Applications and limitations of direct DNA analysis in genetic prediction

Abstract

Direct analysis of DNA has enormous potential for improved carrier detection or exclusion and early prenatal diagnosis in monogenic diseases. The strategy adopted in practice is determined by the fact that in most diseases allelic genetic heterogeneity precludes elucidation of the mutation in all families. Gene tracking asks the question--has a relative or fetus inherited the same relevant chromosome region as a previously affected family member?--and requires a gene-specific or closely linked DNA probe that reveals a restriction fragment length polymorphism (RFLP) in order to do a linkage study within the family. Gene tracking is independent of allelic heterogeneity in the disease, but is limited to those families in which key relatives are heterozygous for an RFLP.