Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of "realized relatedness." QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.
Pharmacology, Toxicology and Pharmaceutical Science
1
2%
Other
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7%
Unknown
8
19%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 September 2014.
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#3,791,329
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#1,368
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Outputs of similar age
#35,759
of 251,644 outputs
Outputs of similar age from Genetics
#41
of 123 outputs
Altmetric has tracked 27,776,330 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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