Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling

Yuval Tabach, Tamar Golan, Abrahan Hernández-Hernández, Arielle R. Messer, Tomoyuki Fukuda, Anna Kouznetsova, Jian Guo Liu, Ingrid Lilienthal, Carmit Levy, Gary Ruvkun

Research output: Contribution to journalArticlepeer-review


Genes with common profiles of the presence and absence in disparate genomes tend to function in the same pathway. By mapping all human genes into about 1000 clusters of genes with similar patterns of conservation across eukaryotic phylogeny, we determined that sets of genes associated with particular diseases have similar phylogenetic profiles. By focusing on those human phylogenetic gene clusters that significantly overlap some of the thousands of human gene sets defined by their coexpression or annotation to pathways or other molecular attributes, we reveal the evolutionary map that connects molecular pathways and human diseases. The other genes in the phylogenetic clusters enriched for particular known disease genes or molecular pathways identify candidate genes for roles in those same disorders and pathways. Focusing on proteins coevolved with the microphthalmia-associated transcription factor (MITF), we identified the Notch pathway suppressor of hairless (RBP-Jk/SuH) transcriptionfactor,and showed that RBP-Jk functions as an MITF cofactor.

Original languageAmerican English
Article number692
JournalMolecular Systems Biology
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • Applied Mathematics
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


Dive into the research topics of 'Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling'. Together they form a unique fingerprint.

Cite this