Francomano C A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Pediatr Nephrol. 1992 Jan;6(1):113-8. doi: 10.1007/BF00856854.
Recent developments in molecular genetic technology have made it possible to diagnose many genetic disorders affecting the kidney before they are clinically manifest. For a disorder to be diagnosed by DNA analysis, either the causative gene must be known and cloned, or a closely linked DNA segment must have been identified. If one of these criteria is met, the disorder may be diagnosed either by direct detection of a mutation, if it is known, or indirectly by linkage analysis of the region using closely linked genetic markers. The methodology currently employed for direct detection of mutation includes the Southern blot, which will detect large structural alterations of genes or mutations altering a restriction recognition site, or the use of allele-specific oligonucleotides, which will detect specific point mutations. Linkage analysis is performed on DNA from multiple family members of the person at risk. Polymorphic markers are "tracked" in the family to determine the allele segregating with the disease gene. These methods are now routinely applied to the diagnosis of mendelian disorders affecting the kidney. It is anticipated that progress over the next decade will extend these applications to detection of the genetic component(s) contributing to multifactorial conditions.
分子遗传技术的最新进展使得在许多影响肾脏的遗传疾病出现临床症状之前就能够进行诊断。要通过DNA分析诊断一种疾病，要么致病基因必须已知并已克隆，要么必须已鉴定出紧密连锁的DNA片段。如果满足这些标准之一，那么该疾病可以通过直接检测已知的突变来诊断，或者通过使用紧密连锁的遗传标记对该区域进行连锁分析来间接诊断。目前用于直接检测突变的方法包括Southern印迹法，它可以检测基因的大结构改变或改变限制性识别位点的突变，或者使用等位基因特异性寡核苷酸，它可以检测特定的点突变。连锁分析是对有患病风险者的多个家庭成员的DNA进行的。多态性标记在家族中被“追踪”，以确定与疾病基因分离的等位基因。这些方法现在已常规应用于影响肾脏的孟德尔疾病的诊断。预计在未来十年中，这些应用将扩展到检测导致多因素疾病的遗传成分。
