Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs
Hernandez Sanchez, Jules, Visscher, Peter, Plastow, Graham, & Haley, Chris (2003) Candidate gene analysis for quantitative traits using the transmission disequilibrium test : the example of the melanocortin 4-receptor in pigs. Genetics, 164(2), pp. 637-644.
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 of in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.
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|Item Type:||Journal Article|
|Additional Information:||Articles free to read on journal website after 12 months|
|Keywords:||melanocortin 4 receptor, allele; allelism; analysis of variance; animal; article; biological model; cross breeding; female; gene linkage disequilibrium; gene locus; gene mapping; gene mutation; genetic analysis; genetic association; genetic linkage; genetic marker; genetic polymo, Alleles; Analysis of Variance; Animals; Crosses, Genetic; Female; Genetic Markers; Genotype; Linkage Disequilibrium; Male; Models, Genetic; Mutation; Phenotype; Polymorphism, Genetic; Quantitative Trait Loci; Receptor, Melanocortin, Type 4; Species Specif, Animalia; Sus scrofa|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Quantitative Genetics (incl. Disease and Trait Mapping Genetics (060412)|
|Divisions:||Current > Institutes > Institute of Health and Biomedical Innovation|
|Deposited On:||26 Mar 2013 22:53|
|Last Modified:||29 Jan 2015 04:42|
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