encode to phencode: combining hbvar with genomic and encode annotations ross hardison, representing:...
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ENCODE to PhenCode: Combining HbVar with Genomic and ENCODE
annotations
Ross Hardison, representing:Curators and staff of HbVar and GenPhen
PSU Center for Comparative Genomics and BioinformaticsUCSC Genome BrowserOther collaborators
Importance of inherited hemoglobinopathies
• Most common inherited diseases in humans• Hemoglobin variants can lead to:
– Pathologies such as sickle cell disease, unstable hemoglobins, altered oxygen affinities
– No alteration in phenotype– Some protection against malarial parasite
• Thalassemias– Inherited anemias resulting from deficit in production of alpha-globin or beta-globin
• Hereditary persistence of fetal hemoglobin– HPFH– Maintain HbF in adult life
Developmental regulation of the HBB gene complex
transcription, in erythroid cells
embryonicfetaladult
locus control region
HbVar: Hemoglobin variants and thalassemia mutations
• Began as Prof. Titus Huisman’s Syllabus of Hemoglobin Variants and Syllabus of Thalassemia Mutations
• Converted to on-line resource about 1997
• Major curators now:– Henri Wajcman, Ph.D.– George Patrinos, M.D., Ph.D.– David Chui, M.D.
Current status of HbVar
• Type Count• Total entries in database 1233• Total hemoglobin variant entries 926• Total thalassemia entries 355• Entries both variant and thalassemia 48• Entries involving the alpha1 gene 250• Entries involving the alpha2 gene 286• Entries involving the beta gene 687
http://www.bx.psu.edu/
Use UCSC Genome Browser as a portal to locus specific data
• MANY more people go to genome browsers than to locus specific databases
• Data on variants and mutations can be easily displayed as a track on the browser
• Information from other resources can be readily be integrated with variation information– E.g. ENCODE data on transcription, factor binding sites, chromatin modifications, etc.
– Viewed on Genome Browser– Accessed via Table Browser
UCSC Genome Browser is a portal to HbVar and an integrator of functional, genomic and
genotype data
Data on function from ENCODE
Genotype data with links to phenotype
Genes and pseudogenes
Comparative genomics
Find mutations associated with high HbF in HbVar
Query in HbVar for mutations associated with a similar phenotype
Start with information on an HPFH mutation upstream from HBG1
Discover that some of the mutations are in a linked gene, HBB
Future prospects
• Add more loci– WayStation: Community-wide Database for participating locus-specific databases
– Individual databases– Harvest protein variants from SwissProt (Fan Hsu, UCSC)
• Better display of phenotype information in browser– Genotype is naturally displayed in genome coordinates– Effects on expression levels, development, cell cycle progression, etc need additional dimensionality
– Current solution is crude (put it on a different page)
• Improve integration among the datasets– Table Browser to obtain data– Integration tools at Table Browser and Galaxy, other servers
Collaborating Institutions and People
• Center for Comparative Genomics and Bioinformatics, Penn State University, University Park, PA
– Belinda Giardine, Ross Hardison, Webb Miller, Cathy Riemer
• Erasmus University, Rotterdam, Netherlands– George Patrinos
• Hospital Henri Mondor, Creteil, France– Henri Wajcman
• Boston University– David H.K. Chui
• IMBB, Crete, Greece– Nick Anagnou
• Macedonian Academy of Sciences and Arts, RCGEB, Skopje, Macedonia– Georgi D. Efremov
• Weatherall Institute of Molecular Medicine, Oxford UK– Richard Gibbons, Doug Higgs, Jim Hughes
• Johns Hopkins University School of Medicine, Baltimore, MD– Garry Cutting, Andrew P. Feinberg
• Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA
– Fan Hsu, Jim Kent, Andrew Kern, Robert Kuhn, Heather Trumbower
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