A new method for identifying informative genetic markers in selectively bred rats |
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Authors: | David Weinshenker Malania M Wilson Katherine M Williams Jay M Weiss Neil E Lamb Simon N Twigger |
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Institution: | (1) Department of Human Genetics, Emory University, Whitehead 301, 615 Michael Street, Atlanta, Georgia 30322, USA;(2) Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA;(3) Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA |
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Abstract: | Microsatellite length polymorphisms are useful for the mapping of heritable traits in rats. Over 4000 such microsatellites
have been characterized for 48 inbred rat strains and used successfully to map phenotypes that differ between strains. At
present, however, it is difficult to use this microsatellite database for mapping phenotypes in selectively bred rats of unknown
genotype derived from outbred populations because it is not immediately obvious which markers might differ between strains
and be informative. We predicted that markers represented by many alleles among the known inbred rat strains would also be
most likely to differ between selectively bred strains derived from outbred populations. Here we describe the development
and successful application of a new genotyping tool (HUMMER) that assigns “heterozygosity” (Het) and “uncertainty” (Unc) scores
to each microsatellite marker that corresponds to its degree of heterozygosity among the 48 genotyped inbred strains. We tested
the efficiency of HUMMER on two rat strains that were selectively bred from an outbred Sprague-Dawley stock for either high
or low activity in the forced swim test (SwHi rats and SwLo rats, respectively). We found that the markers with high Het and
Unc scores allowed the efficient selection of markers that differed between SwHi and SwLo rats, while markers with low Het
and Unc scores typically identified markers that did not differ between strains. Thus, picking markers based on Het and Unc
scores is a valuable method for identifying informative microsatellite markers in selectively bred rodent strains derived
from outbred populations. |
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