Chiano M N, Yates J R
Department of Pure Mathematics and Mathematical Statistics, University of Cambridge, UK.
Ann Hum Genet. 1994 May;58(2):129-43. doi: 10.1111/j.1469-1809.1994.tb01882.x.
Linkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.
离散孟德尔性状的连锁分析对人类基因组图谱绘制做出了重大贡献。然而，在更复杂的情况下，尤其是显示基因座异质性的孟德尔疾病，连锁分析结果有时会产生误导。自展置信区间可评估数据对遗传模型的拟合优度，而异质性的存在会使置信区间膨胀，表明拟合效果不佳。通过使用模拟数据以及37个受异质性疾病结节性硬化症影响的家庭的真实数据，探讨并说明了基于家系材料的小样本或子样本进行连锁分析时统计功效的损失和潜在的不可靠性。
