Transcript PhenCode - Pennsylvania State University

PhenCode
Connecting Genotype and Phenotype
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
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Type
Count
Total entries in database
1237
Total hemoglobin variant entries
930
Total thalassemia entries
355
Entries both variant and thalassemia
48
Entries involving the alpha1 gene
252
Entries involving the alpha2 gene
287
Entries involving the beta gene
688
http://www.bx.psu.edu/
GenPhen
• Records genotype and published phenotype data
– Hemoglobin variants
– Thalassemias
– HPFH
The Problem
• Genotype is well covered by browsers such
as those at UCSC and Ensembl
• Phenotype data is scattered among literature
articles and Locus Specific Databases
(LSDBs)
• No easy way of getting from one to another
Difficulties in making the
connection
• Inconsistencies in fields, coordinate systems, and
nomenclature
• Standards are still being developed by the research
community
– Human Genome Variation Society (HGVS)
– Mammalian Phenotype (MP) Ontology
• Requires a large number of research groups,
representing hundreds of databases, to work
together
Similar projects
• OMIM
– Lack of controlled vocabulary, inconsistent base
numbering
• HmutDb
– Lacks plans for curation
– Requires a reference sequence, but not chromosome
coordinates
• HGVbase
– Not yet available; in progress for years
• The WayStation and its associated central
repository
– Lacks funding
– No chromosome coordinates
PhenCode plan
• Start by incorporating data from a few selected
LSDBs as a proof of concept, and expand as more
LSDB curators become interested
– Currently we have HbVar, PAHdb, and are working on
BGMUT, ARdb, and CFTR.
– In addition, genome-wide variants have been imported
from SwissProt
• Work closely with the central repository and The
WayStation for new mutations.
– Use tools to map HGVS name to chromosome
coordinates
PhenCode plan continued
• Keep a summary of the data in the central
repository as a Human Mutation track at UCSC
• Provide links to the LSDBs and other phenotype
databases from the track to allow more in-depth
queries
• Build a companion Landmarks track containing
reference points provided by the LSDB curators
for each locus
Recent additions
• We have added data for the human
phenylalanine hydroxylase gene (PAH).
This data came from PAHdb at McGill
University.
• Deficiencies in PAH cause phenylketonuria
(PKU)
PAH gene in UCSC Browser
Details page at browser
Follow links back to PAHdb
Liver-specific enhancer of human PAH.
Examples
• Examples are available at http://www.bx.psu.edu