Journal
PHYSIOLOGICAL GENOMICS
Volume 41, Issue 1, Pages 102-108Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00178.2009
Keywords
type 2 diabetes; quantitative trait loci; mapping; mixed model analysis
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK-076977]
- Individualized Medicine Institute of the Medical College of Wisconsin
- Medical Research Council [G0701612] Funding Source: researchfish
- MRC [G0701612] Funding Source: UKRI
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Solberg Woods LC, Holl K, Tschannen M, Valdar W. Finemapping a locus for glucose tolerance using heterogeneous stock rats. Physiol Genomics 41: 102-108, 2010. First published January 12, 2010; doi:10.1152/physiolgenomics.00178.2009.-Heterogeneous stock (HS) animals provide the ability to map quantitative trait loci at high resolution [<5 Megabase (Mb)] in a relatively short time period. In the current study, we hypothesized that the HS rat colony would be useful for fine-mapping a region on rat chromosome 1 that has previously been implicated in glucose regulation. We administered a glucose tolerance test to 515 HS rats and genotyped these animals with 69 microsatellite markers, spaced an average distance of <1 Mb apart, on a 67 Mb region of rat chromosome 1. Using regression modeling of inferred haplotypes based on a hidden Markov model reconstruction and mixed model analysis in which we accounted for the complex family structure of the HS, we identified one sharp peak within this region. Using positional bootstrapping, we determined the most likely location of this locus is from 205.04 to 207.48 Mb. This work demonstrates the utility of HS rats for fine-mapping complex traits and emphasizes the importance of taking into account family structure when using highly recombinant populations.
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