Wong F L, Cantor R M, Rotter J I
Am J Hum Genet. 1986 Jul;39(1):25-37.
The opportunity raised by recombinant DNA technology to develop a linkage marker panel that spans the human genome requires cost-efficient strategies for its optimal utilization. Questions arise as to whether it is more cost-effective to convert a dimorphic restriction enzyme marker system into a highly polymorphic system or, instead, to increase the number of families studied, simply using the available marker alleles. The choice is highly dependent on the population available for study, and, therefore, an examination of the informational content of the various family structures is important to obtain the most informative data. To guide such decisions, we have developed tables of the average sample number of families required to detect linkage for autosomal recessive disorders under single backcross and under "fully informative" matings. The latter cross consists of a marker locus with highly polymorphic codominant alleles such that the parental marker genotypes can be uniquely distinguished. The sampling scheme considers families with unaffected parents of known mating types ascertained via affected offspring, for sibship sizes ranging from two to four and various numbers of affected individuals. The sample-size tables, calculated for various values of the recombination fractions and lod scores, may serve as a guide to a more efficient application of the restriction fragment length polymorphism technology to sequential linkage analysis.
重组DNA技术带来了开发覆盖人类基因组的连锁标记组的机遇，这需要采用具有成本效益的策略来实现其最佳利用。由此产生了一些问题，比如将双态限制性酶标记系统转化为高度多态系统，或者仅仅通过使用现有的标记等位基因来增加所研究家系的数量，哪种方式更具成本效益。这种选择高度依赖于可供研究的人群，因此，考察各种家系结构的信息含量对于获取最具信息量的数据很重要。为指导此类决策，我们编制了表格，列出了在单回交和“完全信息”交配情况下检测常染色体隐性疾病连锁所需的家系平均样本数量。后一种交配类型包含一个具有高度多态共显性等位基因的标记位点，这样就能唯一区分亲本的标记基因型。抽样方案考虑的是通过患病后代确定交配类型已知的未患病亲本的家系，同胞数量从两个到四个不等，且有不同数量的患病个体。针对重组分数和对数优势比分的各种值计算出的样本量表格，可为在连锁分析中更有效地应用限制性片段长度多态性技术提供指导。
