Fine mapping dissects pleiotropic growth quantitative trait locus into linked loci |
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Authors: | Julian K Christians Laura K Senger |
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Institution: | (1) Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, V5A 1S6, Canada;(2) British Columbia Institute of Technology, Burnaby, British Columbia, V5G 3H2, Canada |
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Abstract: | A recurring issue in studies of quantitative trait loci (QTLs) is whether QTLs that appear to have pleiotropic effects are
indeed caused by pleiotropy at single loci or by linked QTLs. Previous work identified a QTL that affected tail length in
mice and the lengths of various bones, including the humerus, ulna, femur, tibia, and mandible. The effect of this QTL on
tail length has since been found to be due to multiple linked QTLs and so its apparently pleiotropic effects may have been
due to linked QTLs with distinct effects. In the present study we examined a line of mice segregating only for a 0.94-Mb chromosomal
region known to contain a subset of the QTLs influencing tail length. We measured a number of skeletal dimensions, including
the lengths of the skull, mandible, humerus, ulna, femur, tibia, calcaneus, metatarsus, and a tail bone. The QTL region was
found to have effects on the size of the mandible and length of the tail bone, with little or no effect on the other traits.
Using a randomization approach, we rejected the null hypothesis that the QTL affected all traits equally, thereby demonstrating
that the pleiotropic effects reported earlier were due to linked loci with distinct effects. This result underlines the possibility
that seemingly pleiotropic effects of QTLs may frequently be due to linked loci and that high-resolution mapping will often
be required to distinguish between pleiotropy and linkage. |
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