STUDY HINTS

The techniques described in the previous chapter can be used to map DNA at several different levels of resolution over several different degrees of scale. At the nucleotide level, a linear array of bases can be ordered by DNA sequencing. Using the techniques currently available in most laboratories, each sequencing experiment resolves contiguous regions on the order of hundreds to thousands of nucleotides. Using cloned DNA and batteries of restriction enzyme digests, a linear array of restriction sites can also be mapped relative to one another. Mapping via restriction enzymes can be used to order DNA regions thousands to tens of thousands of nucleotides in length. Finally, techniques of nucleic acid hybridization can be applied to locate genes to specific chromosomal regions, where any chromosomal band identifiable cytologically contains millions of base pairs.

What advantages are there to localizing genes? One advantage that has already gained clinical importance is the ability to follow the transmission of certain genetic diseases using tightly linked genetic markers. The recent application of recombinant DNA technology to gene mapping is having tremendous significance in identifying DNA sequences that are highly variable in populations, and whose inheritance pattern can be used to follow the transmission of closely linked disease genes. Moreover, once a search has been narrowed to a specific region of the genome by establishing linkage to a particular marker, molecular techniques can be brought to bear on finding and cloning the disease gene itself.