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. 2005 Dec 30;6 Suppl 1(Suppl 1):S61.
doi: 10.1186/1471-2156-6-S1-S61.

Optimizing the evidence for linkage by permuting marker order

Gyungah Jun  1 , Yeunjoo Song, Sudha K Iyengar, Robert C Elston
Affiliations

Optimizing the evidence for linkage by permuting marker order

Gyungah Jun et al. BMC Genet. .

Abstract

We developed a new marker-reordering algorithm to find the best order of fine-mapping markers for multipoint linkage analysis. The algorithm searches for the best order of fine-mapping markers such that the sum of the squared differences in identity-by-descent distribution between neighboring markers is minimized. To test this algorithm, we examined its effect on the evidence for linkage in the simulated and the Collaborative Studies on Genetics of Alcoholism (COGA) data. We found enhanced evidence for linkage with the reordered map at the true location in the simulated data (p-value decreased from 1.16 x 10(-9) to 9.70 x 10(-10)). Analysis of the White population from the COGA data with the reordered map for alcohol dependence led to a significant change of the linkage signal (p = 0.0365 decreased to p = 0.0039) on chromosome 1 between marker D1S1592 and D1S1598. Our results suggest that reordering fine-mapping markers in candidate regions when the genetic map is uncertain can be a critical step when considering a dense map.

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Figures

Figure 1
Figure 1
Linkage analysis of the simulated data in REP001. Linkage analysis of the simulated data using microsatellites only and microsatellites plus SNPs placed in order of the initial map (A and C) and the reordered map (B and D).
Figure 2
Figure 2
Linkage analysis of the COGA data. Linkage analysis of the COGA data using microsatellites only and microsatellites plus SNPs placed in order of the initial map (A) and the reordered map (B).
See this image and copyright information in PMC

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