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Prospects for association mapping in classical inbred mouse strains.

Bret A Payseur1, Michael Place

  • 1Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA. payseur@wisc.edu

Genetics
|February 6, 2007
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Association mapping in classical mouse strains has limited power for complex traits and can yield false positives due to genetic relatedness. Combining association mapping with QTL mapping is recommended for robust results.

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Area of Science:

  • Genetics
  • Genomics
  • Bioinformatics

Background:

  • Classical inbred mouse strains exhibit heritable variation in complex traits.
  • Historical recombination in these strains offers potential for high-resolution quantitative trait loci (QTL) discovery.
  • Association mapping correlates strain genotypes with phenotypes but its performance requires evaluation.

Purpose of the Study:

  • To assess the power and false-positive rate of genome-wide association mapping in classical inbred mouse strains.
  • To evaluate the impact of genetic factors like linkage disequilibrium and allele frequencies on association mapping.
  • To investigate the potential for spurious associations arising from unequal strain relatedness.

Main Methods:

  • Utilized computer simulations based on a dense single-nucleotide polymorphism (SNP) map.
  • Analyzed association mapping performance across 30 commonly used classical inbred mouse strains.
  • Measured statistical power and false-positive rates for detecting quantitative trait loci.

Main Results:

  • Expected power for detecting realistic complex trait effect sizes was often low.
  • Power varied significantly across the genome and was influenced by linkage disequilibrium and allele frequency distributions.
  • Unequal relatedness among strains created a substantial potential for spurious associations.

Conclusions:

  • Association mapping in classical mouse strains has limitations for complex traits due to variable power and false positives.
  • Genomic characteristics like linkage disequilibrium and allele frequencies impact mapping success.
  • Integrating association mapping with other methods, such as QTL mapping, is advisable for reliable genetic discoveries.