A genetic map contains the order and approximate recombinational distance between genetic markers whereas a physical map contains the order and physical locations of physical features of a chromosome. Most often the features used in a physical map are short segments of known sequence. Once a physical map exists, genetic markers can be placed on it. Then the mapping and cloning of the genes responsible for genetic diseases is greatly simplified. For example, the nearest physical marker can be chosen as a starting point and with chromosome walking as described in the previous chapter you can clone the gene.

Two major objectives of genetic engineering are acquiring the ability to detect genetic diseases and learning their biochemical basis. Both of these objectives are greatly aided by cloning of the mutant gene. Once the clone is available, direct screening for the mutant DNA is possible and the study of the wild type and mutant gene product becomes easier. Cloning the DNA involved with most genetic diseases is difficult, however. Frequently all that is known is an approximate map location of the defect. The usual helpful tools such as an altered enzyme, protein, or nucleic acid are missing. Here we will see how this difficulty can be circumvented.

Suppose there existed a highly detailed genetic map of the human genome. Then any new marker or genetic defect could be located by measuring its recombinational distance from the known and mapped markers. Of course, this step might require collecting data from several generations of genetic carriers. Once the map location was obtained, we could use this information in genetic counseling. Furthermore, with the integration of a physical map and a genetic map, we would also know the physical location of the genetic marker. Therefore, we could begin from the nearest physical marker and perform a chromosomal walk to clone the gene responsible for the defect.

Typically we think of the genes that code for blood type, hair color, or those genes encoding known enzymes or proteins as constituting the genetic map. While these genes can be useful, too few of them are known to permit precise mapping. Furthermore, identifying many of these markers requires the intact individual. Often this is inconvenient. Instead, we need a new kind of genetic marker, one that exists in high numbers and which is easy to score in the DNA obtained from a small number of cells.

What constitutes a suitable genetic marker? A genetic marker must be easily detected in a small sample of cells or DNA and it must exist in the population in two or more states. If the population were homozygous, then there would be no useful markers since both parents and all offspring would be genetically identical. No mapping genetic could be done. The existence of markers means that some individuals possess one allele or sequence at a position, and other individuals possess a different allele or sequence. If there are hundreds or thousands of markers at which different individuals in the population are likely to be different, then it is feasible to try to map a genetic defect with respect to these known markers.

مواضيع ذات صلة

Chromosome Mapping

Fate Mapping and Study of Tissue-Specific Gene Expression

Isolating Mutations in Muscle or Nerve in Drosophila

Elements of Drosophila Genetics

Elements of Yeast Genetics

Principles of Bacterial Sex

Crossover

Mapping with Generalized Transducing Phage

Genetic Selections

Growing Cells for Genetics Experiments

Genetic Systems

Elements of Recombination in E. coli, RecA, RecBCD, and Chi