INDIRECT DNA GENE DIAGNOSES VIA ELECTROPHORESIS - AN OBSOLETE PRINCIPLE/

In principle, gene defects can be investigated directly or indirectly via informative polymorphisms in their vicinity. But because many defe cts are not yet defined molecularly, these inherited diseases can only be diagnosed indirectly via analysis of informative family situations . Since (multiple) mutation analyses, e.g. via DNA sequencing, are tim e-consuming and expensive, indirect analysis may still be performed in itially - particularly in diseases caused by heterogenous mutations. W e focus on diagnoses of neurological and (auto)immune diseases by poly merase chain reaction and separation of the DNA fragments via gel elec trophoreses. Even after gene defects have been identified, indirect an alysis might be necessary, for example in Huntington's chorea. Althoug h this genetic defect has been characterized as a trinucleotide diseas e, indirect DNA diagnosis is still performed in particular cases for p sychological reasons. The causes of autoimmune diseases are multifacto rial and the inheritance is complex, involving several genes. Genome-w ide screening programs may involve indirect approaches via analyses of polymorphic microsatellites. Large parts of the immunological genome can be covered when 20 or more genes are investigated simultaneously. Thus the genetic bases of autoimmune diseases are disclosed. Microsate llites themselves could have a biological meaning. We therefore discus s also DNA/protein interactions for simple tandem repeats, the major t argets for indirect gene diagnoses. Only indirect evidence exists that certain simple repeats influence genomic (in)stability. Taken togethe r, indirect gene diagnoses supplement direct approaches in a variety o f different purposes and in combination with standard electrophoresis techniques.