Future Directions in Genes and Genomes

In medicine, a major challenge is to unravel the genetic basis of common diseases, which at some stage during life may affect the majority of individuals in all populations. The Human Genome Project has produced the resources to tackle these multifactorial disorders such as cardiovascular disease, cancer, diabetes, bipolar disorder, asthma, multiple sclerosis, etc. These complex traits do not exhibit mendelian inheritance patterns often observed with single gene disorders such as cystic fibrosis. Instead, the action of several genes, each with a small effect and environmental influences, can be expected to modify the risk of disease. Various types of association studies are used in an attempt to define the genes that underlie the propensity for some individuals to develop such diseases. Population- and family-based association studies such as whole genome association studies and affected sib pair analysis make use of the gene maps, polymorphic marker resources and genometechnologies in the attempt to pinpoint small regions of chromosomes associated with the disease phenotype. Chromosomal regions showing positive association with disease can then be subjected to detailed analysis by efficient resequencing strategies1 and functional studies in the attempt to identify the causative mutations. As the genome becomes better understood, it is expected that more complex trait genes and mutations will be identified, leading to an improved understanding of molecular pathology and, it is hoped, new effective therapies.
Interestingly, except for a few promising cases,106 the optimistic predictions for gene therapy that were made more than 20 years ago have not yet been fulfilled. Understanding the expression patterns of transcription of disease predisposing genes (from microarray data, for example) seems to offer more potential for therapeutic developments.
For instance, there have been considerable advances in the field of RNA silencing or transcriptional inactivation, which fosters the belief that small interfering RNA (siRNA) molecules could one day have a therapeutic role in common diseases, including cancers, by ‘switching off’ deleterious gene expression.
The genome projects and gene analysis in other species can be expected to produce enormous scientific and economic benefits. The information from the genome projects of model organisms such as mouse, fruit fly, yeast and the nematode worm has been integrated with the human data to provide insights into evolution, refining maps, etc.
Animal and plant genome projects are of great importance to agriculture and biotechnology. Transgenesis or genetic modification (GM) of food organisms, both plant and animal, is likely to grow in importance, particularly as world food supplies become more stretched. Genetically modified crops, principally corn, soybean, rapeseed and cotton, have already been produced with a range of GM characters such as herbicide resistance, insect resistance, virus resistance, delayed fruit ripening
(tomato), altered oil content, etc. In the next decades, transgenic animals that produce increased yields of meat, improved health, disease resistance, optimised fat content and ability to thrive in different environments could be produced. Transgenics also holds great promise for the low-cost production of pharmaceuticals such as therapeutic proteins expressed in milk and plants. The growing effort of genome sequencing and gene discovery promises to overcome the previously encumbering difficulties associated with locating genes for species improvement, new antibiotic targets, etc. However, before implementation of these new GM strategies can occur, a full risk assessment is necessary to understand the possible impacts on human health and the environment.