The distribution of linkage disequilibrium over anonymous genome regions

Linkage disequilibrIum (LD), the association of alleles at differentloci, 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 distributionof LD across mammalian genomes. Therefore, a survey was undertaken,using microsatellite loci, to evaluate the distribution of LDover several regions of human chromosome 4. Radiation hybrid(RH) and linkage maps provided information on physical and geneticdistances between these lad. A Finnish popu lation sample wasgenotyped using 32 mlcrosateilite lad, and partial marker haplotypeswere determined. Assessment of LD was performed, between allpairs of iocl, using the Fisher's exact test. LD was detectedbetween several loci that were separated by more than 1 Mb or1 cM. Detection of LD was strongly associated with small physicaldistance; its relation to genetic distance was more equivocal.This result may support the hypothesis that linkage maps arerelatively inaccurate over small distances. Our results suggestthat LD is widely distributed in anonymous regions of the humangenome and its use may allow more accurate measurement of smallgenetic distances than does standard linkage analysis. Alternativeexplanations are considered for comparisons in which LD is notdetected between tightly linked loci.