antonarakis, Session VIII
Hoan Nyugen, Session VIII
Tuuli Lappalainen, Session VIII
Variant Annotation Projects
• INSiGHT: International Society for Gastrointestinal Hereditary Tumors – Mismatch repair genes (Thompson et al Nat Genet 2014)
• CFTR2: Clinical and Functional Translation of CFTR – CFTR (Sosnay et al Nat Genet 2013)
• ENIGMA :Evidence-based Network for the Interpretation of Germline Mutant Alleles– BRCA 1/2
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Maurizio Genuardi, Session IX
Finlay Macrae, Session IX
Christopher Cassa, Session X
Standards Development & Recommended Systems
• HGVS variation nomenclature• Mutalyzer • LOVD• VarioML • Variation Ontology (VariO)
• W01:Disclaimer Statements on G/DSDBs• WG02: Assigning Pathogenicity to a Genetic Variant• WG03 Minimal content for gene variant databases (LSDBS)• WG04 Minimum Content Requirements for HVP Country Nodes• WG05: Variant Database Quality Assessment• WG06: Disease &Phenotype Descriptions in Gene/Disease Specific
Databases
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Summary
Thank you for attending HVP5
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