mutation change in DNA sequence informed consent knowledge of risks involved oooc ,oc are two ways to search for them. The first involves looking across all the chromosomes, using genetic maps, and trying to correlate the occurrence of the disease in a family with the occurrence of one or more genetic markers from the genetic maps. This approach is called genomic screening and tries to find the genes based only on their location. It does not require that anything be known about what any of the genes do. Genomic screening uses a number of special statistical techniques to look at the probability that the disease gene (whose location is unknown) and one or more of the markers (whose location is known) are located near each other. One difficulty is that the location will not be known precisely. That is, this method will point to a region that may contain as many as 500 genes. This is a lot less than the 50,000 or so thought to exist in the human genome, but it is still a lot of genes that need to be tested. Genomic screening has worked spectacularly well for hundreds of diseases where there is a single causative mutation in a gene. A list of some of these genes in given in Table 1.

The second approach is to look at one or more specific genes to see if they might be directly involved in the disease. This is called the candidate gene approach. A gene becomes a candidate when something is known about its function and when this function might have something to do with the disease. For example, if a gene was involved in the development of the cornea of the eye, it would be a good candidate for any disease that affects the development of the cornea. The success of the candidate gene approach depends on two things. The first is how much is known about the disease process, and the second is how much is known about the function of the genes.

It is also possible to combine the two approaches. The genomic screening approach may identify several regions on several chromosomes that might contain a disease gene, but these regions may contain hundreds of genes each. By looking at the functions of these genes, it may be possible to identify one or just a few that are the most likely to be involved in the disease. These genes can then be tested using the candidate gene approach.

What do these genes do? Once a gene has been identified as being involved in the disease, it is important to further study the gene to find out what it does under normal circumstances, and what it is doing when it is changed and causing disease. Sometimes a lot is known about the normal function, but many times very little is known. Studies to look at the function may include studies of the normal gene in living cells that are grown in the laboratory. Another type of study involves testing the same normal genes in other living organisms such as mice, rats, and fruit flies. Animal studies are very helpful because animals can be tested in ways not possible in humans. Studies similar to those done for the normal gene will have to be done on the changed (mutated) copy of the gene, to see how the change in the gene changes the function of the protein that the gene makes. see also Complex Traits; Gene Discovery; Mapping; Twins.

Jonathan L. Haines


Haines, Jonathan L., and Margaret A. Pericak-Vance, eds. Approaches to Gene Mapping in Complex Human Diseases. New York: John Wiley & Sons, 1998.

Internet Resource

Dolan DNA Learning Center. Cold Spring Harbor Laboratory. <http://www>.

Human Genome Project

The genome represents the entire complement of DNA in a cell. The Human Genome Project is the determination of the entire nucleotide sequence of all 3 billion + bases of DNA within the nucleus of a human cell. It is one of the greatest scientific undertakings in the history of mankind. The first draft of the human genome sequence was completed in the year 2001 and published simultaneously in the British journal Nature and the American journal Science.

The data obtained from sequencing the human genome promise to bring unprecedented scientific rewards in the discovery of disease-causing genes, in the design of new drugs, in understanding developmental processes and cancer, and in determining the origin and evolution of the human race. The Human Genome Project has also raised many social and ethical issues with regard to the use of such information.

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