But, just as there are topographic maps and political maps and highway maps of the United States, so there are different kinds of genome maps. One type, a genetic linkage map, is based on careful analysis of human inheritance patterns. It indicates for each chromosome the whereabouts of genes or other "heritable markers," with distances measured in centimorgans, a measure of recombination frequency. During the formation of sperm and egg cells, a process of genetic recombination -- or "crossing over" -- occurs in which pieces of genetic material are swapped between paired chromosomes. This process of chromosomal scrambling accounts for the differences invariably seen even in siblings (apart from identical twins, whose genomes are equivalent). Logically, the closer two genes are to each other on a single chromosome, the less likely they are to get split up during genetic recombination. When they are close enough that the chances of being separated are only one in a hundred, they are said to be separated by a distance of one centimorgan.
The role of human pedigrees now becomes clear. By studying family trees and tracing the inheritance of diseases and physical traits, or even unique segments of DNA identifiable only in the laboratory, geneticists can begin to pin down the relative positions of these genetic markers. By the end of 1994, a comprehensive map was available that included more than 5800 such markers, including genes implicated in cystic fibrosis, myotonic dystrophy, Huntington disease, @Tay-@Sachs disease, several cancers, and many other maladies. The average gap between markers was about 0.7 centimorgan.
Other maps are known as physical maps, so called because the distances between features are measured not in genetic terms, but in "real" physical units, typically, numbers of base pairs. A close analogy can thus be drawn between physical maps and the road maps familiar to us all. Indeed, the analogy can be extended further. Just as small-scale road maps may show only large cities and indicate distances only between major features, so a low-resolution physical map includes only a relative sprinkling of chromosomal landmarks. A well-known low-resolution physical map, for example, is the familiar chromosomal map, showing the distinctive staining patterns that can be seen in the light microscope. Further, by a process known as in situ hybridization, specific segments of DNA can be targeted in intact chromosomes by using complementary strands synthesized in the laboratory. These laboratory-made "probes" carry a fluorescent or radioactive label, which can then be detected and thus pinpointed on a specific region of the chromosome. Fishing for genes shows some results of fluorescence in situ hybridization (FISH). Of particular interest are probes known as @cDNA (for complementary DNA), which are synthesized by using molecules of messenger RNA as templates.
