Efficient designs for fine-mapping of quantitative trait loci using combined linkage disequilibrium and linkage

Title
Efficient designs for fine-mapping of quantitative trait loci using combined linkage disequilibrium and linkage
Publication Date
2004
Author(s)
Lee, Sang Hong
Van Der Werf, JH
( author )
OrcID: https://orcid.org/0000-0003-2512-1696
Email: jvanderw@une.edu.au
UNE Id une-id:jvanderw
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
BioMed Central Ltd
Place of publication
United Kingdom
DOI
10.1051/gse:2003056
UNE publication id
une:765
Abstract
In a simulation study, different designs were compared for efficiency of fine-mapping of QTL. The variance component method for fine-mapping of QTL was used to estimate QTL position and variance components. The design of many families with small size gave a higher mapping resolution than a design with few families of large size. However, the difference is small in half sib designs. The proportion of replicates with the QTL positioned within 3 cM of the true position is 0.71 in the best design, and 0.68 in the worst design applied to 128 animals with a phenotypic record and a QTL explaining 25% of the phenotypic variance. The design of two half sib families each of size 64 was further investigated for a hypothetical population with effective size of 1000 simulated for 6000 generations with a marker density of 0.25 cM and with marker mutation rate 4 x 10-4 per generation.In mapping using bi-allelic markers, 42~55% of replicated simulations could position QTL within 0.75 cM of the true position whereas this was higher for multi allelic markers (48~76%). The accuracy was lowest (48%) when mutation age was 100 generations and increased to 68% and 76% for mutation ages of 200 and 500 generations, respectively, after which it was about 70% for mutation ages of 1000 generations and older. When effective size was linearly decreasing in the last 50 generations, the accuracy was decreased (56 to 70%). We show that half sib designs that have often been used for linkage mapping can have sufficient information for fine-mapping of QTL. It is suggested that the same design with the same animals for linkage mapping should be used for fine-mapping so gene mapping can be cost effective in livestock populations.
Link
Citation
Genetics Selection Evolution, 36(2), p. 145-161
ISSN
1297-9686
0999-193X
Start page
145
End page
161

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