Journal article
High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F-2 and Advanced Intercross Mice
Genetics (Austin), Vol.198(1), p.103
09/01/2014
DOI: 10.1534/genetics.114.167056
PMCID: PMC4174923
PMID: 25236452
Abstract
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 F-2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F-2 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 F-2 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 F-2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.
Details
- Title: Subtitle
- High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F-2 and Advanced Intercross Mice
- Creators
- Clarissa C Parker - Middlebury College (United States, MiddleburyPeter Carbonetto - University of ChicagoGreta Sokoloff - University of ChicagoYeonhee J Park - University of ChicagoMark Abney - University of ChicagoAbraham A Palmer - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.198(1), p.103
- Publisher
- GENETICS SOCIETY AMERICA
- DOI
- 10.1534/genetics.114.167056
- PMID
- 25236452
- PMCID
- PMC4174923
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Number of pages
- 19
- Grant note
- 5R01MH079103; R01HG002899 / National Institutes of Health Human Frontiers Science Program
- Language
- English
- Date published
- 09/01/2014
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984256930902771
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