Schwenger B
Institute for Animal Breeding and Genetics, Hanover Veterinary School, Federal Republic of Germany.
Rev Sci Tech. 1990 Sep;9(3):897-910. doi: 10.20506/rst.9.3.518.
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.
重组DNA技术提供了通过直接分析DNA本身来诊断遗传缺陷的可能性。这对于检测隐性缺陷的携带者尤其有意义。与通过子代检测或生化检测进行的表型筛选相比，DNA筛选不受基因表达时间的影响，也不受非遗传效应的影响。如果导致缺陷的突变已知，DNA序列的改变可以直接鉴定为限制性片段长度多态性（RFLP）或使用等位基因特异性寡核苷酸（ASO）来鉴定。聚合酶链反应进行的DNA扩增使筛选测试更快、更准确。对于大多数缺陷，其遗传基础尚不清楚。利用连锁多态性DNA标记进行系谱分析可用于建立缺陷诊断。连锁分析可以定位导致疾病的基因所在的染色体区域。最终鉴定出该基因和缺陷等位基因中的突变将导致直接的DNA诊断。未来，一个覆盖整个基因组的具有高度多态性遗传标记的密集连锁图谱将有助于增进对多基因疾病的了解。对人类缺陷分子遗传学的了解不断增加将促进其他物种的DNA诊断。
