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Fine-mapping a locus for glucose tolerance using heterogeneous stock rats
Leah C Solberg Woods1, Katie Holl, Michael Tschannen
1Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. lsolberg@mcw.edu
Heterogeneous stock (HS) rats enabled high-resolution mapping of quantitative trait loci. This study fine-mapped a glucose regulation locus on rat chromosome 1, demonstrating HS utility for complex trait genetics.
Area of Science:
- Genetics
- Animal Models
- Metabolic Research
Background:
- Quantitative trait loci (QTL) mapping is crucial for understanding complex traits.
- Heterogeneous stock (HS) animals offer high resolution for genetic mapping.
- A region on rat chromosome 1 is previously linked to glucose regulation.
Purpose of the Study:
- To fine-map a glucose regulation locus on rat chromosome 1 using HS rats.
- To demonstrate the utility of HS rat colonies for high-resolution genetic mapping.
- To investigate the genetic basis of glucose regulation in rats.
Main Methods:
- Administered glucose tolerance tests to 515 HS rats.
- Genotyped animals with 69 microsatellite markers across a 67 Mb region of rat chromosome 1.
- Employed regression modeling, hidden Markov models, and mixed model analysis accounting for family structure.
Main Results:
- Identified a single sharp peak indicating a quantitative trait locus within the targeted chromosomal region.
- Fine-mapped the locus to the interval between 205.04 and 207.48 Mb using positional bootstrapping.
- Confirmed the effectiveness of HS rats for high-resolution QTL fine-mapping.
Conclusions:
- HS rats are a powerful tool for fine-mapping complex traits like glucose regulation.
- Accurate genetic analysis in HS populations requires accounting for intricate family structures.
- This study successfully localized a glucose regulation locus, advancing understanding of metabolic traits.
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