Candidate Gene Analysis for Quantitative Traits Using the Transmission Disequilibrium Test: The Example of the Melanocortin 4-Receptor in Pigs

Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differen...

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Bibliographic Details
Published in:Genetics (Austin) 2003-06, Vol.164 (2), p.637-644
Main Authors: Hernandez-Sanchez, Jules, Visscher, Peter, Plastow, Graham, Haley, Chris
Format: Article
Language:English
Subjects:
Alleles
Analysis of Variance
Animal populations
Animals
Crosses, Genetic
Female
Genes
Genetic Markers
Genotype
Hogs
Linkage Disequilibrium
Male
Models, Genetic
Mutation
Phenotype
Polymorphism, Genetic
Population genetics
Quantitative Trait Loci
Receptor, Melanocortin, Type 4 - genetics
Species Specificity
Swine
Time Factors
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Summary:Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal or in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1093/genetics/164.2.637