The human cancer genome project--one more misstep in the war on cancer.
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Biomedical subjects
Publications and source records attributed to George L Gabor Miklos.
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A problem in analyzing microarray-based gene expression data is the separation of genes causally involved in a disease from innocent bystander genes, whose expression levels have been secondarily altered by primary changes elsewhere. To investigate this issue systematically in the context of a class of complex human diseases, we have compared microarray-based gene expression data with non-microarray-based clinical and biological data about the schizophrenias to ask whether these two approaches prioritize the same genes. We find that genes whose expression changes are deemed to be of importance from microarrays are rarely those classified as of importance from clinical, in situ, molecular, single-nucleotide polymorphism (SNP) association, knockout and drug perturbation data. This disparity is not limited to the schizophrenias but characterizes other human disease data sets. It also extends to biological validation of microarray data in model organisms, in which genome-wide phenotypic data have been systematically compared with microarray data. In addition, different bioinformatic protocols applied to the same microarray data yield quite different gene sets and thus make clinical decisions less straightforward. We discuss how progress may be improved in the clinical area by the assignment of high-quality phenotypic values to each member of a microarray-assigned gene set.
The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.