Linkage analysis of genes with diseases using difference spectrum analysis

摘要

The present invention is directed to a method for rapidly analyzing whether known genetic markers which are found in various lengths in the population, e.g., those containing (CA).sub.n repeats, are associated with a disease of interest. The method involves using polymerase chain reactions to amplify the DNA in the marker regions and comparing the amplified DNA lengths seen in the normal population with those seen in an affected population of persons. The method involves a pooling of DNA samples from normal patients to average out the normal marker genotype found in the population and also involves a pooling of DNA from affected individuals to give a summing effect to give a stronger signal. The amplified DNA fragments are labeled with two distinguishable markers such as two different colored fluorescent markers, one used to label the amplified DNA from the normal population and the other to label the amplified DNA from the affected population. The amplified products from the normals and the affecteds are pooled, run on a sequencing gel, and a difference spectrum is calculated. Markers which are not associated with the disease will result in a zero or near zero difference spectrum whereas a marker which is associated with the disease will result in a difference spectrum with marked peaks.