disease modularity
Similar phenotypes can be begotten by functionally related genes. This is most obvious in the case of genetically heterogeneous diseases such as Fanconi disease (Fanconi anemia), Bardet-Biedl syndrome (BBS) or Usher syndrome, where the various genes work together in a single biological module.
Such biological modules can be a multiprotein complex, a pathway, or a single cellular or subcellular organelle.
This observation suggests a number of hypotheses about the human phenome that are now beginning to be explored.
First, there is now good evidence from bioinformatic analyses that human genetic diseases can be clustered on the basis of their phenotypic similarities and that such a clustering represents true biological relationships of the genes involved.
Second, one may use such phenotypic similarity to predict and then test for the contribution of apparently unrelated genes to the same functional module. This concept is now being systematically tested for several diseases. Most recently, a systematic yeast two-hybrid screen of all known genes for inherited ataxias indicated that they all form part of a single extended protein-protein interaction network.
Third, one can use bioinformatics to make predictions about new genes for diseases that form part of the same phenotype cluster. This is done by starting from the known disease genes and then searching for genes that share one or more functional attributes such as gene expression pattern, coevolution, or gene ontology (GO).
References
Oti M, Brunner HG. The modular nature of genetic diseases.Clin Genet. 2007 Jan;71(1):1-11. PMID: #17204041#