Original Paper

Entropy as a Measure for Linkage Disequilibrium over Multilocus Haplotype Blocks
M. Nothnagel, R. Fürst, K. Rohde

Max Delbrück Center for Molecular Medicine, Berlin, Germany

Address of Corresponding Author

Hum Hered 2002;54:186-198 (DOI: 10.1159/000070664)

  Key Words

• Entropy
• Linkage disequilibrium measure
• SNP
• Multilocus haplotypes
• Block detection
• Likelihood

  Abstract

Objective: The presence of linkage disequilibrium (LD) forms the basis for a range of uses, including the fine-mapping of diseases and studies on human genealogy. Recent findings indicate that single nucleotide polymorphisms (SNP) can occur in blocks of limited haplotypic diversity with high degrees of LD. Commonly used measures for LD, such as r² and D', consider only two loci and might miss information to appropriately describe LD in larger haplotypic structures. Methods: We introduce the Normalized Entropy Difference, , as a new multilocus measure for LD. A related quantity, S, provides an approximate ² test for the significance of LD. The ability of the measure to detect haplotype blocks is investigated using simulated data sets as well as a real data set previously analyzed by Daly et al. (2001). Results: allows for arbitrary numbers of loci, describes LD with regard to the loci sequence, and can be interpreted as a multilocus extension of r². The application of to the data sets demonstrated the measure's ability to appropriately describe simultaneous multilocus LD and to detect haplotype blocks. Conclusions: is a reasonable multilocus LD measure and might be of potential use in the construction of the human haplotype map.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Michael Nothnagel
Max Delbrück Center for Molecular Medicine, Department of Bioinformatics
Robert-Rössle-Str. 10
D-13092 Berlin (Germany)
Tel. +49 30 9406 3893, Fax +49 30 9406 2834, E-Mail michael.nothnagel@mdc-berlin.de

  Article Information

Received: October 10, 2002
Revision received: January 14, 2003
Accepted: January 21, 2003
Number of Print Pages : 13
Number of Figures : 6, Number of Tables : 1, Number of References : 53