Studies of tumors must compare the DNA of normal cells with that of cancer cells. The normal cells usually have two bands, whereas the tumor cells often have only one. This finding is diagnostic of the loss of one copy of a chromosomal region during tumorigenesis. The problem of contamination of a tumor by normal cells presents important issues for studies of this type. Because the PCR involves an amplification process, the amount of material in the starting sample and the amount present in the final amplification product are not necessarily linearly related. Making a judgment about the loss of chromosomal material in a tumor sample contaminated with a substantial number of cells from surrounding normal tissue can be quite challenging. Unlike the results of the PCR, the signal generated by the Southern blotting procedure is directly proportional to the relative amount of each allele present in a tumor sample. Southern blotting has thus been used with particular effect in studies of the loss of chromosomal material by tumor cells ( Figure 1D ).
Genetic mapping can determine the relative positions of highly variable DNA sites on each chromosome. Well-characterized polymorphic DNA sites now number in the thousands. The availability of this large number of closely spaced genetic markers has revolutionized human genetics, because it allows the application of genetic-mapping strategies with great precision. For many medically important genes, particularly those that contribute to a predisposition to common medical conditions, the primary limitation to their identification was until recently the availability of a sufficient number of highly informative genetic markers. The techniques described here have removed this limitation. As a result, many important developments in all aspects of medicine are likely to follow.
One more important class of dna polymorphism is single-nucleotide polymorphism
DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism).Within a population, SNPs can be assigned a minor allele frequency — the lowest allele frequency at a locus that is observed in a particular population. This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. There are variations between human populations, so a SNP allele that is common in one geographical or ethnic group may be much rarer in another.
In the past, SNPs with a minor allele frequency of greater than or equal to 1% (or 0.5%, etc.) were given the title "SNP". [1] Some used " mutation " to refer to variations with low allele frequency. With the advent of modern bioinformatics and a better understanding of evolution, this definition is no longer necessary, e.g., a database such as dbSNP includes "SNPs" that have lower allele frequency than one percent. [2]