PhenCode

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PhenCode

• Connecting Genotype and Phenotype

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HbVar Hemoglobin variants and thalassemia
mutations

• Began as Prof. Titus Huismans 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.

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Current status of HbVar

• 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/
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GenPhen

• Records genotype and published phenotype data
• Hemoglobin variants
• Thalassemias
• HPFH

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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

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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

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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

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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

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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

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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)

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PAH gene in UCSC Browser
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Details page at browser
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Follow links back to PAHdb
Liver-specific enhancer of human PAH.
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Examples

• Examples are available at http//www.bx.psu.edu