Insights from Chromosome-Centric Mapping of Disease-Associated Genes: Chromosome 12 Perspective.

ABSTRACT

In line with the aims of the Chromosome-based Human Proteome Project and the Biology/Disease-based Human Proteome Project, we have been studying differentially expressed transcripts and proteins in gliomas­the most prevalent primary brain tumors. Here, we present a perspective on important insights from this analysis in terms of their co-expression, co-regulation/de-regulation, and co-localization on chromosome 12 (Chr. 12). We observe the following (1) Over-expression of genes mapping onto amplicon regions of chromosomes may be considered as a biological validation of mass spectrometry data. (2) Their co-localization further suggests common determinants of co-expression and co-regulation of these clusters. (3) Co-localization of "missing" protein genes of Chr. 12 in close proximity to functionally related genes may help in predicting their functions. (4) Further, integrating differentially expressed gene-protein sets and their ontologies with medical terms associated with clinical phenotypes in a chromosome-centric manner reveals a network of genes, diseases, and pathways­a diseasome network. Thus, chromosomal mapping of disease data sets can help uncover important regulatory and functional links that may offer new insights for biomarker development.