Diagnosis of Genetic Disorders with Linked DNA Markers

The development of techniques for the analysis of specific DNA sequences has led to the discovery of a vast amount of variation of DNA sequence among different individuals. Consequently, it is now usually possible to distinguish the two parental copies of a particular chromosomal region in an individual. The difference arises either from the presence or absence of a restriction enzyme site in the region, or from a difference in the number of tandemly repeated sequences present in the two alleles. Such differences were originally detected as variations in the length of restriction fragments (restriction fragment length polymorphisms or RFLPs) after blotting and hybridization with probes for unique sequences in the region (see Chapter 15 ), but are now increasingly being detected by means of the polymerase chain reaction or PCR (see Chapters 1 and 6 ).