Control of genetic defects.

Recombinant DNA techniques offer the possibility of diagnosing genetic defects directly by analysing DNA itself. This is especially interesting for detecting carriers of recessive defects. In comparison with phenotypic screening with progeny testing or biochemical tests, DNA screening is independent of the time of gene expression and is not influenced by non-genetic effects. If the mutation causing the defect is known, alterations of DNA sequences can be identified directly as restriction fragment length polymorphisms (RFLPs) or with the use of allele specific oligonucleotides (ASO). DNA amplification with the polymerase chain reaction makes screening tests faster and more accurate. For most defects, the genetic basis is not known. Pedigree analysis with linked polymorphic DNA markers can be used to establish defect diagnosis. Linkage analysis can locate the chromosomal region of the gene responsible for the disease. Identification of the gene and the mutation in the defect allele finally will lead to direct DNA diagnosis. A dense linkage map with highly polymorphic genetic markers covering the entire genome will in future improve understanding of polygenic diseases. Increasing knowledge of the molecular genetics of human defects will promote DNA diagnosis in other species.