Peterson A C, Di Rienzo A, Lehesjoki A E, de la Chapelle A, Slatkin M, Freimer N B
Department of Psychiatry, University of California, San Francisco 94143, USA.
Hum Mol Genet. 1995 May;4(5):887-94. doi: 10.1093/hmg/4.5.887.
Linkage disequilibrium (LD), the association of alleles at different loci, is a powerful tool for genetic mapping and for investigating, at the population level, processes such as recombination, selection, mutation and admixture. Little is known about the distribution of LD across mammalian genomes. Therefore, a survey was undertaken, using microsatellite loci, to evaluate the distribution of LD over several regions of human chromosome 4. Radiation hybrid (RH) and linkage maps provided information on physical and genetic distances between these loci. A Finnish population sample was genotyped using 32 microsatellite loci, and partial marker haplotypes were determined. Assessment of LD was performed, between all pairs of loci, using the Fisher's exact test. LD was detected between several loci that were separated by more than 1 Mb or 1 cM. Detection of LD was strongly associated with small physical distance; its relation to genetic distance was more equivocal. This result may support the hypothesis that linkage maps are relatively inaccurate over small distances. Our results suggest that LD is widely distributed in anonymous regions of the human genome and its use may allow more accurate measurement of small genetic distances than does standard linkage analysis. Alternative explanations are considered for comparisons in which LD is not detected between tightly linked loci.
连锁不平衡（LD），即不同位点上等位基因的关联，是一种强大的工具，可用于基因定位以及在群体水平上研究诸如重组、选择、突变和混合等过程。人们对LD在哺乳动物基因组中的分布了解甚少。因此，开展了一项调查，使用微卫星位点来评估人类4号染色体几个区域上LD的分布。辐射杂种（RH）图谱和连锁图谱提供了这些位点之间物理距离和遗传距离的信息。对芬兰人群样本使用32个微卫星位点进行基因分型，并确定了部分标记单倍型。使用费舍尔精确检验对所有位点对之间进行LD评估。在相隔超过1 Mb或1 cM的几个位点之间检测到了LD。LD的检测与小的物理距离密切相关；其与遗传距离的关系则更为模糊。这一结果可能支持连锁图谱在小距离上相对不准确这一假设。我们的结果表明，LD广泛分布于人类基因组的无名区域，与标准连锁分析相比，其应用可能使小遗传距离的测量更为准确。对于紧密连锁位点之间未检测到LD的比较，我们考虑了其他解释。
