Post-Sequencing Research Challenges

The working draft DNA sequence and the more polished version planned for 2003 or sooner represent an enormous achievement, akin in scientific importance, some say, to developing the periodic table of elements. And, as in most major scientific advances, much work remains to realize the full potential of the accomplishment.

Early explorations into the human genome, now joined by projects on the genomes of dozens of other organisms, are generating data whose volume and complex analyses are unprecedented in biology. Genomic-scale technologies will be needed to study and compare entire genomes, sets of expressed RNAs or proteins, gene families from a large number of species, variation among individuals, and the classes of gene regulatory elements.

Deriving meaningful knowledge from DNA sequence will define biological research through the coming decades and require the expertise and creativity of teams of biologists, chemists, engineers, and computational scientists, among others. A sampling follows of some research challenges in genetics--what we still wont know, even with the full human sequence in hand.

• Gene number, exact locations, and functions
• Gene regulation
• DNA sequence organization
• Chromosomal structure and organization
• Noncoding DNA types, amount, distribution, information content, and functions
• Coordination of gene expression, protein synthesis, and post-translational events
• Interaction of proteins in complex molecular machines
• Predicted vs experimentally determined gene function
• Evolutionary conservation among organisms
• Protein conservation (structure and function)
• Proteomes (total protein content and function) in organisms
• Correlation of SNPs (single-base DNA variations among individuals) with health and disease
• Disease-susceptibility prediction based on gene sequence variation
• Genes involved in complex traits and multigene diseases
• Complex systems biology including microbial consortia useful for environmental restoration
• Developmental genetics, genomics

The electronic form of the newsletter may be cited in the following style:
Human Genome Program, U.S. Department of Energy, Human Genome News (v11n1-2).