Lander E S, Botstein D
Proc Natl Acad Sci U S A. 1986 Oct;83(19):7353-7. doi: 10.1073/pnas.83.19.7353.
Simple single-gene disorders in humans can be genetically mapped by using traditional methods of linkage analysis and increasingly abundant restriction fragment length polymorphisms (RFLPs). Many human diseases and traits, however, can be expected to be genetically heterogeneous (i.e., caused by any one of several genes), and traditional linkage analysis is much less effective in such circumstances. We present two methods, interval mapping and simultaneous search, designed to exploit the full power of a linkage map of the DNA markers. For the simplest situations, only 1/3 as many affected families are needed to map a heterogeneous trait by using these methods. Only 1/5-1/50 as many are needed to detect that genetic heterogeneity is present.
人类中的简单单基因疾病可以通过使用传统的连锁分析方法以及日益丰富的限制性片段长度多态性（RFLP）进行基因定位。然而，许多人类疾病和性状预计在遗传上是异质性的（即由多个基因中的任何一个引起），在这种情况下传统的连锁分析效果要差得多。我们提出了两种方法，区间定位法和同步搜索法，旨在充分利用DNA标记连锁图谱的全部功能。对于最简单的情况，使用这些方法定位一个异质性性状所需的患病家系数量仅为原来的1/3。检测到存在遗传异质性所需的数量仅为原来的1/5至1/50。
