Genomic Approaches to Identify Molecular Basis of Multi-Factorial Diseases

Publisher Summary More than 1,400 human genes have been correlated with diseases. In general, these are single-gene disorders that arise because of mutations that alter the function of a specific protein or lead to its complete absence in the disease phenotype. The availability of complete genome sequences from many organisms has yielded the ability to perform high-throughput, genome-wide screens of gene function. The major model systems used include yeast, flies, worms, and mammals. There are many advantages to using these model organisms to identify signaling pathways activated or altered in a disease and also for drug discovery. The genomes are less redundant, and desired clone variants (mutants) can be generated and screened with both ease and speed. Saccharomyces cerevisiae is a model organism that has been used extensively to characterize cell cycle genes. Cell cycle studies performed in this organism have served as a guideline for understanding eukaryotic cell cycle progression. A wide variety of genomic approaches have been used to get insights into the molecular basis of tumorigenesis and predict clinical outcomes in mammalian cells. Oncogenesis occurs through the acquisition and selection of multiple somatic mutations, each contributing to the growth, survival, and spread of the cancer. Key attributes of the malignant phenotype—such as unchecked proliferation and cell survival—can often be “reversed” by the selective diminution of dominant oncogenes by chemical or genetic means.