1. PhenCode Connecting Genotype and Phenotype

2. 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.

3. Current status of HbVar TypeCount Total entries in database1237 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/

4. GenPhen Records genotype and published phenotype data –Hemoglobin variants –Thalassemias –HPFH

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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)

11. PAH gene in UCSC Browser

12. Details page at browser

13. Follow links back to PAHdb Liver-specific enhancer of human PAH.

14. Examples Examples are available at http://www.bx.psu.eduhttp://www.bx.psu.edu