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. 2009 Jul;182(3):863-74.
doi: 10.1534/genetics.108.098913. Epub 2009 May 4.

Binary Trait Mapping in Experimental Crosses With Selective Genotyping

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Free PMC article

Binary Trait Mapping in Experimental Crosses With Selective Genotyping

Ani Manichaikul et al. Genetics. .
Free PMC article

Abstract

Selective genotyping is an efficient strategy for mapping quantitative trait loci. For binary traits, where there are only two distinct phenotypic values (e.g., affected/unaffected or present/absent), one may consider selective genotyping of affected individuals, while genotyping none or only some of the unaffected. If selective genotyping of this sort is employed, the usual method for binary trait mapping, which considers phenotypes conditional on genotypes, cannot be used. We present an alternative approach, instead considering genotypes conditional on phenotypes, and compare this to the more standard method of analysis, both analytically and by example. For studies of rare binary phenotypes, we recommend performing an initial genome scan with all affected individuals and an equal number of unaffected, followed by genotyping the full cross in genomic regions of interest to confirm results from the initial screen.

Figures

F<sc>igure</sc> 1.—
Figure 1.—
Analysis of intercross data from Boyartchuk et al. (2001) with significant results on chromosomes 5 and 13, and chromosome 2 shown for comparison. LOD curves are generated using four different methods and normalized by their corresponding 5% significance thresholds for comparison: (i) The LOD with full genotypes is calculated by standard interval mapping according to the method of Xu and Atchley (1996) (shaded line), with a 5% permutation threshold of 3.57; (ii) with genotypes on affecteds only, the LOD curve is calculated by the reverse approach using an intercross segregation assumption, LODR,seg (dashed shaded line), and the appropriate 5% simulation threshold is 3.57; (iii) using genotypes on 35 unaffecteds and all 35 affecteds, the LOD curve is calculated by the reverse approach, LODR (solid line), with a corresponding 5% permutation threshold of 3.65; and (iv) using genotypes on 35 unaffecteds and all 35 affecteds, the LOD curve is calculated by the full likelihood with the segregation assumption, formula image (dashed solid line), using constrained maximum likelihood. The corresponding 5% permutation threshold is 3.56.

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