1. PhenCode Linking Human Mutations to Phenotype

2. PhenCode Brings the deep information on genotypes and phenotypes in locus specific databases (LSDBs) into a common database Uses genome sequence coordinates Allows data to be displayed in genome browsers and compared and analyzed with respect to other genome data. Collaboration among many LSDBs, Human Genome Variation Society and genome browsers

3. 23 (142) LSDBs Over 17,000 mutations Swiss-Prot / UniProt Over 23,000 mutations

4. Access to data in PhenCode Home Page www.bx.psu.edu/phencodewww.bx.psu.edu/phencode –Query page –History page Output can be viewed as –a custom track at UCSC Genome Browser (then Table Browser and Genome Graphs) –A custom track at Ensembl –Custom track files for other Genome Browsers –As tab delimited text for downloads

5. “What LSDB variants are NOT in dbSNP and ARE in conserved regions?” Find substitutions in PhenCode / Locus Variants track Remove entries that are already in dbSNP Remove entries that are not intersected by the most conserved track (PhastCons) View results as coverage on genome and details of an single variant

6. PhenCode query page

7. Export the data and view as a track in the UCSC Genome Browser.

8. The Table Browser can now be used to filter out the entries included in dbSNP or not covered by the Most Conserved track.

9. The filters have reduced the numbers, but there are many left.

10. Genome Graphs shows the coverage of the results

12. Genome Graphs displays the coverage back in the Genome Browser.

13. A summary can be found at the PhenCode site and more details at the source LSDB. CMT2 = Charcot-Marie-Tooth disease - OMIM 600882,118210, 605588, 605589, 601472 most common disorder of the peripheral nervous system. (described in 1886) dHMN = distal Hereditary Motor Neuropathies - OMIM 158590, 600794, …

14. The IPNMDB display

15. Conclusion The deep annotations from LSDBs compliment the broad annotations from dbSNP The data from PhenCode is public and available in genome browsers and as text. –www.bx.psu.edu/phencode

16. Acknowledgements Work was supported by –NIH grant HG002238 (Miller) –NIH grant DK65806 (Hardison) –NHGRI grant 1P41HG02371 (Kent)