第17章バイオテクノロジーとゲノミクス

Introducing DNA sequencing and whole genome sequencing projects, particularly the Human Genome project, has expanded the applicability of DNA sequence information. Many fields, such as metagenomics, pharmacogenomics, and mitochondrial genomics are using genomics. Understanding and finding cures for diseases is the most common application of genomics.

Predicting disease risk involves screening currently healthy individuals by genome analysis at the individual level. Health care professionals can recommend intervention with lifestyle changes and drugs before disease onset. However, this approach is most applicable when the problem resides within a single gene defect. Such defects only account for approximately 5 percent of diseases in developed countries. Most of the common diseases, such as heart disease, are multi-factored or polygenic, which is a phenotypic characteristic that involves two or more genes, and also involve environmental factors such as diet. In April 2010, scientists at Stanford University published the genome analysis of a healthy individual (Stephen Quake, a scientist at Stanford University, who had his genome sequenced. The analysis predicted his propensity to acquire various diseases. The medical team performed a risk assessment to analyze Quake’s percentage of risk for 55 different medical conditions. The team found a rare genetic mutation, which showed him to be at risk for sudden heart attack. The results also predicted that Quake had a 23 percent risk of developing prostate cancer and a 1.4 percent risk of developing Alzheimer’s. The scientists used databases and several publications to analyze the genomic data. Even though genomic sequencing is becoming more affordable and analytical tools are becoming more reliable, researchers still must address ethical issues surrounding genomic analysis at a population level.

Pharmacogenomics, or toxicogenomics, involves evaluating drug effectiveness and safety on the basis of information from an individual's genomic sequence. We can study genomic responses to drugs using experimental animals (such as laboratory rats or mice) or live cells in the laboratory before embarking on studies with humans. Studying changes in gene expression could provide information about the transcription profile in the drug's presence, which we can use as an early indicator of the potential for toxic effects. For example, genes involved in cellular growth and controlled cell death, when disturbed, could lead to cancerous cell growth. Genome-wide studies can also help to find new genes involved in drug toxicity. Medical professionals can use personal genome sequence information to prescribe medications that will be most effective and least toxic on the basis of the individual patient’s genotype. The gene signatures may not be completely accurate, but medical professionals can test them further before pathologic symptoms arise.

Traditionally, scholars have taught microbiology with the view that it is best to study microorganisms under pure culture conditions. This involves isolating a single cell type and culturing it in the laboratory. Because microorganisms can go through several generations in a matter of hours, their gene expression profiles adapt to the new laboratory environment very quickly. In addition, the vast majority of bacterial species resist culturing in isolation. Most microorganisms do not live as isolated entities, but in microbial communities or biofilms. For all of these reasons, pure culture is not always the best way to study microorganisms. Metagenomics is the study of the collective genomes of multiple species that grow and interact in an environmental niche. Metagenomics can be used to identify new species more rapidly and to analyze the effect of pollutants on the environment (Figure 17.16).