Hästbacka J, de la Chapelle A, Kaitila I, Sistonen P, Weaver A, Lander E
Department of Medical Genetics, University of Helsinki, Finland.
Nat Genet. 1992 Nov;2(3):204-11. doi: 10.1038/ng1192-204.
Linkage disequilibrium mapping in isolated populations provides a powerful tool for fine structure localization of disease genes. Here, Luria and Delbrück's classical methods for analysing bacterial cultures are adapted to the study of human isolated founder populations in order to estimate (i) the recombination fraction between a disease locus and a marker; (ii) the expected degree of allelic homogeneity in a population; and (iii) the mutation rate of marker loci. Using these methods, we report striking linkage disequilibrium for diastrophic dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06 centimorgans (or about 60 kilobases) of the CSF1R gene. Predictions about allelic homogeneity in Finland and mutation rates in simple sequence repeats are confirmed by independent observations.
在隔离人群中进行连锁不平衡作图为疾病基因的精细结构定位提供了一个强大的工具。在这里，卢里亚和德尔布吕克分析细菌培养物的经典方法被应用于人类隔离的奠基者群体研究，以估计：（i）疾病位点与标记之间的重组率；（ii）群体中等位基因同质性的预期程度；以及（iii）标记位点的突变率。使用这些方法，我们报告了芬兰的脊柱胸段发育不良（DTD）存在显著的连锁不平衡，这表明DTD基因应位于CSF1R基因的0.06厘摩（或约60千碱基）范围内。关于芬兰等位基因同质性和简单序列重复中突变率的预测得到了独立观察结果的证实。
