Overview

Many have compared the genome sequence to a New York City phone book. If you read the names in the phone book, you will not learn much about New Yorkers. Similarly, you will not learn much about the human genome by reading the bases that constitute it. To be able to use the genome, researchers have to completely annotate it; they must locate genes and decipher their functions.

Learning about location and function alone does not tell the whole story of the genome. Every cell in the human body contains all of the genes in the human genome, yet most cells do not express, or use, the same genes. Differing gene expression allows cells to take on varying functions; for example, muscle cells express genes that relate to muscle function and skin cells express those that relate to skin function. Different genes are expressed in muscle cells and skin cells. Understanding where genes are and how they become activated will help researchers develop therapeutic strategies for treating diseases caused by aberrant expression.

Another goal of the genome project is to sequence other organisms' genomes. If similar genes in those other species can be identified, human genes will be easier to find using molecular biology methods that find related genes across organisms. Beyond these scientific aims, the project includes studying the Ethical, Legal, and Social Implications (ELSI) of sequencing the genome.

Finishing the Sequence

Roughly a year away from the expected completion, the public project reports on its website that it has fully sequenced 63% of the genome and another 34.8% at draft quality. It aims to complete sequencing by April 25, 2003, the 50th anniversary of James Watson and Francis Crick's landmark paper on the structure of the genetic material, deoxyribonucleic acid (DNA).

Annotating the Genome

According to LocusLink, a database that houses data for the public project, nearly 14,000 genes with a known functional product have been localized to sites on chromosomes. An additional 4,900 genes that code for proteins with unknown function have also been identified. So far, the public project has characterized close to 20,000 of an estimated 35,000 genes in the human genome.

Few papers have been published about the genome project since the draft sequence was released, so the best way to find data on the progress is through websites. One of these websites, NCBI Genes and Disease, shows the locations of some of the disease genes found so far. Some of the characterized genes code for proteins that may play roles in breast cancer, prostate cancer, cystic fibrosis, and other disorders.

Ethical, Legal, and Social Implications

The ethical, legal and social implications (ELSI) part of the Human Genome Project has progressed more slowly than sequencing and annotation. In 1990, the Department of Energy (DOE) and National Institutes of Health (NIH) believed they would complete the project in 15 years, but technological advances in sequencing accelerated the progress, allowing a draft sequence to be published in 2001, according to About the Human Genome Project, a website maintained by the DOE. No technological advances could speed up the ethical studies to conclude in time for the release of the draft sequence, but a five-year plan established in 1998 has reset the goal for completion for the year 2003.

Five goals of ELSI were outlined by Francis Collins in the October 23, 1998 issue of Science:

Comparative Analysis

Studying the human genome alone will not give researchers all the information they need to learn about what human genes do and what makes humans distinct from other species. However, due to ethical concerns and the long amount of time between generations, many genetic and biochemical studies on gene function and expression cannot be conducted on humans. Researchers, therefore, are trying to sequence the genomes of model organisms to better understand human genes. These model organisms share two characteristics: they are small with short times between generations.

When the draft sequence of the human genome was released in Science and Nature, the bacterium Escherichia coli, the nematode Caenorhabditis elegans, the plant Arabidopsis thaliana, and the fruit fly Drosophila melanogaster had all been sequenced. Since the human draft sequence was announced, a draft of the mouse (Mus musculus) genome was completed and the rice Oryza sativa was sequenced.

Comparisons between model organisms and humans can be very helpful. If a gene sequence is found in all organisms, it most likely codes for a vital product, such as a key metabolic enzyme. In contrast, if a gene is found in only one species, it most likely codes for a product that makes that species different from others. Sequence similarity can also delineate evolutionary relationships between humans and other organisms, since related species have more similar genomes than unrelated species. In this way, comparative analysis could shed light on what makes humans different than all other organisms.

Model organisms can also be experimentally manipulated to determine the function of human genes. If a human gene has a homologue in a model organism, researchers can experimentally prevent expression of that gene in the model. They can then infer the function of the human gene by seeing what functions the model loses in the experiment. Due to ethical considerations and the long time gap between generations, experiments like these, as in the case of gene function and expression studies, cannot be done in humans.

Conclusion

A lot of progress in comparative analysis, along with the main aspects of the Human Genome Project, sequencing, gene annotation, and ELSI, has been made. Scientists are coming closer to the goal of understanding the significance of the human genome and should have sequencing complete by 2003. While sequencing just provides a phone book-like database, the Human Genome Project as a whole is progressing to a more meaningful comprehension of our genetic material.