Journal article
Genome-Wide Association Studies and the Problem of Relatedness Among Advanced Intercross Lines and Other Highly Recombinant Populations
Genetics (Austin), Vol.185(3), pp.1033-1044
07/01/2010
DOI: 10.1534/genetics.110.116863
PMCID: PMC2907190
PMID: 20439773
Abstract
Model organisms offer many advantages for the genetic analysis of complex traits. However, identification of specific genes is often hampered by a lack of recombination between the genomes of inbred progenitors. Recently, genome-wide association studies (GWAS) in humans have offered gene-level mapping resolution that is possible because of the large number of accumulated recombinations among unrelated human subjects. To obtain analogous improvements in mapping resolution in mice, we used a 34th generation advanced intercross line (AIL) derived from two inbred strains (SM/J and LG/J). We used simulations to show that familial relationships among subjects must be accounted for when analyzing these data; we then used a mixed model that included polygenic effects to address this problem in our own analysis. Using a combination of F
2
and AIL mice derived from the same inbred progenitors, we identified genome-wide significant, subcentimorgan loci that were associated with methamphetamine sensitivity, (
e.g
., chromosome 18; LOD = 10.5) and non-drug-induced locomotor activity (
e.g
., chromosome 8; LOD = 18.9). The 2-LOD support interval for the former locus contains no known genes while the latter contains only one gene (
Csmd1
). This approach is broadly applicable in terms of phenotypes and model organisms and allows GWAS to be performed in multigenerational crosses between and among inbred strains where familial relatedness is often unavoidable.
Details
- Title: Subtitle
- Genome-Wide Association Studies and the Problem of Relatedness Among Advanced Intercross Lines and Other Highly Recombinant Populations
- Creators
- Riyan Cheng - University of ChicagoJackie E Lim - Duke UniversityKaitlin E Samocha - University of ChicagoGreta Sokoloff - University of ChicagoMark Abney - University of ChicagoAndrew D Skol - University of ChicagoAbraham A Palmer - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.185(3), pp.1033-1044
- Publisher
- Genetics Society of America
- DOI
- 10.1534/genetics.110.116863
- PMID
- 20439773
- PMCID
- PMC2907190
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Language
- English
- Date published
- 07/01/2010
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984256839702771
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