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Mapping multiple linked quantitative trait loci in non-obese diabetic mice using a stepwise regression strategy
H J Cordell1, J A Todd, G M Lathrop
1Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Genetical Research
|July 23, 1998
Summary
A new regression strategy effectively maps multiple linked quantitative trait loci (QTLs) in inbred populations. This method identified several diabetogenic loci on chromosomes 1 and 3 in NOD mice, with evidence of epistasis.
Area of Science:
- Genetics
- Statistical genetics
- Immunology
Background:
- Mapping quantitative trait loci (QTLs) is crucial for understanding complex diseases.
- Inbred populations offer advantages for genetic studies but require robust mapping strategies.
- Non-obese diabetic (NOD) mice are a valuable model for studying type 1 diabetes.
Purpose of the Study:
- To propose and validate a simple regression strategy for mapping multiple linked QTLs.
- To apply this method to identify diabetogenic loci in an NOD mouse backcross population.
- To investigate potential epistatic interactions between identified loci.
Main Methods:
- A stepwise linear regression approach was employed, involving the addition and deletion of markers.
- The strategy accounts for associations with neighboring markers to isolate individual effects.
- Standard statistical software packages were utilized for analysis.
Main Results:
- At least two, possibly three, diabetogenic loci were detected on both chromosome 1 and chromosome 3 in the NOD mouse backcross.
- Evidence for epistasis was observed between loci on chromosome 1.
- A potential epistatic interaction was also suggested between loci on chromosome 3.
Conclusions:
- The proposed regression strategy is a powerful tool for detecting and characterizing QTLs in inbred populations.
- Results align well with findings from congenic strain analysis, validating the method's efficacy.
- The study highlights the complexity of genetic control for diabetes in NOD mice.